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.

Both cathartic colon （CC） and cathartic-dependent constipation （CDC） are caused by the abuse of stimulant laxatives， while their concepts are not completely the same.Starting from the disease name of CC， this article traced the origin and evolution of the concept of CC， summarizes and compared the similarities and differences between CC， CDC， and slow transit constipation （STC）， and called for strict differentiation among the three.Furthermore， this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine （TCM） syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established， and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally， the paper provides an overview of current research on CDC in both Western medicine and TCM contexts， identifies future research directions， and suggests research pathways for refining and advancing CDC studies.

OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis.

Objective To explore the construction of heart preservation model of empty beating donor based on extracorporeal membrane oxygenation (ECMO). Methods From January 2022 to August 2023, 20 Guangxi Bama miniature pigs weighing 25-30 kg were selected, half male and half female. Under general anesthesia and heparinization, a midline thoracotomy was performed. The pericardium was cut after freeing the anterior and posterior vena cavae, and a perfusion needle was inserted near the brachiocephalic artery in the ascending aorta, connected to a blood collection bag to collect 500-600 mL of blood. The anterior and posterior vena cavae were ligated, the aorta was blocked and perfused with HTK solution to stop the heart beating. The superior and inferior vena cavae were cut off, the right pulmonary vein was decompressed, the aorta and left and right pulmonary arteries and veins were cut off, and the whole heart was removed. An ECMO device was used to continuously perfuse a cardioprotective solution mainly composed of oxygenated warm blood, maintaining the isolated pig heart beating for 8 hours, monitoring (once/hour) ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, inflammatory factors, myocardial enzymes, myoglobin, and troponin levels. Myocardial tissue was taken for hematoxylin-eosin (HE) staining to observe myocardial cell damage and evaluate the quality of heart preservation. Results Among the 20 isolated beating pig hearts, 17 successfully resumed beating, 3 experienced ventricular fibrillation, resuscitated after intracardiac electrical defibrillation, and all 20 pig hearts successfully beat for 8 hours. There was no statistical difference in ECMO perfusion parameters, blood gas indicators, perfusate electrolytes, and inflammatory factors at each time point (P>0.05). There were statistical increases in myocardial enzymes, myoglobin, and troponin levels (P<0.05). HE staining results suggested that there was no severe myocardial damage. Conclusion ECMO technology can be used for pig heart preservation with good results, and this study provides experimental evidence for improving heart preservation research in clinical heart transplantation.

Objective To explore the effect of sex on the incidence of immune-related cutaneous adverse event (ircAE) during immunotherapy for gastric cancer, and to further analyze the correlation between sex, ircAE and prognosis. Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received immune checkpoint inhibitors at the Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, from February 1, 2022, to December 31, 2024. Clinicopathological characteristics, occurrence of ircAE, and survival data were collected. The incidence of ircAE was compared between male and female patients. Kaplan-Meier method was used to plot survival curves, and univariate Cox regression analysis was performed to assess prognostic factors. Results A total of 116 patients with advanced gastric cancer were enrolled, including 76 males (65.5%) and 40 females (34.5%). The overall incidence of ircAE was 23.28%, with a higher incidence in male patients than in female patients (28.95% vs 12.50%, P＝0.046). Kaplan-Meier survival analysis on 86 patients with complete follow-up data indicated that patients with ircAE had longer overall survival (OS) than those without ircAE (P＝0.045). Univariate Cox regression analysis showed that male (HR＝0.43, 95%CI 0.22–0.83, P＝0.012) was associated with prolonged OS. Conclusions In gastric cancer immunotherapy, male patients are more likely to develop ircAE and have longer OS than female patients, and the occurrence of ircAE may be related to prolonged OS.

ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 （TRL4/NF-κB/NLPR3） signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group （n = 12） and a modeling group （n = 60）. The rats in the sham-operated group underwent a caesarean section， while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling， the animals were randomly divided into the model group， progesterone group （0.25 mg·kg^-1）， and modified Shaofu Zhuyutang low-， medium-， and high-dose groups （7.5， 15， 30 g·kg^-1）， with 12 animals in each group. After 4 weeks of drug administration， voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection， and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） was used to detect the protein expression area of tumor necrosis factor-related factor 6 （TRAF6） and NLPR3 in the endometrial tissues. Immunofluorescence （IF） was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D （GSDMD） in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4， myeloid differentiation factor 88 （MyD88）， TRAF6， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group， rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased， and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4， MyD88， TRAF6， NF-κB p65， p-NF-κB p65， and NLPR3 proteins， along with the expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA， were significantly increased （P<0.01）. Compared with the model group， rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity， longer heat pain latency， the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased， and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4， MyD88， TRAF6， p-NF-κB p65， NLPR3 proteins， and TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA expression were reduced （P<0.05， P<0.01）. ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway， reducing NLRP3 inflammasome-induced cellular pyroptosis， antagonizing the fibrosis process in ectopic endometrial tissues， improving the inflammatory microenvironment in the pelvic cavity， and alleviating pain.

