Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
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Wugang Zhu
Abstract
Purpose
This study aimed to assess the clinical effectiveness and safety of combining immunotherapy with chemotherapy for non-small cell lung cancer.
Methods
A comprehensive search of studies published until January 2024 was conducted. Quality assessment was performed using the NOS scale, and a meta-analysis was carried out with RevMan 5.4.1 software. Heterogeneity was assessed using the Q-test, and combined effects were calculated with fixed or random effects models. Results were visualized using forest plots, and a sensitivity analysis was performed.
Results
Out of 1,061 sources, 11 met the inclusion criteria. The meta-analysis indicated that the combination treatment significantly improved 1-year overall survival, objective response rate, and disease control rate compared to chemotherapy alone (P < 0.05), with no significant difference in adverse reactions (P > 0.05). Immune function markers CD4+ and CD4+/CD8+ were higher, and CD8+ was lower in the combined treatment group. Sensitivity analysis confirmed the stability and reliability of the results (OR (95% CI) 3.72 (2.34–5.90), P < 0.00001), although publication bias was indicated by funnel plots.
Conclusion
The combination of chemotherapy and immunotherapy exhibits the potential to enhance both survival rates and clinical effectiveness, without the concomitant rise in severe adverse reactions.
1 Introduction
Recently, a large number of clinical trials have verified the efficacy and safety of immunotherapy in malignant tumors, such as tumor-infiltrating lymphocytes, transgenic T lymphocytes expressing antigen-specific T cell receptors or chimeric antigen receptors, natural killer cells, cytokine-induced killer cells, and dendritic cells, providing new therapeutic strategies for hematological and solid tumors. Based on the data published by the World Health Organization’s International Agency for Research on Cancer in 2023 [1], although lung cancer incidence has decreased globally, it remains the leading cause of cancer-related deaths, comprising approximately 18% of the total number of fatalities [2]. Notably, China recorded approximately 787,000 new cases of lung cancer in 2015, which is equivalent to over 2,100 new cases per day [3]. Among the various types of lung cancer, non-small cell lung cancer (NSCLC) dominates, representing approximately 85% of all cases [2].
Despite the availability of various treatment options for lung cancer, such as surgical resection, chemotherapy, radiotherapy, and targeted therapy, their overall clinical efficacy remains unsatisfactory, leading to a poor prognosis. Five-year survival rates after treatment are less than 15% [2]. Furthermore, many tumors are diagnosed at advanced stages, missing the optimal window for surgical intervention and leaving patients with limited options, such as chemotherapy. Unfortunately, these treatments often come with significant adverse reactions that cause irreversible harm to patients [4,5]. In recent years, the emergence of tumor immunotherapy, specifically through the use of immune checkpoint inhibitors like programmed cell death protein-1 or programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4, has shown promising results. These inhibitors effectively modulate excessive immune responses induced by tumors, thereby promoting long-term anti-tumor effects, leading to improved disease response rates and outcomes for patients [6–11]. Although some studies have indicated the superiority of combining immunotherapy with chemotherapy over chemotherapy alone for NSCLC patients [12–16], these studies often suffer from limitations such as small sample sizes, retrospective design, and lack of large-scale clinical trials. Therefore, the application of meta-analysis methods becomes crucial in quantitatively assessing the efficacy and safety of combining immunotherapy with chemotherapy for NSCLC treatment, providing a solid evidence-based foundation for clinical decision-making.
2 Materials and methods
2.1 Sources of materials and retrieval strategies
In order to gather relevant information, a comprehensive computerized search was performed using several databases including China Knowledge Net, Wanfang, Weipu Chinese scientific journals, Chinese Biomedicine, PubMed, Web of science, Cochrane library, etc. The search period covered the database establishment date up until November 2023. The search strategy in Chinese included the keywords “immunotherapy,” “chemotherapy,” “non-small cell lung cancer,” and “curative effect,” while synonyms were also considered. Similarly, the English search strategy involved the terms “immunotherapy,” “chemotherapy,” “non-small cell lung cancer,” and “curative effect.”
