The ethical review of clinical research involving mental disorders in the ethical governance of scientific and technological has obvious particularities， especially in the field of artificial intelligence and brain-computer interfaces which are reflected in the impact on mental autonomy， the impaired informed consent ability of participants with severe mental disorders in research， and other aspects. In addition， the stigma of illness， the use of placebo， and psychological assessment methods in clinical research have also drawn attention to the ethical review of psychiatry. In 2020， the Beijing Municipal Health Commission issued the Guidelines for Ethical Review of Clinical Research Involving Mental Disorders （Guidelines）. Shen Yucun’s Psychiatry， compiled in 2023， revised the application of the Guidelines in the context of ethical governance. An analysis was conducted on the purpose and significance of its issuance and revision， its scope of application， the principal responsibility of ethical review in medical and health institutions， and the key content of ethical review in psychiatry， to improve the quality of ethical review in clinical research involving mental disorders and promote the standardized development of clinical research in psychiatry.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Purpose To explore the role of translesion synthesis-related gene NmrA like redox sensor 1(NMRAL1)in the development of papillary thyroid carcinoma(PTC).Methods Bioinformatics analysis was em-ployed to investigate the expression of the NMRAL1 gene across various cancer types and its correlation with prognosis.Immunohistochemistry was utilized to analyze the expression pattern of NMRAL1 in PTC and conduct clinicopathological correlation analysis.Additionally,stable cell lines overexpressing NMRAL1 were established in TPC-1 cells.The effects of NMRAL1 overexpression on cell proliferation,migration,and invasion of TPC-1 and Nthy-ori 3-1 cells were assessed using CCK-8 assay,clonogenic assay,Transwell assay,and scratch assay,respectively.Furthermore,RT-qPCR experiments were conducted to investigate the regulatory effect of NMRAL1 on the expression of genes associated with translesion DNA synthesis.Results Bioinformatics analysis revealed that NMRAL1 was highly expressed in all 26 types of tumors compared to normal tissues in the TCGA x GTEx dataset.Patients with high expression of NMRAL1 in thyroid cancer had significantly lower survival rates than those with low expression(P＜0.05).In the immunohisto-chemical validation of 30 PTC samples,NMRAL1 had a positive rate of 73.33％,in PTC tissues,while it was not ex-pressed in adjacent normal thyroid tissues.The staining intensity scores of NMRAL1 in PTC and adjacent tissues exhib-it significant differences(P＜0.000 1).High expression of NMRAL1 was associated with the size of the tumor(P=0.027 4)and lymph node metastasis(P=0.044 1).In vitro functional experiments revealed a significant enhance-ment in both cell proliferation and migration/invasion capacities upon overexpression of NMRAL1(P＜0.05).Moreo-ver,mRNA and protein expression levels of translesion synthesis-related genes were upregulated(P＜0.001).Con-clusion NMRAL1 promotes proliferation and migration of thyroid carcinoma cells,suggesting that this function may be achieved by enhancing DNA damage repair capacity,thereby improving the survival of damaged cells.

Purpose To explore the role of translesion synthesis-related gene NmrA like redox sensor 1(NMRAL1)in the development of papillary thyroid carcinoma(PTC).Methods Bioinformatics analysis was em-ployed to investigate the expression of the NMRAL1 gene across various cancer types and its correlation with prognosis.Immunohistochemistry was utilized to analyze the expression pattern of NMRAL1 in PTC and conduct clinicopathological correlation analysis.Additionally,stable cell lines overexpressing NMRAL1 were established in TPC-1 cells.The effects of NMRAL1 overexpression on cell proliferation,migration,and invasion of TPC-1 and Nthy-ori 3-1 cells were assessed using CCK-8 assay,clonogenic assay,Transwell assay,and scratch assay,respectively.Furthermore,RT-qPCR experiments were conducted to investigate the regulatory effect of NMRAL1 on the expression of genes associated with translesion DNA synthesis.Results Bioinformatics analysis revealed that NMRAL1 was highly expressed in all 26 types of tumors compared to normal tissues in the TCGA x GTEx dataset.Patients with high expression of NMRAL1 in thyroid cancer had significantly lower survival rates than those with low expression(P＜0.05).In the immunohisto-chemical validation of 30 PTC samples,NMRAL1 had a positive rate of 73.33％,in PTC tissues,while it was not ex-pressed in adjacent normal thyroid tissues.The staining intensity scores of NMRAL1 in PTC and adjacent tissues exhib-it significant differences(P＜0.000 1).High expression of NMRAL1 was associated with the size of the tumor(P=0.027 4)and lymph node metastasis(P=0.044 1).In vitro functional experiments revealed a significant enhance-ment in both cell proliferation and migration/invasion capacities upon overexpression of NMRAL1(P＜0.05).Moreo-ver,mRNA and protein expression levels of translesion synthesis-related genes were upregulated(P＜0.001).Con-clusion NMRAL1 promotes proliferation and migration of thyroid carcinoma cells,suggesting that this function may be achieved by enhancing DNA damage repair capacity,thereby improving the survival of damaged cells.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m²）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m²）， and 55.3% had eGFR≥90 mL/（min ·1.73 m²）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m²）vs （78.12 ±7.60） mL/（min ·1.73 m²）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

