Objective To explore the key molecule and signaling pathway involved in the recruitment of cancer-associated fibroblasts (CAFs) by BRAF inhibitor (BRAFi)-resistant melanoma. Methods Tumor tissue sections were collected from 20 melanoma patients who received BRAFi-targeted therapy in Zhongshan Hospital, Fudan University, between September 2024 and September 2025, including 10 cases in the BRAFi-resistant group and 10 cases in the BRAFi-sensitive group. Immunohistochemical staining was performed to compare the number of CAFs in tumor tissues in the two groups. A co-culture model was established to compare the half-maximal inhibitory concentration (IC₅₀) of BRAFi in melanoma cells under co-culture conditions with CAFs versus non-co-culture conditions. Differential gene expression between BRAFi-sensitive and BRAFi-resistant melanoma was analyzed using publicly available sequencing data (GSE196434), and key differentially expressed genes were identified. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were employed to validate the expression differences of CXCL1 between BRAFi-sensitive and BRAFi-resistant melanoma cells, and to detect CXCL1 expression in melanoma cells treated or untreated with the AKT inhibitor (AKTi). Transwell invasion assays were performed to evaluate the recruitment capability of BRAFi-resistant and BRAFi-sensitive melanoma cells toward CAFs, and to compare the differences in recruitment capability of melanoma cells toward CAFs among the AKTi-treated group, the AKTi＋CXCL1-treated group, and the control group. Results The number of CAFs was significantly higher in the BRAFi-resistant group than that in the BRAFi-sensitive group (P＜0.01). The cell viability (P＜0.01) and IC₅₀ were higher in the melanoma co-culture group with CAFs than in the non-co-culture group. CXCL1 was identified as a key differentially expressed gene, with higher expression in BRAFi-resistant melanoma than in BRAFi-sensitive melanoma (P＜0.01). AKTi treatment suppressed CXCL1 expression in BRAFi-resistant melanoma (P＜0.01). BRAFi-resistant melanoma exhibited a stronger CAF-recruiting capacity than BRAFi-sensitive melanoma (P＜0.05), and AKTi treatment reduced its ability to recruit CAFs (P＜0.05). This effect was restored after the addition of exogenous CXCL1 (P＜0.05). Conclusions BRAFi-resistant melanoma activates the AKT pathway to upregulate CXCL1, thereby recruiting CAFs.

To provide scientific guidance and standardization for perioperative clinical nursing practice in patients undergoing percutaneous renal biopsy, relevant evidence on percutaneous renal biopsy nursing care was systematically retrieved and synthesized through an evidence-based approach. After two rounds of Delphi expert consultation and expert panel discussions, expert consensus on perioperative clinical nursing standards for patients undergoing percutaneous renal biopsy (hereinafter referred to as the "Consensus") was developed. The Consensus includes three primary themes: preoperative care, intraoperative care, and postoperative care, encompassing 21 secondary themes. It is characterized by scientific rigor, practical applicability, and comprehensiveness, and serves as a valuable reference and guide for clinical nursing professionals across medical institutions.

To provide scientific guidance and standardization for perioperative clinical nursing practice in patients undergoing percutaneous renal biopsy, relevant evidence on percutaneous renal biopsy nursing care was systematically retrieved and synthesized through an evidence-based approach. After two rounds of Delphi expert consultation and expert panel discussions, expert consensus on perioperative clinical nursing standards for patients undergoing percutaneous renal biopsy (hereinafter referred to as the "Consensus") was developed. The Consensus includes three primary themes: preoperative care, intraoperative care, and postoperative care, encompassing 21 secondary themes. It is characterized by scientific rigor, practical applicability, and comprehensiveness, and serves as a valuable reference and guide for clinical nursing professionals across medical institutions.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88％on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66％on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.

Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t -test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P =0.148), ORR (36.7% vs 18.5%, P =0.098), DCR (65.3% vs 55.6%, P =0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P =0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Cell Cycle Checkpoints/genetics* ; Checkpoint Kinase 1/metabolism* ; Heterozygote ; Humans ; Mitosis/genetics* ; Mutation ; Zygote/metabolism*

Objective:To study the relationship between the relevant chemical elements in the original surface drinking water sources and the prevalence of dental fluorosis in Bijie City, Guizhou Province, and to provide a scientific basis for further studying the distribution of dental fluorosis patients, clarifying the mechanism of endemic fluorosis, and scientifically adjusting relevant prevention and treatment policies.Methods:From August 2021 to March 2022, based on the local census data of endemic fluorosis in Guizhou Province, 385 samples of original surface drinking water sources were collected in 214 townships (towns) of Bijie City. The pH value, and contents of fluorine (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), manganese (Mn), copper (Cu), zinc (Zn), nickel (Ni), arsenic (As), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb), chromium (Cr), iron (Fe), and selenium (Se) in the drinking water were determined. Taking the dental fluorosis index representing the prevalence of dental fluorosis as the dependent variable, a principal component multiple regression model was constructed based on the above chemical elements of drinking water to study the related factors affecting the prevalence of dental fluorosis, and its contribution rate was calculated.Results:The median of dental fluorosis index in 214 townships (towns) of Bijie City was 1.460. The average of pH values and contents of F, Ca, Mg, Al, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Ba and Pb of 385 drinking water samples were 6.369, and 0.209, 179.706, 16.198, 0.163, 0.987, 0.015, 0.073, 0.176, 0.027, 0.014, 0.191, 0.007, 0.005, 0.003, 0.001, 0.155, 0.005 mg/L, respectively. Six principal components ( F1 - F6) were extracted by principal component regression analysis, and the cumulative contribution rate was 72.05%. After multiple linear regression analysis, the chemical elements in drinking water were positively correlated with the prevalence of dental fluorosis in the order of Se, Fe, Cr, Mn, Ni, Cd and Cu, and negatively correlated with the prevalence of dental fluorosis in the order of Ba, F, Ti, Mo, Zn, Al, Pb, Ca, As and Mg. Conclusions:The chemical properties in drinking water of endemic fluorosis areas in Bijie City have obvious synergistic or antagonistic effects on the occurrence and prevalence of dental fluorosis in this area. The F in the drinking water may not play a decisive role in the occurrence and prevalence of local dental fluorosis.