Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

In the context of comprehensively advancing the Healthy China initiative,the high-quality development of public hospitals must be guided by the core principle of"people's health".It provides a systematic analysis of the historical evolution of developmental paradigms in Chinese public hospitals.By integrating the current policy requirements for their high-quality development,it proposes key pathways including the innovation of development concepts,the reconstruction of hospital connotations,the extension of service management,the optimization of the system structure,and the empowerment of digital and intelligent technologies.Through empirical case studies that demonstrate the viability of these pathways,it aims to provide theoretical support and practical reference for the high-quality development of public hospitals centered on people's health.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

It is possible that patients with closed thoracic and abdominal trauma quickly occur death caused by deterioration of the condition in short time if their conditions could not be recognized and intervened timely because their early symptoms are concealed and the processing of their condition is rapid.The pre-examination triage of emergency is the first safety line of defense that patients with closed thoracic and abdominal trauma obtained timely rescue and treatment,and both the accuracy of its judgement and the timeliness of its response are critical.At present,there are many kinds of assessment methods and tools about pre-examination triage of emergency for patients with closed thoracic and abdominal trauma at home and abroad,such as conventional vital sign assessment and various kinds of trauma scoring systems.However,these methods have still limitations in recognizing early concealed injuries of closed thoracic and abdominal trauma.Focused trauma ultrasound(FAST),as a rapidly,non-invasively,and repeatable bedside ultrasound method,can effectively explore whether exists free liquid through conducts systematically scans for key areas such as the pericardium,hepatorenal space,splenorenal space,and pelvis cavity,thus,can provide important basis for early judging internal bleeding and organ damage.Based on this analysis,this article systematically reviewed the current status about the application of standards,assessment methods,and tools in pre-examination triage of emergency for patients with closed thoracic and abdominal trauma,and analyzed the advantages and limitations of FAST that was used in pre-examination triage of emergency,and conducted prospect,which aimed to provide references for pre-examination triage of emergency about closed thoracic and abdominal trauma in looking for the best assessment tools.

After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

BACKGROUND:Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However,whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown. OBJECTIVE:To investigate the causal relationship between cathepsin and bone mineral density.METHODS:Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables,and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran's Q test,pleiotropy was assessed using the MR-Egger intercept test,and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method. RESULTS AND CONCLUSION:The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years[odds ratio (95％ confidence interval)=0.965(0.94-0.99),P=0.04];cathepin Z was negatively associated with bone mineral density in people aged 30-45 year[odds ratio (95％ confidence interval)=1.06 (1.00-1.11),P=0.03]. The results of sensitivity analysis showed a stable causal relationship,and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups,which may increase the risk of osteoporosis and should be given more attention.

Objective To systematically evaluate the impact of continuous renal replacement therapy(CRRT)on the pharmacokinetics of polymyxin B,explore its possible impacting factors.Methods PubMed,Embase,Co-chrane Library,Web of Science,VIP database,China National Knowledge Infrastructure(CNKI),SinoMed,and Wanfang data were retrieved.The study subjects were patients receiving CRRT and polymyxin B.Observational studies,case reports,and reviews were included.The outcome indicators included therapeutic drug monitoring re-sults,pharmacokinetic parameters,and CRRT parameters.The retrieval time was from the inception of each data-base to January 2025.The quality of literatures was evaluated with ClinPK tool.Two researchers independently conducted literature screening,data extraction,and quality evaluation.Results A total of 12 literatures were ulti-mately included in analysis,including 1 review,3 case reports,and 8 observational studies.Five studies showed that the clearance rate during CRRT period(1.3-6.66 L/h)was higher than that during non-CRRT period(0.5-3.9 L/h).Five studies reported that the area under the steady-state 24-hour drug concentration-time curve(AUCss,24h)during CRRT period(21.58-75.1 mg·h/L)was lower than that during non-CRRT period(60.6-118 mg·h/L).Two studies detected drugs in ultrafiltrate or dialysate,with in vitro drug recovery rates ranging from 5.62％to 24.0％.Two studies reported a decrease in drug concentration after passing through a blood filter.Conclusion During CRRT period,polymyxin B presents higher clearance rate and lower blood drug concentration,and some patients have lower AUCss.24h than the therapeutic target.The mechanism of this change during CRRT is not yet clear,the therapy mode and filter type may be potential impacting factors,further research are needed to promote precise anti-infective treatment.

Objective:To provide a scoping review of domestic and international studies on the influencing factors of frailty in stroke inpatients, and to provide guidance for interventional studies on debility in stroke inpatients in China.Methods:A systematic search of domestic and international literature databases, including China National Knowledge Infrastructure, WanFang, VIP, China Biomedical Literature Database, PubMed, Web of Science, Embase, Cochrane Library, CINAHL was conducted about the status and its influencing factors of frailty in stroke inpatients. The retrieval time limit was from database establishment to November 23, 2023. The included literature was extracted, analyzed, and summarized according to the reporting specifications of the scope review guidelines.Results:Thirty-six articles were included, all of the 36 papers reported the prevalence of frailty in patients with stroke. The top three countries with the highest prevalence were China (15.3%-86.9%), the United Kingdom (28%-78%), and Italy (31.37%). The risk factors of stroke frailty were categorized mainly into 4 themes: social demographic factors, physical health factors, disease-related factors, and psychological and social background factors.Conclusions:The confidence of frailty in stroke patients of a higher level at home and abroad, and the risk factors involved are complex and diverse. It is suggested that future studies need to conduct large-sample, multicenter longitudinal studies to clarify the causal relationship, strengthen the exploration of controversial factors of stroke debility, and carry out more targeted intervention studies, so as to reduce the incidence of frailty and improve the recovery process of patients.