2.2 Inclusion and exclusion criteria
Criteria for literature inclusion: (1) patients included in the study were diagnosed with NSCLC; (2) the experimental group received a combination of immunotherapy and chemotherapy, while the control group received chemotherapy alone. There were no restrictions on the specific types and treatment regimens of immunotherapy and chemotherapy; (3) the outcome measures assessed were overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse reactions, CD4+, CD8+, and CD4+/CD8+; and (4) in case of multiple publications by the same author reporting the same data, the study with the largest sample size or the most recent publication were chosen.
The following criteria were applied to the exclusion of literature: (1) removal of duplicate and irrelevant studies as well as review literature; (2) exclusion of non-randomized controlled trials; (3) elimination of studies with inconsistent outcome indicators; (4) exclusion of trials where the experimental group does not receive immunotherapy combined with chemotherapy or the control group receives chemotherapy alone; (5) omission of studies with missing, incomplete, unavailable, or obviously incorrect data; and (6) exclusion of literature studies conducted before 2020 with a sample size smaller than 70.
2.3 Literature screening and data extraction
Two researchers from the research team conducted a thorough review of the literature using predefined inclusion and exclusion criteria. Initially, they assessed the titles and abstracts of the articles and, if necessary, proceeded to examine the full text. In cases where there were discrepancies, they consulted external experts to reach a consensus. Articles that met the inclusion criteria were carefully analyzed using a pre-established literature characteristics table to extract pertinent information. This included details such as study design, total sample size, sample size of the experimental group, sample size of the control group, and outcome measures, among others.
2.4 Literature quality evaluation
In order to assess the methodological quality, we utilized the Newcastle-Ottawa quality assessment scale (NOS). The scoring system ranged from 0 to 9, where scores falling within the range of 7–9 were indicative of high methodological quality (grade A), scores ranging from 4 to 6 reflected fair methodological quality (grade B), and scores below 4 indicated low methodological quality (grade C).
2.5 Statistical methods
Literature management was conducted using Note Express 3.2 software, while Excel2003 software was utilized for literature data collection and extraction. Revman 5.4.1 software was employed for performing the meta-analysis. Heterogeneity analysis was conducted on the extracted data using the Q-test (P-value), with the addition of the I 2 value to assess heterogeneity. In the case where P > 0.10 or I 2 ≤ 50%, indicating the absence of heterogeneity, a fixed-effect model (FEM) was applied. In contrast, if heterogeneity was present, a random-effects model (REM) was used. At the same time, the source of literature heterogeneity was explored by deleting the literature with the largest proportion of weight. The pooled results of the meta-analysis were described using the odds ratio (OR) and its corresponding 95% confidence interval (CI), while illustrating forest plots. Sensitivity analysis was conducted to assess the stability of the meta-analysis results, and publication bias was evaluated through the use of funnel plots. The significance level for testing was set at α = 0.05 (two-sided).
3 Results
3.1 Literature search results
Based on the article search strategy, a total of 1,061 pertinent documents were initially retrieved from various databases such as China Knowledge Net, Wanfang Database, VIP Chinese Science and Technology Journal Database, China Biomedical Database, PubMed, Web of Science, Cochrane library, among others. To eliminate duplicate literature, duplicates found in multiple databases were removed. Subsequently, through careful examination of title, abstract, and full text, 11 pertinent literatures were ultimately included in the study. The literature screening process is illustrated in Figure 1.
Flow chart of literature screening.
3.2 Basic characteristics and quality evaluation of literature
The baseline data comprise primarily information such as gender, age, disease duration, treatment plan, and outcome measures. A comprehensive overview of the baseline data can be found in the 11 literature sources included in this study. The quality of the 11 selected studies is assessed using the NOS scale, with the results presented in Table 1 [17–27].
