BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective:To explore the prognostic value of the age-adjusted Charlson comorbidity index (ACCI) in patients with stage IIB cervical squamous cell carcinoma (CSCC) who received radical concurrent chemoradiotherapy (rCCRT).Methods:Clinical data of 115 patients with stage IIB CSCC who underwent rCCRT at the First Affiliated Hospital of Xinxiang Medical University from January 2017 to January 2023 were retrospectively analyzed. Fourteen clinical factors, including ACCI, were assessed. Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The optimal cut-off value for ACCI was determined using the receiver operating characteristic (ROC) curve analysis, and patients were divided into the high ACCI (ACCI > 3) and low ACCI (ACCI ≤ 3) groups. Survival differences between two groups were evaluated using Kaplan-Meier curves and compared by log-rank tests.Results:Multivariate Cox regression analysis revealed that ACCI was an independent prognostic factor for both PFS and OS ( HR=3.405, 95% CI: 1.108-10.467, P=0.032; HR=4.732, 95% CI: 1.363-16.425, P=0.014). Significant differences were observed in PFS and OS between the high and low ACCI groups ( P=0.023 and 0.003, respectively). The median PFS was 44 months in the high ACCI group and 56 months in the low ACCI group. The 2-year and 3-year PFS rates were 81.9% and 80.1% in the high ACCI group, and 94.4% and 94.4% in the low ACCI group, respectively. The median OS was 46 months in the high ACCI group and 56 months in the low ACCI group. The 2-year and 3-year OS rates were 88.3% and 84.7% in the high ACCI group, and 94.4% and 94.4% in the low ACCI group, respectively. Conclusions:For patients with stage IIB CSCC receiving rCCRT, ACCI is an independent and significant prognostic factor, with patients in the high ACCI group exhibiting worse prognosis.

To summarize and analyze the clinical data of one case of kidney transplantation in an HIV-positive child with end-stage renal disease (ESRD) in the Department of Transplantation, the People's Hospital of Guangxi Zhuang Autonomous Region, and to explore the safety and efficacy of kidney transplantation in HIV-positive children with ESRD. This pediatric recipient was found to be HIV-positive at birth and underwent kidney transplantation due to ESRD, with good postoperative recovery. During the 2.5-year follow-up, no rejection or rebound in HIV RNA levels was observed. The function of the transplanted kidney was good, and the quality of life was comparable to that of healthy individuals. It suggests that kidney transplantation in HIV-positive children with ESRD is safe and effective under adequate preoperative preparation and close postoperative follow-up.

[Summary]Diabetic kidney disease(DKD)caused a huge medical burden to society and has become an increasingly serious public health problem.Different from steroidal mineralocorticoid receptor antagonist,Finerenone,as a new non-steroidal mineralocorticoid receptor antagonist,has higher selectivity and effectiveness.It can effectively delay the progression of DKD through anti-inflammatory and anti-fibrosis effects,reduce urinary protein,and has a low incidence of hyperkalemia and a cardioprotective effect.This article summarizes the benefits of Finerenone in DKD,its advantages over other mineralocorticoid-receptor antagonists,and its efficacy in combination with other drugs for the treatment of DKD.

Objective To investigate the role of Insulin like growth factor 2 mRNA binding protein 1(IGF2BP1)and long non-coding RNA LINC00160(LINC00160)in gastric cancer,and its potential mechanism of regulating the proliferation and invasion of gastric cancer cells.Methods Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression level of LINC00160 in gastric cancer tissues and cells.Bioinformatics prediction,RNA-binding protein immunoprecipitation(RIP)and methylated RNA immunoprecipitation(MeRIP)were used to verify the binding effect of LINC00160 and IGF2BP1.The correlation between the expression of LINC00160 and IGF2BP1 in gastric cancer tissues was analyzed by Pearson assay.CCK-8 assay and Transwell assay were used to detect cell proliferation and invasion.The changes of aerobic glycolysis index[glucose intake,lactate production,and Adenosine-triphosphate(ATP),extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)]were detected and analyzed.Results Compared with normal tissues,the expression of LINC00160 in gastric cancer tissues(5.13±0.62 vs 1.02±0.03)was significantly up-regulated,and the difference was statistically significant(t=-36.266,P<0.001).The expression level of LINC00160 in gastric cancer cells was higher than that of human normal gastric epithelial cell line GES-1,and the difference was statistically significant(F=24.595,P<0.001).Compared with the control group,silenting LINC00160 significantly inhibited the proliferation(0.42±0.03 vs 1.03±0.04)and invasion(22.13%±1.97%vs 42.15%±2.67%)of AGS cells,decreased glucose uptake(2.11±0.26mmol/L vs 4.22±0.37mmol/L)and lactate production(6.84±1.25mmol/L vs 11.68±1.55mmol/L),decreased ECAR,and increased ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)levels and OCR,and the differences were statistically significant(t=4.188～24.423,all P<0.01).The expression of IGF2BP1 protein in gastric cancer tissues(4.07±0.36)was significantly higher than that in adjacent tissues(1.01±0.03),and the difference was statistically significant(t=-46.396,P<0.01),and was positively correlated with the expression of LINC00160(r2=0.774 5,P<0.01).Mechanistic studies revealed that IGF2BP1 upregulated LINC00160 expression by binding m6A modified LINC00160 to promote its stability.Silencing IGF2BP1 significantly inhibited the expression of LINC00160 and the proliferation,invasion and aerobic glycolysis of gastric cancer cells,and the differences were statistically significant(t=4.386～11.989,all P<0.01).Overexpression of LINC00160 reversed the effect of IGF2BP1 silencing on AGS cells.Conclusion LINC00160 is significantly up-regulated in gastric cancer,and IGF2BP1 may stably regulate the expression of LINC00160 through m6A modification,promote the aerobic glycolysis of tumor cells,and participate in the occurrence and development of gastric cancer.

