ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4⁺ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Objective: To explore the pre-exposure prophylaxis (PrEP) awareness, willingness, uptake patterns, barriers and needs among Chinese student men who have sex with men (MSM), so as to provide relevant evidence for targeted interventions with PrEP. Methods: A proportional sampling method was used to conduct a cross sectional survey of MSM aged 16 years and older residing in 21 provinces, municipalities, and autonomous regions in mainland China between October 20 and December 20, 2021, to collect information on demographic and sexual behavioral characteristics, and 923 students of them were selected as the subjects of this study. The chi-square test and Fisher s test were used for univariate analysis, followed by multivariate Logistic regression to analyze the influencing factors of PrEP awareness and uptake. Results: According to the cascade analysis method, the awareness, willingness, uptake and adherence rates of PrEP among the student MSM were obtained as 88.95%, 67.36%, 13.20% and 45.21 %, respectively. HIV testing more than once in the last 3 months, and all of them were aware of the HIV test results of their sexual partners, and those with high frequency of condom use had a higher rate of awareness ( OR =2.32, 1.79, 1.69, P <0.05). Willingness rates were higher for those from the pilot city, using substances, and HIV testing more than once in the last 3 months ( OR =2.13, 1.65, 1.69, P <0.05). Higher rates of uptake were found among those from high risk and pilot areas, presence of commercial sex, substance use, and high literacy ( OR =5.60, 3.54,2.81, 1.92, 4.54, P <0.05). Adherence rates were higher among those who used one pill per day or both ( OR =12.77, 13.26, P <0.05). The barriers and needs faced by student MSM were primarily personal concerns about medication side effects, preventative effects, and confidence in sexual behavioral styles, and the high cost of medication and related service costs. Conclusions The student MSM population in China is characterized by high awareness, low willingness, low uptake, and low adherence to PrEP. Targeted interventions should be considered and tailored by the departments to facilitate PrEP promotion among student MSM.

Objective:To identify the genetic causes of adverse pregnancy outcomes in five families and provide a basis for rational guidance on genetic and reproductive counseling.Methods:A retrospective analysis was conducted on five families with a history of adverse pregnancy outcomes, where one partner was found to have a cryptic balanced translocation. These cases were identified among pregnant women who underwent invasive prenatal diagnosis at the Department of Medical Genetics and Prenatal Diagnosis, Wuxi Maternity and Child Health Care Hospital, from January 2016 to June 2023. Conventional G-banding karyotyping and chromosomal microarray analysis (CMA) were performed on affected children/fetus samples. Chromosome G-banding and fluorescence in situ hybridization (FISH) were used for parental tracing. Genetic counseling was provided for all cases, and the pregnancy outcomes were followed up. Descriptive analysis was applied in this study. Results:Case 1 involved an eldest son with unexplained intellectual disability, and the CMA results showed an 8.6 Mb deletion in the 4p16.3p16.1 region and a 1.0 Mb duplication in the 7q36.3 region. Unbalanced translocations were detected in the current pregnancies of the other four cases, which were a 6.1 Mb duplication in the 14q32.2q32.33 region with a 1.6 Mb deletion in the 21q22.3 region (Case 2), a 10.8 Mb duplication in the 6q25.3q27 region with a 1.2 Mb deletion in the 15q26.3 region (Case 3), a 1.0 Mb duplication in the 5p15.33 region with a 2.9 Mb deletion in the 6q27 region (Case 4), and a 3.2 Mb deletion in the 1q44 region with a 4.8 Mb duplication in the 19p13.3 region (Case 5). FISH confirmed that either the husband or the wife in each of the five families was a carrier of a cryptic balanced translocation. Further CMA testing on amniotic fluid samples from previous terminated pregnancies of Cases 3 and 4 also indicated unbalanced translocations. Both the current pregnancy of Case 1 and the subsequent pregnancy of Case 2 gave birth to healthy babies after non-abnormal prenatal diagnosis and genetic counseling. Cases 3 to 5 are currently preparing for pregnancy.Conclusion:Advances and combined application of genetic technologies will be conducive to improving the diagnosis of cryptic balanced translocations in some families with adverse pregnancy outcomes, providing a sound basis for genetic counseling in future pregnancy.