Basic characteristics and quality evaluation table of literature
| First author | Year of publication | Sample size (example) | Age | Intervention measures | Outcome index | NOS | ||
|---|---|---|---|---|---|---|---|---|
| Test group | Control group | Control group | Test group | |||||
| He Jing [17] | 2022 | 150 | 130 | 40 years old and 80 years old | PD-1/PD-L1 immunization combined with docetaxel chemotherapy | Docetaxel chemotherapy | ①→④⑤⑥⑦⑧ | 5 |
| Yang Juyin [18] | 2023 | 40 | 40 | / | Single chemotherapy group combined with PD-1/PD-L1 inhibitor | AP regimen containing platinum (pemetrexed + platinum) or TP regimen (paclitaxel + platinum) | ②→③ | 5 |
| Zhao Jingjing [19] | 2022 | 44 | 44 | 24 years old and 71 years old | DC/CIK immunotherapy was performed on the basis of simple chemotherapy | Simple chemotherapy | ③→③⑥⑦⑧ | 5 |
| Sun Liling [20] | 2023 | 38 | 44 | 18 years old, 75 years old | Carrell monoclonal antibody combined with platinum-containing double drugs | Platinum-containing dual drug therapy | ①→②③④⑥⑦⑧ | 6 |
| Li et al. [21] | 2023 | 50 | 50 | 60–83 years old | Carrilizumab combined with chemotherapy | Chemotherapy | ④→ | 5 |
| Chen Min [22] | 2023 | 52 | 52 | Test group: 60.47 ± 5.13; control group: 61.58 ± 5.44 | Chemotherapy group was immunized with pablizumab on the basis of chemotherapy | Give | ②→③④⑥⑧ | 6 |
| Sun Xiongying [23] | 2022 | 36 | 35 | The experimental group: 68.13 ± 4.28; the control group: 68.35 ± | Immunotherapy combined with chemotherapy | Platinum-containing dual-drug chemotherapy | ⑤→⑧ | 5 |
| He Siyi [24] | 2021 | 35 | 35 | 4.32 | Albumin paclitaxel + xindiril monoclonal antibody | Simple chemotherapy | ③→③⑥⑦⑧ | 5 |
| Pan Enyuan [25] | 2021 | 40 | 40 | Experimental group: 57.12 ± | On the basis of chemotherapy, combined with bevacizumab | Albumin paclitaxel chemotherapy regimen | ⑥→⑧ | 5 |
| Shiyuan Garden [26] | 2023 | 38 | 35 | 7.05; control group: 56.41 ± 7.14 | Chemotherapy plus immunotherapy | Pemetrexed plus platinum chemotherapy | ④→ | 5 |
| Zhang Jingbao [27] | 2022 | 75 | 75 | / | A single bead for Riley | Simple chemotherapy | ②③⑤⑥⑦⑧ | 5 |
Notes: ① 1 years of OS, ② ORR, ③ DCR, ④ PFS, ⑤ adverse reactions, ⑥ CD4+, ⑦ CD8+, ⑧ CD4+/CD8+.
3.3 Meta-analysis results
3.3.1 Clinical efficacy
3.3.1.1 One-year OS
Two literature reviews were conducted to compare the OS rates of patients in the experimental and control groups over a period of 1 year. The test group consisted of 188 cases, while the control group had 174 cases. Statistical heterogeneity tests were performed on the included literature, and the results indicated no significant variation across different studies. This allowed for the utilization of FEM to combine the data from the literature reviews. The meta-analysis showed significantly higher OS rates in the experimental group (OR = 2.28, 95% CI (1.48–3.50, 0.0002)), as depicted in Figure 2.
Forest map of original 1-year OS comparison between test group and control group.
3.3.1.2 ORR
In total, six articles conducted a comparison between the ORR of patients in the experimental group and the control group. The experimental group consisted of 284 cases, whereas the control group had 290 cases. A heterogeneity test was performed on the collected literature, and the results indicated that there was no statistical heterogeneity among the different studies. Therefore, a FEM was utilized to combine the data from these studies. The meta-analysis showed significantly higher ORR rates in the experimental group, with a statistically significant difference (OR = 3.05, 95% CI (2.10–4.43), P < 0.00001), as illustrated in Figure 3.
