OBJECTIVE To evaluate the effect of clinical pharmacists participating in the treatment of chronic heart failure （CHF） based on the clinical pharmacy pathway （CPP）. METHODS Totally 226 CHF patients recruited from August 24th， 2024 to March 14th， 2025， were divided into an observation group and a control group based on the random number table method， with 113 cases in each group. All patients were treated with conventional therapy. The observation group was additionally given CPP management （including pharmaceutical care during hospitalization， the formulation of individualized discharge medication regimens， and pharmaceutical follow-up after discharge）. The cardiac function parameters at admission， at discharge， at 3 and 6 months after discharge， drug use at 6 months after discharge， economic indicators， as well as the readmission rate and mortality rate at 6 months after discharge were compared between the two groups. Morisky Medication Adherence Scale-8 Items （MMAS-8）， Somatic Self-rating Scale （SSS） and Patient Health Questionnaire-9 （PHQ-9） scores were compared at admission， at discharge and at 3 and 6 months after discharge. RESULTS Six months after discharge， 24 patients dropped out. Eventually， 104 patients in the observation group and 98 patients in the control group completed the study. Compared with at admission， New York Heart Association （NYHA） cardiac functional classification， left ventricular ejection fraction （LVEF） and N -terminal pro-B-type natriuretic peptide （NT-proBNP） of both groups of patients at discharge as well as at 3 and 6 months after discharge were significantly improved； moreover， the improvements at 3 and 6 months after discharge were significantly better than those at discharge. Meanwhile， the above indexes （except for NYHA cardiac functional classification at discharge， NT-proBNP and NYHA cardiac functional classification at 3 months after discharge） of the observation group at discharge， at 3 and 6 months after discharge were significantly better than the control group （ P ＜0.05）. The utilization rates of angiotensin converting enzyme inhibitor （ACEI）/angiotensin Ⅱ receptor blocker （ARB）/angiotensin receptor neprilysin inhibitor （ARNI）， the proportion of β-blockers reaching the target dose， the utilization rate of sodium-glucose linked transporter 2 inhibitor （SGLT2i）， and the proportion of SGLT2i reaching the target dose in the observation group were significantly higher than the control group （ P ＜0.05）， and the proportion of drugs and readmission rate were significantly lower than the control group （ P ＜0.05）. Compared with at admission， MMAS-8 scores of the patients in the observation group at discharge， at 3 and 6 months after discharge were significantly increased， while SSS and PHQ-9 scores were significantly lowered （ P ＜0.05）. And all the above scores gradually decreas ed with the extension of discharge time （ P ＜0.05）. CONCLUSIONS Clinical pharmacists can utilize CPP to significantly improve patients’ cardiac function， medication adherence， somatic symptoms and depression. Additionally， they can significantly improve the utilization rates of ACEI/ARB/ARNI and SGLT2i， as well as the proportion of target doses of β-blockers and SGLT2i， while simultaneously reducing readmission rates.

Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula （参附黄配方） in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group， sepsis group， and Shenfuhuang group， with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture （CLP） procedure. At 4 hours after modelling， Shenfuhuang group were gavaged with 2.5 g/（kg·d） of Shenfuhuang Formula， 0.5 ml each time， at 12 hours intervals， for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling， the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice， and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group， of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications， six key genes were screened， including serine/threonine-protein kinase （Nek1）， myelin-associated glycoprotein （Mag）， endothelial cell-specific tyrosine kinase receptor （Tek）， a disintegrin and metalloproteinase with thrombospondin motifs 20 （Adamts20）， lymphocyte antigen 86 （Ly86）， and E3 ubiquitin-protein ligase （Traip）. Further genetic and protein validation revealed that， compared to the sham surgery group， the mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip in the brain tissue of septic mice significantly reduced （P＜0.05）. In comparison to the sepsis group， Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip （P＜0.05）. ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1， Mag， Tek， Adamts20， Ly86， and Traip genes and their encoded proteins.

BACKGROUND:Endometrial receptivity is a key factor in embryo implantation in northwest Tibetan cashmere goats,and the expression of genes related to endometrial receptivity and their variable splicing are still unclear. OBJECTIVE:To analyze and explore genes and variable splicing events related to endometrial receptivity in northwest Tibetan cashmere goats. METHODS:On days 5 and 15 of pregnancy(representing pre receptive endometrium group and receptive endometrium group),three northwest Tibetan cashmere goats were randomly selected.Endometrial tissue was collected and stained with hematoxylin and eosin to observe tissue morphology.Immunohistochemical staining was used to detect the expression of endometrial receptive marker proteins leukemia inhibitory factor and vascular endothelial growth factor.After the total RNA was extracted and the quality test was qualified,transcriptome sequencing was performed to search differentially expressed mRNAs,lncRNAs,circRNAs,and miRNAs,perform functional prediction,and analyze alternative splicing mRNAs and lncRNAs related to endometrial receptivity. RESULTS AND CONCLUSION:(1)Compared with the pre receptive endometrium group,the expression levels of leukemia inhibitory factor and vascular endothelial growth factor proteins in the endometrial tissue of the receptive endometrium group were significantly increased.(2)The sequencing results showed that the differentially expressed genes were mostly mRNA and lncRNA genes,including 250 upregulated mRNAs,193 upregulated lncRNAs,135 downregulated mRNAs,and 123 downregulated lncRNAs,which were significantly enriched in the Wnt,Hedgehog,and Hippo signaling pathways.(3)Alternative splicing event analysis uncovered 8 differentially expressed variable splicing transcripts,which were all mRNA transcripts,including 2 downregulated and 6 upregulated,and were significantly associated with vascular endothelial growth factor receptor signaling,cell motility,and embryonic development.

