Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.

Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

BACKGROUND:Coptis chinensis can clear heat,dry dampness,relieve fire,and detoxify.Coptis chinensis and its components have a significant protective effect on cerebral ischemia.The action mechanism of anti-cerebral ischemia of Coptidis Rhizoma Alkaloids was explored based on network pharmacology and transcriptome sequencing. OBJECTIVE:Based on the study of the protective effects of Coptidis Rhizoma Alkaloids on cerebral ischemia of rats,the action mechanism of Coptidis Rhizoma Alkaloids intervention in cerebral ischemia was investigated by using network pharmacology and transcriptome sequencing technology. METHODS:The SD rats were randomly divided into sham operation group,ischemia/reperfusion group,positive drug group,and Coptidis Rhizoma Alkaloids group.The ischemia/reperfusion model of middle cerebral artery occlusion was prepared by modified thread method in the latter three groups.No thread was inserted and the other operations were the same in the sham operation group.TTC staining,Longa 5 neurological deficient score,hematoxylin and eosin staining,and Nissl staining were used to evaluate the protective effect of Coptidis Rhizoma Alkaloids on ischemia/reperfusion model rats.Transcriptome sequencing was performed on the brain tissues of rats in sham operation group,ischemia/reperfusion group,and Coptidis Rhizoma Alkaloids group.Differentially expressed genes,gene Ontology analysis,Kyoto encyclopedia of genes and genomes analysis,and Correlation Analysis of Transcriptomics and Network Pharmacology were used to elucidate the effect of Coptidis Rhizoma Alkaloids on cerebral ischemia.Finally,ELISA and immunofluorescence staining were used to verify the key targets of Coptidis Rhizoma Alkaloids in the intervention of cerebral ischemia. RESULTS AND CONCLUSION:(1)Coptidis Rhizoma Alkaloids treatment decreased the Longa 5 neurological deficit scores and cerebral infarction area of ischemia/reperfusion model rats,increased the number of neurons and Nissl bodies.(2)Differentially expressed gene after Coptidis Rhizoma Alkaloids treatment analyzed by functional enrichment analysis of gene ontology includes biological processes such as inflammatory reaction and positive regulation of mitogen-activated protein kinase cascade.The enrichment analysis of Kyoto gene and genome encyclopedia analysis pathway mainly involves interleukin-17 signaling pathway,neuroactive ligand-receptor interaction,cyclic adenosine-3′,5′-mconophosphate signaling pathway and so on.(3)Analysis of transcriptomics showed that the main genes regulated by Coptidis Rhizoma Alkaloids were prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(4)Network pharmacology analysis revealed that nine components in Coptidis Rhizoma Alkaloids may exert their effects by associating with 87 targets related to prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(5)ELISA and immunofluorescence staining results further confirmed that Coptidis Rhizoma Alkaloids regulated the expression of prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(6)It is concluded that Coptidis Rhizoma Alkaloids treatment can significantly improve the injury in ischemia/reperfusion model rats,possibly by regulating prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.

Background The adverse effects of long working hours, shift rotation, and job stress on the physical and mental health of occupational populations require urgent attention. Objective To investigate and compare the positive rates of WMSDs between different industries, analyze the exposure status of long working hours, shift rotation, and job stress among key occupational groups, and evaluate the impacts of these factors on WMSDs in the manufacturing and service industries. Methods The study subjects were derived from key occupational populations in Yunnan Province, recruited by the Chinese National Occupational Health Literacy Monitoring Survey in 2022. A cross-sectional design was used for this survey. The key occupational populations were recruited from the secondary industry (manufacturing industry, metal mining and beneficiation industry, and non-metal mining and beneficiation industry) by stratified random sampling and from the tertiary industry (medical and healthcare industry, education industry, environmental sanitation industry, transportation industry, and express/takeaway delivery industry) by proportional probability sampling, and 12014 front-line workers were finally included as survey participants. General information, work-related factors (shift rotation, weekly working hours, job stress, etc.) and WMSDs assessment results were obtained through a web-based self-reported questionnaire, and the associations of long working hours, shift rotation, and job stress with WMSDs were analyzed using χ² test and logistic regression. Results The average positive rate of WMSDs among the key occupational groups in Yunnan Province was 77.2%. The positive rate of WMSDs in the secondary industry group was 69.4%, while it was 81.6% in the tertiary industry group, with a statistically significant difference (P<0.001). Among the eight surveyed sectors, the education sector had the highest positive rate of WMSDs (94.2%). The single-site WMSDs mainly involved the neck, shoulders, and low back. In the secondary industry, WMSDs was reported in 1−2 body parts, while in the tertiary industry, WMSDs was mainly reported in multiple (≥5) body parts. Long working hours (OR: 1.119, 1.165, 1.163, respectively), shift rotation (OR: 1.094, 1.199, 1.230, respectively), and job stress (OR: 1.795, 1.854, 2.006, respectively) were risk factors for WMSDs in the neck, shoulder, or low back, and all three were also risk factors for multi-site WMSDs. Moreover, as the number of involved body parts increased, the effects of long working hours and job stress became more pronounced. For 1-2, 3-4, and 5 or more body parts compared to no pain reported, their OR values were 0.971 (95%CI: 0.871, 1.082), 1.133 (95%CI: 1.004, 1.279), and 1.285 (95%CI: 1.155, 1.429) for long working hours, respectively, and the OR values were 1.009 (95%CI: 0.878, 1.160), 1.360 (95%CI: 1.174, 1.575), and 2.797 (95%CI: 2.471, 3.166) for job stress, respectively. Conclusion The positive rate of WMSDs is higher in the tertiary industry than that in the secondary industry among the key occupational groups in Yunnan Province. Long working hours, rotating shift work, and job stress could significantly increase the risk of WMSDs.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

