Abstract
The purpose of this study was to examine the characteristics of proximal and distal gastroesophageal reflux in patients with gastroesophageal reflux disorder and analyze their clinical symptoms. A total of 67 patients with typical esophageal symptoms were selected for this study. All participants completed the reflux disease questionnaire and a questionnaire survey of extraesophageal symptoms. Diagnosis was made using a 24-h impedance-pH detection and proton pump inhibitor. The results showed that the proximal reflux group had a higher number of acid reflux episodes compared to the distal reflux group (P < 0.05). Similarly, the proximal reflux group also had a higher number of gas reflux episodes compared to the distal reflux group (P < 0.05). On the other hand, the distal reflux group had a higher number of mixed reflux episodes compared to the proximal reflux group (P < 0.05). These differences were statistically significant. This study revealed that acid reflux and gas reflux were more predominant in the proximal reflux group, while mixed reflux was more predominant in the distal reflux group.
1 Introduction
Gastroesophageal reflux disease (GERD) is characterized by the inadequate functioning of the lower esophageal sphincter (LES), resulting from various local or systemic causes. Here gastric and duodenal contents flow back into the esophagus resulting in a series of symptoms such as heartburn. As per the endoscopic findings, GERD is generally classified into three types, namely, non-erosive reflux disease, reflux esophagitis (RE), and Barrett’s esophagus [1]. GERD has become one of the most common gastrointestinal diseases in China, and is gaining greater attention. Typical symptoms of GERD include heartburn, acid reflux, and chest pain. Atypical symptoms encompass abdominal discomfort, chronic cough, a sensation of a foreign body in the throat, and asthma, among others [2,3].
Epidemiological data show that the incidence of GERD in western countries is higher than the Asia-Pacific region. Estimates suggest that the prevalence of GERD in European and American countries ranges from 10 to 15%, while in Asia, it is reported to be around 5% [4]. The most recent report from China estimates the prevalence to be 3.8% [5].
The pathogenesis of GERD is multifaceted and typically encompasses the following aspects [6]: (1) The pressure of LES is reduced, and the anti-reflux barrier function is weakened. Using esophageal pressure measurement, Hou et al. found that the pressure of LES was decreased in 59% of the 27 patients with GERD in their study. (2) Esophageal peristalsis dysfunction leads to decreased esophageal clearance ability; (3) It involves impairment of the esophageal mucosal barrier function; (4) The diaphragm participates in the anti-reflux barrier; (5) Angle of His; (6) Mental and psychological factors. At the same time, diabetes is also closely related to the incidence of GERD [7]. With improvements in living standards, changes in dietary patterns, and increased daily life stress and work pressures, there has been a global increase in GERD cases in recent years [8].
The 24-h esophageal pH monitoring is a crucial diagnostic method for GERD. This monitoring involves continuous pH monitoring of the esophagus over 24 h under normal physiological conditions. It helps determine if the patient has pathological acid reflux, assess the severity of reflux, examine the pattern of acid reflux throughout the day and night, establish the relationship between acid reflux and symptoms, and assess the patient’s response to treatment. It was previously considered the “gold standard” for diagnosing GERD [9]. Currently, GERD diagnosis mainly relies on the scoring system developed by Johnson and DeMeester [10].
Recent studies have highlighted the significance of weak acid and weak base reflux in GERD. Xu et al. [11] found that weak alkaline reflux also plays an important role in the pathogenesis of GERD. However, the traditional 24-h ambulatory esophageal pH monitoring technology can only measure changes in H+ concentration and cannot detect non-acid reflux (weak acid and weak base reflux), let alone the composition of reflux. Therefore, with the increasing challenge of diagnosing GERD, 24-h esophageal multichannel intraluminal impedance monitoring combined with pH-metry (24 h MII-pH) technology has been widely used in the diagnosis of GERD. 24-h MII-pH monitoring is considered to be the most sensitive method for monitoring reflux events, which can not only help identify whether the reflux is acid reflux, weak acid reflux, or weak base reflux but can also distinguish whether the reflux is liquid, gas, or mixed reflux. This method enables the detection of various types of esophageal reflux characteristics, including fluid, gas, acid, and non-acid characteristics [12].