Forest map of ORR comparison between test group and control group.
3.3.1.3 DCR
A total of six studies were included in the analysis to compare the DCR of patients in the experimental group and the control group. The experimental group consisted of 284 cases, while the control group had 290 cases. Statistical tests were conducted to assess the heterogeneity of the included studies, and the results indicated no significant heterogeneity among them. Therefore, FEM was utilized to combine the data from these studies. The meta-analysis showed significantly higher DCR rates in the experimental group (OR = 3.53, 95% CI (2.41–5.18), P < 0.00001), as depicted in Figure 4.
Forest map of DCR comparison between test group and control group.
3.3.1.4 Progression-free survival (PFS)
The PFS of patients in the experimental group was compared to that in the control group in a total of three literatures. A total of 240 cases were included in the test group and 226 cases in the control group. The included literature underwent a heterogeneity test, which yielded a result of 0.0004, indicating statistical heterogeneity among the different studies. Therefore, a REM was utilized to combine the literature data. The meta-analysis showed significantly longer PFS rates in the experimental group (OR = 1.32, 95% CI (0.25–2.38), PP 0.02), as depicted in Figure 5.
Forest map of PFS comparison between test group and control group.
3.3.1.5 Adverse reaction
There were a total of four studies that conducted a comparison of adverse reactions between the experimental and control groups. The test group consisted of 313 cases, while the control group had 290 cases. Statistical heterogeneity testing was performed on the included studies, yielding a result of 0.004%, indicating the presence of significant heterogeneity among them. Therefore, a REM was employed to combine the data from these studies. The meta-analysis results revealed no statistically significant difference in adverse reactions between the test group and control group (P > 0.05), as illustrated in Figure 6.
Forest map of adverse reactions between the test group and the control group.
3.3.2 Immunity
3.3.2.1 CD4+
A total of eight studies were conducted to compare the CD4+ levels between the experimental and control groups. The test group consisted of 470 cases, while the control group had 455 cases. A heterogeneity test was conducted on the included studies, revealing statistical heterogeneity among them. Hence, a REM was employed to combine the data from these studies. The meta-analysis showed significantly higher CD4+ rates in the experimental group (OR = 4.43, 95% CI (1.78–7.08), PSA 0.001), as illustrated in Figure 7.
Forest map of CD4+ comparison between test group and control group.
3.3.2.2 CD8+
A total of five articles conducted a comparison between the experimental group and the control group regarding the CD8+ level. Among these studies, the number of cases in the experimental group was 342, while in the control group it was 328. The pooled data were subjected to a heterogeneity test, which revealed that there was a significant variability among the different literature studies. To address this, the REM was employed for data synthesis. The meta-analysis showed significantly lower CD8+ rates in the experimental group (OR = −2.80, 95% CI (−5.03 to 0.57), PP01), as illustrated in Figure 8.
Forest map of CD8+ comparison between test group and control group.
3.3.2.3 CD4+/CD8+
A total of eight research papers conducted a comparison between the experimental group and the control group in terms of the CD4+/CD8+ level. Among them, the test group consisted of 470 cases, while the control group consisted of 455 cases. Statistical heterogeneity was detected among the included papers, indicating variations in the study results. Therefore, a REM was utilized to combine the data from different studies. The meta-analysis showed significantly higher CD4+/CD8+ level rates in the experimental group (OR = 0.41, 95% CI (0.20–0.63), P < 0.0001). This finding is depicted in Figure 9.
Forest map of CD4+/CD8+ comparison between test group and control group.
3.4 Sensitivity analysis and literature bias test
Sensitivity analysis was conducted using ORR as a case study to validate the reliability of the findings. By excluding the literature with the highest proportion and integrating the literature effect again, the OR (95% CI) was found to be 3.72 (2.34–5.90), P < 0.00001. The credibility of the study results can be observed in Figure 10.
