BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness， unpredictability， high severity， and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia， to identify the key factors influencing the occurrence of violent behavior in these patients， so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases， eleventh edition （ICD-11） were collected to form the modeling cohort. They were randomly divided into a training set （n=140） and a test set （n=60） at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator （LASSO） regression algorithm， the feature variables were screened and dimension-reduced. The support vector machine （SVM） from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）， accuracy， precision， sensitivity， specificity， F1 value， and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores （r=0.580， P<0.01）， a positive correlation between hospitalization compliance and current disease status （r=0.550， P=0.003）， and a positive correlation between educational level and family per capita monthly income （r=0.367， P<0.01）. The SVM model achieved an AUC of 0.853， accuracy of 0.800， precision of 0.810， sensitivity of 0.895， specificity of 0.636， F1 value of 0.850， and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients， which is helpful for the early identification of violent risks in such patients. ［Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City （number， Y2023006）］

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective To investigate the correlation between serum ubiquitin-specific protease 14(USP14)and growth factor receptor binding protein 2(GRB2)levels and vascular lesions of the lower limbs(LEAD)in elderly patients with type 2 diabetes(T2DM).Methods 153 elderly T2DM patients admitted to Beijing Nuclear Industrial Hospital from July 2020 to August 2023 were selected and divided into lesion group(n=64)and non-lesion group(n=89)according to the presence or absence of LEAD,in addition and 153 healthy volunteers who matched the age of elderly T2DM patients in the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum USP14 and GRB2 levels in patients.Multifactorial Logistic regression was used to analyze the factors affecting the occurrence of LEAD in patients with elderly T2DM.Receiver operating curve(ROC)analysis of USP14 and GRB2 levels in elderly T2DM patients for the diagnostic value of LEAD occurrence.Results Compared with the control group,serum USP14(8.56±1.57ng/ml,6.34±1.27ng/ml vs 4.23±1.02ng/ml),GRB2 levels(7.45±1.56ng/ml,5.23±1.12ng/ml vs 3.19±0.78ng/ml)were significantly increased in the diseased and non-diseased groups,and the differences were statistically significant(q=33.555,18.259;37.326,19.960,all P<0.05).Class A,B and C serum USP14(7.14±1.31ng/ml,8.67±1.52ng/ml,9.98±2.01ng/ml),GRB2 levels(6.31±1.25ng/ml,7.47±1.58ng/ml,8.69±1.74ng/ml)increased in that order,and the differences were all statistically significant(F=14.754,11.404,all P<0.05).Multifactorial Logistic regression analysis showed that USP14,GRB2,TC,TG,LDL-C and HbA1c were all influencing factors affecting the occurrence of LEAD in patients with T2DM(Wald χ2=11.618～41.458,all P<0.05).The results of the ROC curve showed that the area under the curve(AUC)of the combined diagnosis of LEAD by serum USP14 and GRB2 was greater than that of USP14 and GRB2 diagnosed alone(Z=2.706,3.124,all P<0.05).Conclusion USP14 and GRB2 were both highly expressed in the serum of patients with elderly T2DM combined with LEAD,which increased with the increase of LEAD grade,and can be used as serum markers for the diagnosis of elderly T2DM combined with LEAD,and the efficacy of the combined detection of the two is better.

Objective·To investigate the role of interleukin-1β(IL-1β)in predicting the severity of oral and maxillofacial space infection(OMSI),and to explore the key mechanisms regulating IL-1β release,the critical immune cell subpopulations involved,and the intercellular communication networks among immune cells in OMSI patients.Methods·A total of 62 OMSI patients admitted to the Department of Oral Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January to November 2023 were enrolled,including 20 patients with moderate infection,21 with severe infection,and 21 with extremely severe infection.Logistic regression analysis was performed to identify risk factors for extremely severe infection,and receiver operating characteristic(ROC)curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection.Peripheral blood mononuclear cells(PBMCs)from 2 patients in each group(moderate,severe and extremely severe)and 2 healthy controls(GSE224198)were analyzed using single-cell RNA sequencing(scRNA-seq)to identify key pro-inflammatory cell subtypes and genes,and to examine their changing trends with increasing infection severity.Cell-cell communication was assessed using CellChat.Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were used to validate inflammasome activation levels in PBMCs.Results·Compared with patients with moderate and severe infections,levels of procalcitonin(PCT)(P<0.05)and IL-1β(P<0.05)were significantly elevated in patients with extremely severe infection.Logistic regression identified IL-1β as an independent risk factor for extremely severe infection(OR=1.814,95%CI 1.256?2.621,P=0.002).The area under the ROC curve(AUC)for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943.scRNA-seq revealed continuous upregulation of NLRP3(NOD-like receptor family pyrin domain-containing 3)and IL1B gene expression in monocytes as infection severity increased,with intermediate monocytes being the main IL1B-expressing cell subtype.IL-1Β-IL-1R signaling,C-C motif chemokine ligand(CCL)and intercellular adhesion molecule(ICAM)signaling were significantly enhanced in monocytes.Macrophage migration inhibitory factor(MIF)signaling between T cells and monocytes also increased notably.With infection progression,the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily,and the protein levels of NLRP3,caspase-1 p20,apoptosis-associated speck-like protein containing a CARD(ASC)and IL-1β were persistently elevated.Conclusion·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI.NLRP3 inflammasome activation is observed in PBMCs of OMSI patients.The elevation of IL-1β is closely associated with intermediate monocytes.Monocyte-mediated IL-1Β-IL-1R,CCL and ICAM signaling pathways,along with T cell-mediated MIF signaling pathways,collectively promote the inflammatory response.

