Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Objective To investigate the role of HK2 and VDAC1 in diacetylmorphine-induced cardiomyocyte apoptosis.Methods A dose-escalation method was used to establish a rat model of diacetylmorphine addiction.Forty SD rats were randomly divided into three groups,the normal group(n=10)was injected with an equal amount of saline subcutaneously,the model group(n=15)was injected with 5 mg/kg of diacetylmorphine for the first time,and then the dose was increased by 2.5 mg/(kg·d)day by day for 20 days,and the group of model +10 D(n=15)continued to increase the dose based on the model group up to the 10th day.Lactate dehydrogenase(LDH)and glutamic oxaloacetic transaminase(GOT)were detected by ELISA;HE staining was used to observe the pathological changes of myocardial tissues in each group;TUNEL staining was used to detect apoptosis in myocardial tissues in each group;and immunohistochemistry,RT-q-analysis,and immunochemistry were used to detect apoptosis in myocardial tissues in each group.Immunohistochemistry,RT-qPCR and Western bl-ot were used to detect the mRNA and protein expression of HK2,VDAC1 and apoptosis-related factors.Results HE staining revealed that myocardial tissues exhibited different degrees of damage with the prolongation of diacetylmorphine intervention.Compared with the normal group,serum LDH,GOT content and myocardial apoptosis rate increased in the model group,mRNA and protein levels of HK2 and anti-apoptotic factor Bcl-2 decreased,mRNA and protein levels of VDAC1 and pro-apoptotic factors Bax and Caspase-3 increased,and the protein level of Clevead Caspase-3 increased;in the model +10 D group the above indexes,there was a statistically significant difference(P<0.05).Conclusion Diacetylmorphine can cause cardiomyocyte apoptosis,and VDAC1 may be involved in the process of cardiomyocyte apoptosis caused by diacetylmorphine.

Objective To investigate the effect of autophagy activation on cell proliferation in human umbilical vein endothelial cells(HUVECs).Methods HUVECs were treated with rapamycin(Rapa).Western blot assay was performed to examine the expression of protein of microtubule associated protein 1 light chain 3(LC3),Beclin 1 and unc-51-like kinase 1(ULK1).Autophagosomes were detected by transmission electron microscopy(TEM),and autophagy fluorescence was detected by monodansylcadaverine staining(MDC)assay.The effect of autophagy activation on cell proliferation was assessed by CCK-8 assay and EdU assay.Vascular formation experiments were used to detect vasculogenic ability.Results After Rapa treatment,LC3,Beclin1 and ULK1 expressions were en-hanced,while the green autophagy fluorescence expression in the experimental group was stronger than that in the control group,and autophagosomes were visible by TEM;CCK-8 and EdU results showed that compared with the control group,the cell proliferation ability was weakened and tubes formation ability was reduced after the activation of autophagy in experimental cells.Conclusion Rapa upregulates autophagy activity in HUVECs to inhibit cell proliferation under certain time.

Objective To systematically review the risk prediction models for postoperative pancreatic fistula(POPF)after pancreaticoduodenectomy(PD),and to provide a reference for the clinical screening and application of POPF-related risk models.Methods This study was conducted according to the PRISMA guidelines,with a PROSPERO registration number of CRD42023437672.PubMed,Scopus,Embase,Web of Science,the Cochrane Library,CNKI,VIP,Wanfang Data,China Medical Journal Full-text Database,and CBM were searched for studies on establishing risk prediction models for POPF after PD published up to April 26,2024.The PROBAST tool was used to assess the quality of articles,and RevMan 5.4 and MedCalc were used to perform the Meta-analysis.Results A total of 36 studies were included,involving 20 119 in total,and the incidence rate of POPF after PD was 7.4%—47.8%.A total of 55 risk prediction models were established in the 36 articles,with an area under the receiver operating characteristic curve(AUC)of 0.690-0.952,among which 52 models had an AUC of>0.7.The quality assessment of the articles showed high risk of bias and good applicability.MedCalc was used to perform a statistical analysis of AUC values,and the results showed a pooled AUC of 0.833(95%confidence interval:0.808-0.857).The Meta-analysis showed that body mass index,amylase in drainage fluid on the first day after surgery,preoperative serum albumin,pancreatic duct diameter,pancreatic texture,fat score,tumor location,blood loss,sex,time of operation,main pancreatic duct index,and pancreatic CT value were predictive factors for POPF(all P<0.05).Conclusion The risk prediction models for POPF after PD is still in the exploratory stage.There is a lack of calibration methods and internal validation for most prediction models,and only the univariate analysis is used to for the screening of variables,which leads to the high risk of bias.In the future,it is necessary to improve the methods for model establishment,so as to develop risk prediction models with a higher prediction accuracy.