BACKGROUND:Swimming is an important non-pharmacological treatment for knee osteoarthritis,which can effectively alleviate the disease.However,the effect and mechanism of swimming on senile knee osteoarthritis are still unclear. OBJECTIVE:To investigate the effect of swimming exercise on the articular cartilage of aged mice with knee osteoarthritis. METHODS:Six 3-month-old male C57BL/6 mice were selected as the young group,and twelve 18-month-old male C57BL/6 mice were randomized into the aged group and the swimming group,with six mice in each group.Mice in the swimming group received adaptive swimming for 1 week and formal swimming for 8 weeks.After the intervention,stride length analysis and sampling were performed in each group.The total number of leukocytes and lymphocytes in peripheral blood was detected by blood routine examinations.The morphology of the articular cartilage was observed by hematoxylin-eosin and safranin O-fast green staining.Chondrocyte counts and the modified Mankin's score were used to evaluate the degree of articular cartilage damage.The protein and mRNA expressions of type Ⅱ collagen,aggrecan and matrix metalloproteinase 13 in articular cartilage were detected by immunohistochemical staining and RT-qPCR. RESULTS AND CONCLUSION:Compared with the young group,the mice in the aged group showed significantly decreased stride length(P＜0.05),significantly increased numbers of peripheral leukocytes and lymphocytes(P＜0.05),significantly decreased count of chondrocytes(P＜0.05),significantly increased modified Mankin's score(P＜0.05),significantly decreased protein and mRNA expression of type Ⅱ collagen and aggreca(P＜0.05),and significantly increased matrix metalloproteinase 13 expression(P＜0.05).Moreover,hematoxylin-eosin and safranin O-fast green staining showed the uneven surface of the articular cartilage,abnormal chondrocytes,and proteoglycan loss in the aged group.Compared with the aged group,swimming exercise significantly improved the stride length of mice(P＜0.05),decreased the count of peripheral blood lymphocytes(P＜0.05),increased the count of chondrocytes(P＜0.05),decreased the modified Mankin's score(P＜0.05),increased the protein and mRNA expression of type Ⅱ collagen and aggrecan(P＜0.05),and decreased the expression of matrix metalloproteinase 13(P＜0.05).Hematoxylin-eosin and safranin O-fast green staining showed that the articular surface of mice in the swimming group was smooth,chondrocytes were normal,and proteoglycan loss was less.All these findings indicate that swimming exercise can reduce the number of inflammatory cells in the blood of aged mice,improve articular chondrocytes,matrix composition and cartilage tissue morphology;thus,it has a protective effect on the cartilage of aged mice with knee osteoarthritis.

Tuberculosis is a worldwide chronic infectious disease that has become a serious threat to human health.Early diagnosis,drug resistance screening and control of disease transmission are key aspects of TB prevention and treatment.However,existing diagnostic techniques and drug sensitivity tests are time-consu-ming and difficult to realize the purpose of early diagnosis and drug resistance screening,which greatly limits the control of disease transmission.Digital polymerase chain reaction(dPCR)is the third generation of poly-merase chain reaction(PCR),which is a quantitative nucleic acid assay with high sensitivity and no calibration curve.This article provides an overview of the principles of dPCR and its application in tuberculosis diagnosis,drug resistance screening and transmission monitoring,compares dPCR with other tuberculosis detection methods,and looks at the challenges and future prospects of dPCR in clinical tuberculosis laboratory applica-tions.

Objective:To investigate the correlation between gender, age, blood collection time, season and changes in cTnT concentration.Methods:In this study, 3548 patients (non-cardiovascular diseases) in Zhongshan Hospital of Fudan University were selected from 1 January to 31 December 2019. The basic data of the patients were collected, including gender, age, time of blood collection, medical history, clinical diagnosis, and results of cTnT testing. 1 840 males and 1 708 females were finally enrolled, with an age distribution of 65 (53, 75) years. The distribution of the data was assessed using the Kolmogorov-Smirnov (K-S) test, where non-normally distributed data were expressed as M( Q1, Q3). The Mann-Whitney U-test was used to compare cTnT concentrations between men and women, and to analyse the influence of gender on cTnT results. The Kruskal-Wallis test was used to compare cTnT levels between gender groups, to analyse the correlation between different times of blood collection, seasons, and other factors and cTnT concentrations. Result:cTnT concentrations increased with age in both males and females over the age of 60 years. cTnT levels were highest in individuals over the age of 90 years (0.028 ng/ml in males and 0.018 ng/ml in females). cTnT levels were higher in males (0.012 ng/ml) than in females (0.009 ng/ml) in all age groups ( H=6.340, P<0.01). The concentrations of cTnT varied at different time points of blood collection. In both males and females, cTnT concentrations reached a maximum at 8:00 and 13:00 (0.013 ng/ml and 0.012 ng/ml, respectively). Analysis of the physiological effect of season on cTnT secretion showed that cTnT levels were generally higher in spring and winter(0.012 ng/ml) than in summer and autumn(0.010 ng/ml). Conclusions:cTnT concentration is influenced by gender, age, time of blood collection and season. When analysing cTnT results in clinical practice, the gender and age of the individual should be taken into account, as well as the time point of blood collection and seasonal factors.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness