Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P＜0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3％,AP=0.80)and miR-16(AUC=0.83,79.0％,AP=0.83)than for AFP(AUC=0.74,61.7％,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9％)and the AP to 0.85 and was significantly superior to the other markers in this study(P＜0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCsExo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood.This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCsExo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess b-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry.Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

Glucagonoma is a rare neuroendocrine tumor of α cells of the pancreas. The tumor excessively secretes glucagon and causes glucagonoma syndrome.70%-90% of patients with glucagonoma will develop necrolytic migratory erythema (NME). We reported a patient of glucagonoma syndrome who was presented to the dermatology outpatient clinic with a 2-year-history of recurrent erythema and scaling on the skin migrating throughout the body. A skin biopsy was performed and resulting features matched with NME, whilst imaging examinations suggested a soft tissue density tumor present in the tail of the pancreas with somatostatin receptor expression and laboratory tests found an elevated levels of serum glucagon. After the diagnosis was confirmed, the patient was treated with surgical resection of the glucagonoma and the skin eruptions resolved rapidly in 4 days. Meanwhile, we reviewed relevant literature published in recent years and summarized its clinical characteristics in order to improve its understanding by clinicians, including clinical manifestations, laboratory and imaging examinations, diagnosis and treatments.

Objective:To survey the knowledge, attitudes, and practice about chronic obstructive pulmonary disease (COPD) among general practitioners in Sichuan province.Methods:From October to November 2020, a questionnaire survey on knowledge, attitudes and practice (KAP) among 104 general practitioners who participated in the training of the comprehensive prevention and control of COPD organized by Sichuan Provincial Health Commission. The content of the questionnaire included the basic information and the KAP status of COPD. The descriptive analysis, Mann-Whitney U test, and Kruskal-Wallis H were used for statistical analysis. Results:A total of 104 questionnaires were distributed and 102 were returned with a response rate of 98.1%. General practitioners with different ages, professional titles, visits of COPD patients each month, and whether or not to refer COPD patients to higher-level hospitals were not significantly different in the scores of knowledge( U=1 276.00, H=0.78, U=1 074.00, U=589.00), attitude( U=1 141.50, H=1.75, U=1 090.00, U=585.00), and practice( U=1 221.00, H=0.31, U=1 163.00, U=499.50) (all P>0.05). In knowledge part the highest correctness rate was "quitting smoking is the most powerful interventions affecting the natural disease course of COPD" (100.0%, 102/102); the lowest was that"the main objective examination for judging the airflow limitation of COPD patients is the lung function test"(5.9%, 6/102). In the part of the attitude, the highest positive rate was "educating patients to quit smoking and avoid exposure to second-hand smoke" (65.7%,67/102); the lowest positive rate was "provide exercise guidance to patients "(43.1%, 44/102) and " be responsible for long-term treatment follow-up" (43.1%, 44/102). In the part of practice, the highest behavioral rate was "when receiving patients with COPD, actively pay attention to the treatment of comorbid diseases" (95.1%, 97/102); the lowest behavioral rate was "when patients with COPD were seen at the clinic, and the patients were advised of the best time to use the inhaler" (65.7%, 67/102). Conclusions:The study indicates that the relevant departments need to increase the intensity of knowledge training for general practitioners in Sichuan province. General practitioners should continuously improve their education, prevention, and treatment ability and implement the primary responsibilities for COPD management.

Objective:To systematically analyze and evaluate the IgG antibody levels of varicella-zoster virus (VZV) in healthy population in China.Methods:CNKI, Wanfang, CBM and PubMed databases were used for the retrieval of literatures about VZV IgG antibody levels in healthy people in China from January 1, 2000 to November 3, 2020. The quality of the included papers was evaluated by the critical appraisal tools for cross sectional study from Joanna Briggs Institute (JBL). The stratified analysis on the IgG antibody levels in populations in different age groups, provinces, regions, gender groups, and years was performed by using software Stata 14.0.Results:A total of 59 papers were included that met the inclusion criteria, including 51 papers in Chinese and 8 papers in English. There were 22 papers with quality score of 8, 16 papers with quality score of 7, 15 papers with quality score of 6, and 6 papers with quality score of 5. Meta-analysis showed that the positive rate of VZV IgG antibody in healthy population in China was 64% (95% CI:60%-67%, I 2 =98.7%), and the IgG antibody levels were reported in the papers for 22 provinces of China. The positive rate of VZV IgG antibody was highest in Yunnan (79%, 95% CI: 64%-93%, I 2 =94.7%) and lowest in Inner Mongolia (50%, 95% CI: 46%-54%); the positive rate of VZV IgG antibody was highest in Northeastern China (71%, 95% CI: 69%-73%) and lowest in Eastern China (62%, 95% CI: 57%-67%); the positive rate of VZV IgG antibody in urban population was higher than that in rural population ( RR=1.08, 95% CI: 1.04-1.11). The positive rate of VZV IgG antibody in women was higher than that in men ( RR=1.10, 95% CI: 1.08-1.11); the positive rate of VZV IgG antibody in the population increased with age; and the positive rate of VZV IgG antibody increased with the change of sampling time. Conclusion:The positive rate of VZV IgG antibody in healthy population in China was relatively low; the coverage of varicella vaccine should be improved for the outbreak control and incidence reduction of varicella in China.