Currently, due to its limited popularity, high equipment cost, and poor patient tolerance, 24-h esophageal impedance pH monitoring is not commonly available for most GERD patients.
Proximal and distal reflux: These refer to the reflux of impedance channel 15 and 5 cm above LES, respectively. 24-h MII-pH monitoring not only can help monitor the reflux 5 cm above LES, but can also monitor the reflux 15 cm away from the proximal end of LES. However, there is currently no consensus on the reference standard for proximal esophageal reflux.
The findings of these studies indicate that proximal reflux episodes could potentially contribute to respiratory symptoms [13]. There is evidence that the proximal esophagus seems to be more sensitive to the distal esophagus than to heartburn and chest pain (typical symptoms) caused by mechanical dilation, electrical stimulation, [14] and acid reflux. A recent study [15] observed that the afferent nerves in the proximal mucosa are shallower compared to those in the distal region. This anatomical difference may explain the heightened sensitivity to symptoms induced by proximal esophageal reflux.
2 Materials and methods
2.1 Study participants
In this study, we recruited patients with typical esophageal symptoms, including acid reflux, heartburn, chronic cough, and sensation of a foreign body in the throat, from the Department of Gastroenterology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China between November 2018 and October 2019. We included patients aged 18–80 years, regardless of gender, and with chief complaints that included extraesophageal symptoms.
Respondents completed questionnaires on reflux disease (the Reflux Disease Questionnaire or the RDQ) and extraesophageal symptoms [16] under the guidance of physicians, and we calculated the RDQ score. GERD was indicated when the total score was ≥12, and 24-h MII-pH monitoring was done. Based on the symptom scores and 24-h MII-pH monitoring results, we divided the patients into the proximal reflux group and the distal reflux group, with 67 cases in total, consisting of 40 males and 27 females.
Inclusion criteria: (1) Patients who obtained a total score of ≥12 on the RDQ; (2) Patients capable of cooperating with 24-h MII-pH monitoring; (3) Patients within the age range of 18–80 years; (4) Patients who had not taken acid inhibitors, antacids, or prokinetic drugs in the 2 weeks prior to the examination; (5) Among patients reporting a sensation of a foreign body in the throat, only those whose laryngoscopy indicated no significant injury to the throat mucosa were included; (6) Patients with chronic cough whose chest digital radiography results were normal; (7) Patients without a history of neck, nasopharynx, or gastrointestinal surgery.
Exclusion criteria: (1) Pregnant and lactating women; (2) Patients who had participated in a clinical trial within the past 3 months or were currently enrolled in a trial; (3) Chronic cough caused by other factors such as respiratory tract infection or chronic bronchitis; (4) Patients whose sensation of a foreign body in the throat was attributed to other causes, such as chronic pharyngitis or chronic tonsillitis; (5) Patients who had received anti-acid and prokinetic drugs within 2 weeks prior to the examination; (6) Patients with a previous history of neck, nasopharynx, or gastroesophageal surgery.
2.2 General information
We collected various general details from the participants, including age, gender, place of residence, height, weight, smoking history, drinking history, previous surgery history, as well as information on proton pump inhibitor’s (PPI) dosage and duration.
2.3 RDQ and extraesophageal symptom questionnaire
The RDQ was used to evaluate the severity and frequency of acid reflux, heartburn, retrosternal pain, and reflux. The severity of symptoms was evaluated using a 5-point rating scale: 1 for asymptomatic, 2 for very mild symptoms that did not significantly impact daily life, 3 for moderately noticeable symptoms occasionally affecting daily activities, 4 for symptoms ranging between moderate and severe, and 5 for severe symptoms significantly impacting daily life and activities.
