Immunoglobulin A nephropathy （IgAN） is a common primary glomerular disease and a frequent cause of chronic renal failure. Tripterygium wilfordii is a traditional Chinese herbal medicine， which possesses the effects of promoting blood circulation， relieving swelling and pain， and dispelling wind and dampness. Modern pharmacological studies have shown that T. wilfordii multiglucoside exhibit anti-inflammatory and immunomodulatory effects， inhibit mesangial cell proliferation， protect podocytes， ameliorate endothelial cell injury， and regulate gut microbiota disturbances. Triptolide also possesses anti-inflammatory and immunomodulatory properties， suppresses mesangial cell proliferation， and protects podocytes. Celastrol demonstrates anti- inflammatory and immunomodulatory functions as well as the ability to improve endothelial cell damage. Through these mechanisms， T. wilfordii and its active components can play a role in alleviating clinical symptoms and delaying disease progression in the treatment of IgAN. Future research should focus on in-depth analysis and mechanistic investigation of these active ingredients， promote high-quality clinical studies， systematically evaluate the synergistic effects among them， and emphasize strategies for reducing toxicity and enhancing efficacy， thereby providing more comprehensive and reliable evidence-based foundations for the clinical treatment of IgAN.

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Objective:To explore the standardized performance of a FISH probe before clinical detection.Methods:The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test.Results:The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001.Conclusion:For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

Objective:To analyze the F10 gene mutations in a Chinese pedigree affected with the deficiency of the hereditary coagulation factor X (FX), resulting from a new deletion mutation, and to study the associated molecular pathogenesis.Methods:Next generation sequencing (NGS) was performed to screen the genetic mutations in the proband which were then verified by Sanger sequencing. The FX activity (FX∶C) of probands and their family members was detected using the blood clotting method, and the mutation sites of the family members were analyzed using Sanger sequencing. The pathogenicity of the mutation site was predicted by using the online bioinformatics software, Mutation Taster. The SWISS-MODEL software was used for stimulating the three-dimensional models of the wild-type and mutant proteins for analyzing the influence of the mutation site on the structure and function of the proteins, and for analyzing the difference between the catalytic residues of the wild-type and the mutant proteins. The level of the F10 gene mRNA was quantitatively analyzed by qRT-PCR (quantitative reverse transcription polymerase chain reaction) method by constructing plasmids, transfecting human embryonic kidney 293T cells (HEK 293T), and analyzing the splicing of the mutated site by RT-PCR method. The levels of FⅩ∶Ag in cell lysates and cell culture media (both inside and outside the cells) were detected by the ELISA (enzyme linked immunosorbent assay) method.Results:A medium-grade factor X deficiency with a 36.42% FⅩ∶C ratio was detected in the proband by the coagulation method. NGS analysis demonstrated a heterozygous deletion mutation in exon 8:c.902_919del (p.Ala301_Glu306del) in the proband. Sanger sequencing analysis indicated that some members of the family (mother and grandfather) were also carriers of the corresponding deletion mutation. Online bioinformatics software predicted the pathogenic nature of the c.902_919del mutation, with a pathogenic score of 0.999. The 3D protein structure model analysis indicated that the c.902_919del mutation resulted in the disappearance of a segment of β-fold in the protein structure, thereby shortening the preceding segment of the β-fold and a subsequent loss of hydrogen bonds between adjacent amino acids with no significant difference in the side chain conformation of the key catalytic residues compared to the wild-type. mRNA splicing analysis indicated the absence of alternative splicing changes in the mutation, and qRT-PCR results indicated the absence of a statistically significant difference between the mRNA levels of F10 gene and wild-type mRNA in cells expressing c.902_919del mutant. The ELISA results indicated that there was no statistically significant difference in the FX∶Ag levels of the mutant cell culture medium and the lysate.Conclusions:In this pedigree, the heterozygous mutation in exon 8 of F10 gene (c.902_919del, p.Ala301_Glu306del) caused the hereditary factor Ⅹ deficiency.

