ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

Shared Decision-Making （SDM） is a crucial concept in modern medicine， emphasizing the joint participation of doctors and patients in the medical decision-making process. However， the authoritative position of doctors and the passive role of patients in traditional medical models often overlook the personal wishes and needs of patients， leading to tense doctor-patient relationships and medical disputes. By listening to and understanding their stories， narrative medicine helps doctors gain a more comprehensive understanding of patients’ situations and balances medical advice with patient needs in the decision-making process. Through systematic literature analysis and theoretical exploration， this paper investigated the application effects and mechanisms of narrative medicine in different medical contexts， as well as analyzed its specific role in the process of SDM. The aim is to explore the value of narrative medicine in bridging differences in SDM， revealing its role in promoting doctor-patient communication， enhancing decision-making participation， and improving medical outcomes. Researches had found that narrative medicine enhanced doctors’ “narrative ability”， promoted emotional communication and trust between doctors and patients， reduced conflicts and misunderstandings in decision-making， and improved patients’ sense of participation and trust， thus playing an important role in SDM. Therefore， by enhancing doctor-patient communication and understanding， promoting SDM and treatment selection between doctors and patients， personalized care and treatment optimization， advocating for doctor-patient co-construction， improving consultation efficiency， restoring the patient’s subject position， and other methods， it can bridge doctor-patient differences， promote communication and enhance decision-making participation， and improve medical outcomes and patient satisfaction.

Objective To investigate the serum levels of homocysteine(HCY)and cystatin C(Cys-C)in patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)associated renal injury,and to explore the diagnostic value of combined detection of HCY and Cys-C in ANCA-associated renal injury.Methods We selected 70 ANCA-positive patients with renal injury admitted to the Department of Nephrology in our hospital from January 2016 to January 2019.Another 48 patients with ANCA-positive but not complicated with renal injury were in simple ANCA positive group while 50 patients with physical examination who came to the hospital during the same period were in control group.Healthy patients served as the control group.By comparing the differences in the test results of different groups,the area under the curve(AUC)of each test index for ANCA-positive renal injury was determined,and the correlation and diagnostic value of combined detection of HCY and Cys-C for ANCA-related renal injury were calculated.Results The levels of HCY and Cys-C in the ANCA positive combined with renal injury group,the pure ANCA positive group,and the control group differed significantly(P＜0.05).The positive rates of HCY and Cys-C in the two groups were significantly different(P＜0.05).The sensitivity and specificity of HCY and Cys-C in combination for the diagnosis of ANCA-positive related renal injury were significantly higher than those of the above indicators alone(P＜0.05).ROC curve results showed that HCY combined with Cys-C had a better diagnosis for patients with positive ANCA and associated renal injury and a higher correlation.Conclusion HCY combined with Cys-C is closely correlated to ANCA-related renal injury,and the combined detection has a positive effect on the diagnosis of patients with ANCA-positive related renal injury,and has guiding value for the treatment of patients.

Introduction::Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.Methods::In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 –8). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR–Egger, and weighted median regression) were used to ensure that our results more reliable. Results::All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30–1.58, P = 2.51 × 10 -13). The results of MR–Egger and weighted median regression exhibited similar trends (MR–Egger OR = 1.40 [95% CI, 1.08–1.81], P = 1.61 × 10 -2; weighted median OR = 1.39 [95% CI, 1.21–1.61], P = 1.62 × 10 -6). MR–Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. Conclusions::Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

Objective To use network pharmacology to mine and predict the targets and related signaling pathways of Miaoyao Yiai Tang(Miao-Yi-Ai-Tang,MYAT)in the treatment of small cell lung cancer(SCLC).And animal experiments to verify its mechanism of action,to provide a theoretical basis for basic experiments and clinical applications.Methods The active ingredients of MYAT were obtained from the TCMSP database,combined with PubMed data,Swiss Target Prediction database and Uniprot database to obtain potential targets;SCLC-related genes were collected through the DrugBank database,Genecards database,OMIM database and TTD database,and the Venny 2.1 platform After obtaining the intersection genes of MYAT and SCLC,import them into the STRING database,construct a protein-protein interaction(PPI)network,use Cytoscape 3.9.1 software for visual analysis,and use Metascape database for GO enrichment analysis and KEGG pathway analysis,to predict the direct action target and signaling pathway of MYAT in the treatment of SCLC.Using AutoDock Tools 1.5.7 software for molecular docking to verify the close relationship between the two.For cytological experiment verification,the cultured cells were treated with MYAT and the expression of β-catenin,AXIN,c-myc was detected by qPCR,and the expression of β-catenin in the cells was detected by Western blot;animal experiments were established to establish a subcutaneous xenograft tumor model of lung cancer NCI-H446,to observe the effect of MYAT on tumor growth.Results A total of 65 effective components of MYAT,1368 SCLC genes,and 260 MYAT-SCLC intersection genes were obtained.Enrichment analysis showed that they were related to cancer pathways,PD-L1/PD-1 pathways,NF-κB pathways,Wnt and other signaling pathways.The results of molecular docking validation showed that the binding energies of active components and core target proteins were all<0 kJ·mol-1,which indicated that the protein could spontaneously bind to active components and be stable.Cell experiments showed that the expression levels of β-catenin,c-myc and AXIN mRNA were significantly down-regulated in the MYAT group(P<0.05).Animal experiments show that:MYAT can significantly inhibit the growth of tumors in vivo.Conclusion Miao-Yi-Ai-Tang can inhibit the proliferation of small cell lung cancer through Wnt/β-catenin signaling pathway.

Objective To observe the effects of electroacupuncture on the learning and memory abilities of Alzheimer disease(AD)rats;To explore its potential mechanism based on proteomics.Methods Totally 36 SD male rats were randomly divided into sham-operation group,model group and heart meridian acupoints group,with 12 rats in each group.Aβ1-42 were injected into the bilateral hippocampus to establish AD rat model,the sham-operation group was injected with an equal volume of normal saline.The heart meridian acupoints group received electroacupuncture treatment,accompanied by a stimulation time of 20 minutes,rest for 1 day after 6 days of electroacupuncture for 7 consecutive weeks.The Morris water maze experiment was used to evaluate the learning and memory abilities of AD rats,tandem mass tag(TMT)labeling technology and bioinformatics analysis were used to screen core differentially expressed proteins in important typical pathways,and key differentially expressed protein was verified by parallel reaction monitoring(PRM).Results There was no statistically significant difference in swimming speed between each group of rats(P>0.05).Compared with the sham-operation group,the escape latency of Morris water maze experiment in the model group increased significantly(P<0.01);compared with the model group,the escape latency of heart meridian acupoints group was significantly shortened on the 2-4th day(P<0.01).A total of 209 differentially expressed proteins were identified in different groups using TMT labeling quantification,among which 12 proteins showed significant changes among the 3 groups.GO annotation involved biological processes such as metal ion transport,sodium ion transport,and sodium ion transmembrane transport,as well as cellular components such as synapses,presynapse,and synaptic vesicle,involving solute:sodium symporter activity,organic acid:sodium symporter activity,amino acid:cation symporter activity,amino acid:sodium symporter activity,and other molecular functions;KEGG analysis significantly enriched the synaptic vesicle pathway.The PRM validation results indicated that electroacupuncture at the heart meridian acupoints could reduce the expressions of sodium and chloride dependent GABA transporter protein 3(GAT3),which was consistent with the quantitative detection results of TMT labeling quantification.Conclusion Electroacupuncture at the heart meridian acupoints can improve the learning and memory abilities of AD rats,possibly by regulating the expression of synaptic transporter GAT3 on the synaptic vesicle pathway to exert neuroprotective effects.

Purpose: Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and Methods: In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization’s (WHO’s) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, in vitro embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI. Results: Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and high-quality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045). Conclusions Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.

Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ²=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ²=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Uterine Cervical Neoplasms ; Multiplex Polymerase Chain Reaction ; Papillomavirus Infections/diagnosis* ; Cross-Sectional Studies ; Genotype ; Papillomaviridae/genetics*

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.