Vitiligo is an acquired depigmented disease, and neurological factors may play an important role in its pathogenesis. Neurogenic inflammatory factors released by sensory nerves that control the skin can directly or indirectly regulate functions of keratinocytes, melanocytes, Langerhans cells, dermal dendritic cells, mast cells, dermal microvascular endothelial cells and immune cells. This review summarizes roles of several relevant neurogenic inflammatory factors in the occurrence and development of vitiligo, including neuropeptide Y, calcitonin gene-related peptide, catecholamines and nerve growth factor, with a view to providing new ideas for clinical treatment of vitiligo.

Objective·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring.Methods·C57BL/6J female mice were randomly assigned to the normal diet(CON group,n=12)or the high-fat diet(HFD group,n=12)for 5 weeks.The two groups were further subdivided according to pregnancy:a normal diet non-pregnancy group(CON-UN group),a normal diet pregnancy group(CON-P group),a high-fat diet non-pregnancy group(HFD-UN group),and a high-fat diet pregnancy group(HFD-P group).The original diet was maintained during pregnancy and lactation.White adipose tissues(WAT)and brown adipose tissues(BAT)were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d.Offspring from both dietary groups were placed on a normal diet after weaning,and their adipose tissues were collected at the 11th week.H-E staining was used to observe the changes of adipocytes.Flow cytometry was employed to detect the proportions of CD4+T cells,CD8+T cells,total T cells,CD4+T/CD8+T and NK cells in WAT.RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT.Results·After 5 weeks on a high-fat diet,the body weight of female mice in the HFD group was higher than that in the CON group(P<0.05).Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy(both P<0.05).In the WAT from HFD-UN and HFD-P groups,the number of cells within the same visual field decreased,the size of adipose cells varied,the proportion of fat droplets increased and the cell volume expanded.The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group,respectively,and the difference was statistically significant(all P<0.05).BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes,although cell volume remained unchanged.The proportions of CD8+T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups,accompanied by increased mRNA levels of IL-6 and IL-1β,respectively,compared with the CON-UN and CON-P groups,and the differences were statistically significant(all P<0.05).NK cells proportions decreased at reproductive age(HFD-UN group)but increased significantly during pregnancy(HFD-P group),showing a divergent trend.Despite a return to a normal diet after weaning,offspring from the high-fat diet group had significantly higher weight of body,WAT and BAT,compared to those of normal diet(all P<0.05),and the volume of WAT was significantly enlarged.Conclusion·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio,and elevate inflammation levels in adipose tissues before and during pregnancy,which also impacts the adipose structure in offspring.Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.

By summarizing the clinical use of different capsule endoscopes in small intestine,colon,stomach and esophagus,the relevant evaluation indicators of the clinical application of capsule endoscopes for patients with different diseases were sorted out.Combined with the review process of capsule endoscopes that have been marketed at home and abroad,the key points of clinical evaluation of capsule endoscopes products in China that need to be marketed through clinical trials were considered.The clinical evaluation focuses included main evaluation index,secondary evaluation index and safety evaluation index,and the main evaluation index could consider the consistency rate of lesion diagnosis results and the excellent rate of image quality.The inclusion criteria for clinical trials of capsule endoscopy products were the population who intended to use the product,and the exclusion criteria need to consider the circumstances that were not applicable to such products and the circumstances that were not applicable to enrollment.

Objective To investigate the effects of long non-coding RNA(lncRNA)TCRGV on the cell biological behavior and lipid metabolism of colorectal cancer(CRC),along with its potential mechanism.Methods The expression level of lncRNA TCRGV in CRC tissues was analyzed using the GEPIA online database.56 pairs of CRC tissues and paracancer tissues were collected.Normal intes-tinal epithelial cells and CRC cell lines were cultured.The expression level of TCRGV in tissues and cell lines was detected using real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).A lentivirus was used to construct a TCRGV overexpression CRC cell model.The effects of TCRGV overexpression on cell migration and invasion capabilities were examined using the Transwell method.The impact of TCRGV on cellular lipid droplet formation was analyzed through Nile red staining.Triglycerides,total cholesterol,and free cholesterol content detection kits were used to detect the content of lipid metabolites in in CRC cells.The expression of the lipid metabo-lism-related protein stearoyl-coenzyme A desaturase 1(SCD1)was detected using RT-qPCR and Western blot to explore its relation-ship with TCRGV.Results The expression level of TCRGV was significantly downregulated in CRC tissues and cells.Compared with the control group,overexpression of TCRGV significantly inhibited the migration and invasion capabilities of CRC cells,significantly de-creased intracellular lipid droplet accumulation,and significantly reduced the contents of total cholesterol,triglycerides,and free choles-terol.The expression level of SCD1 was significantly higher in CRC tissues than that in paracancer tissues.Overexpression of TCRGV sig-nificantly inhibited the expression of SCD1 at both mRNA and protein levels.Conclusion lncRNA TCRGV is downexpressed in CRC and is a potential anticancer molecule.Overexpression of TCRGV may inhibit the cell migration,invasion and lipid reprogramming of CRC by regulating SCD1.

