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 explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.

ObjectiveTo analyze the characteristics and changing trend of injury cause of mortality of residents in Qingpu District from 2002 to 2020， and to provide scientific reference for formulating regional prevention and control measures. MethodsThe injury mortality data of the registered residents in Qingpu District from 2002 to 2020 were collected. The indicators such as crude mortality rate， standardized mortality rate， and the ranking of causes of death were calculated. ResultsFrom 2002 to 2020， the average annual crude mortality rate was 50.27/100 000， the age-standardized mortality rate based on the world standard population（ASRW） was 30.08/100 000， and the age-standardized mortality rate based on the 2010 Chinese census（ASMRC） was 35.58/100 000. The average annual crude mortality rate of males was higher than that of females ［Z=54.402， Mantel-Hanszel χ²=1 742.509， P<0.01）. The overall injury mortality rate showed a downward trend with an average annual percent change（AAPC）of -4.07% （95%CI： -5.23%‒-2.90%）， P<0.001］. The top four causes of injury death were transportation accident， indeliberate fall， drowning， and suicide. The leading causes of death in 0‒ years old， 15‒ years old and ≥65 years old were drowning， transportation accident and indeliberate fall， respectively. The ASRW of transportation accident， drowning and suicide all showed a decreasing trend， and the AAPC were -8.22% （95%CI： -10.16%‒-6.24%）， -6.99% （95%CI： -9.68%‒-4.22%） and -6.21% （95%CI： -9.38%‒-2.94%）， respectively. ConclusionThe injury death rate of residents in Qingpu District shows a decreasing trend， and the distribution characteristics of injury death are different among different genders and age groups. Corresponding prevention and control strategies should be adopted for different populations.

ObjectiveTo investigate the possible mechanism of Ruyi Heibai Power （如意黑白散， RHP） in the treatment of vitiligo. MethodsTwenty-four C57BL/6 mice were randomly divided into blank group， model group， high-dose and low-dose RHP groups， with 6 mice in each group. Model group， high- and low-dose RHP groups were all applied hydroquinone to establish vitiligo animal model. After modeling， High- and low-dose RHP groups were given 7.02 g/kg and 2.34 g/kg of RHP by gavage， respectively， while the blank group and model group were intragastrically given 10ml/kg of normal saline， once a day for 36 days. After administration， the skin lesions were observed with naked eye， and HE staining was used to observe the melanin content of the skin lesions. Immunohistochemistry was used to determine the expression of CD3⁺ and CD8⁺ T cells in skin tissue. Immunofluorescence staining was used to measure the expression of programmed death receptor 1 （PD-1） in the skin lesion tissue. RT-PCR was used to detect programmed cell death ligand 1 （PD-L1） mRNA expression. ELISA was used to detect serum superoxide dismutase （SOD）， tumor necrosis factor （TNF-α）， and tyrosinase （TYR） levels. ResultsCompared to those in the blank group， the skin of the mice in the model group was pale， and the melanin content was significantly reduced under the microscope after HE staining； the rate of excellent and good skin lesions decreased， and the melanin granules in the cells around the epidermis and hair follicles decreased significantly； the expression of CD3⁺ and CD8⁺ T cells in skin tissue increased significantly， and the expressions of PD-L1 mRNA and PD-1 decreased； the content of TYR decreased， while the content of SOD and TNF-α increased （P＜0.05）. Compared to those in the model group， the skin color of high- and low-dose RHP groups were deepened， and the melanin content increased； the rate of excellent and good skin lesions increased， as well as the melanin granules in the spinous cell layer， basal cells and hair follicles； the expression of CD3⁺ and CD8⁺ T cells in the skin lesions decreased， while PD-L1 mRNA and PD-1 expression increased； the content of TYR increased， while the content of SOD and TNF-α decreased （P＜0.05）. Compared to the low-dose RHP group， the high-dose group had a larger pigment recovery area in the modeling area， an increased rate of excellent and good skin lesions， an increase in spinous cell layer， basal cells， and hair follicle melanin granules， a decrease in CD3⁺ and CD8⁺ T cells expression， an increase in the expression of PD-L1 mRNA and PD-1， an elevated TYR content， and decreased SOD and TNF-α contents （P＜0.05）. ConclusionRHP can increase skin melanin content of vitiligo mice.The mechanism of action may be related to activating the PD-1/PD-L1 signaling pathway， and then reducing the destruction of melanocytes by T cell-mediated autoimmunity.