The frequency of symptoms was rated using a 5-point scale as follows: 0 if the symptom never occurred; 1 if the symptoms lasted less than 1 day in the last 1 week; 2 if the frequency of the symptom in the last 1 week was for 1 day; 3 if the symptom in the last 1 week lasted for 2–3 days; 4 if the symptom occurred on 4–5 days within the last 1 week; 5 if the symptom occurred on 6 days or was felt every day within the last 1 week. The overall RDQ score was calculated by summing the scores for symptom severity and frequency. A score of ≥12 points indicated a diagnosis of GERD (Tables 1–3).
Symptom frequency of reflux disease questionnaire
Symptom | Never | <1 day in 1 week | 1 day in 1 week | 2 or 3 days in 1 week | 4 or 5 days in 1 week | 6 or 7 days in 1 week |
---|---|---|---|---|---|---|
Heartburn | 0 | 1 | 2 | 3 | 4 | 5 |
Acid reflux | 0 | 1 | 2 | 3 | 4 | 5 |
Food reflux | 0 | 1 | 2 | 3 | 4 | 5 |
Chest pain | 0 | 1 | 2 | 3 | 4 | 5 |
Symptom severity of reflux disease questionnaire
Symptom | Asymptomatic | Slight | Obvious | Heavier | Severe |
---|---|---|---|---|---|
Heartburn | 1 | 2 | 3 | 4 | 5 |
Acid reflux | 1 | 2 | 3 | 4 | 5 |
Food reflux | 1 | 2 | 3 | 4 | 5 |
Chest pain | 1 | 2 | 3 | 4 | 5 |
Atypical symptoms and extraesophageal symptoms questionnaire
Burning post-sternal discomfort and pain | Yes | No |
Non-burning chest discomfort and pain | Yes | No |
Feeling of the food sticking, staying, and abnormal sensation of food passing through the esophagus | Yes | No |
Difficulty and pain in swallowing | Yes | No |
Lump sensation, foreign body sensation, burning sensation, pain in the throat | Yes | No |
Snoring, nocturnal sleep apnea | Yes | No |
Hoarse voice | Yes | No |
Pain in the upper abdomen (before/after meals) | Yes | No |
Bloating | Yes | No |
Food nausea and nausea | Yes | No |
Hiccups, belching | Yes | No |
Sour/bitter taste in the mouth | Yes | No |
Dental caries, tooth erosion | Yes | No |
Bronchiectasis, chronic bronchitis | Yes | No |
Chronic or long-lasting cough | Yes | No |
Asthma | Yes | No |
Chronic obstructive pulmonary disease | Yes | No |
2.4 Research methodology
2.4.1 Grouping method
Participants in the study completed the RDQ and a questionnaire survey on extraesophageal symptoms under the supervision of doctors. RDQ scores were calculated, and a diagnosis of GERD was established if the total score was equal to or higher than 12. All participants also underwent 24-h MII-pH monitoring. Based on the symptom scale and 24-h MII-pH monitoring results, we divided the participants into the proximal reflux group and the distal reflux group. There were 67 cases in total, consisting of 39 cases in the proximal reflux group and 28 cases in the distal reflux group.
2.4.2 Preparation before the examination
Pre-procedural preparation for patients: Patients were required to be fasting and avoid drinking water for at least 6–8 h to prevent vomiting and aspiration. Before the examination, patients were required to also stop taking medications that affect esophageal motility and change the gastric pH value, PPI drugs, and other acid-inhibiting drugs for 2 weeks, and asked to remain off motility drugs for more than 1 week prior to the procedure;
After the electronic gastroscopy, high-resolution manometry was arranged following an interval of more than 3 days;
We collected the detailed medical history, including symptoms (heartburn, acid reflux, dysphagia, chest pain, and so on) and duration, heart disease, severe lung disease, operation history, PPI usage, and history of use of gastrointestinal motility drugs, and so on;
Participants were given detailed information before the examination to make them understand the process of investigation, its necessity and importance, allay their fears and stress to make them cooperate better and successfully complete the examination;
All participants provided their informed consent and signed the necessary documentation for the 24 h MII-pH monitoring and examination.
