Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

Objective To retrospectively analyze the prevention and control effect and epidemic characteristics of elderly tuberculosis in Hubei Province from 2016 to 2020, and to provide a scientific basis for the prevention and treatment of elderly tuberculosis in Hubei Province． Methods The data on tuberculosis patients aged 60 and above who registered their current address in Hubei Province from 2016 to 2020 were collected and analyzed. The registration rates and composition ratios were analyzed using χ² test and χ² test for trend. Results A total of 135 976 tuberculosis patients were reported in Hubei from 2016 to 2020. The annual average registration rate of elderly tuberculosis among the elderly registered residence population (referring to the registration rate of elderly registered residence population aged 60 and above as the denominator, and tuberculosis patients aged 60 and above as the numerator) was 263.51/100 000. The highest rate was 300.02/100,000 in 2017, and the lowest was 188.19/100,000 in 2020 (χ²=70,227.603, P<0.001). In terms of composition, the average annual proportion of tuberculosis patients in the 60-70 years old group was 59.60%, which decreased year by year (χ²_trend=40.448，P<0.001 ). The average annual proportion of males was 73.35%, which was significantly higher than that of females (26.65%). The average annual proportion of farmers was 62.03%. From the perspective of case management, the annual average proportion of major epidemic online reports was 85.17%. The classification of cases was mainly based on clinical diagnosis, accounting for 48.33% annually and showing a decreasing trend year by year (χ²_trend=740.911, P<0.001). The proportion of confirmed cases was 25.08%, which showed an increasing trend (χ²_trend=380.557, P<0.001). From 2016 to 2019, the delay rate of diagnosis and treatment of elder tuberculosis patients was 49.42% (67 876/135 967), and the delay rate decreased year by year (χ²_trend=323.764, P<0.001). Conclusion The elderly population with pulmonary tuberculosis in Hubei Province shows a downward trend. It is necessary to focus on the efforts of designated hospitals to proactively identify cases, increase the proportion of confirmed cases, maintain a high tracking in place, reduce medical delays, and ensure the effectiveness of tuberculosis prevention and treatment for the elderly.

