[Objective] To analyze the loss rate of platelet donors and evaluate the strategies for establishing a platelet donor bank. [Methods] A total of 1 443 donors who joined the HLA and HPA gene donor bank for platelets in Henan Province from 2018 to 2020 were included in this study. Data on the total number of apheresis platelet donations, annual donation frequency, age at enrollment, donation habits (including the number of platelets donated per session and whether they had previously donated whole blood), and enrollment location were collected from the platelet donor information management system. Donor loss was determined based on the date of their last donation. The loss rates of different groups under various conditions were compared to assess the enrollment strategies. [Results] By the time the platelet bank was officially operational in 2022, 421 donors had been lost, resulting in an loss rate of 29% (421/1 443). By the end of 2023, the overall cumulative loss rate reached 52% (746/1 443). The loss rate was lower than the overall level in groups meeting any of the following conditions: total apheresis platelet donations exceeding 50, annual donation frequency of 10 or more, age at enrollment of 40 years or older, donation of more than a single therapeutic dose per session, or a history of whole blood donation two or more times. Additionally, loss rates varied across different enrollment locations, with higher enrollment numbers generally associated with higher loss rates. [Conclusion] Through a comprehensive analysis of donor loss, our center has adjusted its strategies for establishing the donor pool. These findings also provide valuable insights for other blood collection and supply institutions in building platelet donor banks.

Polycystic ovary syndrome（PCOS） and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway is relatively well-studied in the development of intervention in PCOS， and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper， 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria， and the objective situation and existing problems of the selected research projects were analyzed from five aspects， namely， baseline data， modeling and treatment， grouping， evaluative indexes， and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project， such as the observation indicators of modeling， criteria for judging the success of the model， the treatment period， the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined， which could easily lead the bias of the results or reduce the validity of experimental data. Based on this， the list of PCOS rat experimental research operations was formed， involving five categories of experimental rats， model construction， study implementation， outcome measures and analysis and report with a total of 21 operation lists， with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases. As the global population ages, incidence, morbidity and mortality of AD have increased significantly. The core pathological features of AD include β-amyloid (Aβ) deposition and phosphorylated tau aggregation, resulting in neuronal damage, abnormal mental behavior, and cognitive decline. In recent years, research breakthroughs have not only deepened the Aβ cascade hypothesis and the pathological theory of tau protein, but also made important progress in the fields of neuroimmune regulation, "microbiota-gut-brain" axis, genetic factors, especially the ApoEε4 allele. At the same time, AD has been continuously enriched in blood, cerebrospinal fluid and imaging markers, and sensitivity of markers has been improved and detection tends to be non-invasive. Therapeutic strategies for AD include traditional drugs, novel drugs targeting Aβ/tau protein, and non-pharmacological interventions such as cognitive training, non-invasive brain stimulation and exercise. This review systematically expounds the pathological mechanism, biomarkers, and treatment strategies of AD, aiming to provide a scientific basis for the establishment of a biomarker-based precision diagnosis and treatment paradigm.

Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective:To investigate the effect of hydrogen on the expressions of stromal interaction molecule 1 (STIM1) and Ca 2+-release-activated-Ca 2+ channel protein 1 (Orai1) and the protective effect of hydrogen on septic mice acute lung injury (ALI). Methods:Forty-eight male ICR mice were divided into sham operation group (Sham group), hydrogen control group (Sham+H 2 group), sepsis group (SS group) and hydrogen intervention group (SS+H 2 group) according to a random number table method, with 12 mice in each group. Sepsis mice model were established by cecal ligation and puncture (CLP). Sham group and Sham+H 2 group did not undergo CLP, other operations were the same as follow. Sham+H 2 group and SS+H 2 group received 1 hour inhalation of 2% H 2 at 1 hour and 6 hours after CLP or sham operation. At 24 hours after CLP, 6 mice in each group were sacrificed for observing pulmonary microvascular permeability after injecting Evans blue (EB) through tail vein. Other 6 mice in each group were sacrificed for obtaining fresh lung tissue to observe the lung pathological change and lung wet/dry (W/D) weight ratio. The protein expressions and distribution of STIM1 and Orai1 in lung tissue were detected by Western blotting and immunofluorescence staining. The mRNA expressions of STIM1 and Orai1 in lung tissue were detected by reverse transcriotion-polymerase chain reaction (RT-PCR). Coimmunoprecipitation was used to observe STIM1-Orai1 interaction. Finally, pulmonary microvascular endothelial cells (PMVEC) of mice were cultured in vitro and randomly divided into four groups for inoculation onto culture plates: Control group, rich hydrogen solution group (Control+H 2 group), lipopolysaccharide (LPS) group and rich hydrogen solution intervention group (LPS+H 2 group). PMVECs in Control group and LPS group were cultured in normal medium. Control+H 2 group and LPS+H 2 group were cultured in saturated hydrogen medium. LPS group and LPS+H 2 group were added with LPS at 5 μg/mL. Intracellular Ca 2+ ([Ca 2+]i) concentration of PMVECs were detected by Fluo-4/AM green dye. Results:Compared with Sham group, the pathological score and lung W/D ratio were significantly increased in SS group at 24 hours after CLP (pathological score: 11.00±1.41 vs. 1.00±0.63, lung W/D ratio: 7.63±0.52 vs. 3.45±0.58, both P < 0.05), the content of EB in the lung tissue was increased (μg/g: 0.16±0.02 vs. 0.09±0.02, P < 0.05). Compared with SS group, the pathological score and lung W/D ratio were decreased in SS+H 2 group (pathological score: 3.50±1.05 vs. 11.00±1.41, lung W/D ratio: 4.45±0.45 vs. 7.63±0.52, both P < 0.05), the content of EB in the lung tissue was decreased (μg/g: 0.13±0.02 vs. 0.16±0.02, P < 0.05), which prove that hydrogen can improve ALI caused by sepsis. Compared with Sham group, the protein and mRNA expressions of STIM1 and Orai1 were up-regulated in SS group (relative expression level of STIM1 protein: 3.08±0.32 vs. 1.00±0.00, relative expression level of STIM1 mRNA: 3.65±0.24 vs. 1.00±0.00, relative expression level of Orai1 protein: 3.63±0.23 vs. 1.00±0.00, relative expression level of Orai1 mRNA: 3.80±0.22 vs. 1.00±0.00, all P < 0.05), while the protein and mRNA expressions of STIM1 and Orai1 were down-regulated in SS+H 2 group compared with SS group (relative expression level of STIM1 protein: 1.78±0.13 vs. 3.08±0.32, relative expression level of STIM1 mRNA: 1.76±0.28 vs. 3.65±0.24, relative expression level of Orai1 protein: 1.92±0.22 vs. 3.63±0.23, relative expression level of Orai1 mRNA: 1.85±0.18 vs. 3.80±0.22, all P < 0.05). Coimmunoprecipitation staining results showed that there was no statistically significance in the association between STIM1 and Orai1 in Sham group and Sham+H 2 group. Compared with Sham group, the STIM1-Orai1 interaction was increased in SS group (relative expression level: 3.71±0.37 vs. 1.00±0.00, P < 0.05), while the STIM1-Orai1 interaction was decreased in SS+H 2 group compared with SS group (relative expression level: 2.17±0.29 vs. 3.71±0.37, P < 0.05). There were no statistically significant differences in various indicators between Sham group and Sham+H 2 group. In vitro, the intracellular [Ca 2+]i concentration in PMVECs was increased in LPS group compared with Control group using Fluo-4/AM green dye. The intracellular [Ca 2+]i concentration in PMVECs was decreased in LPS+H 2 group compared with LPS group. Conclusion:The protective effect of hydrogen on lung tissues in septic mice is related to the inhibition of STIM1, Orai1 and the interaction between them.

AIM:To investigate the effect of Biejiajian pill(BJJP)in reducing carbon tetrachloride(CCl4)-in-duced liver fibrosis in rats and to explore the underlying mechanism of the TLR4-NF-κB signaling pathway.METHODS:A total of 40 male Wistar rats were randomly assigned to 4 groups:control group,model group,low-dose BJJP group,and high-dose BJJP groups,with 10 rats per group.The rat model of liver fibrosis was established by intraperitoneal injection of CCl4,and two doses of BJJP(2.2 g/kg and 0.55 g/kg)were administered simultaneously.After 8 weeks of modeling and BJJP administration,the enzyme-linked immunosorbent assay(ELISA)was used to measure liver injury indicators,including alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Masson trichrome staining and Sirius red staining were performed to assess the fibrin deposition in liver tissue.Immunohistochemistry and Western blot analysis were conducted to detect the expression of extracellular matrix produced by hepatic stellate cells(HSCs).The expression of fibrosis-related proteins was examined using morphological assessment and Western blot.Finally,Western blot analysis was performed to detect the expression of proteins related to the Toll-like receptor 4(TLR4)/myeioid differentiation factor 88(MyD88)/NF-κB signaling pathway.RESULTS:The ELISA results indicated that BJJP treatment significantly re-duced ALT and AST levels in the serum of rats with liver fibrosis(P<0.01).Hematoxylin-eosin staining confirmed the protective effect of BJJP on liver tissue.Morphological analysis using Masson trichrome staining,Sirius Red staining,and alpha smooth muscle actin(α-SMA)immunohistochemical staining demonstrated that BJJP effectively reduced fibrin depo-sition in CCl4-induced rat liver fibrosis.Furthermore,the decreased expression of other markers associated with hepatic stellate cell activation,including fibronectin,collagen type Ⅰ,and α-SMA(P<0.01).Additionally,BJJP treatment sig-nificantly inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway induced by CCl4(P<0.05).CONCLU-SION:BJJP alleviates CCl4-induced liver injury and fibrosis in rats.This effect may be attributed to its inhibition of the TLR4-NF-κB signaling pathway,which subsequently suppressed the HSCs activation.