Forest map of sensitivity analysis between test group and control group.
The outcome indicators examined in this study presented inherent biases, and the findings demonstrated an asymmetrical pattern in the funnel plot, suggesting the presence of bias. Refer Figure 11 for visual representation.
Funnel diagram of test group and control group.
4 Discussion
Currently, there is a debate surrounding the application of combined immunotherapy and chemotherapy in individuals diagnosed with NSCLC. Therefore, this study aims to quantitatively assess and analyze previous research on the effectiveness and safety of combining immunotherapy and chemotherapy, in order to shed light on this controversial issue.
The results obtained from meta-analysis revealed that the immunotherapy combined with chemotherapy group exhibited significantly higher rates of 1-year OS, ORR, DCR, and PFS compared to the control group. Conversely, there was no notable variation in adverse reactions between the two groups. Concerning immune function, the experimental group demonstrated notably higher levels of CD4+ and CD4+/CD8+ in comparison to the control group. However, the experimental group displayed a lower level of CD8+ compared to the control group. Furthermore, sensitivity analysis demonstrated the stability and reliability of the combined effect (OR (95% CI) 3.72 (2.34–5.90), P < 0.00001). The results derived from the funnel chart pointed to the existence of publication bias. In order to reduce the sources of bias analysis, it is recommended to apply more stringent inclusion and exclusion criteria in future studies. In addition, expanding the source of databases, not limited to Chinese and English databases, can also be one of the important ways to reduce bias analysis.
There are several limitations to this study. First, the study includes a small sample size and a limited number of relevant literature sources, which restricts the support from multicenter and large sample studies. Second, individual patients exhibit variations in disease state and progression, leading to potential confounding factors. Lastly, the usage of different immune or chemotherapy regimens and treatment durations may introduce bias into the results of this study.
To summarize, the combination of chemotherapy and immunotherapy exhibits the potential to enhance both survival rates and clinical effectiveness, without the concomitant rise in severe adverse reactions. Additionally, there seems to be a tendency toward enhancing immune function, thereby rendering this approach highly suitable for clinical implementation. Therefore, it is suggested that the combination of chemotherapy and immunotherapy can be used clinically for patients with NSCLC, which can improve the potential of survival and clinical efficacy, and will not be accompanied by an increase in serious adverse reactions. Nevertheless, specific suggestions on the need for more randomized controlled trials with a larger sample size or suggestions for standardizing chemotherapy/immunotherapy combinations in future trials could be added.
Acknowledgments
Not applicable.
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Funding information: The authors state no funding involved.
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Author contributions: Wugang Zhu and Xiaolan Lu: conceptualization, methodology, writing – original draft preparation. Wenjing Xu, Degan Liu, and Lei Wan: data analysis. All authors read and approved the final manuscript.
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Conflict of interest: The authors state no conflict of interest.