Objective To investigate the effect of N6-methyladenosine (m⁶A) reading protein human antigen R (HuR) on the migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1 (PFK1). Methods The tissue samples of 33 patients who were first diagnosed as colorectal cancer in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April to December 2022 were collected. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of HuR and PFK1 mRNA in colorectal cancer tissues and adjacent tissues. The expression of HuR mRNA in normal intestinal epithelial cells NCM460 and colorectal cancer cells HCT8, SW480, SW620, HCT116, LoVo, RKO and COLO205 was detected. Small interfering RNA (siRNA) was used to construct a HuR knockdown colorectal cancer cell model. The effects of HuR on the migration and invasion of colorectal cancer cells were detected by cell scratch assay and Transwell assay. The expression of PFK1 mRNA and protein was detected by qRT-PCR and Western blot. Glucose intake and pyruvate production were detected by glucose content kit and pyruvate content kit, respectively. The relationship between HuR and PFK1 was analyzed by bioinformatics analysis, and the effect of HuR on the stability of PFK1 mRNA was evaluated by actinomycin D assay. Results In colorectal cancer tissues, HuR and PFK1 were highly expressed at mRNA level; HuR was highly expressed at mRNA level in colorectal cancer cell lines. Down-regulation of HuR significantly inhibited the migration and invasion of colorectal cancer cells, as well as glucose consumption and pyruvate production. Knockdown of HuR could reduce the stability of PFK1 mRNA and its expression at mRNA and protein levels. There were m⁶A modification sites on PFK1. Conclusion The m⁶A reading protein HuR may regulate the migration, invasion and glycolysis of colorectal cancer cells by recognizing the m⁶A site on PFK1 and reducing the stability of PFK1 mRNA.

ObjectiveTo analyze the occurrence of suspected adverse events following immunization （AEFI） after changing the priority vaccination sites of the adsorbed acellular diphtherior-pertussis-tetanus vaccine （hereinafter referred to as DPT vaccine）， so as to provide scientific basis for mass vaccination. MethodsMonitoring data of AEFI for the DPT vaccine in Wujiang District from September 2020 to August 2022 were collected from China's disease prevention and control information system， and the vaccination information of DPT vaccine in all children's vaccination clinics in Wujiang District during the same period was selected. The incidence of AEFI for the DPT vaccine was analyzed and compared. ResultsThe reported incidence of AEFI was significantly lower in the buttocks than that in other sites （P<0.05）. The reported incidence of AEFI was significantly higher in booster immunization than that in basic immunization （P<0.05）. After inoculation at different sites， the main clinical symptoms of AEFI were local redness and swelling. There were significant differences in the incidence of local redness and swelling， local induration， pruritus and other symptoms （lethargy， abnormal crying， etc.） （P<0.05）. There were significant differences in the severity of local redness and swelling in different sites （P<0.05）. The degree of redness and swelling in the anterolateral thigh was lower than that in other sites （P<0.05）. The local strong reaction of swelling （>5.0 cm） in the deltoid muscle of the upper arm was significantly higher than that in the buttocks （P<0.05）. ConclusionThe DPT vaccine is safe in different parts of the body and is worth popularizing.

