Home Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
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Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C

  • Haiyan Lan , Gongchen Duan , Yunxia Zuo , Tianzheng Lou , Junlong Xu , Chuxiao Shao and Jimin Wu EMAIL logo
Published/Copyright: October 17, 2023

Abstract

Malignant hyperthermia (MH) is an inherited skeletal muscle disorder caused primarily by a genetic mutation, usually in the calcium channel gene of the muscle. This mutation can lead to muscle hypersensitivity to volatile anesthetics (such as sevoflurane) and the depolarizing muscle relaxant succinylcholine, resulting in hyperthermia, muscle stiffness, metabolic disturbances, and other severe physiological reactions. This condition may prove fatal unless it is recognized in its early stages and treatment is administered promptly and aggressively. We report a 13-year-old adolescent who underwent laparoscopic appendectomy and developed MH after the use of inhalational anesthetics, manifested by unremitting hyperthermia with a maximum temperature of 44.2°C, muscle rigidity, tachycardia, hypercapnia; and malignant arrhythmias, cardiogenic shock, hyperkalemia, metabolic, and respiratory acidosis. After early and timely recognition, multidisciplinary management and administration of dantrolene, the case was successfully treated. Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu). Due to the lack of ready-made dantrolene in our hospital, the patient in this case received dantrolene treatment only 6 h after the first observation of high body temperature. We review the development of the disease and summarize the success of treatment and what can be done to improve the chances of saving the patient’s life if dantrolene is not available in time.

1 Introduction

Malignant hyperthermia (MH) is a relatively rare familial genetic muscle disease. In most patients, MH is triggered by conventional inhalation anesthetics or depolarizing muscle relaxants (succinylcholine), typically resulting in systemic muscle rigidity, an abnormally rapid increase in body temperature, and hypermetabolic state. Although the incidence of MH is low, the disease progresses rapidly and has a high mortality rate if not diagnosed and treated promptly [1]. The exact incidence of MH is unknown, but is estimated at 1:10,000–1:250,000 of anesthetic procedures, and children seem to be more susceptible than adults [2]. The mortality of MH is very high, and early diagnosis and treatment are very important.

In May 2022, we successfully treated a patient with fulminant MH, when dantrolene was not available in time, and herein summarize the case.

2 Case presentation

A healthy 13-year-old Chinese (Han ethnicity) boy presented for an emergency laparoscopic appendicectomy weighing 46 kg and 160 cm tall with an American Society of Anesthesiologists class I. He had a history of attention-deficit/hyperactivity disorder and premature birth (1 month premature). Prior to surgery he was clinically stable with a febrile temperature of 38.1°C and heart rate (HR) was 117 beats/min.

The patient was admitted to the operating room with the following preoperative vital signs: noninvasive blood pressure of 89/48 mmHg, HR of 85 beats/min, and pulse oxygen saturation of 99%. General anesthesia was induced with midazolam (2 mg), propofol (100 mg), sufentanil (15 µg), and cisatracurium (10 mg) followed by endotracheal intubation. Mechanical ventilation was set up and the end-tidal carbon dioxide (PetCO2) and nasopharyngeal temperature (NT) were continuously measured. The airway pressure was 14 mmHg, PetCO2 was 35 mmHg, and temperature was 37.3°C. Anesthesia was maintained with sevoflurane inhalation, propofol infusion, and remifentanil infusion.

One hour after the start of the procedure, the patient’s NT rose to 37.5°C, PetCO2 rose to 48 mmHg, HR rose to 100 beats/min, airway pressure reached 25 mmHg, and stiffness of the neck muscles developed. In the subsequent 15 min, despite making several adjustments to increase minute ventilation, the end-expiratory carbon dioxide (PetCO2) continued to rise from 48 to 81 mmHg. At the same time, his temperature rose to 38.5°C, his HR increased to 120 beats/min, and he developed mixed metabolic and respiratory acidosis on arterial blood gas (ABG) analysis (Table 1). The clinical diagnosis of MH was suspected. Sevoflurane inhalation was immediately stopped, the sodium lime and breathing circuit were replaced, and hyperventilated with 100% oxygen, surgeons were told to end the operation as soon as possible and the hospital crisis management system was activated.