Objective To evaluate the application of the Huaxi Intelligent Endoscopic Skill Training and Assessment System in minimally invasive surgery (MIS) skills training and provide insights for optimizing MIS training models, we analyzed trainee performance during training and assessment. Methods A retrospective analysis was conducted on the use of this system across 28 medical institutions from January 2022 to January 2025. Results By January 2025, the standardized deployment of 139 simulation units had been completed. A total of 403 trainees from various surgical specialties, including thoracic surgery and general surgery, participated in five customized endoscopic skill training modules: endoscopic recognition, grasping training, positioning and placement, cutting training, and suturing training. Throughout the training period, a total of 78 participants took part in 27 formal assessments. Correlation analysis based on Spearman showed that pre-assessment training pass rates were significantly correlated with final assessment scores, indicating enhancing the quality of each training module and overall training efficacy is a key to improving the effectiveness of MIS training. Conclusion The Huaxi Intelligent Endoscopic Skill Training and Assessment System effectively supports MIS training and evaluation.

Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase Ⅰ)to gastric precancerous lesions(Phase Ⅱ)and finally to GC(Phase Ⅲ).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases Ⅰ and Ⅱ,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase Ⅰ,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resis-tance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase Ⅱ,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase Ⅲ,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.

Objective:To analyze risk factors for early trauma-induced coagulopathy (TIC) in pediatric patients with moderate-to-severe traumatic brain injury (msTBI), develop a predictive model and evaluate its predictive performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 290 pediatric patients with msTBI who were admitted to Children′s Hospital of Soochow University between January 2016 and December 2024, including 188 boys and 102 girls, aged 0.2-15.7 years [5.2(2.8, 9.3)years]. Based on the coagulation test results at admission, the patients were divided into TIC group ( n=162) and non-TIC group ( n=128). The patients were randomly allocated into training set ( n=203) and validation set ( n=87) at a ratio of 7∶3. Demographic characteristics, clinical data, vital signs, imaging findings, arterial blood gas analysis results, and coagulation profiles of the patients were collected. Univariate analysis and Lasso regression analysis were used to identify risk factors associated with early TIC in children with msTBI and multivariate Logistic regression analysis was performed to determine independent risk factors and construct a predictive model. The model′s discrimination and calibration were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), Hosmer-Lemeshow (H-L) test, and calibration curve. Its clinical utility was assessed through decision curve analysis (DCA). Results:Significant differences were observed between the TIC group and non-TIC group in terms of age, weight, time from injury to admission, child′s Glasgow coma scale (CGCS) score, pediatric trauma score (PTS), shock index, heart rate, respiratory rate, systolic blood pressure, Rotterdam CT score, intraventricular hemorrhage, cerebral contusion, brain herniation, long bone fracture, pelvic fracture, hemopneumothorax, pulmonary contusion, intra-abdominal organ injury, actual bicarbonate, base excess, base excess in the extracellular fluid, blood glucose, hemoglobin (Hb), osmolarity, blood calcium, anion gap, blood lactate, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelet count ( P<0.05). With coagulation-related variables excluded, the following features were identified with Lasso regression including CGCS score, PTS, heart rate, systolic blood pressure, long bone fracture, blood glucose, and Hb. Multivariate Logistic regression analysis revealed that CGCS score≤8 points ( OR=3.05, 95% CI 1.65, 5.63), PTS>5 points ( OR=0.45, 95% CI 0.23, 0.89), systolic blood pressure ( OR=0.98, 95% CI 0.97, 0.99), blood glucose ( OR=1.09, 95% CI 1.01, 1.17), and long bone fracture ( OR=2.47, 95% CI 1.13, 5.42) were influencing factors for early TIC in children with msTBI ( P<0.05). The regression equation of the predictive model was established as follows: Logit[ P/(1- P)]=1.01×"CGCS score≤8 points"-0.69×"PTS>5 points"- 0.02×"systolic blood pressure"+0.89×"long bone fracture"+0.08×"blood glucose"+1.32. The ROC curve analysis showed that the training set had an AUC of 0.86 (95% CI 0.78, 0.94), with sensitivity and specificity of 76.6% and 92.5%, while the AUC was 0.80 (95% CI 0.74, 0.86), with sensitivity and specificity of 75.7% and 79.6% in the validation set. H-L test results showed a χ2 value of 8.18 ( P=0.416) in the training set and 5.30 ( P=0.216) in the validation set. The calibration curves for both sets demonstrated good agreement with the actual curves, indicating that the predicted probabilities closely matched the observed probabilities. The DCA results indicated that both the training set and validation set demonstrated positive net benefits within threshold probabilities ranges of 10%-100% and 15%-96%. Conclusions:Independent risk factors for early TIC in pediatric msTBI patients include CGCS score≤ 8 points, PTS≤5 points, low systolic blood pressure, long bone fracture, and high blood glucose. The predictive model constructed based on these factors demonstrates favorable predictive performance and clinical application value.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.