Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

The efficacy of root canal therapy, as a core intervention for endodontic and periapical diseases, is highly dependent on the effectiveness of antimicrobial drugs. Although traditional drugs such as calcium hydroxide, chlorhexidine, and antibiotic pastes commonly used in the clinic play a role in preventing and controlling infections, they have obvious limitations. These drugs influence the mechanical properties of dentin, insufficiently solubilize necrotic tissues, and are susceptible to bacterial resistance, which makes achieving the desired effectiveness and safety difficult. Traditional macromolecular root canal drugs also face the challenge of the complexity of the root canal system. With the rapid development of material science in recent years, new antimicrobial agents have emerged. Metallic nanomaterials such as silver nanoparticles and zinc oxide nanoparticles are widely used in the medical field due to their unique physicochemical properties and superior antimicrobial properties. Chitosan nanoparticles have superior biosafety, calcium hydroxide nanoparticles compensate for the limitations of traditional calcium hydroxide formulations, and quaternary ammonium polyethyleneimine nanoparticles can confer antimicrobial properties to existing oral materials. Novel antimicrobial nanoparticles using nano-delivery systems, such as mesoporous calcium silicate and mesoporous silica, carry antimicrobial molecules with significant advantages in terms of anti-biofilm, biosafety, and promotion of tissue repair. Further, these agents reduce drug resistance, which improves prospects for application compared to traditional root canal disinfection drugs. The breakthrough of nanotechnology provides a novel direction for the innovation of root canal treatment drugs. Therefore, this paper reviews the research progress of nano-antimicrobial materials in root canal therapy.

Objective: To investigate the recreational use status of electronic products among high school students in Shanxi Province and the influencing factors for excessive use, so as to provide insights into the promotion of rational use of electronic products among high school students. Methods: The high school students from 117 schools in Shanxi Province were selected using the stratified random sampling method, and basic information, lifestyle behaviors and recreational use of electronic products were collected using questionnaire surveys. The prevalence of excessive recreational use of electronic products was analyzed, and the factors affecting excessive recreational use of electronic products among high school students were analyzed using a multivariable logistic regression model. Results: A total of 13 804 valid questionnaires were recoverd, with an effective rate of 98.32%. There were 6 634 males (48.06%) and 7 170 females (51.94%), with a median age of 17.00 (interquartile range, 1.00) years. There were 7 024 students in Grade One (50.88%) and 6 780 students in Grade Two (49.12%). The prevalence of recreational use of electronic products was 14.18% (1 958 cases). Multivariable logistic regression analysis showed that males (OR=1.461, 95%CI: 1.325-1.611), students in Grade Two (OR=1.720, 95%CI: 1.559-1.897), students whose parents had below high school education (OR=1.391, 95%CI: 1.156-1.674), students without parental support (OR=1.281, 95%CI: 1.078-1.523), students not living on campus (OR=1.142, 95%CI: 1.026-1.271), students without myopia (OR=1.121, 95%CI: 1.008-1.248), and students with sufficient sleep (OR=1.162, 95%CI: 1.054-1.281) had a higher risk of excessive recreational use of electronic products. Conclusion The prevalence of excessive recreational use of electronic products among high school students in Shanxi Province was relatively high, which was related to gender, grade, parental education, parental attitudes, boarding status, myopia and sleep quality.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

Gastric cancer is one of the most common malignant tumors of the digestive system.Most gastric cancer patients are already in advanced stage when initially diagnosed.Advanced gastric cancer has a poor prognosis and has received limited benefit from chemotherapy-based therapies.In the recent years,with the development of biomolecular technologies,more and more researches have set their focus on the search for key molecules that affect the progression of gastric cancer,prognostic indicators,and therapeutic targets.Claudin-18.2 is a promising novel tumor therapeutic target which brings new hope for targeted therapy for gastric cancer.Various types of Claudin-18.2-targeting drugs have been developed,including monoclonal antibody,bispecific antibody(BsAb),antibody-drug conjugate(ADC),chimeric antigen receptor T cell(CAR-T),and so on.At present,several clinical trials have been carried out and the results are encouraging.This review summarizes the progress in clinical trials of Claudin-18.2 targeted therapy,in the hope to provide reference for improving the prognosis of patients with advanced gastric cancer.