2.4.3 Instructions for participants
24 h MII-pH monitoring would record all types of gastroesophageal reflux;
Fasting for 6–8 h before the examination was required;
Withdrawal requirements before the examination: PPI drugs and other acid inhibitors were stopped for 2 weeks and prokinetic drugs were stopped for more than 1 week prior to the procedure;
Participants were given normal diet during the 24 h MII-pH and asked to avoid acidic or alkaline food;
Participants were required to fill in the inspection log carefully and avoid smoking and drinking; if otherwise, this was to be recorded in the log;
During the 24 h MII-pH monitoring, the catheter should be in place and prevented from falling off;
Participants were requested to protect the examination instrument from damage as it was a valuable and delicate tool;
Participants were requested to contact the team if there was no digital display or if they noticed any abnormal condition during the monitoring period;
Participants were asked to return to the examination room the next morning to remove the recorder and hand over the inspection log.
2.4.4 24 h pH impedance combined monitoring procedure
A new No.5 battery, electrode catheter, calibration solution of pH 4 and pH 7.01, data recorder, and satchel were prepared for each participant. The new No. 5 battery for the data recorder was fitted and the data recorder was placed in the satchel. Once the electrode conduit connector was connected to the interface of the corresponding color, the data recorder displayed the calibration mode. After setting the date and time, the confirm key was pressed to start soaking the catheter. After soaking for 60 s, the catheter was wiped dry and put into the pH 4.0 buffer to start the calibration. About 3 min later, after the calibration of pH 4.0, the catheter was put into clean water and wiped dry. After that, a buffer solution of pH 7.01 was added to start the calibration; After 3 min of pH 7.01 calibration, the catheter was placed in clean water and wiped dry. With this, the pH calibration of the catheter was completed.
A lubricant (liquid paraffin) was applied along a 20 cm length at the front end of the electrode catheter. The patient was asked to sit and the catheter was inserted into the nasal cavity. When the catheter was inserted about 15 cm into the pharynx, the patient was instructed to breathe normally and swallow. The catheter was inserted into the esophagus in parallel to the patient swallowing, until it was 5 cm above the LES, and allowed to enter the stomach first and then pulled back. The position of LES was determined by the change in pH value of the instrument and compared with the position during manometry. After determining the position, the catheter was fixed, the strap position was adjusted, and the “start recording” button was pressed.
The doctor recorded the starting time and guided the patient on how to fill in the record log. After the 24-h monitoring, the patient returned the instrument. The data were imported into the data analysis software in the computer along with the patient information and saved. After confirming that the 24-h data were complete, the participants were requested to stay for half an hour and then leave. The data were transferred to the corresponding patient’s file, double-clicked to enter the curve interface, and the system automatically analyzed the data and gave the report.
2.4.5 Observation index
Depending on the pH value of the reflux, it was divided into acid reflux (pH < 4), weak acid reflux (pH 4–7), and non-acid reflux (pH > 7). According to the impedance value of the reflux, reflux was divided into liquid reflux (at least two continuous impedance channels appeared retrogradely from the end impedance channel, and the impedance value decreased by more than 50%), gas reflux (at least two impedance channels appeared, and the impedance value increased by more than 500 Q), and mixed reflux (gas reflux occurred immediately before or simultaneously with liquid reflux). Esophageal acid exposure time (AET) refers to the percentage of episodes of pH < 4 in the total monitoring time as measured by the pH electrode 5 cm above LES. AET > 4.2% indicated pathological acid reflux.
In this study, the main acquisition indicators included reflux, total acid exposure time percentage, percentage of episodes of pH < 4 in the total time which is the most effective indicator to observe pathological acid reflux, acid exposure time, frequencies of gas-liquid mixed reflux, acid, weak acid, and non-acid reflux, liquid, gas, and mixed reflux, proximal reflux, and distal reflux, symptom correlation index, and DeMeester score, amongst others.
DeMeester score [17]: According to the longest number of reflux episodes (>5 min), the number of episodes of reflux, the number of episodes (percentage) of pH < 4 in supine position, the number of episodes (percentage) of pH < 4 in upright position, and the number of episodes (percentage) of total pH < 4. If the final comprehensive score was more than 14.72, it was diagnosed as pathological acid reflux. If the symptom correlation index was >50% and symptom correlation probability was >95%, it indicated that the symptoms were related to reflux, and reflux referred to all types of reflux events.
