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.

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.

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.

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.

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.

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 explore the biocompatibility of Polydimethylsiloxane/Chlorhexidine gluconate ( PDMS/ CHG) composite coating on titanium surface . Methods : CHG with different concentrations were covalently grafted to the surface of titanium through PDMS and divided into 5 groups: Group Ti: blank control group; Group P:PDMS coating group; Group C1:treated with PDMS and 0.2 mg/ml CHG;Group C2:treated with PDMS and 0.4 mg/ml CHG;Group C3:treated with PDMS and 0.8 mg/ml CHG;the surface morphology of titanium was observed with scanning electron microscope(SEM),and rat gingival fibroblasts(RGFs) were inoculated to the sample surface co-cultivation.Confocal laser scanning microscope(CLSM)was used to observe the cells, on the surface of titanium, morphology and the state of the cell after FITC-labeled phalloidin and AO/EB staining, besides, CCK-8 was used to detect cells proliferation. Results: It could be seen by SEM that films had been formed on the surface of titanium sheets in each experimental group.Combined with elemental analysis, the films on the surfaces of C2 and C3 groups were uniform and dense; CLSM showed that the cell morphology of each experimental group was consistent with that of the titanium group, with better extension, and the results of AO/EB staining showed that there was a lot of green fluorescence in each group, and the cells were in good shape.CCK-8 results showed that there was no difference between each group(P>0.05). Conclusion Titanium surface combined with concentration of no more than 0.8 mg/ml PDMS/CHG coating has good biocompatibility.

Objective : To explore the antibacterial coating of polydimethylsiloxane⁃chlorhexidine gluconate (PDMS⁃CHXG) constructed on the smooth titanium surface and antibacterial properties for Porphyromonas gingivalis of CHXG solution with different concentrations. Methods : The titanium was polished to 7 000 mesh to mirror shape of abutment, cleaned and dried, then treated with alkalization. The samples were randomly divided into 5 groups: blank control group (C), test groups: grafted CHXG concentration of 0 (T0 ), 0. 4 (T1 ), 0. 8 (T2 ), 1. 6 mg/ml (T3 ) . The surface structural changes were observed by cold field emission scanning electron microscope (CFESEM), and the component elements of coating were analyzed semi⁃quantitatively. The antibacterial properties of the coating were evaluated by antibacterial zone, live/dead bacteria staining and crystal violet experiments. Results: A dense film was formed on the surface of titanium under the CFESEM compared with C group. The content of Cl element increased with the increase of CHXG concentration. There was no inhibition zone around the samples in C and T0 groups, but it was found in T1 , T2 and T3 groups. Live/dead bacteria staining showed no viable bacteria in the T2 and T3 groups. The results of crystal violet staining showed that T1 , T2 and T3 groups were statistically different from C and T0 groups, but the difference between the groups T2 and T3 was not statistically significant. Conclusion The antibacterial coating of PDMS⁃CHXG is constructed successfully. The PDMS⁃CHXG coating displays an exceptional antibacterial property when the concentration of CHXG reaches 0. 8 mg/ml.

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*

Objective:To explore the clinical efficacy and adverse reactions of albumin-bound paclitaxel (Nab-P) and conventional paclitaxel combined with cisplatin and concurrent radiotherapy for the treatment of patients with locally advanced esophageal squamous cell carcinoma.Methods:Forty-nine patients with locally advanced esophageal squamous cell carcinoma admitted to the First People's Hospital of Suqian from November 2016 to May 2020 were included. Of the 49 patients, 23 cases were treated with Nab-P combined with cisplatin and concurrent radiotherapy (NP group), 26 cases were treated with conventional paclitaxel combined with cisplatin and concurrent radiotherapy (TP group). All patients received 2 cycles of chemotherapy. The curative efficacy was evaluated one month after the end of radiotherapy, and the curative effect and adverse reactions of the two treatment regimens were compared.Results:The objective remission rate in NP group was 78.3% (18/23), and the disease control rate was 100.0% (23/23). The objective response rate in TP group was 61.5% (16/26), and the disease control rate was 92.3% (24/26). The objective response rate and disease control rate in NP group were higher than those in TP group, but the differences were not statistically significant (both P > 0.05). The common adverse reactions were mainly hair loss, loss of appetite, bone marrow suppression, radiation esophagitis, radiation pneumonia, malaise and myalgia. The incidence rate of grade 3-4 acute bone marrow suppression in NP group (8.7%, 2/23) was lower than that in TP group (38.5%, 10/26), and the difference was statistically significant ( χ2 = 4.35, P = 0.037). The incidence rate of myalgia in NP group (26.1%, 6/23) was lower than that in TP group (61.5%, 16/26), and the difference was statistically significant ( χ2 = 4.85, P = 0.028). Conclusions:Nab-P combined with cisplatin and concurrent radiotherapy has good efficacy in the treatment of patients with locally advanced esophageal squamous cell carcinoma, and the incidence rate of adverse reactions is lower than that of conventional paclitaxel combined with cisplatin and concurrent radiotherapy, so that the regimen is safe.