AIM:To investigate the activation of Cl-channels by sodium taurocholate(NaTC)in mouse pan-creatic acinar cells.METHODS:The single isolated pancreatic acinar cells from FVB/N mice were prepared using colla-genase digestion method.Whole-cell patch clamp technique was performed to record the currents.Intracellular adenosine triphosphate(ATP)dependence of the channels was examined via eliminating ATP from the pipette solution.Anion per-meability of the channels was investigated with ion-exchange method.The pharmacological characteristics of the channels was confirmed by two Cl-channel blockers.The volume sensitivity of the channels was detected using 47%hypertonic bathing solution.Extracellular Ca2+dependence of activating the channels was examined through eliminating Ca2+from the bathing solution.Intracellular reactive oxygen species(ROS)level was detected by an oxidation-sensitive fluorescent probe,2',7'-dichlorofluorescin diacetate.The experiment was repeated 6 times in each group.RESULTS:Extracellular application of 5 mmol/L sodium taurocholate induced a Cl-current,exhibiting the properties of outward-rectification,a se-lectivity sequence of I->Br-≥Cl->gluconate-and intracellularATP dependence(P<0.01).The currents were inhibited by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate(DIDS)and tamoxifen and by 47%hypertonicity stimulation(P<0.01).When ROS production was scavenged by N-acetyl-L-cysteine,the sodi-um taurocholate-induced Cl-currents were unaffected.The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS.Sodium taurocholate failed to induce Cl-currents when Ca2+was absent in extracellular bath-ing solution(P>0.05).CONCLUSION:Sodium taurocholate activates Cl-channels in mouse pancreatic acinar cells,which is dependent on extracellular Ca2+but not ROS pathway.

Objective:To investigate the clinical features, diagnosis and treatment of oblique vaginal septum syndrome (OVSS).Methods:The clinical data of 80 patients with OVSS admitted to The Second Hospital of Hebei Medical University from July 2005 to July 2023 were retrospectively analyzed. According to the classification system of OVSS proposed by Female Genital Anomalies Study Group, Chinese Obstetricians and Gynecologists Association in 2021, the patients were divided into four groups. The clinical manifestations, accompanied urinary system abnormalities, diagnosis and treatment methods and treatment outcomes were observed.Results:According to the above classification system, among the 80 patients with OVSS, 35 patients (44%, 35/80) were categorized as type Ⅰ, 33 patients (41%, 33/80) were categorized as type Ⅱ, 2 patients (3%, 2/80) were categorized as type Ⅲ and 10 patients (13%, 10/80) were categorized as type Ⅳ. The main onset symptom of patients was periodic abdominal pain (70%, 56/80), vaginal bleeding (20%, 16/80), dysuria or fecal impaction (15%, 12/80), vaginal mucopurulent discharge (10%, 8/80). The morbidity of combined urinary system abnormalities was 88% (70/80), and the most common urinary system abnormality was ipsilateral renal agenesis (81%, 65/80). Bilateral kidneys were normal in 13% (10/80) patients, and 6% (5/80) were combined with other urinary system abnormalities. A total of 74 patients underwent vaginal oblique septectomy or septum excision. Five of the 10 patients with type Ⅳ underwent hysterectomy on the cervical atresia side, 4 patients received hysteroscopy combined with cervicoplasty+oblique septotomy or septum excision, and one patient selected delayed menstruation. Two patients underwent laparoscopic resection of the dysplasia kidney and ectopic ureter which opening to the vagina. Eleven patients with endometriosis cyst, hydrosalpinx or empyema underwent laparoscopic surgery.Conclusions:The main symptom of type Ⅰ and Ⅳ patients is abdominal pain, while the main symptom of type Ⅱ and Ⅲ patients is bleeding. Magnetic resonance imaging (MRI) has advantages in the evaluation of complex OVSS, and MRI is recommended before operation to exclude other axial reproductive tract dysplasia and complex urinary system dysplasia. If there is leakage of urine, vaginal discharge or complex deformity, it is necessary to multidisciplinary discussion and formulate a reasonable surgical plan. The first treatment is related to the prognosis of patients especially children, and should be highly valued.

ObjectiveTo explore the prevalence difference between northwest dryness syndrome and blood stasis syndrome of coronary heart disease （CAD） and their correlations with major adverse cardiovascular events （MACE）. MethodsThe medical records including general information and risk factors for vascular diseases （gender， age， smoking history， diabetes history， hypertension history， chronic kidney disease history and body mass index）， laboratory indicators （fasting blood glucose， triglyceride， high density lipoprotein cholesterol， etc.） of 499 CAD patients in the Department of Cardiology of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from November 1st， 2015 to September 30th，2020 were collected， and whether they suffered from northwest dryness syndrome or blood stasis syndrome was judged. The incidence of MACE was followed up for one year. The differences of cardiovascular risk factors between the northwest dryness syndrome and blood stasis syndrome of CAD were compared， and the correlation with MACE was analyzed. ResultsAmong the 499 CAD patients， there were 128 cases （25.65%） of simple blood stasis syndrome， 33 cases （6.61%） of simple northwest dryness syndrome， 209 cases （41.88%） of northwest dryness syndrome plus blood stasis syndrome， and 129 （25.85%） cases of not blood statis syndrom either northwest dryness syndrome. Univariate regression analysis showed that smoking history， diabetes history， fasting blood glucose abnormality， triglyceride abnormality， and high density lipoprotein cholesterol abnormality were positively correlated with northwest dryness syndrome in CAD patients （OR＞1， P＜0.05）， while smoking history， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome in CAD patients （OR＞1， P＜0.05）. Multivariate regression analysis showed that the history of diabetes， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with northwest dryness syndrome of CAD （P＜0.05）. Smoking history， abnormal triglycerides and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome （P＜0.05）. Association rule analysis showed that the confidence of CAD patients with northwest dryness syndrome complicated with blood stasis syndrome was 86.36%， and that of patients with blood stasis syndrome complicated with northwest dryness syndrome was 62.02%. Among the 499 patients， 96 had MACE in one year， accounting for 19.24% of the total. Logistics regression analysis showed that the correlation with incidence of MACE in CAD patients within one year from strong to weak was northwest dryness syndrome plus blood stasis syndrome ［OR = 5.113， 95%CI （3.118， 8.387）， P＜0.001）］， blood stasis syndrome［OR = 4.630， 95%CI （2.394， 8.955）， P＜0.001］， northwest dryness syndrome ［OR = 4.395， 95%CI （2.642， 7.309）， P＜0.001］. ConclusionBlood stasis syndrome is the main syndrome type of CAD in Xinjiang Uygur Autonomous Region. CAD patients with northwest dryness syndrome are more likely to have blood stasis syndrome， and most suffer from both northwest dryness syndrome and blood stasis syndrome simultaneously. There is the strongest correlation between northwest dryness syndrome plus blood stasis syndrome and 1-year occurrence of MACE in CAD.

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg^-1·d^-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg^-1·d^-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E₂， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

Objective To observe the differences in motor function and quality of life among mild-to-moderate Parkinson's disease(PD)patients with or without freezing of gait(FOG),and the correlation of FOG to motor function and quality of life. Methods From April,2021 to December,2022,132 mild-to-moderate PD patients aged 60 to 80 years were selected from Peking Union Medical College Hospital,and were divided into FOG group(n = 43)and non-FOG group(n = 89)according to the clinical features.They were assessed with Freezing of Gait Questionnaire(FOGQ),Berg Balance Scale(BBS),Timed"Up&Go"Test(TUGT),Five Times Sit to Stand Test(FTSST),isokinetic muscle strength,Unified Parkinson's Disease Rating Scale(UPDRS)and 39-item Parkinson's Disease Question-aire-39(PDQ-39). Results The BBS score was lower(Z =-2.354,P<0.05),and the TUGT,FTSST,UPDRS part 2 and part 3 scores,and the Parkinson's disease summary index(PDSI)were higher in FOG group than in non-FOG group(Z>3.074,t = 2.748,P<0.01).FOGQ score correlated with BBS score,UPDRS Part 2 and Part 3 scores,and PDSI(|r|>0.392,P<0.001). Conclusion FOG would impair motor function,activities of daily living and quality of life in mild-to-moderate PD pa-tients,and increase the risk of falls.