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Data availability statement: All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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- GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
- Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
- MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
- Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
- Trends in research on preterm birth in twin pregnancy based on bibliometrics
- Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
- Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
- Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
- Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
- Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
- CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
- Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
- Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
- Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
- Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
- Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
- Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
- Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
- The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
- The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
- Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
- Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
- The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
- Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
- Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
- Correlation of serum calprotectin with outcome of acute cerebral infarction
- Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
- Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
- The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
- Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
- Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
- Analysis of serum metabolomics in patients with different types of chronic heart failure
- Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
- Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
- Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
- METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
- The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
- Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
- Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
- Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
- Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
- Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
- Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
- Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
- Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
- Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
- Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
- Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
- HALP score in Demodex blepharitis: A case–control study
- Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
- Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
- Comparison of the two intestinal anastomosis methods in pediatric patients
- Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
- Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
- Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
- Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
- Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
- Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
- Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
- Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
- A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
- Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
- 10.1515/med-2025-1200
- Review Articles
- The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
- Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
- Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension
- Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
- The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
- The application of augmented reality in robotic general surgery: A mini-review
- The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
- Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
- Plant polyphenols, terpenes, and terpenoids in oral health
- Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
- End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
- The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
- Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
- PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
- Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
- Giant borderline ovarian tumours – review of the literature
- Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
- Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
- Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
- Supplement strategies for infertility in overweight women: Evidence and legal insights
- Case Reports
- Delayed graft function after renal transplantation
- Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
- Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
- Giant right atrial hemangioma presenting with ascites: A case report
- Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
- EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
- Rapid Communication
- Biological properties of valve materials using RGD and EC
- Letter to the Editor
- Role of enhanced external counterpulsation in long COVID
- Expression of Concern
- Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
- Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
- Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
- Corrigendum
- Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
- Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
- Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
- Retraction
- Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
- Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
- Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
- Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
- The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
- Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
- Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
- Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
- Special Issue The evolving saga of RNAs from bench to bedside - Part III
- Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
- The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
- Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
- Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
- A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
- Special Issue Diabetes
- Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
- Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
- A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
- A review of brain research on T2DM-related cognitive dysfunction
- Special Issue Biomarker Discovery and Precision Medicine
- CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
Artikel in diesem Heft
- Research Articles
- Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
- Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
- Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
- Risk factors for severe adverse drug reactions in hospitalized patients
- Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
- Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
- CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
- Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
- Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
- Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
- Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
- Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
- Association between statin administration and outcome in patients with sepsis: A retrospective study
- Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
- A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
- Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
- Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
- Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
- Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
- Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
- The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
- Health literacy and health-related quality of life: The mediating role of irrational happiness
- Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
- Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
- Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
- Clinical analysis of ten cases of HIV infection combined with acute leukemia
- Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
- Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
- Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
- Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
- Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
- The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
- The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
- Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
- Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
- Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
- The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
- Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
- A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
- A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
- Identifying early screening factors for depression in middle-aged and older adults: A cohort study
- Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
- Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
- High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
- RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
- Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
- Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
- The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
- Expression and clinical significance of ITGA3 in breast cancer
- Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
- rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
- Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
- Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
- Gender beliefs and legitimization of dating violence in adolescents
- Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
- Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
- Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
- Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
- Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
- Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
- GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
- Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
- MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
- Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
- Trends in research on preterm birth in twin pregnancy based on bibliometrics
- Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
- Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
- Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
- Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
- Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
- CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
- Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
- Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
- Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
- Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
- Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
- Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
- Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
- The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
- The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
- Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
- Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
- The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
- Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
- Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
- Correlation of serum calprotectin with outcome of acute cerebral infarction
- Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
- Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
- The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
- Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
- Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
- Analysis of serum metabolomics in patients with different types of chronic heart failure
- Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
- Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
- Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
- METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
- The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
- Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
- Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
- Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
- Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
- Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
- Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
- Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
- Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
- Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
- Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
- Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
- HALP score in Demodex blepharitis: A case–control study
- Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
- Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
- Comparison of the two intestinal anastomosis methods in pediatric patients
- Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
- Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
- Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
- Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
- Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
- Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
- Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
- Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
- A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
- Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
- 10.1515/med-2025-1200
- Review Articles
- The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
- Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
- Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension
- Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
- The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
- The application of augmented reality in robotic general surgery: A mini-review
- The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
- Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
- Plant polyphenols, terpenes, and terpenoids in oral health
- Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
- End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
- The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
- Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
- PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
- Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
- Giant borderline ovarian tumours – review of the literature
- Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
- Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
- Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
- Supplement strategies for infertility in overweight women: Evidence and legal insights
- Case Reports
- Delayed graft function after renal transplantation
- Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
- Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
- Giant right atrial hemangioma presenting with ascites: A case report
- Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
- EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
- Rapid Communication
- Biological properties of valve materials using RGD and EC
- Letter to the Editor
- Role of enhanced external counterpulsation in long COVID
- Expression of Concern
- Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
- Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
- Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
- Corrigendum
- Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
- Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
- Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
- Retraction
- Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
- Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
- Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
- Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
- The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
- Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
- Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
- Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
- Special Issue The evolving saga of RNAs from bench to bedside - Part III
- Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
- The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
- Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
- Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
- A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
- Special Issue Diabetes
- Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
- Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
- A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
- A review of brain research on T2DM-related cognitive dysfunction
- Special Issue Biomarker Discovery and Precision Medicine
- CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