Objective:To explore the prognosis of patients with gastric cancer peritoneal metastasis (PM) receiving programmed cell death-1 (PD-1) antibody therapy, and investigate the biomarkers that affect the prognosis of anti-PD-1 therapy.Methods:This restrospecific study collected the clinic-pathological data of 56 patients with peritoneal metastasis of gastric cancer who received first-line treatment in the Nanjing Drum Town Hospital from March 2020 to September 2023, among which 41 had received anti-PD-1 immunotherapy and 15 hadn't. The relationship between overall survival (OS) and anti-PD-1 immunotherapy was evaluated by Kaplan-Meier analysis. The relationship between baseline peripheral blood indicators and treatment response of patients with anti-PD-1 treatment was analyzed using unpaired t-test. Subsequently, the Cox proportional risk regression model was used to explore the clinical prognostic factors that may affect anti-PD-1 immunotherapy by univariate and multivariate analysis. The clinical prognostic factors included baseline data and baseline peripheral blood indexes such as anti-PD-1 treatment lines, Eastern Cooperative Oncology Group performance status (ECOG PS), combined positive score (CPS), expression of human epidermal growth factor receptor 2 (Her-2), EBER status, pathological types, other metastatic lesions, ascites content before immunotherapy, with or without abdominal drainage during anti-PD-1 treatment, blood lipid indicators, inflammatory indicators, and tumor indicators. Results:Kaplan-Meier survival statistics showed similar OS (15.9 vs. 15.2 months, P=0.600) in patients with anti-PD-1 therapy compared to those without anti-PD-1 therapy. Patients with baseline high-density lipoprotein (HDL) ≥0.97 mmol/L ( n=22) demonstrated a significantly longer median OS compared to those with HDL＜0.97 mmol/L (15.2 vs. 13.5 months; P=0.018). Similarly, the cohort with apolipoprotein A1 (ApoA1) levels ≥0.86 g/L ( n=21) showed superior survival outcomes, with a median OS of 17.7 months versus 12.3 months in the ApoA1＜0.86 g/L group ( n=20; P=0.006). In contrast, elevated baseline alpha-fetoprotein (AFP) levels ( n=2) were associated with markedly reduced survival (median OS: 5.7 vs. 15.2 months in normal AFP group, n=37; P=0.005). Notably, elevated pretreatment ApoA1 levels correlated with enhanced immunotherapy response ( P=0.017). Multivariate Cox regression analysis revealed that ApoA1 deficiency (≥0.86 g/L) independently predicted better OS following PD-1 antibody therapy ( HR=0.35, 95% CI: 0.12-0.98, P=0.046) in gastric cancer patients with PM. Conclusions:In our study, it is first proposed that ApoA1 could be a significant predictor of the survival advantages of immunotherapy in gastric cancer patients with PM.

Objective To establish a reliable Pseudomonas aeruginosa(PA)-induced sepsis model,providing an effective experimental method for investigating the pathogenicity,antibiotic resistance mechanism and infection-related inflammatory pathways of PA.Methods PA ATCC 27853 was selected as experimental strain.Different concentrations of bacterial suspension were applied to the surface of erector spinae muscle in mice.Echocardiography was performed 24 h after infection to examine cardiac function.Heart,lung,kidney tissue and blood samples were collected.Serum creatinine(Cr),blood urea nitrogen(BUN),inflammatory factors,and cardiac troponin Ⅰ(CTNI)were detected.The pathological changes in the heart,lung,and kidney tissues were observed.Results The survival rates of the 107 CFU/mL group,108 CFU/mL,109 CFU/mL,and 1010 CFU/mL groups were 100%,93.3%,73.3%,and 26.7%,respectively.The concentration of interleukin-6(IL-6)in the PA-infected group was significantly higher than that in the non-infected group.The concentration of tumor necrosis factor-α(TNF-α)in 108 CFU/mL group and 109 CFU/mL group were significantly higher than that in the non-infected group.The left ventricular ejection fraction(LVEF)of 108 CFU/mL and 109 CFU/mL groups decreased significantly compared to the non-infected group,and the CTNI level increased significantly in infected group compared to the non-infected group.Compared with the non-infected group,only the 109 CFU/mL group showed significant statistical differences in Cr and BUN levels,while no significant differences were observed in the other PA-infected groups.The results of histopathology showed that the heart,lung,and kidney tissues of mice in the 109 CFU/mL group were significantly infiltrated by inflammatory cells,with obvious edema of tissue cells,disordered structural arrangement,thickening of alveolar septa,and renal interstitial stenosis.Conclusion The experiment successfully established a sepsis model induced by PA with a bacterial concentration of 109 CFU/mL,which is stable and reliable,and can provide a model basis for exploring sepsis and PA infection diseases.

The left maxilla of a patient was resected because of tumor,and the defect was reconstruted with fibular transplantation.The autonomous dental implant robot technology was used to achieve precise implantation of multiple implants and immediate denture restoration within the limited left maxilla.The surgery was minimally invasive and efficient,and significantly reducing patient post-operative discomfort.The final restoration was completed 6 months after surgery.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.