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: To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage. Methods: The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration. Results: The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug. Conclusion Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

Objective:To investigate the effects of butylphthalide combined with ozagrel sodium on the National Institutes of Health Stroke Scale (NIHSS) score, activities of daily living (ADL) score, and coagulation function in patients with acute cerebral infarction.Methods:Ninety-four patients with acute cerebral infarction who were admitted to Gujiao Medical Group Central Hospital from January 2019 to November 2021 were included in this study. They were randomly assigned to undergo treatment with either ozagrel sodium (control group, n = 47) or butylphthalide combined with ozagrel sodium (observation group, n = 47) for 14 consecutive days. Before and after treatment, NIHSS score, ADL score, coagulation function (thrombin time, prothrombin time, D-dimer, activated partial thrombin time), bilateral middle cerebral artery blood flow status (mean blood flow velocity (Vm), resistance index, pulsatility index), brain tissue damage factor (brain natriuretic peptide, neuron-specific enolase, S100 β protein) and the incidence of adverse drug reactions were compared between the two groups. Results:Before treatment, there were no significant differences in NIHSS and ADL scores between the two groups (both P > 0.05). After treatment, the NIHSS score was significantly lower in the observation group than that in the control group [(8.70 ± 1.62) points vs. (9.45 ± 1.2) points, t = 2.51, P < 0.05]; the ADL score was significantly higher in the observation group than that in the control group [(65.15 ± 7.41) points vs. (61.20 ± 6.32) points, t = 2.78, P < 0.05]. Before treatment, there were no significant differences in thrombin time, prothrombin time, D-dimer, and activated partial thrombin time between the two groups (all P > 0.05). After treatment, thrombin time, prothrombin time, and activated partial thrombin time were significantly higher in the observation group than those in the control group ( t = 4.34, 3.00, 2.63, all P < 0.05). After treatment, D-dimer level in the observation group was significantly lower than that in the control group ( t = 3.39, P < 0.05). Before treatment, mean blood flow velocity, resistance index, and pulsatility index were similar between the two groups (all P > 0.05). After treatment, the mean blood flow velocity in the observation group was significantly higher than that in the control group ( t = 3.23, P < 0.05). The pulsatility index and resistance index were significantly lower in the observation group than those in the control group ( t = 2.14, 3.16, both P < 0.05). Before treatment, there were no significant differences in brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels between the two groups (all P > 0.05). After treatment, brain natriuretic peptide, neuron-specific enolase, and S100 β protein levels in the observation group were significantly lower than those in the control group ( t = 3.09, 2.18, 3.33, all P < 0.05). There was no significant difference in incidence of adverse reactions between the observation and control groups [6.38% (3/47) vs. 2.13% (1/47), P > 0.05]. Conclusion:Butylphthalide combined with ozagrel sodium for the treatment of acute cerebral infarction can reduce neurological dysfunction and brain tissue injury, and improve coagulation function, hemodynamic state of the middle cerebral artery, and activities of daily life, without increasing adverse reactions.

Objective:To explore the genetic causes of cerebellar hypoplasia (CH) diagnosed by prenatal ultrasound.Methods:This retrospective study involved 32 fetuses with CH diagnosed by prenatal ultrasound in Wuxi Maternal and Child Health Hospital from January 2014 to December 2022. Prenatal ultrasound findings and genetic testing results for amniotic fluid were collected and analyzed. The correlation between fetal CH and genetic abnormality was analyzed. A descriptive statistical method was used for data analysis.Results:(1) General data: The 32 mothers were (28.0±4.9) years old, ranging from 18 to 37 years old; the gestational age at amniocentesis was (24.2±4.0) weeks, ranging from 18 +3 weeks to 37 +2 weeks. Apart from one case lost to follow-up, the other 31 cases terminated the pregnancies, including 30 terminated before 28 weeks of gestation and one at 33 weeks of gestation due to unmarried status. (2) Ultrasonic features: Among the 32 cases, 30(93.8%) were complicated by intracranial or extracranial abnormalities including cardiac abnormalities (15 cases), dilated lateral ventricles (ten cases), and abnormalities in limbs (eight cases) and face (nine cases). Two CH cases (6.2%) were isolated. (3) Genetic testing: Among the 32 cases, 13 cases (40.6%) had normal results of amniotic fluid karyotype analysis and single nucleotide polymorphism (SNP) array. Among the 19 cases with abnormal amniotic fluid test results (59.4%), 16 cases have abnormal results in amniotic fluid karyotype analysis and SNP array detection [nine cases were numerical abnormalities, including five cases of trisomy-18, three of trisomy-21, and one of trisomy-13; seven cases were chromosomal structural abnormalities, including four cases of terminal deletion of chromosome 5 (Cri-du-Chat syndrome) and three cases of reciprocal translocation of chromosomes]. There was no abnormality in karyotype analysis of amniotic fluid in three cases. Still, their SNP array test results showed copy number variations (CNV) [one of 6q terminal deletion, one of 6q terminal deletion with 5p15.33 duplication, and one of 6q terminal deletion with 15q26.3 duplication; all variations were of unknown significance]. (4) Of the 19 cases with abnormal SNP array results, 17 were accompanied by abnormal intracranial/extracranial ultrasound findings. Among them, ten cases showed cardiac malformation, seven showed lateral ventricular widening, and seven showed limb abnormality. Conclusions:Numerical abnormalities, CDCS, and 6q terminal deletion are the most common genetic causes of CH diagnosed by prenatal ultrasound. Chromosome microarray analysis should be recommended for fetuses with ultrasound-diagnosed CH to evaluate fetal prognosis accurately.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.