Objective To explore the epidemic characteristics and spatial clustering of pulmonary tuberculosis in Wuhan from 2011 to 2019, and to provide a scientific basis for formulating intervention strategies and measures. Methods Descriptive statistical analysis was conducted on the epidemic characteristics of tuberculosis data in Wuhan registered in the national tuberculosis information management system in the last 9 years, and spatial autocorrelation analysis was performed on the incidence of tuberculosis in 155 communities or in the city using Arcgis10.5 software. Results From 2011 to 2019, there were 56,432 cases of tuberculosis reported in Wuhan, and the annual average reported incidence rate of tuberculosis was 59.24/100 000. The overall incidence rate showed a fluctuating downward trend, with an average annual decline rate of 1.99%. The ratio of the number of cases between men and women was 2.35:1, and the incidence rate in males was higher than that in females (χ²=285.36，P<0.001). The 45-64 years old group had the largest number of patients, accounting for 35.33% of the total. The peak incidence of the disease was from March to June, while the lowest was from December to February of the next year. The main occupations were housekeepers, house and unemployed workers, and farmers and retirees, accounting for 31.93%, 18.81% and 12.84% of the total number of cases, respectively. Spatial correlation analysis showed that there was a positive spatial autocorrelation in the incidence of tuberculosis in Wuhan from 2011 to 2019 (Moran's I>0,P<0.001), and the high-high aggregation areas of tuberculosis were mainly distributed in Erqi community, Baibuting community, Liujiaoting community, Yijiadun community, Heping Street, Changqian Street, Tonghu farm, Yuxian Town, Zhifang Town, Wulijie Town, Fenghuang Street, Liji Street, and Daoguanhe Street. Conclusion The overall epidemic situation of pulmonary tuberculosis in Wuhan showed a slow downward trend. The main population and the clustering time of cases were relatively fixed, and the overall epidemic showed a certain spatial clustering. Active screening should be carried out for high-risk populations and high-aggregation areas, and effective prevention and control strategies should be developed based on time and location classification.

BACKGROUND: Mycosis fungoides (MF) is the most common types of cutaneous T cell lymphoma. It typically presents with erythematous patches and plaques in the early stage and tumors and extracutaneous involvement with possibly fatal outcomes in the late stage. To facilitate early and accurate diagnosis of MF, it is essential to be knowledgeable of classic and variants of this disease. However, there is limited published data in the Chinese population. OBJECTIVE: To characterize our patient group and to provide additional insight into these malignancies. METHODS: Patients diagnosed with mycosis fungoides and its variants from October 2012 to January 2018 were retrospectively analyzed. Disease-specific survival (DSS) rate and curve according to early and advanced stages were also calculated. RESULTS: The mean age at diagnosis of ninety-three MF patients was 38.9±1.73 years (range: 6~77). Forty-five males (48.4%) and 48 females (51.6 %) were included in this study. The DSS rate of early-stage MF was 98.6%, while that of advanced stage MF was 88.9%. There was a significant difference in DSS rate between early stage and advanced stage MF (p=00.042, log-rank test). The median age of 10 patients with hypopigmented MF (hMF) was 10.5 years (range: 6~28). The age of hMF was younger than that of classical MF patients (p < 0.05). CONCLUSION Early-stage MF has a better prognosis than advanced stage and hMF affects younger people than classic MF among Chinese. This study provides an insight into mycosis fungoides and its variants in a Chinese population.

Objective To investigate the changes of gamma-aminobutyric acid (GABA) in the anterior cingulate cortex of perimenopausal women with depression.Methods Forty perimenopausal women as the experimental group and ten healthy women as the control group were recruited and followed up for 18 to 24 months.The proton magnetic resonance spectroscopy (1H-MRS) was used to acquire the concentrations of GABA in the anterior cingulate cortex.The experimental group was examined before and after menopause.The control group was examined before into the group and after out of the group.The experimental group after menopause was further divided into the anxiety group and the depression group according to the Classification and Diagnostic Criteria of Mental Disorders in China-Third Edition (CCMD-3), 14-item Hamilton Anxiety Scale (HAMA-14) and 17-item Hamilton Depression Scale (HAMD-17).The data of three groups were compared respectively.Results The results showed that the concentrations of GABA after menopause in both of the anxiety group and depression group were significantly lower (P<0.05) than those before menopause, and were also significantly lower (P<0.05) than those in the control group.The concentrations of GABA after menopause in the depression group were significantly lower(P<0.05) than those in the anxiety group.Conclusion The changes of GABA in the anterior cingulate cortex are related with the pathophysiology mechanism of perimenopausal depression and the symptoms of perimenopausal depression.