Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China. Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment. Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics. Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL⁻¹. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73). Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

BACKGROUND: As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034. METHODS: The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC). RESULTS: Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases that need rehabilitation increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively. CONCLUSIONS The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.
Humans ; China/epidemiology* ; Global Burden of Disease ; Female ; Male ; Musculoskeletal Diseases/epidemiology* ; Rehabilitation/trends* ; Quality of Life ; Middle Aged ; Aged ; Bayes Theorem

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

In recent years, China's manned space program has advanced rapidly, with deep space exploration missions such as manned lunar landing steadily progressing, leading to a significant extension of astronauts' duration in outer space. In this context, the impact of the space magnetic field environment on astronaut health has become increasingly conspicuous. Characterized by its complexity, the spatial magnetic field indirectly regulates the circadian rhythm system by interfering with mitochondrial functions, such as electron transport chain activity, ATP synthesis efficiency, and reactive oxygen species (ROS) balance. This disruption can lead to circadian misalignment, sleep disorders, metabolic dysregulation, and other issues, severely compromising astronauts' physical and mental well-being, as well as mission performance. Currently, researchers have carried out extensive investigations into the influence of the space magnetic environment on circadian rhythms. Nevertheless, due to disparities in magnetic field parameters, exposure durations, and the model organisms employed in experiments, the results have been inconsistent. This review systematically elaborates on ground-based simulation technologies for spatial magnetic field environments and their applications, summarizes the effects of magnetic fields with varying intensities and types on core circadian rhythm biomarkers in model organisms and humans, and explores the underlying molecular and physiological mechanisms of magnetic field-induced circadian rhythm perturbation. This work aims to deepen the understanding of the mechanisms of the space magnetic environment on biological rhythms, and establish a scientific basis for formulating adaptive protective strategies centered on circadian regulation for astronauts, thereby ensuring the successful implementation of long-term deep-space missions.
Circadian Rhythm/physiology* ; Humans ; Magnetic Fields/adverse effects* ; Space Flight ; Animals ; Extraterrestrial Environment

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.