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 study clinical outcomes, genetic etiology, efficacy and safety of continuous renal replacement therapy (CRRT) for neonatal hyperammonemia.Methods:From September 2016 to June 2023, neonates with hyperammonemia receiving CRRT in NICU of our hospital were retrospectively analyzed. Their perinatal conditions, clinical manifestations, laboratory results, genetic tests, treatments and outcomes were collected. The patients were assigned into survival group and death group according to their conditions at discharge. SPSS 22.0 statistical software was used to analyze the differences between the two groups.Results:A total of 10 patients were enrolled, including 8 males and 2 females. The gestational age was 39.3(38.2,39.8)weeks and birth weight 3 300(3 050, 3 583) g. The age of onset was 2.0(2.0, 4.3) d. The main clinical manifestations included seizures, coma and high blood ammonia level (up to 586-1 250 μmol/L). The patients received CRRT at 3.0(2.0, 8.3) d of age and CRRT lasted for 20.5(16.5, 42.8) h. Before CRRT, average time of coma was 10.0(3.5, 12.8) h and the total duration of coma was 20.5(12.5, 29.0) h. After CRRT, blood ammonia decreased (52.6±22.2) μmol/L every hour for 6 h. The genetic tests showed ornithine transcarbamylase deficiency in 5 cases, methylmalonic acidemia in 2 cases, propionic acidemia in 1 case, carnitine acylcarnitine translocase deficiency in 1 case and transient hyperammonemia in 1 case. 6 patients survived. 4 patients died at discharge, including 2 withdrawal treatment. The duration of coma before CRRT and the total duration of coma in the death group were significantly longer than the survival group ( P<0.05). Conclusions:Inborn metabolic error are common causes of neonatal hyperammonemia. Timely CRRT can safely and effectively reduce blood ammonia levels and may improve clinical outcomes.

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 explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer (NSCLC) and their relationship with prognosis.Methods:A total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group, and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups, and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up, the patients were divided into survival group and death group, and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic (ROC) curves.Results:The serum miR-499 level in the NSCLC group (0.34±0.10) was lower than that in the control group (1.25±0.21), while the miR-362 level (1.13±0.27) was higher than that in the control group (0.63±0.15) ( t=18.26, P<0.001; t=16.32, P<0.001). There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation ( t=11.12, P<0.001; t=16.35, P<0.001), TNM staging ( t=13.64, P=0.002; t=8.73, P=0.010) and lymph node metastasis ( t=10.02, P=0.003; t=9.65, P=0.004). The serum miR-499 level in the death group ( n=77) (0.24±0.06) was lower than that in the survival group ( n=26) (0.35±0.09), while the miR-362 level (1.54±0.32) was higher than that in the survival group (1.08±0.21), with statistically significant differences ( t=8.06, P=0.006; t=8.67, P=0.005). ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%, respectively, with specificity of 64.42% and 65.61%, AUC of 0.739 (95% CI: 0.662-0.805) and 0.743 (95% CI: 0.640-0.793) ; the sensitivity, specificity, and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%, 85.34%, and 0.875 (95% CI: 0.698-0.897), respectively; the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction ( Z=4.83, P=0.013; Z=5.17, P=0.009) . Conclusion:Advanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362, and as the severity of the disease progressed, the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients.

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.

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 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 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.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.