Objective:To compare the clinical data and peripheral blood levels of CXC chemokine ligand (CXCL) 9 and CXCL10 between patients with progressive non-segmental vitiligo who were sensitive to systemic glucocorticoid treatment and those who were resistant, and to clarify key clinical factors influencing the sensitivity to systemic glucocorticoid treatment.Methods:From May 2021 to May 2023, a cohort of patients with progressive non-segmental vitiligo receiving systemic glucocorticoid treatment was established in Huashan Hospital, Fudan University. Clinical data and peripheral blood samples were prospectively collected from all enrolled patients. Standard treatment, i.e., intramuscular injections of 1 ml of compound betamethasone once a month, was administered. After 3-month treatment, the improvement of patients′ skin lesions was estimated, and the vitiligo area and severity index (VASI) score and the Vitiligo European Task Force assessment tool (VETFa) were used to evaluate the efficacy. Patients with VASI changes ≥ 0 and VETFa progression scores ≤ 0 point were included in the glucocorticoid-sensitive group (i.e., the patients′ condition was stable or improved), otherwise those with VASI changes < 0 and VETFa progression scores of 1 point were included in the glucocorticoid-resistant group. Associations of lesion locations, specific clinical markers (trichrome lesions, confetti-like depigmentation, and Koebner phenomenon), previous medication history, family history of vitiligo, etc. with the response to systemic glucocorticoid treatment were analyzed. At baseline and after 3-month treatment, peripheral blood samples were collected from the patients, and enzyme-linked immunosorbent assay was performed to detect the plasma levels of CXCL9 and CXCL10. Statistical analysis was carried out by using the chi-square test, Fisher′s exact test, binary logistic regression analysis, Mann-Whitney U test, and Wilcoxon signed-rank test. Results:A total of 142 patients with vitiligo were enrolled, and 127 completed 3-month treatment, including 77 males and 50 females. Their age at diagnosis was 18 to 65 (36.6 ± 11.4) years, and the disease duration ranged from 2 months to 58 (13.5 ± 10.7) years; 25 (19.7%) had a family history of vitiligo; the percentage of lesion area to total body surface area before treatment ranged from 1% to 70% (11.5% ± 12.7%), and the VASI score was 1% to 70% (10.8% ± 11.6%). Multivariate logistic regression analysis showed that the absence of specific clinical markers (odds ratio [ OR] = 6.900, 95% confidence interval [ CI]: 1.228, 38.757, P = 0.028), carrying a single specific clinical marker ( OR = 2.579, 95% CI: 1.012, 6.574, P = 0.047), having a history of topical glucocorticoid treatment ( OR = 2.643, 95% CI: 1.019, 6.850, P = 0.041), the absence of family history of vitiligo ( OR = 5.090, 95% CI: 1.070, 24.215, P = 0.030), and lesions on the proximal extremities ( OR = 3.767, 95% CI: 1.315, 10.793, P = 0.037) were risk factors for the resistance to systemic glucocorticoid treatment in the patients with vitiligo. After 3-month treatment, the glucocorticoid-sensitive group showed a significant decrease in plasma CXCL10 levels compared with those before treatment ( W = 571.00, P < 0.001), while there was no significant difference between the pre- and post-treatment CXCL10 levels in the glucocorticoid-resistant group ( W = 48.00, P = 0.524). Additionally, no significant difference was observed in changes of the plasma CXCL9 level before and after treatment between the glucocorticoid-sensitive and glucocorticoid-resistant groups ( P > 0.05) . Conclusions:Carrying no or a single specific clinical marker, having a history of topical glucocorticoid treatment, the absence of family history of vitiligo, and lesions on the proximal extremities appeared to be risk factors for the resistance to systemic glucocorticoid treatment in patients with progressive non-segmental vitiligo. Changes in CXCL10 levels after treatment may be used as an important evaluation indicator for determining whether patients with progressive vitiligo were resistant to systemic glucocorticoid treatment.

ObjectiveThis study conducted a "6 + 1" clinical comprehensive evaluation of the existing research on Zhichuanling oral liquid （ZOL） in the treatment of asthma，so as to clarify the clinical advantages and precise clinical positioning of ZOL in the treatment of asthma， lay a foundation for further research and academic promotion of ZOL， and provide new directions for patent cultivation. MethodAn evaluation method featuring a qualitative and quantitative combination was used， which considered the dimensions of safety，effectiveness，economy，innovation，suitability，accessibility， and traditional Chinese medicine （TCM） characteristics. According to Expert Meeting Law， relevant weights were obtained through voting. CSC_v2.0 software was used to calculate each dimension and convert it into the corresponding grade score. ResultBased on the existing materials，① ZOL instruction indicates the adverse reactions，taboo， and notes. Multiple data of clinical research before and after marketing and spontaneous reporting system shows that ZOL has controllable risk and good safety. Safety is rated as B grade. ② Multiple data of clinical research before marketing， systematic evaluation of clinical effectiveness， and Meta-analysis shows that ZOL has good effectiveness and clinical significance. Effectiveness is rated as a B grade. ③ Analysis of the cost-effectiveness of ZOL combined with conventional treatment shows that the economy of the drug is good and rated as a B grade. ④ ZOL has better innovation， which is rated as an A grade. ⑤ ZOL can basically meet the clinical drug needs based on the result of the questionnaire survey and has good suitability， which is rated as a B grade. ⑥ ZOL has better accessibility， and accessibility is rated as A grade. ⑦ ZOL involves a rich theory of TCM but insufficient experience of human usage. It is thus rated as a C grade in terms of TCM characteristics. Based on the results of "6 + 1" dimension，the clinical comprehensive evaluation of ZOL in the treatment of asthma （cold syndrome and heat syndrome）is rated as B category. ConclusionZOL has good clinical value and outstanding innovation and accessibility in the treatment of asthma （cold syndrome and heat syndrome）. It is recommended that ZOL be transformed into the relevant policy results of basic clinical drug management procedurally. At the same time，it is recommended to actively cultivate patents with TCM characteristics.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-a and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/b-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt b-catenin pathways.

Objective:To investigate the effect of intensive care unit (ICU) admission model on acute kidney injury (AKI) development and the prognosis in patients with sepsis.Methods:Patients with sepsis admitted to the ICU of Xinjiang Uygur Autonomous Region People's Hospital from January 2019 to July 2020 were retrospectively analyzed. According to the ICU admission model, the patients were divided into emergency group (first admission or emergency transfer from relevant surgical departments) and delayed group (transferred from the general ward due to disease evolution). Patients were divided into AKI group and non-AKI group according to whether AKI was accompanied. The gender, age, underlying diseases, surgical history, heart rate, laboratory test indicators, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), organ failure and acute complications were collected. The incidence of AKI, 28-day mortality and length of ICU stay were recorded. Univariate and multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis.Results:A total of 185 patients with sepsis were enrolled, including 96 cases in the emergency group and 89 cases in the delayed group. 119 cases of AKI occurred while 66 cases without AKI development. The incidence of AKI within 7 days and the 28-day mortality of patients in the delayed group were significantly higher than those in the emergency group [AKI incidence rate: 77.53% (69/89) vs. 52.08% (50/96), 28-day mortality: 24.72% (22/89) vs. 10.42% (10/96), both P < 0.05], and the length of ICU stay was significantly longer than that of the emergency group (days: 18.70±7.29 vs. 14.56±4.75, P < 0.05). Univariate Logistic analysis showed that there were significant differences in age, diabetes, hypertension, organ failure, heart failure, APACHEⅡscore, SOFA score, white blood cell count (WBC), absolute neutrophil value, platelet count (PLT), blood lactate, total bilirubin, and ICU transferred from general wards between AKI group and non-AKI group. Multivariate Logistic regression analysis showed that transfer from general ward to ICU due to disease evolution was an independent risk factor for AKI in ICU sepsis patients [odds ratio ( OR) = 5.165, 95% confidence interval (95% CI) was 3.911-6.823, P < 0.001]. Conclusion:Septic patients transferred from general ward to ICU due to disease evolution are more likely to develop AKI, and also had a higher mortality and longer ICU stay. It may be an independent risk factor for AKI complicated by patients with sepsis in ICU.

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.
Acute Generalized Exanthematous Pustulosis ; Adrenal Cortex Hormones ; Allopurinol ; Anti-Bacterial Agents ; Carbamazepine ; China ; Cicatrix ; Drug Hypersensitivity Syndrome ; Eosinophilia ; Humans ; Lymphatic Diseases ; Mortality ; Prognosis ; Public Health ; Retrospective Studies ; Skin ; Stevens-Johnson Syndrome ; Tertiary Healthcare

Objective To prepare quality control samples for St.Louis encephalitis virus(SLEV)molecular detection by constructing pseudovirus containing target sequences of SLEV.Methods According to the principles of armored RNA technique, the prM gene sequence of SLEV was cloned into the prokaryotic expression vector to generate recombinant plasmid pSE380-MS2-SLEV.Then, recombinant E.coli transformed with the corresponding plasmid was induced with IPTG to produce recombinant pseudovirus particles.The particles were purified by chloroform and further characterized by double enzyme digestion and transmission electron microscopy.The temperature sensitivity experiments and quantitative RT-PCR were performed to validate the potential of these pseudovirus particles as quality control samples.Results PCR amplification and sequencing analysis confirmed that the prM gene sequence of SLEV was cloned into vector pSE380-MS2.Transmission electron microscopy showed that homogenous spherical particles with a diameter of about 25 nm were produced upon IPTG induction.The SLEV genomic RNA within the pseudovirus particles was resistant to DNaseⅠand RNase A digestion, and remained stable for 20 days at 37℃.These samples were validated with quantitative RT-PCR for SLEV.Conclusion The RNase-resistant and stable pseudovirus particles containing prM fragment of SLEV are constructed successfully, which can be used as positive quality control samples for RNA extraction and molecular detection.