OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

To investigate the association between the systemic inflammatory response index (SIRI) and lung cancer prevalence based on the National Health and Nutrition Examination Survey (NHANES) database.

Various dynasties of herbs and prescription books recorded the specifications, processing, and clinical application of Schisandrae Chinensis Fructus. The clinical application of Schisandrae Chinensis Fructus mainly focuses on astringency, tonifying qi and generating fluids, nourishing the kidneys and calming the heart. There have been few reports on the exploration on textual study on other functions and usage precautions of Schisandrae Chinensis Fructus; at present, the classic prescriptions containing Schisandrae Chinensis Fructus do not clearly indicate their specific specifications and processing in the prescription composition. Textual study has found that different processed products of Schisandrae Chinensis Fructus have different clinical therapeutic effects. For raw use, it is more suitable to use light agents to bring adversely risen qi downward, steam to produce light agents to increase transparency, honey to produce leveling agents is better for moistening the lungs and nourishing yin, wine honey to produce leveling agents can supplement deficiency and promote blood circulation, wine to produce heavy agents can strengthen acid absorption. It is suggested further in-depth research on steamed products, honey products, and honey wine products to broaden clinical application options and improve the accuracy of clinical medication. The clinical application of Schisandrae Chinensis Fructus has different emphases and evolution in different dynasties. In the Tang Dynasty, Schisandrae Chinensis Fructus could reduce the qi of the upper, middle, and lower energizers, and eliminate deficiency heat; during the Five Dynasties period, Schisandrae Chinensis Fructus could nourish qi, improve eyesight, warm the middle, and bring adversely risen qi downward; During the Jin and Yuan dynasties, Schisandrae Chinensis Fructus was used to warm water and treat cholera, as well as to improve muscle function; in the Ming Dynasty, Schisandrae Chinensis Fructus was proposed to reduce qi and strengthen yin, treating the critical condition of yin and yang deficiency; during the Qing Dynasty, Schisandrae Chinensis Fructus could prevent summer heat, and external application to sores could astringent and invigorate the muscles. Schisandrae Sphenantherae Fructus has records of dispersing phlegm and fire, and dispelling wind pathogens. This article reviewed the relevant records of Schisandrae Chinensis Fructus in traditional Chinese herbs and prescriptions throughout history, summarized the efficacy characteristics of Schisandrae Chinensis Fructus under different processing methods, clinical applications under historical evolution, and main contraindications for use, proposed recommendations for the application of Schisandrae Chinensis Fructus in classic and commonly used prescriptions, which can provide scientific basis for the precise selection of different specifications and processed products of Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus, as well as scientific guidance for their rational application in drug development.

Objective : To establish an enzyme-linked immunosorbent assay (ELISA) for exosome B7-H3 in plas- ma , and to explore the clinical significance and diagnostic value of exosome B7-H3 in plasma from non-small cell lung cancer (NSCLC) . Methods : The plasma of 70 NSCLC patients (NSCLC group) and 36 healthy controls (HC group) were collected . Exosomes and microvesicles in plasma were separated by ultra-fast centrifuge method , and the expression levels of B7-H3 in plasma exosomes in NSCLC groups and HC groups were compared by Western blot method . In NSCLC group , the expression levels of B7-H3 in plasma exosomes and microvesicles in NSCLC group were compared . A simple and feasible ELISA method was established to detect the expression level of exosome B7 - H3 in plasma by means of polyethylene glycol (PEG) precipitation and its clinical significance was analyzed . Lo- gistic regression model was established to predict plasma-derived exosome B7-H3 as a risk factor , and receiver op- erating characteristic curve (ROC) was used to investigate the diagnostic value of exosome B7-H3 in NSCLC . Results: For exosomes and microvesicles in plasma which were extracted by ultracentrifugation , Western blot results showed that the expression level of B7-H3 in plasma exosomes of NSCLC group was higher than that of HC group (P = 0. 032) , and the expression level of B7-H3 in plasma exosomes was higher than that of microvesicles of NSCLC group (P = 0. 012) . The expression level of exosome B7-H3 in plasma extracted by PEG precipitation was also higher in NSCLC group than that in HC group (P = 0. 024) . The expression level of exosome B7-H3 in plasma of NSCLC patients was not related to gender , age , smoking or pathological type , but was related to T stage (P = 0. 002) , N stage (P < 0. 001) , M stage (P = 0. 010) and AJCC stage (P < 0. 001) . Multivariate Logistic regres- sion analysis identified exosome B7-H3 in plasma as a risk factor for NSCLC . ROC analysis showed that the sensi- tivity of exosome B7-H3 in plasma for the diagnosis of NSCLC (0. 843) was higher than that of carcinoembryonic antigen (CEA) (0. 743) , whereas the specificity (0. 722) was lower than that of CEA (0. 833) . Combined de- tection of exosome B7-H3 and CEA (AUC = 0. 928 , 95% CI:0. 877 - 0. 979) had a higher diagnostic performance for NSCLC . Conclusion B7-H3 in plasma exosomes is related to the cancer staging of NSCLC , and the combined detection of exosome B7-H3 and CEA in plasma is conducive to the laboratory diagnosis of NSCLC .

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

ObjectiveTo explore the mechanism of total saponins of Dioscoreae Nipponicae Rhizoma （TSDN） in treating gouty arthritis （GA） by regulating cyclooxygenase-2 （COX-2）-mediated M1 macrophage reprogramming by in vivo and in vitro experiments. MethodsIn vivo experiment： 24 male SD rats were randomly allocated into blank， model （GA）， TSDN， and celecoxib groups， with 6 rats in each group. After 7 days of administration， pathological changes in the ankle synovial tissue were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to quantify the mRNA levels of NOD-like receptor protein 3 （NLRP3） inflammasome， apoptosis-associated speck-like protein （ASC）， Caspase-1， COX-2， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the synovial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of inducible nitric oxide synthase （iNOS）， IL-1β， CD86， CD80， CD206， and arginase-1 （Arg-1）. In vitro experiment： The GA model was established by lipopolysaccharide （LPS） + MSU induction， and the inhibitor concentration was screened by the methyl thiazolyl tetrazolium （MTT） assay. RAW264.7 cells were allocated into blank， model， TSDN， dexamethasone， COX-2 inhibitor （celecoxib）， and TSDN + COX-2 inhibitor groups. The levels of iNOS， IL-1β， CD86， CD80， CD206， and Arg-1 in the cell supernatant of each group were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in each group were determined by Real-time PCR and Western blot， respectively. ResultsIn vivo experiment： compared with the model group， TSDN reduced the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α in the synovial tissue （P<0.05， P<0.01）. ELISA results showed that TSDN lowered the serum levels of iNOS， IL-1β， CD86， and CD80 （P<0.01） while increasing the serum levels of CD206 and Arg-1 （P<0.01）. In vitro experiment： compared with the model group， TSDN and inhibitor down-regulated the mRNA levels of NLRP3 inflammasome， COX-2， IL-1β， and TNF-α and the protein levels of NLRP3 inflammasome， COX-2， cleaved IL-1β， and TNF-α （P<0.01）. Compared with TSDN alone， TSDN + COX-2 inhibitor further reduced the mRNA and protein levels of the markers above （P<0.01）. Compared with the model group， TSDN and COX-2 inhibitor decreased the levels of IL-1β， iNOS， CD80， and CD86 （P<0.01） and increased the levels of CD206 and Arg-1 （P<0.01） in cells. Compared with TSDN alone， TSDN + COX-2 inhibitor reduced IL-1β， iNOS， CD80， and CD86 levels （P<0.05， P<0.01） and elevated CD206 and Arg-1 levels （P<0.01） in cells. ConclusionTSDN can alleviate GA by downregulating COX-2-mediated M1 macrophage reprogramming and suppressing the inflammatory factors.

OBJECTIVES: To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). METHODS: Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. RESULTS: The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. CONCLUSIONS Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
Animals ; Gastrointestinal Microbiome/drug effects* ; Metabolic Syndrome/microbiology* ; Bile Acids and Salts/metabolism* ; Rats, Wistar ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Male ; Fibroblast Growth Factors/metabolism* ; Liver/metabolism* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism*

Objective:To investigate the role of a modified positioning device in improving image quality and diagnostic efficacy for thyroid cancer in contrast-enhanced neck CT imaging.Methods:This prospective cross-sectional study included 137 patients with pathologically confirmed thyroid lesions who underwent contrast-enhanced neck CT at Zhangzhou Affiliated Hospital of Fujian Medical University from January to April 2024. Patients scanned in January and February (modified positioning group, n=62) underwent scanning using the modified positioning device, whereas those scanned in March and April (traditional positioning group, n=75) underwent scanning with conventional positioning. The estimated volume CT dose index (CTDI vol) in the thyroid region was recorded. Subjective image quality for thyroid and neck regions was evaluated using a 5-point Likert scale. Diagnostic assessments for thyroid cancer, capsule invasion, and lymph node metastasis were independently conducted by one junior radiologist and one senior radiologist using a 5-point scoring system, with scores≥3 considered positive diagnoses. The differences of CTDI vol and image quality scores between the 2 groups were compared using Mann-Whitney U test. The diagnostic performance was evaluated by the receiver operating characteristic curve analysis. Results:The estimated CTDI vol values for the thyroid region were significantly lower in the modified positioning group compared to the traditional positioning group [11.20 (8.37, 13.56) vs. 12.46 (10.10, 19.43) mGy, Z=1.99, P=0.026]. Subjective image quality scores for thyroid and neck regions were significantly higher in the modified positioning group than in the traditional positioning group (all P<0.001). For thyroid cancer diagnosis by the senior radiologist, the modified positioning group had a significantly higher area under the curve (AUC) of 0.842 (95% CI 0.728-0.956) compared to the traditional positioning group (AUC=0.666,95% CI 0.554-0.777, Z=2.17, P=0.031). No significant differences were observed in diagnostic performance between the junior and senior radiologists for thyroid cancer, capsule invasion, and lymph node metastasis in other subgroup comparisons (all P>0.05). Conclusion:The modified positioning device using in contrast-enhanced neck CT imaging can improve image quality and diagnostic efficacy for thyroid cancer while reducing radiation exposure to the thyroid gland.

Objective:To investigate the characteristics of serum immunoglobulin G (IgG) N-glycans in male patients with different subtypes and severity grades of androgenetic alopecia (AGA) .Methods:A cross-sectional study was conducted on male patients diagnosed with male-pattern hair loss (MPHL) or female-pattern hair loss (FPHL) who attended the Department of Dermatology, Huashan Hospital, Fudan University between June and December 2022. Clinical data were collected, and serum IgG N-glycans were quantitatively analyzed using ultra-performance liquid chromatography (UPLC) . The content of serum IgG N-glycan structures was compared between patients with different AGA subtypes and among patients with different severity grades of MPHL or FPHL, while derived traits were compared between patients with different AGA subtypes. Point-biserial correlation analysis was conducted to assess associations between serum IgG N-glycans and hair loss severity.Results:A total of 85 male patients with AGA were included, comprising 44 MPHL patients and 41 FPHL patients. No significant differences were observed between the two subgroups in terms of age, age at onset, or serum levels of testosterone, sex hormone-binding globulin, uric acid, and 25-hydroxyvitamin D (all P > 0.05) . UPLC showed 23 serum IgG glycans and 5 derived glycan traits (afucosylation, fucosylation, bisecting GlcNAc, terminal galactosylation, and terminal sialylation) . Compared with the MPHL patients, the FPHL patients exhibited significantly increased levels of N-glycans GP5, GP11, GP17, and GP20 (all P < 0.05) , significantly elevated levels of afucosylated IgG N-glycans ( P = 0.047) , but significantly reduced core fucosylated IgG N-glycans ( P = 0.047) . No significant differences in serum IgG N-glycan composition were observed among patients with varying severity grades of MPHL (all P > 0.05) . In the FPHL patients, the levels of N-glycans GP10 ( r = 0.32, P = 0.039) and GP22 ( r = -0.32, P = 0.045) were significantly positively and negatively correlated with hair loss severity respectively; receiver operating characteristic curve analysis showed that both GP10 and GP22 had moderate diagnostic value for predicting hair loss severity, with the area under the curve values being 0.69 (95% CI: 0.52 - 0.86) and 0.71 (95% CI: 0.55 - 0.86) , respectively. Conclusion:Serum IgG N-glycan profiles differed among male patients with different AGA subtypes, and N-glycans GP10 and GP22 may serve as potential biomarkers for early assessment of hair loss severity in male FPHL patients.