As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Andrological diseases have become an important public health problem threatening men's health worldwide， which significantly affects the quality of life of patients and brings a heavy disease burden. Western medicine often faces the dilemma of obvious side effects and limited efficacy. Traditional Chinese medicine has unique advantages in the prevention and treatment of andrological diseases and has accumulated rich clinical experience. Epimedii Folium， as a traditional Chinese medicine for strengthening kidney and Yang， exerts a key therapeutic effect on andrology diseases through multi-component synergy， multi-target regulation， and multi-pathway intervention. Recent studies have found that the main active components of Epimedii Folium， such as icariin， icariside， and icaritin， are the key material basis for the treatment of andrological diseases. The active components of Epimedii Folium can play a role in common andrological diseases such as erectile dysfunction， male infertility， and prostate cancer by regulating the activity of the nitric oxide/cyclic guanosine monophosphate （NO/cGMP） pathway， participating in oxidative stress response， regulating the secretion of hypothalamic-pituitary-gonadal axis hormones， improving spermatogenic dysfunction， and inhibiting the proliferation of cancer cells. However， the systematic action network and molecular mechanisms of the active components of Epimedii Folium have not been fully elucidated， thereby limiting its potential for clinical translation and application. In the future， it is necessary to combine cutting-edge technologies such as metabolomics， single-cell sequencing， and targeted nanoscale drug delivery systems， strengthening the research on the compatibility rules of active components and organ-specific delivery， providing a scientific basis for the development of innovative andrology traditional Chinese medicine formulas with international competitiveness， and promoting the innovation and breakthrough of andrology disease treatment modes.

Objective To analyze the disease burden and its changing trends of tracheal, bronchus, and lung cancer (TBL) attributable to high fasting plasma glucose (HFPG) in China from 1990 to 2021, and to provide key strategic evidence for the prevention and treatment of TBL. Methods Data related to TBL attributable to HFPG in China from 1990 to 2021 were collected from the Global Burden of Disease Study 2021 database, including mortality rate, disability-adjusted life years (DALYs), age-standardized rates, and other indicators. The Joinpoint regression model was applied to analyze the temporal trends of these indicators. Furthermore, the grey prediction model GM (1, 1) was used to forecast the disease burden of TBL attributable to HFPG in China from 2022 to 2031. Results From 1990 to 2021, the overall disease burden of TBL attributable to HFPG in China showed an upward trend. The total number of deaths, DALYs, crude mortality rate, age-standardized mortality rate, crude DALYs rate, and age-standardized DALYs rate increased from 4700, 121300 person-years, 0.40/100000, 0.61/100000, 10.31/100000, and 14.10/100000 in 1990 to 17400, 386500 person-years, 1.22/100000, 0.82/100000, 27.16/100000, and 17.72/100000 in 2021, with growth rates of 270.21%, 218.63%, 205.00%, 34.43%, 163.43%, and 25.67%, respectively. The increase rates among females were higher than those among males. Analysis using the Joinpoint regression model indicated that both the age-standardized mortality rate and age-standardized DALYs rate exhibited a significant upward trend, with average annual percentage changes (AAPC) of 1.01% and 0.82%, respectively, during 1990-2021 (P<0.05). The disease burden across different age and gender groups generally increased from 1990 to 2021. Mortality and DALYs rates for both males and females rose with advancing age, with elderly individuals and males constituting the primary affected populations. The GM (1, 1) grey prediction model projected continued increases in mortality rate, age-standardized mortality rate, DALYs rate, and age-standardized DALYs rate of TBL attributable to HFPG in China from 2022 to 2031, reaching 1.64/100000, 1.06/100000, 36.45/100000, and 21.81/100000, respectively, by 2031. Conclusion The disease burden of TBL attributable to HFPG remains substantial in China from 1990 to 2021, with males and elderly populations bearing the highest burden. However, the growth rate of disease burden is faster among females compared to males. It is predicted that the disease burden will continue to rise over the next decade, necessitating enhanced focus on early diagnosis and treatment for women and older adults.

Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Xenotransplantation is one of the effective ways to overcome the shortage of donor organs. However, the molecular incompatibility between xenotransplantation donors and recipients can cause rejection, which greatly limits the clinical application of xenotransplantation. In recent years, researchers have deeply explored the mechanism of xenotransplantation rejection through xenotransplantation models of pig-to-monkey and pig-to-brain death recipients, and found that the innate immune system plays an important role in rejection. Macrophages, as phagocytes in the innate immune system, not only damage xenografts through phagocytosis but also interact with other immune cells to influence the immune microenvironment of xenotransplantation. However, due to the heterogeneity of macrophages, their phenotypes and functions in xenotransplantation rejection remain unclear. Therefore, it is necessary to further explore the role of macrophages in xenotransplantation rejection. This article reviews the latest research progress of macrophages in xenotransplantation rejection, aiming to explore the mechanisms of macrophages in xenotransplantation rejection and provide references for future research.

Objective: To investigate the distribution of IgM anti-A/B titers among group O whole blood donors in Jiangsu, establish a low-titer threshold, and analyze the demographic characteristics of low-titer donors, so as to provide data for recruiting low-titer group O whole blood (LTOWB) donors. Methods: Plasma samples from 1 009 group O whole blood donors were tested for IgM anti-A and anti-B titers using the microplate technique. The distribution of antibody titers was analyzed to establish a low-titer threshold. The distribution trends of titers across different demographic groups were also analyzed. Results: The peak titer for anti-A, anti-B were 64 (31.5%), 4 (23.8%), respectively, The proportion of donors with both anti-A and anti-B titers below 64 was 97.3% (982/1 009). The mean anti-A titer was higher than anti-B titer. Anti-A titers were higher in female donors than in male donors (P<0.05). The anti-A titers differed significantly among different age groups (P<0.05). However, no significant difference in titers was observed based on the number of donations (P>0.05). Conclusion: A titer of 64 can be used as the reference threshold of LTOWB in Jiangsu. Male donors of appropriate age are more suitable than female donors for establishing an emergency panel of LTOWB mobile donors.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Objective:To observe the effect of isokinetic sensorimotor training on the hand function of stroke survivors.Methods:Forty-two stroke survivors with hand dysfunction were randomly divided into an isokinetic group of 22 and a control group of 20. Both groups were given sensorimotor training in addition to routine drug treatment and rehabilitation therapy, but the isokinetic group was additionally provided with sensorimotor training based on isokinetic techniques for 45 minutes daily, 5 days a week for 4 consecutive weeks. Before and after the intervention, both groups were evaluated using the Semmes-Weinstein monofilament examination (SWME), their two-point discrimination (2-PD) was documented, proprioception of their wrist joints was quantified, and the Fugl-Meyer upper extremity assessment (FMA-UE) and the simplified upper limb function assessment (STEF) were applied.Results:In both groups after treatment, there was a significant improvement in the SWME scores and 2-PD distance of the index finger and the thenar, and there was a significant decrease in the angle of motion perception (at 30° of flexion). The average FMA-UE and STEF scores of both groups had improved. After the treatment, the SWME scores of the index finger and the thenar, as well as well as the average FMA-UE and STEF scores of the isokinetic group were significantly higher than the control group′s averages. Angle of motion perception was also significantly superior.Conclusions:Sensorimotor training based on isokinetic techniques can significantly improve touch, motion sense, gross motor function and the fine motor ability of stroke survivors.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*