2.4.6 Statistical analysis
Data analysis was performed using SPSS 23.0 statistical software. If the measurement data were normally distributed and showed homogeneity of variance, they were presented as mean value ± standard deviation. In this case, an independent sample t-test was used to compare the data between groups. If the measurement data did not follow a normal distribution, quartiles (lower quartile, median, and upper quartile) were used to represent the data. Non-parametric rank sum tests were employed to compare the data between groups in such cases. Count data were presented as the number of cases and percentages. A chi-square test was used to compare count data between groups, with a significance level of P < 0.05 considered statistically significant.
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Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of the First Affiliated Hospital of Henan University of Science and Technology. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.
3 Results
3.1 Comparison of clinical baseline data
Based on the symptom rating table and 24-h MII-pH monitoring results, the 67 patients in our study were divided into two groups: the proximal reflux group and the distal reflux group. The proximal reflux group consisted of 28 patients (41.8%), including 17 males and 11 females, with ages ranging from 34 to 77 years and a mean age of (57.46 ± 10.83) years. The average body mass index (BMI) was (20.92 ± 3.21), and the RDQ score was 14 (13, 15.25).
In the distal reflux group, there were 39 patients (58.2%), comprising of 23 males and 16 females, with ages ranging from 18 to 77 years and a mean age of (52.31 ± 11.85) years. The average BMI was (21.02 ± 2.56), and the RDQ score was also 14 (13, 15.5). There were no significant differences in gender, age, and BMI between the two groups (Table 4). RDQ scores of both groups were ≥12, and the statistical analysis showed no significant difference between them (details are given in Table 5).
General information of patients included
Distal reflux group | Proximal reflux group | P | |
---|---|---|---|
Number of cases (persons) | 28 | 39 | — |
Male/female ratio (person) | 17/11 | 23/16 | 0.886 |
Age | 57.46 ± 10.83 | 52.31 ± 11.85 | 0.078 |
BMI (kg/m2) | 20.92 ± 3.21 | 21.02 ± 2.56 | 0.800 |
RDQ score of proximal and distal reflux patients
Proximal reflux group | Distal reflux group | Statistics | P | |
---|---|---|---|---|
RDQ | 14.00 (13.00, 15.50) | 14.00 (13.00, 15.25) | z = −1.466 | 0.143 |
3.2 Manifestation of symptoms
Based on the results of 24-h MII-pH monitoring, in addition to experiencing typical symptoms, the proximal reflux group frequently reported extraesophageal symptoms such as foreign body sensation in the throat and chronic cough. The number of episodes of weak acid reflux, gas-liquid mixed reflux, total number of proximal refluxes, number of proximal weak acid reflux, and number of proximal non-acid reflux in GERD patients with extraesophageal symptoms were higher than those in GERD patients without extraesophageal symptoms. There were no significant differences in the total reflux times of pH ≤ 4, the percentage of total reflux times of pH ≤ 4, the longest reflux time, DeMeester score, acid reflux episodes, liquid reflux episodes, proximal acid reflux episodes, or standing and lying position-related reflux episodes.
3.3 24 h pH impedance monitoring results
The frequency of acid reflux in the proximal reflux group was 37 times (31, 41), which was more than that in the distal reflux group of 35 (30, 39), and the difference was statistically significant (z = −3.456, P < 0.05). The number of gas reflux episodes in the proximal reflux group was 27 times (23, 31.5), which was more than 19 (16, 23) in the distal reflux group, and the difference was statistically significant (z = −22.023, P < 0.05). The number of mixed reflux episodes in the distal reflux group was 29 (24.75, 35.25), which was higher than 21 (18, 25) in the proximal reflux group (z = −24.444, P < 0.05). In addition, there was no significant difference in the number of times of weak acid reflux, non-acid reflux, and liquid reflux between the two groups (details are given in Tables 6 and 7).
Comparison of acid and base reflux in proximal reflux group and distal reflux group
Group | Number of cases | Reflux acidity and alkalinity | ||
---|---|---|---|---|
Acid reflux | Weak acid reflux | Non-acid reflux | ||
Distal reflux group | 28 | 35 (30, 39) | 31 (25.75, 35) | 4.5 (2.75, 6.25) |
Proximal reflux group | 39 | 37 (31, 41) | 31 (25.5, 36) | 5 (3, 6.5) |
Statistics | — | z = −3.456 | z = −2.517 | z = −1.725 |
P | — | P = 0.001 | P = 0.120 | P = 0.084 |
Comparison of physical properties between proximal reflux group and distal reflux group
Group | Number of cases | Reflux acidity and alkalinity | ||
---|---|---|---|---|
Liquid reflux | Gas reflux | Mixed reflux | ||
Distal reflux group | 28 | 20 (17, 26.25) | 19 (16, 23) | 29 (24.75, 35.25) |
Proximal reflux group | 39 | 20 (18, 24.5) | 31 (25.5, 36) | 21 (18, 25) |
Statistics | — | z = −2.312 | z = −22.023 | z = −24.444 |
P | — | P = 0.210 | P = 0.000 | P = 0.000 |
4 Discussion
In this study, we compared the pH of reflux between the proximal reflux group and the distal reflux group and found that the frequency of weak acid reflux in GERD patients with extraesophageal symptoms was significantly higher than that in the typical GERD group, which can explain why some patients only had cough symptoms but no obvious acid reflux, heartburn, and other typical manifestations. At the same time, compared with the typical GERD group, the number of episodes of gas-liquid mixed reflux in GERD patients with extraesophageal symptoms was more, and the total number of episodes of proximal reflux, the number of episodes of proximal weak acid reflux, and the number of episodes of proximal non-acid reflux were significantly higher, indicating that due to the lighter gas mass, it was easier for the gas-liquid mixed reflux to move to the proximal esophagus than the liquid reflux.
As the last barrier of anti-reflux, the high pressure of the upper esophageal sphincter (UES) can cause a foreign body sensation in the pharynx and even dysphagia. However, the low pressure of UESP makes it easier for the reflux to break through the anti-reflux barrier of the UES and enter the pharynx and larynx, which can cause cough symptoms by directly stimulating the cough receptors in the pharynx and larynx. Under normal circumstances, cough symptoms are a protective mechanism for the body, which can, to a certain extent, prevent reflux from being inhaled into the airway by mistake. Thus, it increases the risk of cough caused by direct stimulation of the airway by reflux inhalation, aspiration pneumonia, and even asphyxia.
Some research results have proved that [18] there is a relationship between the occurrence of esophagitis and gastroesophageal reflux. Acids in reflux can cause esophageal squamous epithelium damage and produce inflammatory reaction. At present, it has been confirmed in GERD patients and RE models that inflammatory products that cause esophagitis include prostaglandin and reactive oxygen species [19]. This study provides a reference for further research on esophagitis caused by gastroesophageal reflux by exploring the substances of proximal reflux and distal reflux.
Current research and understanding pertaining to GERD is that esophageal motility disorders are generally considered as due to the following factors: (1) Low or lack of LES pressure, transient LES relaxation; (2) The function of clearing esophageal reflux is weakened due to esophageal motility disorder; (3) Changes in esophagogastric angle (angle of His); (4) The barrier function of esophageal mucosa is damaged; (5) The changes in mucosal function in the cardia; (6) Psychological factors.
Among these, the dysfunction of esophageal anti-reflux barrier is one of the important factors in the pathogenesis of GERD, mainly manifested as transient relaxation of LES, decreased LES pressure, and ineffective esophageal movement. However, some studies suggest that the induction of cough is related to the retention time of reflux in the esophagus but not to the acidity of reflux. Gastroesophageal reflux cough, as a form of GERD, with cough as the main symptom, is generally considered as one of the most common causes of chronic cough, like cough variant asthma, upper airway cough syndrome, and eosinophilic bronchitis [20].