Modified electroconvulsive therapy(MECT)has a good therapeutic effect on major depressive disorder(MDD),but its mechanism of action is still unclear.In recent years,accumulated studies have confirmed the effects of MECT on brain structure and function using neuroimaging techniques and large datasets obtained through global collaborations and the conclusions are becoming increasingly consistent.For example,there is an increase in gray matter volume in specific brain regions such as the hippocampus and amygdala,an increase in white matter microstructural integrity and normalization of brain functional connections associated with MDD,such as the hippocampus-amygdala-subgenual anterior cingulate cortex-prefrontal cortex network,hippocampus-thalamus-temporal cortex-parietal cortex network,etc.However,the relationship between these changes and the mechanism of MECT action still needs further investigation.This review provides an overview of the research progress on the structural and functional changes of the brain by MECT to provide methodological support and theoretical basis for its better application in clinical diagnosis and treatment.

Objective To explore the clinical features,diagnostic methods,and treatment strategies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)encephalitis confirmed through cerebrospinal fluid(CSF)analysis.Methods The clinical data of patients diagnosed with SARS-CoV-2 encephalitis through CSF analysis in the Neurology Intensive Care Unit of the First Affiliated Hospital of Nanchang University from March 2022 to March 2023 were collected.Additionally,the relevant literature published in both domestic and international databases was analyzed and synthesized.Results The main neurological manifestations of five cases included decreased consciousness(5/5),psychiatric disorder(2/5),seizures(2/5),quadriplegia(1/5),and headaches(1/5).Two cases had abnormal brain magnetic resonance imaging(MRI)changes,involving the temporal lobe,insular lobe,thalamus,hippocampus,and pons.Additionally,CSF analysis showed mildly elevated protein levels in two cases.Next-generation sequencing(NGS)of the CSF identified SARS-CoV-2 in all five cases(sequence:41-1620),and human herpesvirus 1 in one case(sequence:21).The treatment regimen for all cases included antiviral therapy,three were additionally treated with glucocorticoids and one received immunoglobulin therapy.All cases achieved a favorable outcome(mRS:0-2).Conclusion SARS-CoV-2 has the potential to induce encephalitis/meningitis due to its neurotropic nature.The consideration of this condition is warranted in patients with relevant epidemiological history and symptoms related to the central nervous system.CSF NGS serves as a valuable tool for early diagnosis,while active antiviral therapy and immunotherapy may improve patient outcomes.

