Rabies is a zoonotic disease that poses a global public health threat.Rabies virus(RABV)is neurotropic and can cause severe neurological disorders and behavioral abnormalities in host,with a fatality rate nearly 100％.In order to identify the key genes for RABV affecting neuronal cell function,we established and analyzed the mRNA expression profile of Neuro-2a(N2a)cell in-fected with challenge virus standard(CVS)-11 by RNA sequencing(RNA-seq).Biological func-tions of differentially expressed genes(DEGs)were determined by GO and KEGG enrichment a-nalysis.The results showed that there were 415 differentially expressed genes in N2a infected with CVS-11 strain,of which 89 were up-regulated and 326 were down-regulated.These genes were re-lated to a variety of biological processes,such as axon guidance pathway,cholesterol metabolism pathway,nitrogen metabolism pathway,and glycosphingolipid biosynthesis pathway,many of them have been shown to be closely associated with RABV infection.A total of 12 DEGs related to axon conduction,antigen processing and presentation pathways were selected and detected by real-time PCR,and their expression trends were consistent with the RNA-seq results.The genomic tran-scriptomic data on N2a cell under RABV infection will provide new clues for probing the mecha-nisms of RABV infection and transmission in the nervous system in the future.

With the intensification of the global population aging trend, the problem of obesity in the elderly has become increasingly prominent, which is closely related to the increase of the risk of various diseases and mortality.However, there are still many challenges in dealing with this problem.First, body mass index, waist circumference and waist-to-hip ratio, which are widely used for weight assessment, have certain limitations.Secondly, the screening and management of weight-related complications should be strengthened, and management concepts should be established to improve physical function and enhance health outcomes.At the same time, attention should be paid to the management of body composition, especially the monitoring and management of sarcopenia and sarcopenic obesity, which are common in the elderly.In the management of obesity in the elderly, it is necessary to consider the overall health status of patients, living habits and other factors, and formulate lifestyle intervention measures in line with their physiological characteristics.If lifestyle interventions do not work well, the drug regimen should consider the combined effects of cardiovascular, renal, and metabolic syndrome.With the continuous advancement of artificial intelligence technology, weight management in the elderly is expected to improve health outcomes by building risk prediction models through machine learning and enabling precise personalized treatment.This will provide a new strategy and method for solving the problem of obesity in the elderly.

Objective To explore the mechanism of acute liver injury induced by Cortex dictamni through network pharmacology and in vivo experiment in animal.Methods The chemical constituents and targets of Cortex dictamni were retrieved from TCMSP,TCMIP and SwissTargetPrediction databases,and the related targets of liver injury diseases were identified through GeneCards and CTD databases.The protein interaction network of the intersection targets was analyzed by STRING database and the core targets were selected.The GO function and KEGG pathway enrichment analysis were completed by DAVID database,and the multi-level association network diagram of"drug-component-target"was constructed by Cytoscape software.In the animal study,Cortex dictamni was administered to mice at a dosage of 92.7 g/(kg·d)via intragastric administration,and the biological samples were collected after 7 days.The pathological changes of liver were observed by hematoxylin-eosin(HE),Masson and Oil Red O staining.The expression levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in serum,as well as malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin(IL)-1β in liver tissues,were quantified using enzyme-linked immunosorbent assay(ELISA).The expressions of protein kinase B1(AKT1),IL-6,TNF-α,tumor protein p53(TP53),cystatin 3(CASP3),and IL-1β mRNA in liver tissues were determined using real-time quantitative reverse transcription PCR(qRT-PCR).Molecular docking was employed to verify the binding affinity of potentially toxic components to their respective targets.Results A total of 14 chemical constituents,244 predicted targets and 202 intersection targets with liver injury were obtained.The GO biological process analysis mainly involved positive regulation of gene expression,negative regulation of apoptosis process.KEGG pathway enrichment analysis mainly included cancer pathway and PI3K-Akt,TNF,IL-17 signaling pathways.The pathological sections revealed severe hemorrhage,a considerable amount of hepatocyte necrosis,nuclear fragmentation or dissolution in the liver tissues of mouse with HE staining after the administration of Cortex dictamni.Masson staining showed evident fibrosis in the liver tissues,while Oil Red O staining indicated a substantial production of lipid droplets.Compared with the control group,the ELISA results demonstrated a significant increase in serum AST,ALT,ALP,LDH levels,as well as hepatic MDA,TNF-α,and IL-1β levels(P<0.05),and a decrease in hepatic SOD levels(P<0.05)in the treated group.The qRT-PCR results indicated a significant elevation in the expression levels of relevant mRNAs in the liver tissues of the treated mice(P<0.05).Molecular docking showed that the potentially toxic components of obacunone,dictamnine and fraxinellon had good binding affinity to AKT1,IL-6,TNF-α,TP53,CASP3 and IL-1β.Conclusion Obacunone,dictamnine,fraxinellon,and limonin might be the potential toxic components of acute liver injury induced by Cortex dictamni in mice.Cortex dictamni could act on the liver by changing the expressions of AKT1,IL-6,TNF-α,TP53,CASP3,IL-1β and other proteins,affecting energy metabolism,cell differentiation,inflammation,oxidative stress and immunity,leading to liver injury.