Objective:To study the effectiveness and safety of PD-1(programmed cell death protein-1,PD-1)inhibitors for the treatment of patients with advanced cancer in real-world in a Chinese cohort. Methods:Data of patients with advanced cancer who were admitted to the Department of Oncology,Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between May 2018 and September 2019 and received PD-1 inhibitor alone orcombined with otheranti-cancer therapies were collected.The clinical characteristics,therapeutic efficacy and adverse events were analyzed retrospectively. Results:A total of 75 patients with advanced cancer were included in this study.The cohort consisted of 53 males and 22 females with an average age of 60 years,among whom 60 patients had metastasis.Lung cancer(27 cases)and gastric cancer(12 cases)accounted for the largest proportion.Other cancer types included cancers of the digestive system(colorectal,liver,pancreatic,esophageal,and bile duct cancer),urinary system(kidney,pelvis,ureter,and bladder cancer)and female reproductive system(breast,cervical,and ovarian cancer),malignant melanoma,and head and neck cancer(nasopharyngeal and laryngeal cancer).Among all the patients studied,55 patients(73.3％)received PD-1 inhibitors as first-line and(or)second-line therapy,and 62 patients(82.7％)received PD-1 inhibitors in combination with other anti-cancer therapies.The objective response rate was 1 4.5％,disease control rate was 65.2％,the median progression-free survival was 6.1 months[95％confidence interval(C/):4.356-7.844],and the median overall survival was 1 8.0 months(95％CI:9.565-26.435).Adverse events,mainly grade 1 or grade 2,accured in 5 5 patients.The progression-free survival was 6.3 months in patients treated with PD-1 inhibitors as first-line and(or)second-line therapy,significantly longer than the 3.0-month-long progression-free survival of the patients treated with PD-1 inhibitors as third-line or multiline therapy[hazard ratio(HR)=0.492,95％Cl:0.244-0.992,P=0.048]. Conclusions:Immunotherapy with PD-1 inhibitors was effective and safe for patients with advanced cancer in real-world,especially in those who received PD-1 inhibitor treatment as first-or second-line therapy.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To investigate the clinical features and associated influencing factors of cognitive impairment in middle-aged and elderly Chinese adult patients undergoing maintenance hemodialysis (HD).Methods:A cross-sectional study was conducted among HD patients from 11 centers in Beijing city from April 2017 to June 2017. A neuropsychological battery covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied in cognitive function assessment. Patients were classified as normal cognitive function group and cognitive impairment group according to the fifth version of the diagnostic and statistical manual of mental disorders criteria (DSM-V). Multivariate binary logistic regression was used to analyze the independent influencing factors of cognitive impairment. Results:A total of 613 HD patients were included in the study, and the prevalence of cognitive impairment was 80.91% (496/613). Attention impairment (81.05%) and memory impairment (63.51%) were the most common impaired domains, and 79.23% was concomitant impairment across two or more cognitive domains among those with cognitive impairment. Compared with the patients in the normal cognitive function group, the patients in the cognitive impairment group had senior age, longer dialysis vintage, higher proportion of diabetes, hypertension, and stroke, higher level of serum intact parathyroid hormone (iPTH), lower education level, and lower urea clearance index (Kt/V) (all P<0.05). Factors were independently associated with cognitive impairment including increasing age ( OR=1.110, 95% CI 1.072-1.150, P<0.001), education time>12 years (with education time<6 years as reference, OR=0.323, 95% CI 0.115-0.909, P=0.032), history of diabetes ( OR=2.151, 95% CI 1.272-3.636, P=0.004), history of stroke ( OR=2.546, 95% CI 1.244-5.210, P=0.011), increased dialysis vintage ( OR=1.016, 95% CI 1.010-1.022, P<0.001), reduced Kt/V( OR=0.008, 95% CI 0.002-0.035, P<0.001), and increased iPTH level ( OR=1.002, 95% CI 1.002-1.003, P=0.012). Conclusions:The prevalence of cognitive impairment in middle-aged and elderly adult Chinese patients undergoing HD is high. Memory and attention are the most commonly impaired domains. Increasing age, low education level, history of diabetes and stroke, increased dialysis vintage, reduced Kt/V and increased serum iPTH are the independent influencing factors associated with cognitive impairment.

Objective:To investigate the association between cognitive impairment and all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis (HD).Methods:A prospective cohort study was conducted. Patients from 11 HD centers in Beijing between April and June 2017 were enrolled. Baseline data were collected, and a series of neuropsychological batteries covered 5 domains of cognitive function were applied for the assessment of cognitive function. The patients were then classified as normal and cognitive impairment groups according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V) and followed-up until June 2018. The clinical characteristics of the two groups of patients were compared. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the independent influencing factors of all-cause mortality, to determine the relationship between cognitive impairment and different cognitive domain impairments and all-cause death.Results:A total of 613 patients were enrolled, of which 496(80.91%) patients had cognitive impairment. Compared with the normal cognitive function group, the patients in the cognitive impairment group tended to be older, longer dialysis vintage, a higher proportion of diabetes, hypertension, and stroke, increased serum iPTH level, and lower education level and urea clearance index (Kt/V) (all P<0.05). After (49.53±8.42) weeks of follow-up, Kaplan-Meier survival analysis showed that the cumulative survival rate of cognitive impairment group was significantly lower than that of cognitive normal group (Log-rank χ2=8.610, P=0.003). Multivariate Cox regression analysis showed that history of diabetes ( HR=2.742, 95% CI 1.598-4.723, P<0.001), coronary heart disease ( HR=1.906, 95% CI 1.169-3.108, P=0.010), dialysis vintage (every increase of 1 month, HR=1.007, 95% CI 1.003-1.011, P=0.001), serum level of albumin (every increase of 1 g/L, HR=0.859, 95% CI 0.809-0.912, P<0.001), cognitive impairment ( HR=2.719, 95% CI 1.088-6.194, P=0.032) were independently associated with all-cause mortality. Multivariate Cox regression analysis on different cognitive domains also indicated that memory impairment ( HR=2.571, 95% CI 1.442-4.584, P<0.001), executive function impairment ( HR=3.311, 95% CI 1.843-5.949, P=0.001) and three, four, five domains combined impairment ( HR=5.746, 95% CI 1.880-17.565, P=0.002; HR=12.420, 95% CI 3.690-41.802, P<0.001; HR=13.478, 95% CI 3.381-53.728, P<0.001) were independently related to all-cause mortality. Conclusions:Cognitive impairment is an independent risk factor of all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis, and the risk is significantly increased in patients with the impairment of the domains of memory, executive function, or in the combination of three to five cognitive domains.