OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective To explore the clinicopathological characteristics,prognosis and influencing factors of different pathological subtypes of gastric signet ring cell carcinoma(GSRC).Methods A retrospective analysis was performed on the clinical data of 232 patients with GSRC collected from January 2016 to December 2018 in Lanzhou University Second Hospital.According to the WHO classification criteria for GSRC,the patients were divided into pure gastric signet-ring cell carcinoma(pGSRC,n=36)and mixed gastric signet-ring cell carcinoma(mGSRC,n=196).The follow-up as of September 30,2022,the survival analysis was done using Kaplan-Meier method,the univariate and multivariate Cox regression were performed to analyze the risk factors affecting the prognosis of GSRC patients.Results The median survival time of pGSRC and mGSRC patients was 41.0(6.0-70.0)months and 24.0(2.0-74.0)months,respectively.Kaplan-Meier analysis showed that combination with diabetes,anemia,tumor diameter,nerve invasion,lymphovascular invasion,T stage,N stage,GSRC pathological subtype,CA125 and tumor diameter could affect the overall survival(OS)of patients with GSRC after radical gastrectomy(P＜0.05),but Her-2,whether adjuvant chemotherapy or not and others elements had no significant effect on OS of GSRC patients after radical gastrectomy(P＞0.05).Univariate Cox regression analysis showed that the combination with diabetes(P=0.031),anemia(P=0.028),tumor diameter＞5 cm(P=0.009),nerve invasion(P=0.002),lymphovascular invasion(P=0.002),mGSRC pathological type(P=0.039),T2-T4 stage(P=0.001),N1-N4 stage(P=0.004),pTNM stage Ⅲ(P=0.044),the number of lymph node metastasis＞30(P=0.044)and CA125 positive(P=0.009)were related to the prognosis of patients with GSRC after radical gastrectomy.Multivariate Cox regression analysis showed that mGSRC pathological type(P=0.035),T2-T4 stage(P=0.003),CA125 positive(P=0.010)were independent risk factors for poor prognosis of patients with GSRC after radical gastrectomy.Conclusion Compared with pGSRC,patients with mGSRC at diagnosis have higher pTNM stages,more aggressive,and shorter median survival time.mGSRC pathological type,T2-T4 stage,and CA125 positive were all independent factors affecting the prognosis of patients with GSRC.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Aim To observe the behavioral effects of exogenous allopregnanolone(ALLO)and its inhibitor finasteride on the receptive period(R)and non-recep-tive period(NR)of PMDD liver-qi inversion model rats and the expression of GABAARα4,GABAARδ mR-NA and protein effects to explore its pathogenesis.Methods The PMDD liver-qi reverse syndrome rat model was prepared.The rats were divided into the normal group R and NR(control-R,control-NR),model group R and NR(Model-R,Model-NR),nor-mal group R+ALLO and NR+ALLO(Control+A-R,Control+A-NR),and model group R+ALLO and NR+ALLO(Model+A-R,Model+A-NR),model group R+finasteride and NR+finasteride(Model+F-R,Model+F-NR).The elevated cross labyrinth ex-periment and social interaction experiment were used to detect the behaviors of rats;fluorescence quantitative PCR and immunofluorescence were used to detect the expression of GABAARα4 and 8 mRNA and protein in rat amygdala and hippocampus.Results In the be-havioral evaluation,in the NR period,in the elevated cross maze test and in the social interaction test,the rats in the model group had anxiety behavior and de-creased social communication ability(P＜0.05),while the rats in the Model+A group could effectively relieve anxiety symptoms and improve their social com-munication ability(P＜0.05),and the rats in the Model+F group had increased anxiety behavior and social disorder(P＜0.05).In fluorescence quantita-tive PCR and immunofluorescence experiments,the ex-pression of GABAARα4 subunit in the model group was up-regulated in the hippocampus(P＜0.01),and the expression of δ subunit was down-regulated(P＜0.01);the expression of GABAARα4 subunit in the a-mygdala and hippocampus of the Model+A group de-creased(P＜0.01),and the expression of δ subunit increased in the hippocampus(P＜0.01).Conclu-sions The abnormal expression of GABAARα4 and 8 subunits mediated by ALLO improves the anxiety symptoms and social interaction ability of PMDD,which is the pathogenesis of PMDD liver-qi reverse syndrome,and provides basis and support for subse-quent exploration of the pathogenesis of PMDD liver-qi reverse syndrome.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.
Humans ; Severe Fever with Thrombocytopenia Syndrome/epidemiology* ; Bunyaviridae Infections/epidemiology* ; Thrombocytopenia/complications* ; Phlebovirus/genetics* ; Disease Outbreaks ; China/epidemiology*