AIM To explore the mechanism of Yiqi Wenyang Huwei Decoction on airway inflammation improvement of rats with bronchial asthma based on IL-25/NF-κB signaling pathway.METHODS 60 rats were randomly divided into the control group,the model group,the dexamethasone group(0.2 mg/mL),the low-dose,medium-dose and high-dose Yiqi Wenyang Huwei Decoction groups(1,2,4 g/mL),with 10 rats in each group.Intraperitoneal injection of ovalbumin(OVA)and aluminum hydroxide suspension was applied to establish the rat asthma model,followed by 2-week corresponding dosing of the drugs.The rats of each group had their daily diet,mental status,hair growth and respiration observed;their differential count of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by automatic hematology analyzer;their pathological changes of lung tissue observed by HE staining;their pulmonary IL-25 protein expression detected by immunohistochemistry(IHC);their levels of IL-4,IL-5 and IL-13 in BALF measured by ELISA;their pulmonary expression of IL-25 and TRAF6 mRNA detected by RT-qPCR;and their pulmonary protein expressions of IL-25,TRAF6,IκBα,p-IκBα,NF-κB p65 and p-NF-κB p65 detected by Western blot.RESULTS Compared with the control group,the model group displayed severe damage of the lung tissue and infiltration of a large number of inflammatory cells;increased number of inflammatory cells and levels of IL-4,IL-5 and IL-13 in BALF(P<0.01);increased mRNA expressions of IL-25 and TRAF6,and pulmonary protein expressions of IL-25,TRAF6,p-IκBα/IκBα and p-NF-κB p65/NF-κB p65(P<0.01).Compared with the model group,all of the Yiqi Wenyang Huwei Decoction groups shared improved pulmonary infiltration of inflammatory cells;decreased number of inflammatory cells and levels of IL-4,IL-5 and IL-13 in BALF(P<0.05,P<0.01);and decreased mRNA expressions of IL-25 and TRAF6,and pulmonary protein expressions of IL-25,TRAF6,p-IκBα/IκBα and p-NF-κB p65/NF-κB p65(P<0.01).CONCLUSION Yiqi Wenyang Huwei Decoction can inhibit the airway inflammation in the rat model of bronchial asthma,which may be related to the inhibited activation of IL-25/NF-κB signaling pathway and the reduced expression of inflammatory factors.