The typical symptoms of GERD are heartburn and acid reflux, and extraesophageal symptoms are also common in GERD patients. Extraesophageal symptoms refer to a series of symptoms caused by the reflux of gastric contents above the UES [21,22]. Extraesophageal symptoms of GERD may exist alone or simultaneously with typical symptoms [23]. In literature, GERD extraesophageal symptoms are referred to by using a variety of different labels such as laryngopharyngeal reflux, posterior laryngitis, reflux laryngitis, supraesophageal reflux, extraesophageal reflux, and gastroesophageal laryngeal reflux, amongst others [24].
Patients with GERD commonly experience a variety of extraesophageal symptoms, including throat clearing, chronic cough, voice hoarseness, excessive laryngeal mucus, postnasal drip sensation, dysphagia, chronic cough, burning sensation in the throat, sensation of a foreign body in the throat, and so on. The American Broncho-Esophagological Association found that the most relevant symptoms of reflux were clearing the throat (98.3%), intractable cough (96.6%), heartburn or dyspepsia (95.7%), change in quality of the voice (94.9%), sensation of a foreign body in the throat (94.9%), choking asphyxia (90.7%), and dysphagia (86.3%) [25]. Extraesophageal symptoms of GERD are also very common in children. In children, gastroesophageal pharyngeal reflux can lead to apnea, recurrent upper respiratory tract infections, laryngeal chondromalacia, subglottic stenosis, otitis, and other conditions [26].
Compared to the typical symptoms of GERD, extraesophageal symptoms tend to occur more frequently in the upright position during the daytime, while typical symptoms are more commonly experienced in a regular pattern during the supine position at night [27,28]. In a study conducted by Lewin et al. in 2003 [29], they found that among 34 patients with GERD and extraesophageal symptoms, reflux episodes occurring in the upright position accounted for 91% of cases, which aligns with the distinction between extraesophageal and typical GERD symptoms. With the global attention and continuous research on GERD, there has been steady research on GERD in China based on the actual situation of Chinese people. This has resulted in the establishment of the consensus for GERD treatment in China through the efforts of the dynamic group of experts from the gastrointestinal society of the Chinese Medical Association.
Currently, there are limited studies both domestically and internationally focusing on reflux types in patients with GERD. More large-scale multicenter clinical studies and related animal experiments are needed to explore the mechanisms and influencing factors of reflux, aiming to enhance the diagnosis and treatment efficacy of GERD.
5 Conclusion
The proximal reflux group exhibited a significantly higher frequency of acid reflux and gas reflux compared to the distal reflux group, indicating that acid reflux and gas reflux were more predominant in the proximal region. The number of episodes of mixed reflux in the distal reflux group was more than that in the proximal reflux group, and the difference was statistically significant, which confirmed that the distal reflux group was predominated by mixed reflux episodes. The number of episodes of weak acid reflux and gas-liquid mixed reflux in patients with GERD who had chronic cough were significantly more than those in the control group. This finding suggests that symptoms such as acid reflux and heartburn may not be apparent in some patients. The increased frequency of proximal weak acid and non-acid reflux further supports the possibility of cough triggered by throat stimulation.
Abbreviations
- AET
-
acid exposure time
- GERD
-
gastroesophageal reflux disease
- LES
-
lower esophageal sphincter
- PPI
-
proton pump inhibitor
- RDQ
-
questionnaires on reflux disease
- RE
-
reflux esophagitis
- UES
-
upper esophageal sphincter
- 24 h MII – pH
-
24-h esophageal multichannel intraluminal impedance monitoring combined with pH-metry
Acknowledgements
We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.
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Funding information: Scientific Research Fund of Henan Provincial Science and Technology Department (No. 182102310302, No. 222103810046, No. 232103810047) and Luoyang public welfare special project (No. 2022001A).
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Author contributions: Conceive and design of experiments: Ping Wang; data analysis and interpretation: Jie Yu, Bing-Lin Heng, and Hong Guo; data reduction: Yan Chen, and Hong Guo; writing the manuscript: Ping Wang, Jie Yu, and Yan Chen; manuscript revision: Ying-Jian Zhang, Hong Guo, and Bing-Lin Heng.
