The increasing global prevalence of diabetes mellitus (DM) necessitates the development of innovative therapeutic strategies that effectively address its symptoms and alleviate its enduring pathological consequences. Stem cells (SCs), which have biological advantages such as multidirectional differentiation capabilities and immune regulatory functions, exhibit tremendous potential for diabetes treatment. Human embryonic SCs or induced pluripotent SC-derived insulin-producing cells offer a promising source for islet cell replenishment in the treatment of insulin-depleted diabetes; however, immune rejection and safety concerns remain significant challenges in further clinical applications. Transplantation of hematopoietic and mesenchymal SCs also shows remarkable potential for the treatment of diabetes. These cells possess the ability to modulate the immune system, stimulate endogenous β-cell regeneration, and preserve residual β-cell function, ultimately leading to enhanced pancreatic islet function and reduced insulin resistance. However, safety and efficacy considerations for SCs remain paramount. This review comprehensively summarizes the recent advancements and molecular mechanisms of SCs in the treatment of DM, underscoring the feasibility, benefits, and current limitations of SC therapy for DM, and offering a lucid perspective on their therapeutic possibilities.
Ruiying Wang, Yahong Chen, Xiansheng Liu, Peter J. Barnes
中华医学杂志英文版2026年 139卷 16期
DOI: 10.1097/CM9.0000000000004208
摘要
Chronic lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, obstructive sleep apnea, asthma, bronchiectasis, and lung cancer, are intricately linked to the aging process. These diseases are characterized by a high prevalence rate and a paucity of effective treatment options. Emerging evidence highlights the critical role of extracellular vesicles (EVs) in the pathogenesis and progression of these diseases. EVs, released by senescent cells, mediate intercellular communication and modulate immune responses through their cargo of microRNAs, proteins, and other molecules. These vesicles contribute to disease progression by promoting inflammation, fibrosis, tissue remodeling, and cellular senescence. Specifically, certain microRNAs, such as miR-21, miR-34a, and miR-570-3p, along with several proteins in EVs, have been identified as key factors influencing these processes. Additionally, EVs play significant roles in immune regulation and have potential anti-inflammatory effects, making them promising candidates for therapeutic applications. Recent advances in the use of EVs as therapeutic agents, including their application in nanotechnology for targeted drug delivery, have demonstrated potential in reducing inflammation, modulating immune responses, and enhancing tissue repair. Understanding the role of EVs in these diseases offers insights into potential therapeutic targets to mitigate disease progression and improve patient outcomes. Future research should focus on standardizing EV isolation and characterization methods, verifying the safety and efficacy of EV-based therapies in clinical trials, and elucidating the complex biological mechanisms of EVs in aging and disease.
Lanlin Shen, Jinhu Ma, Xiao Wei, Gang Shi, Hongxin Deng
中华医学杂志英文版2026年 139卷 16期
DOI: 10.1097/CM9.0000000000004136
摘要
The development of organoid technology has led to notable advances in regenerative medicine, disease modeling, and drug screening. However, given the pivotal role of vascular systems in growth maintenance and nutrient delivery, the lack of functional vascular networks within organoids limits the scalability and physiological functionality of these organoids. Efforts to explore strategies for organoid vascularization, such as co-culture, transcription factor induction, microfluidic technology, and the application of biomaterial scaffolds, are underway. These methods have shown distinct advantages across different types of organoids, partially addressing vascularization challenges. However, issues such as limited vascular network integration and insufficient functional maturity remain unresolved. Future efforts should prioritize the development of multi-tiered vascular networks, the application of smart biomaterials, and the creation of personalized vascularized organoids. This review summarizes the advances in this field and explores the potential translation of vascularized organoids into clinical practice, offering recommendations for further research.
Sarcopenia, characterized by the age-related decline in skeletal muscle mass, strength, and function, is associated with high healthcare costs and significant health risks, including falls, fractures, functional decline, and mortality. Despite its prevalence and extensive research, there are currently no Food and Drug Administration (FDA)-approved drugs to modify its course, likely due to an incomplete understanding of its underlying mechanisms. Recent evidence highlights two key factors in sarcopenia development: (1) Disrupted circadian rhythms affecting pathways such as protein remodeling, insulin resistance, and mitochondrial function; (2) systemic chronic low-grade inflammation (SCLGI). This review focuses on circadian rhythm regulators implicated in skeletal muscle deterioration, examining their roles, potential interactions, and the impact of circadian disruption on sarcopenia progression. Additionally, we explore how clock genes reciprocally influence the inflammatory profile, which is crucial for developing treatment strategies to mitigate the detrimental effects of sarcopenia. We also examine factors that influence the clock and have the potential to restore circadian rhythm mechanisms that are deregulated in sarcopenia. Drawing from these insights, strategies aimed at restoring circadian synchrony and resolving inflammation are proposed as a novel therapeutic approach to effectively mitigate the manifestations of sarcopenia.