Objective To observe the effects of wheat grain moxibustion for"Huantiao"on sciatic nerve function,pathological morphology of sciatic nerve stem and expressions of TLR4/MyD88/NF-κB signaling pathway expression in spinal cord tissue of rats with sciatic nerve injury(SNI);To explore the possible mechanism of wheat grain moxibustion for the treatment of SNI.Methods Totally 24 SD male rats were randomly divided into blank group,sham-operation group,model group and wheat grain moxibustion group,with 6 rats in each group.The model group and the wheat grain moxibustion group used a rat model with sciatic nerve clamping injury.From the 7th day after modeling,the rats were treated with moxibustion on the affected side of"Huantiao"for 6 strokes each time,once a day,for consecutive 10 days.The sciatic nerve function index(SFI)of rats on the 7th day after modeling and after intervention were observed,mechanical withdraw threshold(MWT)in rats were measured using a fiber optic pain gauge,ELISA was used to detect NO and iNOS content in spinal cord tissue,HE staining was used to observe the morphology of sciatic nerve stem,the expression of TLR4,NF-κBp65,p-NF-κBp65,MyD88,IκBα and p-IκBα in spinal cord tissue were detected by Western blot.Results Compared with the sham-operation group,the SFI and MWT of the rats in the model group significantly decreased(P<0.01),the arrangement of nerve fibers in sciatic nerve stem was disordered,with a significant increase in the number of Schwann cells and a large number of vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα protein in spinal cord tissue significantly increased(P<0.01).Compared with the model group,the SFI and MWT of the rats in the wheat grain moxibustion group increased significantly(P<0.01),the damage of sciatic nerve stem was reduced,with orderly cell arrangement,a decrease in the number of Schwann cells,and a decrease in axonal demyelination and cellular vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα in spinal cord tissue significantly decreased(P<0.05).Conclusion Wheat grain moxibustion for"Huantiao"can down-regulate TLR4,p-NF-κBp65,MyD88 and p-IκBα protein expressions in spinal cord tissue of SNI rats,reduce the secretion of NO and iNOS,thereby relieve pain and damaged nerve tissue inflammation response.

Objective To observe the effects of electroacupuncture(EA)at"Hegu"and"Taichong"on the expressions of cytochrome C(Cyt-C)and Caspase-9 in the hippocampus of rats with chronic pain and depression comorbidity(CPDC);To explore its potential mechanism for the treatment of CPDC.Methods A total of 60 SD rats were randomly divided into sham-operation group,model group,medication group and EA group,with 15 rats in each group.The CPDC model was induced by twice injection of complete Freund's adjuvant into the plantar of the left hind paw.EA group was applied to bilateral"Hegu"and"Taichong"for 20 min,the medication group were treated with duloxetine suspension 10 mg/kg by gavage for 14 days.The mechanical paw withdrawal threshold and thermal withdrawal latency were measured on day 7,14,21 and 28 after the first injection,tail suspension test and sucrose preference test were performed on day 14 and 28,Nissl staining was used to observe hippocampal neurons and the number of Nissl body,the protein expressions of Cyt-C and Caspase-9 in hippocampal tissue were detected by Western blot and immunohistochemistry.Results Compared with the sham-operation group,the mechanical paw withdrawal threshold and thermal withdrawal latency of the model group significantly decreased(P<0.01),the tail suspension immobility time increased(P<0.01),the percentage of sucrose preference decreased(P<0.01),the neurons were thinly arranged,the neurons were damaged and lost,and the number of Nissl body were less(P<0.01),the apoptotic rate of hippocampal neurons increased(P<0.01),the expression of Cyt-C,Caspase-9 and cleaved-Caspase-9/Caspase-9 ratio in hippocampal tissue increased(P<0.01).Compared with the model group,the mechanical paw withdrawal threshold and thermal withdrawal latency of the EA group and medication group significantly increased(P<0.01),the tail suspension immobility time decreased(P<0.01),the percentage of sucrose preference increased(P<0.01),the loss of neurons in hippocampus was reduced,the cells were arranged neatly,and the nucleoli were clear,the number of Nissl body increased(P<0.01),the apoptotic rate of hippocampal neurons decreased(P<0.01),and the expression of Cyt-C,Caspase-9 and cleaved-Caspase-9/Caspase-9 ratio in hippocampal tissue decreased(P<0.01).Conclusion EA at"Hegu"and"Taichong"can alleviate pain and depression in CPDC rats,which may be related to inhibiting the expressions of Cyt-C and Caspase-9 in hippocampal tissue and inhibiting the apoptosis of hippocampal neurons,thus playing a neuroprotective effect.