Dictamni cortex is the root bark of Rutaceae plants.It is the main medicinal part and the key drug of 'Zhuhuang Fengbi'.It has the effects of clearing heat and detoxifying,dispelling wind and drying dampness,and relieving itching.Dictamni cortex mainly contains 228 chemical components such as alkaloids,sesquiterpenes,limonoids,fatty acids,volatile oils,flavonoids,steroids,etw.Its pharmacological activities in vivo and in vitro include antibacterial activity,anti-inflammatory activity,hepatoprotective activity,cardiovascular protection activity,insecticidal activity,anticancer activity,anti-allergic activity,and improvement of gastrointestinal activity.It has been reported that Dictamni cortex also has potential hepatotoxicity,among which dictamnine,fraxinellone and limonin compounds are potential hepatotoxic components.In this paper,the chemical constituents,pharmacological effects and toxicity of Dictamni cortex are reviewed by consulting domestic and foreign literature,to provide theoretical support for the clinical rational application and related product development of Dictamni cortex.

Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.

Objective:To investigate the application of digital scanning combined with reverse engineering technology in the teaching of full crown preparation.Methods:A total of 30 undergraduate students in the fifth grade of stomatology were selected from Shantou University Medical College and were divided into experimental group and control group using a random number table. Two resin teeth were distributed to each student and were placed on dental head simulators to perform full crown preparation. The students in the control group received teaching with analogies of experience, and those in the experimental group received teaching with digital scanning, i.e., full crown preparation for the second time after digital scanning for the first time of full crown preparation. The score was determined based on China Stomatological Association Standards: Guideline for the tooth preparation of dental ceramic crowns (T/CHSA 008—2023), with a total score of 100 points. SAS9.4 software was used for the two-independent-samples t test and the paired t-test, and the Kendall W concordance coefficient was used to investigate the consistency of evaluators. Results:There were significant changes after teaching in the preparation scores of the right maxillary central incisor (76.27 pre-demonstration vs. 84.70 post-demonstration, P<0.001) and the right maxillary first molar (72.10 pre-demonstration vs. 82.37 post-demonstration, P<0.001). Compared with the control group, the experimental group had a significant increase in the mean preparation score of the right maxillary first molar (14.00 vs. 6.53, t=2.64, P=0.014). In the experimental group, there were significant increases in the preparation scores of the right maxillary first molar for the occlusal surface (15.40 pre-demonstration vs. 19.33 post-demonstration, P<0.001), the buccolingual surface (18.13 pre-demonstration vs. 20.87 post-demonstration, P=0.016), and the proximal surface (12.40 pre-demonstration vs. 14.07 post-demonstration, P=0.004), as well as significant increases in the scores of the convergence angles of the buccolingual surface (2.80 pre-demonstration vs. 4.07 post-demonstration, P=0.004) and the proximal surface (3.47 pre-demonstration vs. 4.47 post-demonstration, P=0.008). Conclusions:Application of digital teaching for difficult crown preparation of posterior teeth can effectively improve the quality of crown preparation among students, standardize the teaching process of crown preparation, and increase the precision of crown preparation, thereby laying a foundation for promoting uniformity in talent cultivation for dental prosthodontics.