Background:
The prognosis of geriatric intertrochanteric fractures (ITF) remains unfavorable even with early surgical treatment due to the fragility associated with aging and stress induced by the fracture. Low-dose dexamethasone has been proposed to improve short-term survival. However, whether a single preoperative dose of low-dose dexamethasone improves survival one year after surgery remains unknown.
Methods:
This single-center, single-blinded, randomized, placebo-controlled study was conducted at Guangzhou First People’s Hospital. A total of 160 participants admitted between June 2020 and October 2022 were randomly assigned to the dexamethasone group or the placebo group (80 participants per group). The dexamethasone group received 10 mg (2 mL) of dexamethasone and the placebo group received 2 mL of saline intravenously 30 min before surgery. The primary outcome was the prespecified 1-year mortality after surgery. Secondary outcomes included adverse events during hospitalization, Barthel activity of daily living (BADL) score and Parker-Palmer score (PPS) at 30 days, 90 days, 180 days, and 1 year after surgery. Statistical analyses included Studen’s t-test or Mann-Whitney U test for quantitative variables, chi-squared test for categorical variables, and Log-rank test for survival differences.
Results:
All participants completed the follow-up. A total of 41 participants died within one year after surgery. There were 15 deaths (18.8%) in the dexamethasone group and 26 deaths (32.5%) in the placebo group (hazard ratio [HR] = 0.51, 95% confidence intervals [CI] = 0.27-0.96, P = 0.04). There were no significant differences in the risk of infection events or hyperglycemia during hospitalization between the dexamethasone and placebo groups (P >0.05). Although survivors in the dexamethasone group had higher BADL and PPS scores at 30 days, 90 days, 180 days, and 1 year after surgery compared to those in the placebo group, no significant differences were found between the groups at these time points (P >0.05).
Conclusions:
A single preoperative low-dose dexamethasone administration reduces 1-year mortality in geriatric ITF patients following internal fixation surgery and may positively impact functional recovery in survivors.
Songbo Li, Xuezhi Li, Xiaojing Zhu, Xingyu Zhao, Xiaodong Qu, Kexin Lin, Nuo Yao, Na Wang, Min Chen, Lifeng Zhang 等
中华医学杂志英文版2026年 139卷 16期
DOI: 10.1097/CM9.0000000000003675
摘要
Background:
Currently, standard therapeutic agents are not available for treating gastric intestinal metaplasia (IM). However, emerging evidence suggests the potential efficacy of metformin in addressing this issue. Our aim was to assess the efficacy and safety of metformin in reversing IM.
Methods:
We initially investigated the impact of metformin on reversing gastric IM in mice. An open-label, prospective, randomized controlled trial was subsequently conducted at a tertiary hospital in China from April 2022 to May 2023. A total of 140 nondiabetic patients with pathologically confirmed IM and negative Helicobacter pylori tests were recruited. Patients were randomly assigned at a 1:1 ratio to receive either 500 mg of metformin daily for six months or 5 mg of folate three times daily as a control. The primary outcome was defined as the regression rate of IM in different groups at the end of the treatment.
Results:
Metformin improved gastric mucosal pathology in mice. A total of 158 patients were screened, 140 of whom were randomized to the two groups. Among these, 85/140 (60.7%) were male, and the mean age was 55.9 ± 8.3 years. Six-month follow-up data were available for 129 patients. Compared with folate users (control group), metformin users had a greater rate of regression of IM (48.6% [34/70] vs. 31.4% [22/70]; relative risk [RR] = 1.55, 95% confidence interval [CI] 1.01-2.36; P = 0.04) in the intention-to-treat population. Furthermore, in the per-protocol population, metformin users had a higher rate of regression of IM (53.1% [34/64] vs. 33.9% [22/65]; RR = 1.57, 95% CI 1.04-2.37; P = 0.03). The metformin group had a low incidence of self-alleviating mild adverse reactions.
Conclusion:
This randomized clinical trial revealed that metformin can be safely administered to promote the regression of IM in nondiabetic individuals without Helicobacter pylori infection.
Jingxuan Peng, Sha Li, Boyu Xiang, Zhongyi Li, Zhengyan Tang
中华医学杂志英文版2026年 139卷 16期
DOI: 10.1097/CM9.0000000000003973
摘要
Background:
Male infertility is a major yet understudied global health concern. This study aims to analyze the temporal trends in the global and regional burden of male infertility from 1990 to 2021, explore influencing factors, assess the relationship with sociodemographic development, analyze health inequalities, and forecast future trends.
Methods:
Using epidemiological data on male infertility from the Global Burden of Disease Study database for 1990-2021, we calculated prevalence, disability-adjusted life years (DALYs), and other indicators. Joinpoint regression, age-period-cohort analysis, and decomposition analysis were used to examine temporal trends and influencing factors. Data envelopment analysis was used to assess the relationship between male infertility and the sociodemographic index (SDI). The slope index of inequality (SII) and concentration index were used to analyze health inequalities. Autoregressive integrated moving average (ARIMA) and Bayesian age-period-cohort (BAPC) models were used to forecast prevalence from 2022 to 2036.