Table 1

Intraoperative body temperature and ABG analysis results

Time Body temperature (℃) pH value PCO2 (mmHg) K+ (mmol/L) Lac (mmol/L) HCO3 (mmol/L) Blood sugar (mmol/L) BE (mmol/L)
8:23 39.4 7.015 100.1 4.59 2.76 25.0 6.3 −8.3
8:56 44.2 6.974 118.9 6.30 6.14 27.0 7.6 −7.3
9:08 42.7 6.990 76.5 6.14 9.49 18.0 6.5 −13.9
9:19 41.6 6.770 134.0 6.03 8.89 19.0 6.3 −17.5
9:35 40.2 7.089 73.5 5.80 9.69 21.7 6.3 −8.6
9:59 38.1 7.247 45.2 4.62 9.37 19.2 5.2 −7.7
10:45 36.8 7.003 88.3 3.86 7.25 21.4 7.6 −11.2
11:20 36.2 7.031 87.3 3.76 6.53 22.6 5.6 −9.7
11:57 36.4 7.108 69.0 3.83 6.11 21.3 4.3 −9.2

Note: General anesthesia was induced at 06:45, sevoflurane started to inhale at 06:55, the procedure was started at 07:15.

Considering the unavailability of dantrolene in our hospital, a multidisciplinary evaluation was performed, and renal replacement therapy was immediately initiated. Symptomatic treatment was carried out, including: (1) cooling therapy (brain protection with ice caps and alcohol wipe downs, intravenous infusion of cold saline, ice bags placed on the neck, armpits, popliteal fossa, and groin, and cold saline rinses in the abdominal cavity); (2) correction of acidosis (hyperventilation and intravenous administration of sodium bicarbonate); (3) correction of electrolyte disturbances, mainly hyperkalemia (calcium, sodium bicarbonate, furosemide diuresis, glucose, and insulin) and monitoring of blood glucose; (4) appropriate use of vasoactive drugs (norepinephrine and epinephrine) to maintain hemodynamic stability; and (5) administration of high-dose methylprednisolone shock therapy (500 mg) to alleviate systemic inflammation. Intravenous administration of heparin (2 mg) was also given to prevent disseminated intravascular coagulation (DIC). During this period, the body temperature continued to rise, reaching a maximum of 44.2°C and PetCO2 increased to 143 mmHg. Within 10 min after starting continuous renal replacement therapy (CRRT), his temperature began to drop and recovered to 38.1°C. PetCO2 levels also decreased to 81 mmHg and acidosis improved (Table 1). After stabilization, the patients were transferred to the intensive care unit (ICU) for further treatment.

After obtaining dantrolene, the initial dose of 2 mg/kg (Li Zhu De Le Pharmaceutical, China) was immediately administered, followed by intermittent bolus of 1 mg/kg every 4–6 h. Intravenous dantrolene was continued for another 2 days, during which time he did not have any signs of recrudescence, renal impairment, or other overt complications of MH. During his ICU stay, he initially developed rhabdomyolysis, resulting in elevated creatine kinase (CK) and myoglobinuria. His CK and myoglobinuria levels both decreased after peaking on postoperative day (POD) 5 (Table 2). Liver function tests, complete blood count, and cardiac troponin levels gradually returned to normal after appropriate treatment.

Table 2

Changes in CK and myoglobin

Index Before anesthesia After anesthesia 4 h POD2 POD3 POD4 POD5 POD8 POD11
CK (U/L) 222 2,500 79,378 87,020 >80,000 120,450 12,818 8,478
Myoglobin (μg/L) Not measured >10,000 >10,000 >10,000 >10,000 >10,000 7,018 3,521

POD: postoperative day.

With the consent of the patient’s family, the patient underwent whole-exome sequencing. The sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu) (Figure 1). However, the patient’s parents declined further testing to confirm the suspicion of MH.

Figure 1 
               Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu).
Figure 1

Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu).

  1. Consent for publication: The authors have obtained the patient’s father written informed consent for print and electronic publication of this case report.

3 Discussion

MH is an abnormal metabolic hyperactivation of skeletal muscle spasms that is induced by exposure to inhaled anesthetics and depolarizing muscle relaxants. As medical treatment has improved, the number of operations performed under general anesthesia has increased annually; additionally, with the progress of anesthesia monitoring methods and the improvement of doctors’ knowledge of MH, the number of reported cases of MH has increased in recent years [3]. The current gold standard for diagnosing MH is the caffeine-halothane contracture test. However, this test is not widely available or commonly used. Nowadays, the identification of a pathogenic mutation is also considered diagnostic for MH. A clinical diagnosis of MH can be assisted by calculating the Clinical Grading Score, in which a score of 50 points and grade of 6 almost certainly indicates MH [1,4]. Our patient had a score of 83 points (systemic muscle stiffness, 15 points; CK of >10,000 U/L without succinylcholine after anesthesia, 15 points; PetCO2 of >55 mmHg with sufficient minute ventilation, 15 points; abnormally rapid increase in perioperative body temperature, 15 points; abnormal tachycardia, 3 points; the base excess more negative than −8 on ABG analysis, 10 points; pH of <7.25 on ABG analysis, 10 points).