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Conflict of interest: The authors declare that they have no competing interests.
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Data availability statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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© 2023 the author(s), published by De Gruyter
This work is licensed under the Creative Commons Attribution 4.0 International License.
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- Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
- Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
- Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
- Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
- Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
- Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
- Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
- Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
- Special issue The evolving saga of RNAs from bench to bedside - Part I
- FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
- Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
Artikel in diesem Heft
- Research Articles
- Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
- Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
- circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
- circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
- WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
- Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
- Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
- 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
- Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
- PVT1/miR-16/CCND1 axis regulates gastric cancer progression
- Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
- Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
- SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
- Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
- lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
- SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
- Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
- Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
- Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
- circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
- Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
- UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
- Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
- Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
- UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
- LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
- Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
- Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
- circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
- Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
- Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
- A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
- WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
- Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
- Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
- Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
- Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
- Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
- Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
- Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
- CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
- Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
- Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
- HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
- The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
- Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
- A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
- Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
- Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
- TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
- The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
- miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
- Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
- IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
- Comprehensive analysis of the role of SFXN family in breast cancer
- Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
- Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
- AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
- Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
- Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
- Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
- The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
- Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
- Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
- F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
- Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
- Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
- Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
- Cholesterol induces inflammation and reduces glucose utilization
- circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
- NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
- The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
- miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
- Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
- α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
- Changes of microbiota level in urinary tract infections: A meta-analysis
- Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
- Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
- Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
- Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
- Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
- Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
- Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
- An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
- Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
- Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
- PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
- miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
- lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
- Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
- Subjective well-being in informal caregivers during the COVID-19 pandemic
- Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
- Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
- Bladder cancer screening: The new selection and prediction model
- circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
- Prone position effect in intensive care patients with SARS-COV-2 pneumonia
- Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
- Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
- Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
- Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
- Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
- Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
- Clinical significance of serum MBD3 detection in girls with central precocious puberty
- Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
- Collagen treatment of complex anorectal fistula: 3 years follow-up
- LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
- Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
- SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
- A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
- circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
- hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
- Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
- lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
- Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
- Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
- Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
- Analysis of somatic mutations and key driving factors of cervical cancer progression
- Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
- Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
- Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
- Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
- Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
- Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
- Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
- Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
- The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
- Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
- Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
- The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
- Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
- Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
- Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
- The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
- Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
- Clinical characteristics of current COVID-19 rehabilitation outpatients in China
- Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
- miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
- The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
- Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
- The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
- Identification of cuproptosis-related genes for predicting the development of prostate cancer
- Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
- Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
- A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
- Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
- Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
- Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
- A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
- A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
- Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
- The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
- Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
- AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
- Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
- Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
- LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
- Factors associated with gastrointestinal dysmotility in critically ill patients
- Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
- Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
- Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
- Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
- Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
- The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
- Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
- Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
- Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
- Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
- Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
- Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
- D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
- WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
- Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
- Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
- Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
- Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
- Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
- Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
- A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
- Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
- A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
- Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
- The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
- Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
- CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
- Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
- KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
- Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
- The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
- Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
- Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
- Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
- Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
- Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
- Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
- lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
- Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
- The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
- The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
- Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
- MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
- Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
- Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
- Predictors of gastrointestinal complaints in patients on metformin therapy
- Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
- A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
- Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
- miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
- Clinical features and management of lymphoepithelial cyst
- Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
- ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
- Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
- The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
- Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
- Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
- Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
- miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
- Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
- Review Articles
- Prenatal diagnosis of fetal defects and its implications on the delivery mode
- Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
- Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
- Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
- Vitamin C and epigenetics: A short physiological overview
- Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
- Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
- Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
- Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
- The progress of autoimmune hepatitis research and future challenges
- METTL16 in human diseases: What should we do next?
- New insights into the prevention of ureteral stents encrustation
- VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
- Case Reports
- Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
- Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
- Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
- Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
- Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
- Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
- Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
- Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
- Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
- Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
- CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
- Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
- Anesthetic management of fetal pulmonary valvuloplasty: A case report
- Rapid Communication
- Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
- Erratum
- Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
- Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
- Retraction
- Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
- Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
- Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
- Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
- Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
- Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
- Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
- Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
- Special issue The evolving saga of RNAs from bench to bedside - Part I
- FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
- Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer