Lung transplantation is the optimal treatment for end-stage lung diseases and can significantly improve prognosis of the patients. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury, and other challenges (like shortage of donor lungs) , limit the practical application of lung transplantation in clinical practice. Chinese research teams have been making continuous efforts and have achieved breakthroughs in basic research on lung transplantation by integrating emerging technologies and cutting-edge achievements from interdisciplinary fields, which has strongly propelled the development of this field. This article will comprehensively review the academic progress made by Chinese research teams in the field of lung transplantation in 2024, with a focus on the achievements of Chinese teams in basic research on lung transplantation. It aims to provide innovative ideas and strategies for key issues in the basic field of lung transplantation and to help China's lung transplantation cause reach a higher level.

OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Background::Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods::Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results::The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.Conclusion::With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Objective:To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China.Methods:A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described.Results:The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age ( P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area ( P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions:The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.