Objective To compare the early embryonic developmental potential and clinical outcomes of oocytes matured in vivo and those matured by modified in vitro maturation(LVM)technology during the same controlled ovarian hyperstimulation(COH)cycle,and to explore the clinical application of melatonin-supplemented IVM technology.Methods 159 patients were recruited into the study.920 mature oocytes were collected during their COH cycles processed for conventional IVF/ICSI protocols,while 1 283 immature oocytes from the same cycles were matured in a melatonin-supplemented IVM medium before ICSI was performed.A retrospective analysis was conducted to compare the impact of conventional assisted reproductive technology and improved IVM technology on the outcomes of assisted reproductive therapy and pregnancy outcomes.Results Compared with mature oocytes collected from COH cycles treated with conventional IVF/ICSI,oocytes promoted by improved melatonin-supple-mented IVM technology had a lower rate of high-quality blastocyst formation.However,after embryo transfer,there was no significant difference in the clinical outcomes of mature oocytes obtained through two methods,including clinical pregnancy rate,full-term birth rate,neonatal length,and neonatal Apgar score.Conclusion The applica-tion of melatonin-supplemented IVM significantly increases the utilization of immature oocytes collected from COH cycles,improving the pregnancy outcomes of patients assisted by assisted reproductive technology.

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease(KBD)in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion(ROM)with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients.Methods To investigate the registered KBD patients from KBD areas in Shaanxi Province,we measured the general demographic data of the patients were collected and the ROM of the knee joint(flexion and extension),the ankle joint(dorsiflexion and plantar flexion),and the muscle atrophy related indexes such as the upper arm circumference,thigh circumference,calf circumference and grip strength.According to the population characteristics,i.e.,gender,age,body mass index(BMI)and KBD grade,the median and quartile of joint ROM and muscle atrophy of KBD patients were reported,and then the differences in each index among different groups were analyzed.Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender,age and BMI.Results A total of 480 patients with KBD were investigated in this study,who consisted of 249(51.9％)males and 231(48.1％)females,with an average age of(63.10±7.32)years and an average BMI of(23.49±8.90)kg/m2.The knee flexion ROM,knee extension ROM,ankle dorsiflexion ROM and ankle plantar flexion ROM were[105.0(95.0,120.0)]°,[0.0(-15.0,0.0)]°,[5.0(0.0,15.0)]° and[20.0(15.0,30.0)]°,respectively,in KBD patients in Shaanxi Province.The left thigh circumference,right thigh circumference,left calf circumference,right calf circumference,and upper arm circumference were[43.0(40.0,47.0)]cm,[43.0(39.0,47.0)]cm,[29.0(27.0,32.0)]cm,[29.5(27.0,32.0)]cm,[27.0(25.0,30.0)]cm,respectively.The left hand grip strength and right hand grip strength were[13.4(9.5,18.4)]kg and[13.9(9.8,18.2)]kg,respectively.With the increase of age,the extension range of the left and right knee joints of KBD patients showed a decreasing trend(H=31.499,31.847;all P＜0.001).The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group,with statistically significant differences(H=7.753,12.333;P=0.021,0.002).The knee flexion,thigh circumference,and calf circumference of the left and right sides showed a decreasing trend under different KBD grades(H=14.345,17.256,8.000,8.462,8.558,9.633;all P＜0.05).Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference,calf circumference,and grip strength in patients with KBD(all P＜0.05).There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD(P＜0.01).Conclusion The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province,and there is a correlation between joint motion and muscle atrophy.

Objective To systematically evaluate the effect of speech and language therapies and educational interventions on chil-dren with intellectual and developmental disabilities(IDD). Methods A systematic review was conducted by searching relevant literature in PubMed,PsycINFO,ERIC,Cochrane Library and Web of Science databases,ranging from January,2018 to May,2024. Results A total of eight English articles were included,from six countries including the United States,France,Italy,Nor-way,Poland and New Zealand,involving 610 children with IDD,from journals about speech language pathology,Down syndrome research and speech language hearing research.The publication time was mainly from 2018 to 2023.The age of the subjects was two to twelve years,and the main health conditions included intellectual dis-ability,autism and Down syndrome.The intervention methods included routine speech therapy(individualized therapy and group therapy),augmentative and alternative communication(device-assisted and sign language and picture cards),family-involved language training programs(parent training and family interaction),computer-as-sisted language learning(language learning software and telehealth),and play-based interventions(interactive games and structured games);15 to 150 minutes a time,one to ten times a week,for ten to 144 weeks.The out-comes were reflected in five aspects:increasing the vocabulary in speaking;improving the language comprehen-sion,symbol recognition and vocabulary comprehension;improving both expressive and receptive language skills;improving participation in game diversity and game participation levels,communication,social interaction and interaction skills;and improving overall language and non-verbal communication skills. Conclusion Combining a variety of methods,such as individualized therapy,family participation,technologic assistance and interactive games,speech and language therapies and education are effective on spoken language production,language comprehension,speech production,social interaction and communication skills for children with IDD.