AIM: To explore the clinical effect of atomization fumigation of self-formulated Zhibai Dihuang Decoction in the treatment of dry eye syndrome after diabetic cataract(DC)surgery with Yin deficiency and dry heat pattern.METHODS: This study is a prospective controlled study. From February 2022 to June 2024, 80 patients(97 eyes)with Yin deficiency and dry heat type DC postoperative dry eye who met the inclusion and exclusion criteria in our hospital were selected. They were randomly divided into an observation group of 40 cases(49 eyes)and a control group of 40 cases(48 eyes)using a random number table method. The control group was treated with sodium hyaluronate eye drops, while the observation group was treated with a combination of atomization fumigation of self-formulated Zhibai Dihuang Decoction on the basis of the control group. The clinical efficacy, subjective symptom scores, visual indicators [tear film break-up time(BUT), Schirmer's test(SIt), corneal fluorescein staining(FL)], tear inflammatory factors [interleukin-1 β(IL-1β), macrophage chemoattractant protein-1(MCP-1), lipid peroxidation(LPO)], and safety between the two groups.RESULTS: The improvement rate of the observation group was 96%, which was higher than that of the control group(79%, P<0.05). After treatment, the 4 subjective symptom scores in both groups were lower than those before treatment, and the subjective symptom scores of ocular dryness, foreign body sensation, burning sensation, and photophobia in the observation group were lower than those in the control group(all P<0.05). After treatment, BUT and SIt in both groups were higher than those before treatment, and FL was lower than that before treatment, with the observation group having higher BUT and SIt and lower FL than the control group(all P<0.05). After treatment, IL-1β, MCP-1, and LPO in both groups were lower than those before treatment, and the observation group had lower levels of IL-1β, MCP-1, and LPO than the control group(all P<0.05). No adverse reactions were observed in either group.CONCLUSION: The atomization and fumigation of self-formulated Zhibai Dihuang Decoction is significantly effective in treating dry eye syndrome after DC surgery with Yin deficiency and dry heat pattern. It can effectively reduce subjective symptom scores, improve visual indicators and tear inflammatory factors, and has a high level of safety.

Objective To analyze the epidemiological characteristics of varicella epidemic in kindergartens and schools in Jinshan District of Shanghai from 2015 to 2022，and to understand the varicella antibody level in students aged under 30 years old，to provide evidence for developing control and prevention strategies． Methods Data of varicella epidemic situation at schools and kindergartens and varicella cases were analyzed by descriptive methods．Collect serum from healthy individuals under 30 years old to detect IgG antibody levels of varicella zoster virus.Results From 2015 to 2022, a total of 91 cases of chickenpox were reported in kindergartens and schools in Jinshan District, Shanghai, involving 412 cases.The peak incidence occurs from October to December，kindergarten childcare and primary school children were at high risk of varicella .The incidence of fever(χ²=12.93，P＜0.001) and moderate to severe rash(χ²=28.79，P＜0.001) in patients with varicella vaccination was lower than that in patients without varicella vaccination. A total of 227 people were surveyed，the positive rate of varicella antibody was 62. 56%，the geometric mean titer ( GMT) was 2.22±0.68（165.96mIU/ml）．The difference of GMT(F=6.87，P＜0.001) and positive rate (χ²=29.14，P＜0.001)of antibody in different age groups was statistically significant，the positive rate was lowest in the age group of 1-3 years, and gradually increased with the increase of age. Conclusion Autumn and winter in Jinshan District are the seasons with high incidence of chickenpox in kindergartens and primary schools，two doses of chickenpox inoculation can not only reduce clinical symptoms, but also block the transmission of chickenpox epidemic，it is suggested schools and health facilities make chicken pox monitoring work, get the chickenpox vaccine on time.

BACKGROUND:Bone tissue defects are one of the most common diseases in orthopedics,and the current treatments for this disease are inadequate.The development of tissue engineering brings new hope for bone defect repair:by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site,it can effectively improve the microenvironment of bone tissue and promote osseointegration,which is the most promising research idea for large-size bone defect repair. OBJECTIVE:To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances,vascularization and neurotization on three aspects of bone microenvironment changes,and to provide new ideas and strategies for the treatment of large-size bone defects. METHODS:The search terms"bone tissue engineering,angiogenesis,neurotization,cytokines,bone morphogenetic protein,vascular endothelial growth factor,neuropeptides,bone microenvironment"in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1,2001 to December 31,2022 on CNKI,WanFang,Web of Science,Science Direct,and PubMed.Finally,109 articles were included for review. RESULTS AND CONCLUSION:(1)The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation,and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions,the local blood circulation network and the surrounding nerve tissue.(2)Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines,and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases.(3)Neovascular regeneration is key to initiating bone repair,as neovascularisation not only provides essential nutrients,osteoblasts and growth factors for bone repair,but is also a gateway for repair cells to enter the injury zone.(4)In addition to regulating the type,dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction.The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects.(5)Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing,bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways.(6)In the establishment of neuralized tissue-engineered bone,the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional.Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier.Neuropeptides secreted by glial cells act on the bone microenvironment,affecting bone healing,bone regeneration and the balance between osteogenesis and osteolysis.(7)There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis,such as the rapid diffusion and degradation of cytokines in the body and their loss of activity,the temporal and spatial distribution of angiogenesis-related growth factors,and the establishment of neurogenesis through the body's feedback regulatory mechanism,which need to be improved by subsequent studies.