Oral lichen planus (OLP) is a common chronic inflammatory disease and potentially malignant disorder of the oral mucosa. Clinical manifestations include bilateral symmetrical distributions of pearly white reticular streaks, and its subtype erosive oral lichen planus (EOLP) is often accompanied by local congestion, erosion, obvious pain, and other symptoms, which affects the patient's eating and swallowing. Oral hygiene and environmental factors, lifestyle and dietary factors, psychological factors, medication factors, and systemic disease factors all contribute to the recurrence of EOLP lesions, which increases the cancer potential of this condition. Therefore, measures to prevent the recurrence and cancerous transformation of EOLP have attracted much attention. In the clinical treatment strategy for EOLP, attention should be given to its influencing factors for comprehensive management. Patients should be provided with multidisciplinary and multifaceted oral comprehensive management measures across the following strategies: maintaining a good oral hygienic environment, dietary therapies and healthy living habits, psychological therapies, systemic/local therapeutic guidance, and active follow-up and treatment of systemic diseases. This article provides multidisciplinary and multifaceted comprehensive oral management measures for patients with the goal of cancer prevention, minimizing recurrence, and improving the quality of life of patients.

Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

Objective To explore the role and molecular mechanism of major vault protein (MVP) in tumor-associated macrophages in the occurrence and development of liver cancer. Methods The expression of MVP in macrophages was analyzed by bioinformatics method and multi-fluorescent immunohistochemical staining. Mice with MVP deficiency in macrophages were constructed by Cre/LoxP recombinant enzyme system. The proliferation and migration abilities of tumor cells were detected by cloning formation and Transwell migration assays. The effect of MVP in macrophages on tumorigenesis and development was investigated by mouse primary liver cancer model and subcutaneous tumor transplantation model. The effect of MVP on the tumor microenvironment was investigated by multi-fluorescent immunohistochemical staining. The effect of MVP on CD8⁺ T cells was detected by cell co-culture, flow cytometry, qPCR, and ELISA. Results The high expression of MVP in tumor-associated macrophages. The downregulation of the expression of MVP in tumor-associated macrophages compared with para-carcinoma tissues. MVP deficiency in macrophages promoted the proliferation and migration of tumor cells (P<0.05), promoted the development of tumor in vivo (P<0.05), formed an immunosuppressive microenvironment and weakened CD8⁺ T cell-mediated anti-tumor immunity (P<0.05). Conclusion MVP deficiency in macrophages can promote the occurrence and development of liver cancer by suppressing the function of CD8⁺ T cells.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

OBJECTIVE To construct a prediction model of mild cognitive impairment(MCI)in elderly patients with hyperten-sion based on the bi-dimensional features of Chinese and western medicine with the help of machine learning(ML).METHODS The clinical data of 502 patients over 60 years old with essential hypertension treated in hospital from January 2020 to March 2023 were collected and analyzed,randomly divided into training set and verification set according to a ratio of 7∶3,and divided into cognitive impairment group(n=104)and cognitive normal group(n=398).LASSO regression analysis was used to reduce the dimension of clin-ical indicator data and screen out the core predictors.Six ML algorithms,logistic regression,XGBoost,AdaBoost,SVM,GNB,and MLP were used to construct the models,and ROC curves were plotted to compare the AUC,accuracy,sensitivity,specificity,and F1 scores of the 6 models.SHAP models were adopted to reveal the characteristic importance of predictors.RESULTS Waist-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose were the core predictors of early MCI in elderly hypertensive patients.The AUC,accuracy,sensitivity,specificity,and F1 scores of the XGBoost model were 0.938,0.885,0.846,0.896,and 0.755 respectively,which were superior to those of other algorithmic models.CONCLUSION The XGBoost model constructed on the basis of waist-to-hip ratio,qi depression,age,total cholesterol,phlegm-dampness,damp-heat,qi deficiency and fasting blood glucose has the best prediction performance,which can provide a reference basis for early identifi-cation of MCI risk and diagnostic and therapeutic decision-making in the clinical elderly hypertensive population.