Objective:To analyze clinical, immunopathological, therapeutic, and prognostic features of epidermolysis bullosa acquisita (EBA) .Methods:A retrospective study was conducted on patients with confirmed EBA at the Department of Dermatology, West China Hospital, Sichuan University from January 1, 2015 to July 30, 2022. Their clinical, immunopathological, therapeutic and prognostic features were analyzed. The autoimmune bullous skin disorder intensity score (ABSIS) was used to assess the severity of lesions in patients with EBA, and the visual analogue scale (VAS) to assess itch intensity. Descriptive statistical analysis was primarily carried out, and the correlation between disease severity scores and itch scores was analyzed using Pearson correlation analysis.Results:A total of 13 patients with EBA were included, including 9 males and 4 females, with the age at the clinic visit being 49.0 ± 20.6 years and ABSIS scores being 24.2 ± 10.7 points. One patient was diagnosed with classical EBA, while the remaining 12 patients with inflammatory EBA. Mucosal involvement was observed in 6 cases, whose oral mucosae were all affected. All patients had itching to varying degrees, with VAS scores of 5.6 ± 2.2 points; 9 of the 12 inflammatory EBA patients had VAS scores of ≥ 5 points, whereas 1 classical EBA patient had a VAS score of 2 points; there was no significant correlation between the ABSIS scores and VAS scores ( r = -0.02, P > 0.05). Histopathological examination showed subepidermal cleavages or blister formation and varying degrees of perivascular inflammatory cell infiltration in the superficial dermis of patients with inflammatory EBA. Direct immunofluorescence assay demonstrated linear IgG deposits along the basement membrane zone in all 13 patients, including 12 with concomitant linear C3 deposits in the basement membrane zone, 5 with linear IgA deposits, and 2 with IgM deposits. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side of the salt-split skin in the 13 patients. An elevated eosinophil count in the peripheral blood was observed in 1 out of 11 patients, while increased total IgE levels were noted in 3 out of 9 patients. Among the 13 EBA patients, 11 were treated with systemic glucocorticoids (equivalent to 10 - 100 mg/d of prednisone), and the other 2 were treated with compound glycyrrhizin tablets, sulfasalazine, hydroxychloroquine sulfate, and minocycline hydrochloride alone or in combination. During the follow-up period of 34.0 (27.5, 66.0) months in the 13 patients, 8 achieved complete remission after drug withdrawal, 2 achieved complete remission on therapy, 1 achieved partial remission on minimal therapy, and 2 presented with uncontrolled condition. The time to complete remission off/on therapy was 6.0 (3.8, 17.5) months. Conclusions:The inflammatory phenotype seems to be relatively common in EBA patients, with itching to varying degrees, and oral mucosa was the most commonly involved mucosa in those with mucosal damage. After treatment with systemic glucocorticoids alone or in combination with immunomodulators, most patients could achieve complete remission.

Objective:To explore the clinical application pathway of the CT generative adversarial networks (CTGANs) algorithm in mandibular reconstruction surgery, aiming to provide a valuable reference for this procedure.Methods:A clinical exploratory study was conducted, 27 patients who visited the Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University between January 2022 and January 2024 and required mandibular reconstruction were selected. The cohort included 16 males and 11 females, with the age of (46.6±11.5) years; among them, 7 cases involved mandibular defects crossing the midline. The CTGANs generator produced 100 images, and the mean squared error (MSE) was calculated for differences between any two generated images. Preoperative cone-beam CT data from 5 patients were used to construct a labeled test database, divided into groups: normal maxilla, normal mandible, diseased mandible, and noise (each group containing 70 cross-sectional images). The CTGANs discriminator was used to evaluate the loss values for each group, and one-way ANOVA and intergroup comparisons were performed. Using the self-developed KuYe multioutcome-option-network generation system (KMG) software, the three-dimensional (3D) completion area of the mandible under cone-beam CT was defined for the 27 patients. The CTGANs algorithm was applied to obtain a reference model for the mandible. Virtual surgery was then performed, utilizing the fibular segment to reconstruct the mandible and design the surgical expectation model. The second-generation combined bone-cutting and prebent reconstruction plate positioning method was used to design and 3D print surgical guides, which were subsequently applied in mandibular reconstruction surgery for the 27 patients. Postoperative cone-beam CT was used to compare the morphology of the reconstructed mandible with the surgical expectation model and the mandibular reference model to assess the three-dimensional deviation.Results:The MSE for the CTGANs generator was 2 411.9±833.6 (95% CI: 2 388.7-2 435.1). No significant difference in loss values was found between the normal mandible and diseased mandible groups ( P>0.05), while both groups demonstrated significantly lower loss values than the maxilla and noise groups ( P<0.001). All 27 patients successfully obtained mandibular reference models and surgical expectation models. In total, 14 162 negative deviation points and 15 346 positive deviation points were observed when comparing the reconstructed mandible morphology with the surgical expectation model, with mean deviations of -1.32 mm (95% CI:-1.33- -1.31 mm) and 1.90 mm (95% CI: 1.04-1.06 mm), respectively. Conclusions:The CTGANs algorithm is capable of generating diverse mandibular reference models that reflect the natural anatomical characteristics of the mandible and closely match individual patient morphology, thereby facilitating the design of surgical expectation models. This method shows promise for application in patients with mandibular defects crossing the midline.