Objective To investigate the status quo of pain catastrophizing(PC)in the patients with di-abetic peripheral neuropathic pain(DPNP),and to analyze the influencing factors to provide reference for for-mulating clinical preventive intervention strategies.Methods A total of 206 patients with DPNP admitted and treated in the People's Hospital of Guangxi Zhuang Autonomous Region were selected as the research sub-jects by convenience sampling method.The general data questionnaire,Numerical Rating Scale(NRS),Pain Catastrophizing scale(PCS),Perceived Social Support Scale(PSSS)and diabetes distress scale(DDS)were used to conduct the investigation.Results The incidence rate of PC in 206 cases of DPNP patients was 44.66％(92/206),and the total score of PCS was(30.10±5.16)points.The results of multiple linear regres-sion analysis showed that the gender,duration of diabetes(≥10 years),multiple drug use,number of compli-cations(＞5),NRS score,PSSS score and scores of DDS dimensions were the main influencing factors of PC(all P＜0.05),which could explain 92.3％of the total variation of PC.Conclusion The PC incidence rate in the patients with DPNP is high.Clinical healthcare workers should pay attention to the evaluation of PC in these patients,and formulate the scientific and effective targeted intervention measures according to the main influen-cing factors to help the patients to reduce the pain burden in order to reduce the level of PC.

Objective:Adverse cardiovascular events are the leading cause of death in peritoneal dialysis patients.Identifying indicators that can predict adverse cardiovascular events in these patients is crucial for prognosis.This study aims to assess the value of dual-specificity phosphatase 6(DUSP6)in peripheral blood mononuclear cells as a predictor of adverse cardiovascular events after peritoneal dialysis in diabetic nephropathy patients. Methods:A total of 124 diabetic nephropathy patients underwent peritoneal dialysis treatment at the Department of Nephrology of the First Affiliated Hospital of Hebei North University from June to September 2022 were selected as study subjects.The levels of DUSP6 in peripheral blood mononuclear cells were determined using Western blotting.Patients were categorized into high-level and low-level DUSP6 groups based on the median DUSP6 level.Differences in body mass index,serum albumin,high-sensitivity C-reactive protein,and dialysis duration were compared between the 2 groups.Pearson,Spearman,and multiple linear regression analyses were performed to examine factors related to DUSP6.Patients were followed up to monitor the occurrence of adverse cardiovascular events,and risk factors for adverse cardiovascular events after peritoneal dialysis were analyzed using Kaplan-Meier and Cox regression. Results:By the end of the follow-up,33(26.61%)patients had experienced at least one adverse cardiovascular event.The high-level DUSP6 group had higher body mass index,longer dialysis duration,and higher high-sensitivity C-reactive protein,but lower serum albumin levels compared to the low-level DUSP6 group(all P<0.05).DUSP6 was negatively correlated with serum albumin levels(r=-0.271,P=0.002)and positively correlated with dialysis duration(rs=0.406,P<0.001)and high-sensitivity C-reactive protein(rs=0.367,P<0.001).Multiple linear regression analysis revealed that dialysis duration and high-sensitivity C-reactive protein were independently correlated with DUSP6 levels(both P<0.05).The cumulative incidence of adverse cardiovascular events was higher in the high-level DUSP6 group than in the low-level DUSP6 group(46.67%vs 7.81%,P<0.001).Cox regression analysis indicated that low serum albumin levels(HR=0.836,95%CI 0.778 to 0.899),high high-sensitivity C-reactive protein(HR=1.409,95%CI 1.208 to 1.644),and high DUSP6(HR=6.631,95%CI 2.352 to 18.693)were independent risk factors for adverse cardiovascular events in peritoneal dialysis patients. Conclusion:Dialysis duration and high-sensitivity C-reactive protein are independently associated with DUSP6 levels in peripheral blood mononuclear cells of diabetic nephropathy patients undergoing peritoneal dialysis.High DUSP6 levels indicate a higher risk of adverse cardiovascular events.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.