The patient underwent whole-exon sequencing to identify the mutations in the RYR1 gene. This variation locus has been classified in the ClinVar database as suspected pathogenic, and it has been detected in multiple patients with MH episodes or individuals with a family history. But this is the first time that the point mutation has been reported in the general East Asian population, and the prediction result of both REVEL software and ClinPred software was “harmful” (score of 0.890 and 0.9740, respectively). Studies have confirmed that ryanodine receptor type 1 gene (RYR1) abnormalities are the molecular basis for MH in most patients [57]. Mutation in the RYR1 gene results in abnormalities in the sarcoplasmic reticulum of skeletal muscle, leading to a high calcium concentration when the patients touched trigger factor such as inhalation anesthetics, followed by continuous tonic contraction of skeletal muscle [8]. MH is an autosomal dominant disorder, and the offspring of MH patients have a 50% risk of developing this disease. Consequently, it is important to fully inform individuals that test results may impact their access to health insurance, employment opportunities, and even marriage [9]. Dantrolene, as a special treatment medication for MH, can effectively inhibit the release of calcium ions in the sarcoplasmic reticulum, thereby inducing muscle relaxation [10]. Early use of dantrolene can reduce perioperative mortality of MH. However, the drug is expensive and difficult to preserve, and only a few hospitals have its stocks in China. Therefore, this reminds us that patients using inhalation anesthesia or depolarizing muscle relaxants should continuously monitor their body temperature and timely differential diagnosis and early treatment should be performed.

Typically, CK peaks after 72 h. However, there was a delay in peak in this case, which may be related to compartment syndrome, and the fact that the patient had rhabdomyolysis symptoms such as systemic muscle rigidity and elevated CK does not rule out compartment syndrome. Moreover, the patient’s CK peak exceeded 100,000 U/L, similar to those previously reported in some patients with MH.

Our experience illustrates several important issues in MH management, if dantrolene is not immediately available. (1) Improved monitoring is very important for the early detection and diagnosis of MH, and early diagnosis and early treatment are the basis of successful rescue of MH. (2) It is critically important to quickly convene the whole hospital for multidisciplinary joint diagnosis and treatment. (3) It is important to use a variety of cooling techniques. In this case, a variety of cooling methods are used to bring the body temperature down below the danger range as quickly as possible. Extracorporeal circulation can be used for cooling if necessary. (4) CRRT is beneficial to maintain internal environmental homeostasis, correct electrolyte disturbance and acidosis, maintain hemodynamic stability, and more effectively remove myoglobin and part of inflammatory mediators by means of convection and adsorption. It can lower the body temperature of patients with hyperthermia by lowering the temperature of replacement fluid, and provide nutritional support under high metabolic state. Prevent and treat renal failure. (5) Early application of heparin therapy reduces the consumption of coagulation factors and platelets by DIC. Ensure hemodynamic stability and give adrenocorticosteroids and diuretics if necessary. (6) Extracorporeal membrane oxygenation (ECMO) may be used as a last resort in patients with sustained cardiac arrest. (7) MH is rare, and many hospitals have insufficient experience in rescue. Timely and effective contact with anesthesia experts in other hospitals to guide the treatment is also important for successful rescue.

4 Conclusion

The characteristics of MH are rapid onset, high mortality rate, and numerous complications. Dantrolene can greatly improve the prognosis of patients. However, if dantrolene is not routinely available in the hospital, it is necessary to take correct symptomatic treatment measures, including CRRT, lowering body temperature, brain protection, maintaining stable vital signs, ECMO, etc., to save valuable time for obtaining dantrolene. Furthermore, dantrolene should be routinely equipped in every hospital or region whenever possible.

Abbreviations

ABG

arterial blood gas

CK

creatine kinase

CRRT

continuous renal replacement therapy

DIC

disseminated intravascular coagulation

HR

heart rate

ICU

intensive care unit

MH

malignant hyperthermia

PCO2

partial pressure of carbon dioxide

PetCO2

the end-tidal carbon dioxide

RYR1

ryanodine receptor type 1 gene


# Contributed equally to this work.

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Acknowledgments

The authors sincerely thank the family for the permission for reporting this case.

  1. Funding information: The authors declare no funding for this report.

  2. Author contributions: H.L. and G.D. wrote the initial draft of the manuscript; Y.Z. and J.W. critically revised the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors declare that they have no conflict of interest.

  4. Data availability statement: This is a case report of a single patient, to protect privacy and respect confidentiality; none of the raw data has been made available in any public repository. The original reports, laboratory studies, imaging studies, and outpatient clinic records are retained as per normal procedure within the medical records of our institution.

References

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Received: 2023-06-17
Revised: 2023-07-30
Accepted: 2023-09-01
Published Online: 2023-10-17

© 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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  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. 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
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. 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
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. 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
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. 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
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. 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
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. 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”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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