Results:
The global crude prevalence rate of male infertility was 1389.1 per 100,000 population in 2021, and the age-standardized prevalence rate was 1354.8 per 100,000 population. Among the 21 GBD regions, Eastern Europe had the highest ASPR, whereas Australasia had the lowest ASPR. Overall, prevalence showed a decreasing-then-increasing trend from 1990 to 2021, with the fastest growth occurring from 2010 to 2014. The trend of DALY changes is basically consistent with the incidence rate, with a rapid increase after 2010. The risk of infertility increased with age up to approximately 37.5 years and subsequently declined, with an overall downward trend observed after 1994. Population growth was the main driver of increasing prevalence. The increase in DALY rates is also mainly driven by population growth, contributing up to 68.06% globally, and the impact of population aging in high-SDI regions on DALY rates initially shows a significant negative effect. As SDI increased, the DALY rate generally decreased, but there was room for improvement in some countries. The inequality between high and low-SDI regions increased. Prevalence was predicted to rise in the future.
Conclusions:
The global burden of male infertility is increasing overall, with lower prevalence in high-SDI regions and higher DALYs in low-SDI regions. Attention should be paid to rapidly growing populations, improving reproductive health services, and equitable access. Screening and interventions for high-risk populations should be strengthened to curb the rising prevalence trend.
Xuefen Lin, Jianfeng Zheng, Yanhong Li, Siping Wang, Qinying Liu, Lijun Chen, Sang Li, Yang Sun
中华医学杂志英文版2026年 139卷 16期
DOI: 10.1097/CM9.0000000000004130
摘要
Background:
Epigenetic-related genes (ERGs) play a pivotal role in cancer development and progression. However, their potential for cervical cancer (CC) diagnosis and prognosis remains underexplored.
Methods:
Clinical data and gene expression profiles were sourced from publicly available databases. Epigenetic associations were predicted using the least absolute shrinkage and selection operator (LASSO) Cox regression model, and multiple algorithms were employed to evaluate the impact of ERGs on immune responses, treatment outcomes, and predictive accuracy. Western blotting analysis and quantitative real-time polymerase chain reaction were used to assess gene expression. Subsequently, DNMT3B was selected for further in vitro and in vivo study.
Results:
A total of 567 ERGs were identified from open-access databases, with 59 found to be significantly associated with prognosis of CC. Five ERGs (DNMT3B, SMYD2, IKZF3, L3MBTL2, and CHD7) were deemed instrumental in constructing a prognostic signature for CC. The predictive accuracy of the ERG signature was evaluated, revealing a robust correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the ERG signature. DNMT3B was found to be highly expressed in CC, and both in vitro and in vivo experiments confirmed its role in promoting tumor growth.
Conclusions:
The epigenetic signature developed in this study holds considerable promise for prognostic prediction and therapeutic guidance in patients with CC. DNMT3B was identified as an oncogenic gene, highlighting its potential as a therapeutic target.
Background:
Chimeric antigen receptor T (CAR-T) cells have been demonstrated to be an effective treatment for relapsed B-cell acute lymphoblastic leukemia (B-ALL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells for CAR-T therapy can be derived from the peripheral blood (recipient) of the patient or donor. Despite having identical genomes, the different maturation environments of these T cells can lead to functional differences. This study aimed to compare the clinical outcomes of CAR-T cells derived from these two sources.
Methods:
This multicenter, retrospective cohort study collected clinical data from 36 patients who experienced B-ALL relapse after allo-HSCT and received CD19 CAR-T cell therapy between January 2016 and October 2023 across seven centers. The primary endpoint was complete remission (CR)/CR with an incomplete hematologic recovery (CRi) rate at 28 days post-CAR-T cell infusion. Secondary endpoints included the 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, incidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and CAR-T cell-related encephalopathy syndrome (CRES).
Results:
A retrospective analysis was performed on 36 patients: 12 in the recipient group and 24 in the donor group. The recipient and donor groups showed no statistically significant differences in CR/CRi rates (83.3% vs. 100.0%, P = 0.105), 2-year EFS rates (50.8% vs. 51.6%, P = 0.617), or 2-year OS rates (49.5% vs. 63.6%, P = 0.215). In addition, the incidences of GVHD, CRS, and CRES did not significantly differ between the two groups. Further analysis within the donor group revealed 12 matched sibling donors (MSDs) and 12 haploidentical donors (HIDs). The 2-year EFS rate was statistically significantly greater in the HID group than in the MSD group (75.0% vs. 30.7%, P = 0.043), whereas no significant differences were observed in the CR/CRi rates, 2-year OS, or the incidence of GVHD, CRS, and CRES between these subgroups.
Conclusions:
Both recipient-derived and donor-derived CD19 CAR-T cell therapies are effective treatment options for B-ALL relapsed post-allo-HSCT patients. HID-derived CAR-T cells offer a longer EFS and may be considered the optimal choice.