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.

Objective To analyze the epidemic characteristics of plague epidemics, host and vector community structure, and abundance in plague focus of wild rodents in Yunnan Province, 2017-2023, providing a scientific basis for formulating plague prevention strategies and forecasting warning for this epidemic foci. Methods　Following the requirements of the "National Plague Surveillance Plan" and the "Yunnan Provincial Plague Surveillance Plan", host-vector surveillance, etiology, and serological testing were carried out, and plague epidemic data and host-vector surveillance data in plague focus of wild rodents in Yunnan Province, 2017-2023 were collected and sorted using Excel 2019 software to create a database for descriptive analysis. Results From 2017 to 2023, 11 animal plague epidemics were discovered in the wild plague foci of Yunnan Province, with 18 epidemic spots. From the altitude distribution point of view, 7 epidemic spots were distributed at an altitude of 2 800-3 000 meters, another seven at 3 000 and 3 200 meters, and four spots were located in areas with an altitude of ≥3 200 meters; a total of 36 samples of host and vector animals were detected positive, including 28 positive samples of host animals and 8 positive samples of vector animals, and 29 strains of Yersinia pestis were isolated; in terms of species composition, Eothenomys miletus accounted for the largest proportion of 41.67%, followed by Apodemus chevrieri at 22.22%; Ctenophthalmus quadratus at 11.11%; Rattus tanezumi and Neopsylla specialis each at 8.33%, and Dremomys pernyi, rat carcass, and Frontopsyllas padix each accounted for 2.78%; the epidemic peaked in April, and no human cases were found. A total of 453 220 rat cages (traps) were placed, capturing 27 677 rodents, with an average capture rate of 6.11%. A total of 25 075 main hosts, Apodemus chevrieri and Eothenomys miletus, were captured, accounting for 90.60% of the total capture rate. A total of 14 700 fleas were seized on the surface of small animals, with a total flea infection rate of 23.13% and a flea index of 0.59. The main vectors were Ctenophthalmus quadratus and Neopsylla specialis, with constituting ratios of 45.71% and 22.69%, respectively. Conclusions From 2017 to 2023, the population density of main host animals in Yunnan's wild rodent plague foci was relatively high and showed an upward trend, possibly related to the local planting structures. Plague plays a regulatory role in host population structures. Epidemics among animals showed obvious seasonality, with a trend of expanding epidemic areas. No human cases were found, but Yersinia pestis was detected in Rattus tanezumi in human settlements, raising the possibility that animal plague could spread to humans. It suggests strengthening the monitoring of areas adjacent to the epidemic source, eradicating rats and fleas in spring, improving the accuracy of plague prediction and early warning, providing strong technical support for the early detection of plague among animals, and preventing the spread of the epidemic to humans.

OBJECTIVE To construct a double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies， and to provide a reference for building a talented team of licensed pharmacists and promoting the high-quality development of pharmaceutical care. METHODS Based on the competency iceberg model and double helix structure theory， literature analysis and the Delphi method were adopted to explore the model indicators； questionnaires were designed to survey licensed pharmacists in retail pharmacies from Shandong Province. The exploratory factor analysis was used to correct the model indicators and establish a double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies， which was examined by validation factor analysis. RESULTS The recovery rate of the questionnaires in the two rounds of expert consultation was greater than 90%， the expert authority coefficients were both more than 0.86， and the overall Kendall’s W values were 0.288 and 0.510， respectively； after the correction of the exploratory factor analysis， the double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies was established， which contained 4 first-level indexes such as occupational literacy， occupational knowledge， occupational competency and internal motivation， and 23 second-level indexes. The model contained occupational knowledge and occupational competency in the explicit competency chain， occupational literacy and internal motivation in the implicit competency chain， and policy support， incentive mechanism， education and training as the hydrogen bonds connecting the two main chains. The validation factor analysis showed that the model’s goodness of fit index， comparative fit index， and normed fit index all exceeded 0.9； the reliability of the combination of the four first-level indexes ranged from 0.89 to 0.95； the average variance extracted ranged from 0.58 to 0.75， and Cronbach’s α coefficients for both the overall model and the first-level indicators were all greater than 0.84. CONCLUSIONS The constructed double helix model for evaluating the job competency of licensed pharmacists in retail pharmacies is scientific， reasonable and practical.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

The complex barriers to drug delivery in the eye make it difficult for traditional ophthalmic preparations to reach pathological tissues in the posterior segment of the eye via ocular surface. Therefore, intravitreal drug injection has been widely used for treating posterior segment diseases, but this invasive approach to drug delivery has disadvantages such as short drug half-lives, repeated injections, and many complications. Ophthalmic nanodrug delivery systems, which can overcome ocular drug delivery barriers, enhance drug permeability, and improve drug bioavailability, now make it possible to efficiently deliver drugs to the posterior segment of the eye. However, the carrier materials utilized for nanomedicine delivery are inherently intricate, and substantial disparities exist among research findings, posing a hindrance to the subsequent advancement of pertinent drug formulations. Consequently, this review centers on the principal physiological obstacles encountered in ocular drug delivery, emphasizing the utilization of diverse nanomedicine delivery systems in posterior segment pathologies. It aims to delve into their research progress in posterior segment diseases and establish a safer, more effective therapeutic approach for treating these ocular conditions.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

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 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.