AIM:To investigate the effect of Biejiajian pill(BJJP)in reducing carbon tetrachloride(CCl4)-in-duced liver fibrosis in rats and to explore the underlying mechanism of the TLR4-NF-κB signaling pathway.METHODS:A total of 40 male Wistar rats were randomly assigned to 4 groups:control group,model group,low-dose BJJP group,and high-dose BJJP groups,with 10 rats per group.The rat model of liver fibrosis was established by intraperitoneal injection of CCl4,and two doses of BJJP(2.2 g/kg and 0.55 g/kg)were administered simultaneously.After 8 weeks of modeling and BJJP administration,the enzyme-linked immunosorbent assay(ELISA)was used to measure liver injury indicators,including alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Masson trichrome staining and Sirius red staining were performed to assess the fibrin deposition in liver tissue.Immunohistochemistry and Western blot analysis were conducted to detect the expression of extracellular matrix produced by hepatic stellate cells(HSCs).The expression of fibrosis-related proteins was examined using morphological assessment and Western blot.Finally,Western blot analysis was performed to detect the expression of proteins related to the Toll-like receptor 4(TLR4)/myeioid differentiation factor 88(MyD88)/NF-κB signaling pathway.RESULTS:The ELISA results indicated that BJJP treatment significantly re-duced ALT and AST levels in the serum of rats with liver fibrosis(P<0.01).Hematoxylin-eosin staining confirmed the protective effect of BJJP on liver tissue.Morphological analysis using Masson trichrome staining,Sirius Red staining,and alpha smooth muscle actin(α-SMA)immunohistochemical staining demonstrated that BJJP effectively reduced fibrin depo-sition in CCl4-induced rat liver fibrosis.Furthermore,the decreased expression of other markers associated with hepatic stellate cell activation,including fibronectin,collagen type Ⅰ,and α-SMA(P<0.01).Additionally,BJJP treatment sig-nificantly inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway induced by CCl4(P<0.05).CONCLU-SION:BJJP alleviates CCl4-induced liver injury and fibrosis in rats.This effect may be attributed to its inhibition of the TLR4-NF-κB signaling pathway,which subsequently suppressed the HSCs activation.

[Objective]To explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment(MCI).[Methods]Based on the baseline survey of the Hubei memory and aging cohort study(2018-2023),the participants completed a thorough neuropsychological assessment and physical examination,and self-reported a history of general anesthesia and surgery.The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model.In addition,the stratification and interaction analysis of anesthesia history,anesthesia number and physical intellectual exercise were conducted separately.[Results]A total of 5 069 older adults aged 65 and above were included in this study,including 3 692 city dwellers and 1 377 rural people,among whom were 2 584 women(51%).Out of the 1 472 participants with history of general anesthesia,249 people(17.4%)had MCI.After controlling for confounding factors,there was a 39.6%increased risk of MCI in older adults who underwent general anesthesia[OR=1.396,95%CI(1.169,1.668),P<0.001],suggesting that general anesthesia may be an independent influence on MCI.For the older adults who had one general anesthesia[OR=1.235,95%CI(1.001,1.523),P=0.049],two general anesthesia[OR=1.779,95%CI(1.292,2.450),P<0.001],and three OR more general anesthesia[OR=2.395,95%CI(1.589,3.610),P<0.001],their risks of MCI were increased by 23.5%,77.9%,and 139.5%,respectively.Compared with the older adults without a history of general anesthesia who did not exercise,the risk of developing MCI was significantly negatively correlated with the exercise group,cognitive exercise group,and combined exercise and cognitive exercise groups(all P<0.001).The risk of developing MCI in the exercise group was 60.2%of that in the no exercise group[OR=0.602,95%CI(0.456,0.795)],the risk in the cognitive exercise group was 42.4%of that in the no exercise group[OR=0.424,95%CI(0.294,0.613)],and the risk in the combined exercise and cognitive exercise group was 27.0%of that in the no exercise group[OR=0.270,95%CI(0.208,0.353)].In the older adults with a history of general anesthesia,compared with the no exercise group,the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group(all P<0.05).The risk of developing MCI in the cognitive exercise group was 47.7%of that in the no exercise group[OR=0.477,95%CI(0.256,0.892)],the risk in the combined exercise and cognitive exercise group was 34.5%of that in the no exercise group[OR=0.345,95%CI(0.220,0.540)],while the risk in the exercise-only group did not show a significant difference.[Conclusion]The risk of MCI increased significantly in older adults with a history of general anesthesia,and this risk increased with the times of anesthesia.Physical and mental exercise reduces the risk of MCI.it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.