Objective To explore the implementation effect of PDCA(plan-do-check-action)style training of severe ultrasound and hemodynamics in standardized training(residential training)for residents majoring in internal medicine on improving their clinical decision-making ability.Methods A retrospective research method was conducted,60 residents in Xinyang Central Hospital from July 2017 to July 2023 were selected as the research objects,and patients were randomly divided into experimental group and control group,with 30 residents in each group.After the routine entrance education,the experimental group applied the PDCA mode training of severe ultrasound and hemodynamics.The control group was trained with the training objectives and requirements of the department of critical care medicine in the contents and standards of standardized training for internal medicine residents for 2 months.At the end of the training period,the residents of the two groups were assessed and investigated by questionnaire,and the differences of theoretical knowledge assessment,clinical practice skills assessment,case assessment scores and satisfaction between the two groups were compared.Results The results of theoretical knowledge examination,diagnosis and differential diagnosis,and clinical decision-making in the experimental group were significantly higher than those in the control group(theoretical knowledge examination score:90.5±2.7 vs.85.7±3.8,diagnosis and differential diagnosis score:92.0±2.4 vs.87.9±3.7,clinical decision-making score:90.3±3.1 vs.85.5±3.9,all P<0.05),satisfaction with teaching methods,stimulating learning interest,firmly mastering knowledge,enhancing problem-solving ability,improving learning enthusiasm,improving clinical thinking ability and enhancing team consciousness was also significantly higher than that of the control group[teaching methods:80.0%(24/30)vs.46.7%(14/30),stimulate learning interest:83.3%(25/30)vs.56.7%(17/30),firmly mastering knowledge:80.0%(24/30)vs.40.0%(12/30),enhance problem-solving ability:70.0%(21/30)vs.43.3%(13/30),improving learning enthusiasm:83.3%(25/30)vs.50.0%(15/30),improving clinical thinking ability:60.0%(18/30)vs.40.0%(12/30),enhancing team consciousness:73.3%(22/30)vs.46.7%(14/30),all P<0.05].Conclusion The application of PDCA-style training of severe ultrasound and hemodynamics can help internal medicine residents master the basic theory and skills of severe diseases faster and better in the rotation of critical medicine departments,which is more conducive to improving the clinical decision-making ability of internal medicine residents.

Objective:To discuss the clinical manifestations and laboratory examination results of agranulocytosis and reactive plasmacytosis(RP)in the patient with Graves'disease(GD)after treated with methimazole(MMI),and to provide the basis for the clinicians to differentiate RP from multiple myeloma(MM).Methods:The clinical manifestations,laboratory examinations,diagnosis and treatment processes of one patient with GD agranulocytosis complicated with RP were analyzed,and the related literatures were reviewed.Results:The patient had a history of GD and abdominal infection.Upon admission,a complete blood count revealed a significant decrease in white blood cell count accompanied by neutropenia,and a smear re-examination showed suspicious plasma cells.The bone marrow cytology examination results showed the percentage of bone marrow plasma cells was 33％,and the percentage of plasma cells in peripheral blood was 4％;the serum immunoglobulin results showed polyclonal hyperplasia;the serum immunofixation electrophoresis results were negative;the flow cytometry analysis results indicated the immunophenotype of the plasma cells was normal.Based on the medical history and laboratory results,MM was largely excluded,supporting the diagnosis of RP.Neutropenia was considered to be related to medication,so MMI was discontinued,granulocyte colony-stimulating factor was administered to increase the number of white blood cells,and specialized GD treatment was conducted after controlling the abdominal infection.The patient had a good prognosis,and his blood count was normal upon re-examination 6 months later.Conclusion:Agranulocytosis complicated with RP in the GD patients is clinically rare.Serum immunofixation electrophoresis,blood cell morphology,and cell immunophenotype analysis are helpful for the accurate diagnosis.After actively treating the primary disease causing RP,the patient's prognosis is favorable.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

This article reviews relevant literature on the prevention and treatment of cancer with hesperidin published in the past 10 years by searching electronic databases such as China National Knowledge Infrastructure（CNKI）， Wanfang， and PubMed， and summarizes the research progress on the anticancer mechanism of hesperidin. Hesperidin has a wide range of pharmacological effects， including anti-inflammatory， antioxidant， antibacterial， antiviral， anticancer， immune-regulatory， anti-radiation， neuroprotective and cardiovascular protective properties and so on. Its anticancer mechanisms mainly include inhibiting cancer cell proliferation， promoting apoptosis， reducing angiogenesis， inhibiting invasion and migration of cancer cells， regulating immunity and autophagy， and exerting antioxidant and anti-inflammatory effects. As a broad-spectrum anticancer drug， hesperidin manifests chemo-preventive and therapeutic effects across various cancers， contingent upon its multifaceted anticancer mechanisms. Furthermore， this article summarizes the synergistic effects of hesperidin in combination with cisplatin， doxorubicin， cyclophosphamide and paclitaxel. It elucidates that hesperidin can enhance the cytotoxicity of these anticancer drugs against cancer cells while mitigating drug resistance and adverse side effects. Nonetheless， the clinical use is somewhat constrained due to its poor water solubility and limited bioavailability. Therefore， this article also outlines the current strategies for enhancing hesperidin's bioavailability， including structural modification， combination with other chemical substances， and utilization of nano drug carriers.The discovery of derivatives of hesperidin not only preserves the anticancer efficacy of hesperidin, but also effectively overcomes the shortcomings of poor water solubility and low bioavailability of hesperidin, effectively predicting the good application prospects of hesperidin and its derivatives.