We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective: To analyze the epidemiological and molecular characteristics of norovirus outbreaks in schools in Xicheng District of Beijing from 2017 to 2022, so as to provide evidence for the prevention and control of norovirus outbreaks in schools. Methods: Data of norovirus outbreaks in schools in Xicheng District, Beijing during 2017 to 2022 were collected and analyzed by descriptive epidemiological methods. Realtime PCR was used to detect the nucleic acid of group GⅠand GⅡnorovirus, the positive norovirus nucleic acid samples were sent to Beijing Center for Disease Control and Prevention for molecular typing. Results: From 2017 to 2022, 185 norovirus outbreaks were reported in schools in Xicheng District, including 166 cluster outbreaks and 19 outbreaks. A total of 2 044 cases were reported, with a total attack rate of 13.92%. There were two peaks in the outbreak time, which were from March to June after the spring semester and from October to December after autumn semester. Primary schools were the most common place of occurrence (101 cases), followed by nursery institutions (68 cases) and secondary schools (16 cases). There were statistically significant differences in the incidence rates among different sites(12.37%, 22.78%, 8.47%, χ2=263.34, P<0.01). There were significant differences in the incidence of vomiting, diarrhea, nausea and stomachache among different students (χ2=263.33, 90.58, 20.42, 30.29, P<0.01). Vomiting was the main symptom in primary school and nursery school children (96.41%, 98.28%), and the diarrhea rate was higher in middle school students (68.22%). The outbreaks were mainly caused by type GⅡ norovirus. The genotype from 2017 to 2021 showed the characteristics of diversity, mainly GⅡ.2[P16], but there was no significant advantage for the GⅡ.2 [P16] during 2019 to 2021. Conclusions The norovirus outbreak in schools in Xicheng district of Beijing from 2017 to 2022 are mainly caused by GⅡ type genome. The main genotype is GⅡ.2[P16]. Norovirus infection mainly occurred in primary schools and kindergartens. For the vulnerable populations, it is necessary to improve the capacity to early identification, student infectious disease management, active infection control and prevention measures, and pathogen surveillance and sporadic case monitoring.

Objective To construct a machine learning prediction model for postoperative liver injury in patients with non-liver surgery based on preoperative and intraoperative medication indicators.Methods A case-control study was conducted on 315 patients with liver injury after non-liver surgery selected from the databases developed by 3 large general hospitals from January 2014 to September 2022.With the positive/negative ratio of 1 ∶3,928 cases in corresponding period with non-liver surgery and without liver injury were randomly matched as negative control cases.These 1243 patients were randomly divided into the modeling group(n=869)and the validation group(n=374)in a ratio of 7∶3 using the R language setting code.Preoperative clinical indicators(basic information,medical history,relevant scale score,surgical information and results of laboratory tests)and intraoperative medication were used to construct the prediction model for liver injury after non-liver surgery based on 4 machine learning algorithms,k-nearest neighbor(KNN),support vector machine linear(SVM),logic regression(LR)and extreme gradient boosting(XGBoost).In the validation group,receiver operating characteristic(ROC)curve,precision-recall curve(P-R),decision curve analysis(DCA)curve,Kappa value,sensitivity,specificity,Brier score,and F1 score were applied to evaluate the efficacy of model.Results The model established by 4 machine learning algorithms to predict postoperative liver injury after non-liver surgery was optimal using the XGBoost algorithm.The area under the receiver operating characteristic curve(AUROC)was 0.916(95%CI:0.883～0.949),area under the precision-recall curve(AUPRC)was 0.841,Brier score was 0.097,and sensitivity and specificity was 78.95%and 87.10%,respectively.Conclusion The postoperative liver injury prediction model for non-liver surgery based on the XGBoost algorithm has effective prediction for the occurrence of postoperative liver injury.

In recent years,there have been significant advancements in tumor immunotherapy.Immune checkpoint inhibitors have emerged as a pivotal approach for treating advanced malignant tumors.The use of immunotherapy has been widely recommended and applied in clinical treatment both domestically and internationally.However,its clinical treatment efficacy still falls short of expectations.Improving the efficacy of immunotherapy for patients with advanced malignant tumors is currently a prominent research focus.Studies indicate that the combined use of immune enhancers and immune checkpoint inhibitors in various advanced malignant tumors significantly enhances the outcomes of immunotherapy.This article primarily highlights the combined application of immune enhancers and immune checkpoint inhibitors in cancer therapy,offering insights into their potential in the field of oncology treatment.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.