Objective: To systematically analyze the current status and influencing factors of platelet supply in medical institutions across China, and to explore the problems and future development directions of the existing supply models. Methods: From February 25 to March 5, 2025, a web-based questionnaire survey was performed. A self-designed questionnaire was distributed to staff in the blood transfusion departments of medical institutions nationwide in China. Data on the current status and influencing factors of platelet supply were collected and analyzed. Results: A total of 2 268 responses were collected in this survey, with 1 366 valid questionnaires finally included, covering 33 provinces, autonomous regions, and municipalities directly under the central government across China. The survey revealed that platelet supply in Chinese medical institutions exhibited a pattern of "sufficient in the eastern region, stable in the central region, and scarce in the western region": adequate in East China; generally favorable in South China except Guangxi; centered on Beijing and Tianjin in North China; basically met but with insufficient reserves in Central China; subject to seasonal fluctuations in Northeast China; only meeting the baseline supply in Yunnan, Guizhou, and Sichuan in Southwest China; and notably short in Qinghai, Ningxia, and Xinjiang in Northwest China. Family donor mobilization was required in 81.2% (1 109/1 366) of institutions, whereas this proportion was only 12.7% (173/1 366) among institutions with sufficient supply. Tertiary hospitals constituted the main users, among which tertiary Class A hospitals had the highest sufficiency rate, and secondary Class B hospitals showed the most pronounced shortage. A total of 84% (1 147/1 366) of institutions lacked a professional management team; only 19% (266/1 366) had an inventory warning system, of which 88% (234/266) considered it effective. Platelet reservation required 3 days in 33% (458/1 366) of institutions. The mandatory transfusion rate was 30.55% (29/118) when the reservation lead time exceeded 3 days, representing an increase of 5.98% compared with 24.57% (55/180) in the same-day reservation group. For optimization, most institutions called for improved blood donation services, strengthened education and incentives, establishment of regional coordination and policy collaboration, and supplementary suggestions focused on technologies for extending platelet shelf life. Conclusion: Regional imbalance in platelet supply across China is prominent, with supply shortages in some provinces, reliance on family donor mobilization in most institutions, weak grassroots support capacity, imperfect management systems, and supply timeliness constraining clinical practice. Systematic improvements are needed in optimizing blood donation services, strengthening regional coordination, improving relevant policies, and developing platelet preservation technologies, so as to enhance the level of supply security and patient safety.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

Objective To investigate the mechanism of Achyranthoside Ⅰ inhibits pyroptosis in chondrocytes through the nuclear factor-κB(NF-κB)/NOD receptor protein structure domain related proteins 3(NLRP3)/cystine containing aspartate specific proteins-1(caspase-1)signaling pathway.Methods Primary mouse chondrocytes were divided into blank group(phosphate buffered solution with the same volume),model group[10 ng·mL-1 interleukin-1β(IL-1 β)],control group(10 ng·mL-1 IL-1β+20 μmol·L-1 celecoxib)and experimental group(10 ng·mL-1 IL-1β+3 μg·mL-1 Achyranthoside Ⅰ).After 24 hours of intervention,the cell proliferation was measured by cell counting kit 8,the levels of superoxide dismutase(SOD),malondialdehyde(MDA),IL-1 and IL-6 were detected by enzyme-linked immunosorbent assay,the protein expression levels of NF-κB p65,NLRP3 and caspase-1 were detected by Western Blot.Results The apoptosis rates in experimental,control,model and blank groups were(13.34±0.61)％,(15.64±1.01)％,(21.81±1.10)％and 0;the SOD levels were(147.03±16.49),(130.09±7.33),(122.03±10.71)and(164.40±22.74)nU·mL-1;the MDA levels were(6.43±0.71),(7.63±1.01),(8.89±1.84)and(5.69±0.81)nmol·L-1;the IL-1 levels were(338.69±40.95),(361.78±32.15),(391.44±30.59)and(289.23±25.19)pg·mL-1;the IL-6 levels were(89.96±8.81),(101.10±11.59),(120.39±14.71)and(60.29±6.03)pg·mL-1;the relative expression levels of NF-κB p65 were 0.68±0.05,0.97±0.05,1.26±0.05 and 0.57±0.05;the relative expression levels of NLRP3 were 0.71±0.08,1.02±0.10,1.50±0.06 and 0.31±0.05;the relative expression levels of caspase-1 were 0.70±0.07,1.29±0.08,1.66±0.07 and 0.51±0.07,respectively.Compared with the model group,the differences of above indexes were statistically significant in the experimental group(all P＜0.05).Conclusion Achyranthoside Ⅰ can improve the oxidative stress status induced by IL-1 β in chondrocytes,reduce the expression of proteins related to the NF-κB signaling pathway,and thereby decrease the occurrence of caspase-1 dependent pyroptosis,providing a protective effect on chondrocytes.

AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

Objective To investigate the mechanism of Achyranthoside Ⅰ inhibits pyroptosis in chondrocytes through the nuclear factor-κB(NF-κB)/NOD receptor protein structure domain related proteins 3(NLRP3)/cystine containing aspartate specific proteins-1(caspase-1)signaling pathway.Methods Primary mouse chondrocytes were divided into blank group(phosphate buffered solution with the same volume),model group[10 ng·mL-1 interleukin-1β(IL-1 β)],control group(10 ng·mL-1 IL-1β+20 μmol·L-1 celecoxib)and experimental group(10 ng·mL-1 IL-1β+3 μg·mL-1 Achyranthoside Ⅰ).After 24 hours of intervention,the cell proliferation was measured by cell counting kit 8,the levels of superoxide dismutase(SOD),malondialdehyde(MDA),IL-1 and IL-6 were detected by enzyme-linked immunosorbent assay,the protein expression levels of NF-κB p65,NLRP3 and caspase-1 were detected by Western Blot.Results The apoptosis rates in experimental,control,model and blank groups were(13.34±0.61)％,(15.64±1.01)％,(21.81±1.10)％and 0;the SOD levels were(147.03±16.49),(130.09±7.33),(122.03±10.71)and(164.40±22.74)nU·mL-1;the MDA levels were(6.43±0.71),(7.63±1.01),(8.89±1.84)and(5.69±0.81)nmol·L-1;the IL-1 levels were(338.69±40.95),(361.78±32.15),(391.44±30.59)and(289.23±25.19)pg·mL-1;the IL-6 levels were(89.96±8.81),(101.10±11.59),(120.39±14.71)and(60.29±6.03)pg·mL-1;the relative expression levels of NF-κB p65 were 0.68±0.05,0.97±0.05,1.26±0.05 and 0.57±0.05;the relative expression levels of NLRP3 were 0.71±0.08,1.02±0.10,1.50±0.06 and 0.31±0.05;the relative expression levels of caspase-1 were 0.70±0.07,1.29±0.08,1.66±0.07 and 0.51±0.07,respectively.Compared with the model group,the differences of above indexes were statistically significant in the experimental group(all P＜0.05).Conclusion Achyranthoside Ⅰ can improve the oxidative stress status induced by IL-1 β in chondrocytes,reduce the expression of proteins related to the NF-κB signaling pathway,and thereby decrease the occurrence of caspase-1 dependent pyroptosis,providing a protective effect on chondrocytes.

Objective To explore the role of plasma exosome microRNA-622(miR-622)in cachexia of hep-atocellular carcinoma(HCC).Methods Select preoperative blood samples from 40 patients with stage Ⅲ-ⅣHCC and 33 patients with non HCC liver benign diseases collected at Huashan Hospital,Fudan University from 2021 to 2024 as the research subjects.Exosomes were isolated from the plasma of patients,human HCC cell lines(HepG2,Hep3B,PLC,Huh7),and the culture supernatants of primary human hepatocytes(PHH)by differential centrifugation.The relative expression level of miR-622 was detected by real-time fluorescence quantitative polymerase chain reaction.The level of lipolysis was assessed by determining the concentration of glycerol and fatty acids in adipocyte culture medium.Results Plasma exosome miR-622 levels in HCC pa-tients were positively correlated with subcutaneous adipose index and visceral adipose index(r=0.516,0.539,P＜0.05).HCC cell conditional medium was able to significantly increase the lipolysis level of adipo-cytes.The relative expression levels of miR-622 in exosomes from HCC cells(HepG2,Hep3B,PLC,Huh7)were significantly lower than those in exosomes from PHH,with values of 0.13±0.04,0.28±0.08,0.23±0.07,and 0.24±0.04,respectively,compared to 1.00±0.18 in PHH exosomes.Further studies revealed that plasma exosome of HCC patients treatment was able to lead to a decrease in the relative expression level of miR-622 in adipocytes,as well as an enhancement of lipolysis.Conclusion The expression of plasma exosomal miR-622 is downregulated in HCC patients.HCC cells can deliver miR-622 to adipocytes via exosomes to reg-ulate lipolysis.Plasma exosomal miR-622 may serve as a potential biomarker for predicting HCC cachexia and a therapeutic target.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA