OBJECTIVES: To analyze the disease burden of melanoma among middle-aged and elderly populations in China, and to predict the future trend. METHODS: Data from the Global Burden of Disease (GBD) 2021 were utilized to collect incidence and mortality rates of melanoma, disability-adjusted life years (DALYs), and corresponding age crude rates among the middle-aged and elderly population in China during 1990 and 2021. Additionally, the estimated annual percentage change (EAPC) was employed to assess the temporal trends. Age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models were utilized to compute age, period, and cohort effects on incidence and mortality rates of melanoma, as well as to predict future trends up to 2035. RESULTS: During 1990-2021, the incidence rate of melanoma for males was higher than that for females among the middle-aged and elderly population in China, and the overall incidence rate increased annually with an EAPC of 2.13 (1.90-2.36), while the overall mortality rate and DALY rate showed a declining trend with an EAPC of －0.28 (－0.41-－0.15) and －0.54 (－0.68-－0.41), respectively. The results of the APC model analysis revealed that age effects on both incidence and mortality rates of melanoma in China's middle-aged and elderly population were significant, with both increasing with age. Period and cohort effects showed an upward trend for incidence rates but a downward trend for mortality rates. Moreover, the period and cohort effects for mortality rates were not significant among females. In the BAPC prediction model, the number of incidences of melanoma in middle-aged and elderly people in China would increase dramatically. By 2035, the number of incidence cases is expected to reach approximately 9600 (males) and 10 300 (females), corresponding to an incidence rate of 2.66/10⁵ and 2.67/10⁵, respectively. The number of deaths is projected to be about 2600 (males) and 3500 (females) by 2035, corresponding to a mortality rate of 0.72/10⁵ and 0.91/10⁵, respectively. CONCLUSIONS The disease burden of melanoma among the middle-aged and elderly population in China remains substantial and is expected to increase over the next decade.
Humans ; Melanoma/mortality* ; China/epidemiology* ; Aged ; Middle Aged ; Male ; Female ; Incidence ; Disability-Adjusted Life Years ; Bayes Theorem ; Cost of Illness ; Skin Neoplasms/epidemiology*

OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Central line associated bloodstream infection (CLABSI) is the most severe complication of indwelling intravascular catheters and one of the most common causes of intensive care unit (ICU)- or hospital-acquired infections. Once CLABSI occurs, it significantly increases the risk of mortality, long of hospital stay, and healthcare economic burden. In recent years, multiple large-scale clinical studies on the diagnosis, treatment, and prevention of CLABSI have been completed, providing evidence-based medical support for related practices. Additionally, evolving global trends in antibiotic resistance epidemiology and the development of novel antimicrobial agents necessitate adjustments in clinical management strategies. Based on these developments, the Chinese Society of Critical Care Medicine has updated and revised the Guideline on the Prevention and Treatment of Intravascular Catheter-Related Infections (2007). This guideline was developed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for evidence quality assessment. Guided by clinical questions, the working group initiated the process by defining key clinical issues, conducting literature searches, screening studies, performing meta-analyses, and synthesizing evidence-based findings to draft preliminary recommendations. These recommendations underwent iterative revisions through expert panel reviews, remote and in-person meetings, and two rounds of voting by the Standing Committee of the Chinese Society of Critical Care Medicine before finalization. The guideline comprises 52 recommendations, focusing on adult patients with central venous catheters in ICU. Key areas addressed include: selection of catheter insertion sites and techniques, catheter type and design, catheter management, prevention, diagnosis, and treatment of CLABSI. The guideline aims to provide ICU healthcare professionals with best practices for central line management, ensuring standardized clinical protocols for adult CLABSI.
Humans ; Catheter-Related Infections/therapy* ; Catheterization, Central Venous/adverse effects* ; Bacteremia/therapy* ; Intensive Care Units ; Cross Infection/prevention & control*

OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Objective This study was designed to investigate the effects of corilagin on morphine-tolerant rats and discuss the reaction mechanism.Methods A rat model of chronic morphine analgesia tolerance was established.The tail-flick latency of rats was detected by using the water bath tail-flick method.The positive cell rate of ionized calcium binding adapter molecule-1(Iba-1)was detected by using immunofluorescence assay.The protein expressions of Iba-1 and mitogen-activated protein kinase(MAPK)pathway-related proteins were detected by Western blotting.The release of interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α)and interleukin-1 beta(IL-1β)was detected by using enzyme-linked immunosorbent assay(ELISA).The mRNA levels of IL-6,TNF-α and IL-1β were detected by using quantitative reverse transcriptase polymerase chain reaction(qRT-PCR).Results Compared with the morphine(Mor)group,the analgesic effect of morphine in morphine+corilagin(Mor+Cor)group was strengthened with the increase of corilagin concentration.Compared with the Control group,the positive cell rate of Iba-1,Iba-1 protein expression level,levels of inflammatory factors IL-6,TNF-α,IL-1β,and the phosphorylated expression levels of MAPK signaling pathway-related proteins extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK)and p38 were significantly increased in the Mor group,which were then decreased in Mor+Cor group with the increase of corilagin con-centration.Morphine and corilagin treatment(alone or in combination)had no significant effects on the expression levels of ERK,JNK and p38.Conclusion Corilagin reduces morphine tolerance in rats by inhibiting MAPK pathway.