This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Objective To investigate the risk factors of postoperative complications in patients with spinal tuberculosis and analyze the value of prognostic nutritional index(PNI)in predicting these complications.Methods The clinical data of 156 patients with spinal tuberculosis who underwent surgery in the Affiliated Hospital of Zunyi Medical University from January 2018 to July 2022 were retrospectively analyzed.The patients were divided into a complication group and a non-complication group based on the presence or absence of postoperative complications.Baseline data,laboratory indicators,and surgery-related indicators were compared between the two groups.The risk factors for postoperative complications in spinal tuberculosis were analyzed,and receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of PNI for postoperative complications in the patients.Results Among all of 156 patients,68 contracted a total of 82 instances of postoperative complications,with an incidence of 43.59%.Coinfection with pulmonary tuberculosis,preoperative anti-tuberculosis treatment duration more than 4 weeks,surgical operation duration,and drainage days were identified as independent risk factors for postoperative complications in spinal tuberculosis(P<0.05).On the other hand,a higher PNI was found to be a protective factor against postoperative complications of the spinal tuberculosis(P<0.05).The area under the ROC curve for PNI predicting postoperative complications ofthe spinal tuberculosis was 0.805.Conclusion The risk of postoperative complications in patients with spinal tuberculosis is subject to such factors ascoexistence of pulmo-nary tuberculosis,preoperative anti-tuberculosis treatment duration,surgery duration,drainage duration,and preoperative PNI.Preoperative PNI has a certain value for predicting the postoperative complications in the patients.

Objective To investigate the efficacy and safety of ultrafiltration therapy in elderly patients with congestive heart failure(CHF)and frailty.Methods A total of 88 hospitalized elderly patients with CHF and frailty were randomly assigned to the ultrafiltration group(n=44)and the control group(n=44).The control group treated with standard drug therapy.The ultrafiltration group treated with ultrafiltration,however,diuretics were not used during ultrafiltration treatment.Efficacy assessment was compared between the two groups,including patient body weight,N-terminal pro-brain natriuretic peptide(NT-proBNP)levels at 48 hours after treatment,dyspnea severity scores at 48 hours and 1 week after treatment,hospitalization duration and readmission rate within 3 months.Safety assessment parameters included serum creatinine,urea nitrogen,Na+and K+concentration at 48 hours after treatment and creatinine level 1 week after treatment.Results Efficacy assessment indicated that at 48 hours after treatment,both groups showed a significant reduction in patient body weight and NT-proBNP levels compared to pre-treatment levels(P＜0.05).However,there were no significant difference in body weight and NT-proBNP levels before and after treatment between the two groups(P＞0.05).Dyspnea severity scores for both groups increased at 48 hours after treatment,then decreased at 1 week after treatment.The ultrafiltration group exhibited higher dyspnea severity scores than that of the control group at 48 hours after treatment(P＜0.05).The length of hospital stay and the rate of re-hospitalization within 3 months were lower in the ultrafiltration group compared to those of the control group(P＜0.05).Safety assessment revealed that there were no significant differences in serum urea nitrogen and Na+levels before and 48 hours after treatment between the two groups(P＞0.05).However,serum K+levels were higher after 48-hours treatment in the ultrafiltration group than those of the control group(P＜0.05).There were no significant changes in creatinine levels before and after treatment in the control group(P＞0.05),while creatinine levels were lower 1 week after treatment in the ultrafiltration group compared to those of pre-treatment and 48 hours after treatment,and were lower than those of the control group(P＜0.05).Conclusion Ultrafiltration is a safe and effective method for elderly patients with CHF and frailty.

Objective:To summarize the clinical characteristics of patients with combined pneumocystis jiroveci pneumonia (PJP ) after allogeneic hematopoietic stem cell transplantation (allo-HSCT ). Methods:The clinical manifestations,laboratory tests,imaging findings,and treatment outcomes of 21 allo-HSCT patients with PJP diagnosed at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital from July 2018 to July 2023 were retrospective analyzed.Results:Among the 21 patients,the male-to-female ratio was 2.5:1,and the median age was 36 years old with a range of 15-62 years.The median time to diagnosis of PJP after transplantation was 225 days.The clinical manifestations lack specificity,and the main clinical symptoms include respiratory symptoms (dyspnea,cough,sputum,etc.) and fever.Laboratory examination revealed peripheral blood lymphocyte counts decreased in 15 cases,CD4+T lymphocyte absolute values less than 200 cells/μl in 19 patients,C-reactive protein levels significantly increased in 20 patients,lactate dehydrogenase levels increased in 14 patients,and 1,3-β-D-glucan detection levels increased in 14 patients.Chest CT manifestations can be divided into three types:ground glass type,nodular type,and mixed type.Among them,the incidence of ground glass type was the highest (18/21),with 2 cases of nodular type and 1 case of mixed type.The sequence number of Pneumocystis jiroveci was detected through mNGS (15-57570),and 11 patients had mixed infections.In terms of treatment,TMP-SMX,Caspofungin,and methylprednisolone were administered,and 17 patients achieved improvement in their condition.Four patients died,all of whom died from respiratory failure.Conclusion:PJP is a critically ill condition after hematopoietic stem cell transplantation,and diagnosis is difficult.Early diagnosis can achieve better prognosis.The sensitivity of mNGS in diagnosing PJP is high,providing the possibility of early and accurate diagnosis for clinical practice,which is worthy of application and promotion.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective The aim of this study is to investigate the efficacy of using transcatheter aortic valve replacement(TAVR)with self-expanding valve(SEV)to treat patients with pure aortic regurgitation(PAR)and to understand the preliminary experience of such procedure.Methods A total of 20 PAR patients who underwent TAVR using the TaurusElite system at Wuhan Asia Heart Hospital and Wuhan Asia Heart Disease Hospital from April 2022 to May 2023 were included in the study.Patient baseline data,echocardiographic data,follow-up data during hospitalization and 30 days after the procedures were collected and analyzed.Results The mean age of the patients was(73.5±5.5)years,and the mean STS score was(8.7±3.6)％.16(16/20)cases had severe PAR before the procedure.After TAVR treatment,the success rate of the procedure was 20/20,with only 1 case of valve-in-valve(ⅥⅤ).The 30-day follow-up results showed that none of the 20 patients experienced death,disabling stroke,myocardial infarction,and conversion to surgery.The degree of residual PAR after the procedure was none or mild in all patients.The interventional outcome was ideal.Conclusions The preliminary experience shows that,with strict patient selection and standardized procedural steps,using TAVR with SEV to treat patients with PAR could have high feasibility and ideal early clinical outcomes and can potentially be popularized.Such experience will be further validated in future clinical trials.