Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.

BACKGROUND:Exercise has a regulatory effect on intestinal flora dysbiosis,which can effectively protect the beneficial flora and improve the intestinal environment.However,the effect of treadmill exercise on the structure and diversity of intestinal microbial community in Parkinson's disease and the specific mechanism are not clear. OBJECTIVE:Using 16S rDNA technique to analyze the effect of treadmill exercise on the structure and diversity of the intestinal flora of rats with Parkinson's disease,and to investigate the mechanism of non-pharmacological treadmill exercise to improve Parkinson's disease. METHODS:Twelve of the 18 Sprague-Dawley rats were randomly selected to make animal models of Parkinson's disease using unilateral 2-point nigrostriatal injection of 6-hydroxydopamine.The remaining six rats were used as sham-operation group,which were injected with the same dose of saline containing 0.2%ascorbic acid using the same positioning and injection method.After successful modeling,12 rats with Parkinson's disease were randomly divided into model group and treadmill exercise group(n=6 per group).The treadmill exercise group was subjected to a middle and low intensity tread mill exercise,10 m/min,30 minutes per day,5 days per week for 4 weeks.Fresh feces were collected and stored in liquid nitrogen 24 hour after the last exercise session,and the changes in fecal flora were analyzed by 16S rDNA sequencing technique. RESULTS AND CONCLUSION:Treadmill exercise significantly improved behavior and nigrostriatal tyrosine hydroxylase-positive cell expression in rats with Parkinson's disease model and alleviated changes in the structure and diversity of the gut microbial community caused by Parkinson's disease,increased the number of operational taxonomic units and modulated Alpha and Beta diversity in rats.At the phylum and genus levels,the abundance ratio of Firmicutes/Bacteroidetes in the model group decreased compared with the sham-operated group,while beneficial bacteria such as Prevotella,Bacteroides,and Clostridium_XlV increased significantly after treadmill exercise.To conclude,treadmill exercise has a significant modulating effect on behavioral abnormalities,toxic damage to dopaminergic neurons and gut microbial imbalance caused by Parkinson's disease,alleviates the symptoms of flora-related diseases,and has a positive effect on the improvement of Parkinson's disease.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Objective To investigate the clinical efficacy of preoperative therapeutic plasma exchange(TPE)in pre-venting acute rejection after ABO incompatible kidney transplantation(ABOi-KT).Methods Nine patients with ABOi-KT who were admitted to the renal transplant department of our hospital from April 2022 to April 2024 were retrospectively ana-lyzed.They received a total of 28 TPEs before kidney transplantation,and the treatment plan was summarized as follows:The proportion of the substitute fluid,as well as the frequency and volume of TPE were determined based on the patient′s ABO blood group system antibody titer,gender,height,weight,hematocrit and other indicators upon admission.The pa-tient′s relevant laboratory indicators,including hemoglobin,platelets,leukocytes,coagulation function,total protein,albu-min,globulin,A/G,creatinine and urea nitrogen upon admission and after TPE were monitored and statistically analyzed.After transplantation,changes in renal function indicators such as ABO blood group system antibody titers,creatinine and u-rinary excretion were observed,and clinical symptoms of acute rejection,such as swelling,pain and edema in the transplan-ted kidney area were observed.Results Nine ABOi-KT patients had an average of about 3 TPEs before transplantation sur-gery,with an average total volume of approximately 2 500 mL to 3 500 mL per TPE,or approximately about 1.01 to 1.16 plasma volume(PV).After multiple TPEs,pre-transplantation antibody titers decreased by an average of 3 times compared to before TPE.There were no statistically significant differences in Hb,PLT,PT,PTA,INR,TBil,ALB,Cr and BUN(P＞0.05),while statistically significant differences were found in WBC,APTT,Fbg,TP,GLB and A/G(P＜0.05).After surgery,the creatinine level of 9 patients dropped to approximately 100 to 140 μmol/L,the urine output was normal,and the urine protein dropped to weakly positive or negative values.None of the nine patients experienced acute rejection.Con-clusion TPE can effectively reduce the level of ABO blood group antibody and prevent the occurrence of acute rejection in ABOi-KT patients.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

This paper analyzed the "non-standardization" phenomenon of syndrome differentiation in traditional Chinese medicine （TCM） from the diagnosis process. It is proposed that the symptoms and signs collected by the four examinations of inspection， listening/smelling， inquiry， and palpation naturally have a certain "ambiguity"， which can be reduced by the comparison and comprehensive condensation （comprehensive analysis of the four examinations） of a large amount of multi-dimensional clinical data， thereby realizing the sublimation of TCM diagnosis from "ambiguity" of four examinations to "accuracy" of diagnostic conclusion. Based on the above assumptions， this paper further proposed that a research idea of intelligent syndrome differentiation in TCM， that is， by taking the clinical thinking ability of TCM physicians as the core， adopting artificial intelligence technology based on knowledge graph visualization， integrating the complex network association and reasoning method of "symptom-pathogenesis-syndrome" linked by pathogenesis， and through the automatic analysis and reasoning process of a large amount of multi-dimensional and ambiguous clinical data， the intelligent TCM diagnosis based on syndrome differentiation can be realized.

Based on the"pivot movement"theory of distinguished physician Huang Yuanyu in the Qing Dynasty,it is believed that the core mechanism of abdominal flatulence disease is the unfavorable operation of the central axis pivot,and the ascent and descent disorder of qi movement in the central earth.The pathogenesis of abdominal flatulence disease was explained from the perspectives of mistakenly dropping the damage to yang,keeping the lung qi from falling,and declining central qi deficiency.The main concept of clinical practice was to promote the movement of the middle earth,promote the movement of the spleen and stomach,and restore position of yin and yang and clearing and turbidity.Examples were given of the five commonly used TCM prescriptions,including Xiaqi Decoction,Banxia Xiexin Decoction,Gancao Xiexin Decoction,Shengjiang Xiexin Decoction and Xuanfu Daizhe Decoction,to explain the treatment approach guided by the theory of"pivot movement",in order to provide reference for clinical diagnosis and treatment.

Objective:To establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.

The clinical demand for occlusal reconstruction increases rapidly with increasing number of patients who have lost their normal occlusion because of tooth wear and dentition defects.Occlusal reconstruction is a special type of restoration defined as a comprehensive restoration of the function of the stomatognathic system by reestablishing a uni-form and stable occlusal relationship between the upper and lower dentitions.Occlusal function analysis is an important part of occlusal reconstruction to achieve accurate restora-tion design and adjustment.Digital occlusal function analysis was conducted to monitor the movement of the mandible and obtain related data for the parameter design of occlusal reconstruction.Preoperative design,intraoper-ative adjustment,and postoperative verification were achieved,thereby improving the efficiency and accuracy of occlusal reconstruction.