Objective:To investigate the early right heart function management strategy and prognosis after left ventricular assist device(LVAD) implantation in patients with preoperative right ventricular dysfunction.Methods:A retrospective study was conducted. From March 2022 to April 2024, a total of 28 patients with end-stage heart failure underwent LVAD implantation at Nanjing First Hospital and were admitted to the intensive care unit(ICU) after surgery. Among them, patients with preoperative right ventricular dysfunction were enrolled. All patients were implanted with Corheart 6 implantable left ventricular assist device. The clinical data, occurrence of postoperative right heart failure and postoperative survival situations of enrolled patients were collected and analyzed.Results:A total of 12 patients were included in this study, including 11 males and 1 female, the mean age was(58.4±7.6) years old. Upon postoperative admission to ICU, the most commonly used positive inotropic agent was epinephrine(9 cases), followed by dobutamine(8 cases). By the second day after surgery, the most frequently utilized vasoactive medications were epinephrine and phosphodiesterase type Ⅲ inhibitors, both with 9 cases of usage. None of the enrolled patients utilized temporary mechanical circulatory assist devices. The LVAD pump speed of the patients enrolled in the study was set at approximately 2 700 revolutions per minute, and the pump flow was approximately 3 liters per minute. During the first two days after the operation, the fluid balance of the enrolled patients ranged from(-523.4±775.6)ml to(-1 248.0±1 023.9)ml. At 48 h following the operation, the mean pulmonary artery pressure(MPAP)[(26.2±4.8) mmHg vs.(32.1±6.5) mmHg(1 mmHg=0.133 kPa), P=0.042] and the pulmonary artery wedge pressure(PAWP)[(15.6±5.5)mmHg vs.(24.9±5.9) mmHg, P=0.003) ] of the enrolled patients were significantly decreased compared to preoperative levels, while the cardiac index(CI) was significantly improved[(2.7±0.2)L·min -1·m -2 vs.(2.1±0.5)L·min -1·m -2,P=0.024]. Echocardiography showed that the left atrial diameter(LAD)[(51.5±7.6)mm vs.(57.2±9.0)mm, P=0.005] and left ventricular end diastolic diameter(LVDd)[(73.5±11.5)mm vs.(78.3 ± 12.3)mm, P=0.012) ] were significantly reduced post LVAD implantation as compared to before LVAD implantation, while there was no significant difference in tricuspid annular plane systolic excusion(TAPSE). Postoperative total bilirubin(TBIL) decreased significantly compared to preoperative levels[(15.5±5.0)μmol/L vs.(27.5±17.0)μmol/L, P=0.038]. Three patients experienced right heart failure after the LVAD implantation, with an incidence rate of 25%. Nevertheless, the right heart failure was rectified during the ICU treatment period. The mean ICU treatment time for all enrolled patients was(8.6±2.9) days, the average postoperative hospital stay was(24.3±4.8) days. All enrolled patients survived at 3 months after LVAD implantation. Conclusion:Despite the presence of right ventricular dysfunction in patients before LVAD implantation, with strict fluid management, reasonable LVAD parameters, and appropriate vasoactive drugs, they are able to smoothly pass through the perioperative period, achieve the goals of left ventricular decompression, increase cardiac output, improve perfusion of the end organs, and obtain favorable short-term therapeutic effects.

[Summary]Diabetic kidney disease(DKD)caused a huge medical burden to society and has become an increasingly serious public health problem.Different from steroidal mineralocorticoid receptor antagonist,Finerenone,as a new non-steroidal mineralocorticoid receptor antagonist,has higher selectivity and effectiveness.It can effectively delay the progression of DKD through anti-inflammatory and anti-fibrosis effects,reduce urinary protein,and has a low incidence of hyperkalemia and a cardioprotective effect.This article summarizes the benefits of Finerenone in DKD,its advantages over other mineralocorticoid-receptor antagonists,and its efficacy in combination with other drugs for the treatment of DKD.