Objective:To investigate the neuroprotective effect of non-invasive vagus nerve stimulation(nVNS)on traumatic brain injury(TBI).Methods:Male SD rats were used to prepare controlled cortical impact(CCI)rat mod-el.nVNS treatment was performed.The motor function of rats was detected by beam walking test.The water content of rats was evaluated by the dry-wet ratio of rat brain tissue.The content of lactate dehydrogenase(LDH)in cerebrospinal fluid was detected by commercial kit.The expression of bain-derived neurotrophic factor(BDNF)and nerve growth fac-tor(NGF)mRNA in rat cortex was detected by RT-qPCR.Results:After nVNS stimulation,CCI rats significantly im-proved the neurological function deficit,improved the motor ability,decreased the cerebral water content,decreased the level of LDH in cerebrospinal fluid,and upregulated the expression of BDNF and NGF mRNA in cortex.Conclusion:nVNS has a neuroprotective effect on TBI rats,and its mechanism may be related to the increased expression of BDNF and NGF.

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective To explore the effects and mechanisms of Changpu Yujin Tang(CPYJT)on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/Gasdermin D(NLRP3/Caspase-1/GSDMD)signaling pathway-mediated neuroinflammation in rats with Tourette syndrome(TS).Methods SPF-grade male SD rats were randomly divided into the Control and TS groups.After successful modeling in the TS group,the rats were randomly divided into the Model,Tiapride,and CPYJT groups,and were treated with the corresponding drugs for 4 weeks.After the treatment,the rats' behavior was scored,H & E staining was used to observe pathological changes in the striatum,ELISA was used to measure the content of IL-1β and IL-18,RT-qPCR was used to detect the expression of NLRP3 and ASC mRNA,and Western blot was used to detect the expression of NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins.Results Compared with the Control group,the Model group showed increased scores of stereotyped and motor behaviors(P＜0.01),pathological changes in the striatal tissue,increased content of IL-1β and IL-18(P＜0.01),and upregulated expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Compared with the Model group,the Tiapride group and the CPYJT group showed decreased scores of stereotyped and motor behaviors(P＜0.01),improved pathological damage in the striatal tissue,reduced content of IL-1β and IL-18(P＜0.01),and inhibited expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Conclusion The therapeutic effect of CPYJT on TS is related to the inhibition of the neuroinflammatory response mediated by the NLRP3/Caspase-1/GSDMD signaling pathway.

Objective:To investigate the ability to diagnose, treat and manage kidney disease in Shanghai community health service centers.Methods:This was a cross-sectional survey. An online questionnaire survey was conducted in November 2023 among 248 Shanghai community health service centers and 2 140 general practitioners in Shanghai. The main topics of the institutional research were the kidney disease-related inspection items that medical institutions could carry out, the kidney disease diagnosis and treatment drugs, the kidney disease grass-roots management training, the opening of kidney disease clinics and the establishment of kidney disease standard diagnosis and treatment records. The main topics of the survey of general practitioners were general information, standardized diagnosis and management measures of kidney disease, knowledge based on the diagnosis and treatment guidelines of chronic kidney disease, and difficulties in standardized management of kidney disease.Results:Among the laboratory examination items in Shanghai community health service centers, the rates of routine urine (99.60%, 247 centers), renal function (95.16%, 236 centers) and urinary microalbumin (89.11%, 229 centers) were high. Among the imaging examinations, B-ultrasound of urinary system had the highest rate (92.34%, 229 centers). The preparation rate of kidney disease drugs varied widely among the centers, and the preparation rate of Chinese drugs such as Jinshuibao, nephritis Kangfu tablet and Shenshuaining was more than 90%. Sixty-six (26.61%) community health service centers had established kidney disease clinics. The overall accuracy rate of community general practitioners was 63.81% (13 656/21 400), of which the accuracy rate for diagnosis and screening method, referral indication and emergency dialysis indication was more than 85%, but the accuracy rate for drug treatment and careful medication was low at 28.93% (1 238/4 280) and 33.22% (711/2 140), respectively. There was a willingness for Community general practitioners to provide all aspects of life guidance for patients with kidney disease, but for patients with end-stage renal disease replacement therapy, there was a preference for this to be provided by the appropriate specialist.Conclusions:The community health service centers in Shanghai has already had the basic conditions for the management of kidney disease in terms of basic examination and testing equipment, drugs, etc. The community general practitioners have a certain knowledge of kidney disease, and the drug treatment needs to be strengthened.

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.