ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Objective To determine the content and distribution characteristics of the artificial radionuclide ¹³⁷Cs and the natural radionuclides ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K in wild edible fungi, and calculate the committed effective dose due to ¹³⁷Cs and ²¹⁰Pb in wild edible fungi. Methods Thirty samples of wild edible fungi were collected and their caps and stems were separated. A total of 60 samples were measured for ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K using a BE5030 wide-energy, low-background, high-purity germanium γ spectrometer. The paired analysis of the four radionuclides ²²⁶Ra, ²¹⁰Pb, ¹³⁷Cs, and ⁴⁰K was performed using SPSS 11.5. Results Among the 60 samples, the detection rates and dry weight specific activity ranges of ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra, and ⁴⁰K were 97% and 0.62-384 Bq/kg, 73% and 6.4-159 Bq/kg, 52% and 0.7-28.8 Bq/kg, 5% and 0.43-2.18 Bq/kg and 100% and （77.4-264) × 10 Bq/kg, respectively. Conclusion Based on the analysis of the 60 samples, the detection rate of radionuclides is in the order of ⁴⁰K, ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, and ²²⁸Ra. In terms of the specific activity, the distribution of ⁴⁰K and ²²⁶Ra in wild edible fungi in the same region is basically uniform, while the content of ²¹⁰Pb and ¹³⁷Cs fluctuates in different samples. Although ¹³⁷Cs and ²¹⁰Pb can be detected in most of the wild edible fungi, the annual committed effective dose due to ingestion of wild edible fungi is negligible.

Objective As an important monitoring target for gaseous effluents from nuclear facilities, the radioactive inert gas ⁸⁵Kr requires accurate measurement, which is crucial for nuclear safety and radiation protection. This study organized an inter-laboratory comparison activity for ⁸⁵Kr gamma-ray spectrometry measurements, with the aims of identifying potential problems in ⁸⁵Kr measurement and improving detection capabilities and proficiency. Methods Four laboratories participated in this comparison. Each laboratory employed gamma-ray spectrometry to measure the comparison samples, and the results were evaluated using the E_n value. Results The measurement results from all participating institutions were acceptable, with the maximum E_n value being 0.73. The results demonstrate that despite the low gamma-ray branching ratio of ⁸⁵Kr and its susceptibility to interference from the 511 keV positron annihilation peak, gamma-ray spectrometry can achieve reliable activity measurements of ⁸⁵Kr. Conclusion The comparison for ⁸⁵Kr gamma-ray spectrometry tested the capabilities of the participating laboratories in ⁸⁵Kr measurement. It promoted technical exchange and experience sharing among laboratories, laying a foundation for future comparisons involving more complex radioactive inert gases.

Objective To explore the effects of Shaoyao Gancao granule on hair growth,behavior,and the hypothalamic pituitary adrenal(HPA)axis in mice with alopecia areata(AA).Methods Forty-two C3H/HeJ mice were randomly divided into control,model,Shaoyao Gancao granule high-,middle-,low-dose,corticotropin-releasing hormone receptor 1(CRHR1)antagonist,and compound glycyrrhizin tablet(CGT)groups.Photography,dermoscopy,weight analysis,and behavioral measurement were performed.Corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol,glucocorticoid receptor(GR),and brain-derived neurotrophic factor(BDNF)were also assessed.Results Compared with the model group,high-dose Shaoyao Gancao granules improve hair regeneration and weight gain(P＜0.05),increased the percentage of total exercise distance and central area exercise distance in an open field test(P＜0.05),reduced the immobility time in the forced swimming and tail suspension experiments(P＜0.05),reduced peripheral blood levels of CRH,ACTH,and cortisol(P＜0.05),and increased expression of GR and BDNF in the hippocampus(P＜0.05).Conclusions Shaoyao Gancao granule promotes hair growth and improves behavioral performance in mice with AA.These effects may be related to downregulating CRH,ACTH,and cortisol expression,upregulating GR and BDNF expression,and inhibiting excessive activation of the HPA axis.

Objective:To explore the effects of depressive symptoms on sleep quality in adolescents with depressive disorder, and the mediating roles of cognitive fusion and sleep belief.Methods:A sample of 210 adolescents with first episode depressive disorder aged 12-18 years were recruited to complete 17-item Hamilton depression scale (HAMD-17), Pittsburgh sleep quality index (PSQI), cognitive fusion questionnaire (CFQ), and dysfunctional beliefs and attitudes about sleep scale (DBAS-16) from November 2021 to July 2022. SPSS 26.0 software was used to perform descriptive analysis and correlation analysis. The mediating effect was tested by Bootstrap analysis using PROCESS V 3.4 Macro program.Results:The incidence of low sleep quality in adolescents with depressive disorder was 69.0%(145/210). HAMD-17 score was (22.4±7.9), PSQI score was (9.7±3.7), CFQ score was (51.6±7.8), DBAS-16 score was (43.5±8.4).PSQI was positively correlated with the scores of HAMD-17 and CFQ( r=0.613, 0.463, both P<0.001).HAMD-17 was positively correlated with CFQ score ( r=0.488, P<0.001).DBAS-16 was negatively correlated with scores of PSQI, HAMD-17 and CFQ( r=-0.326, -0.284, -0.354, all P<0.001). The direct effect of depression on sleep quality was 0.230(95% CI=0.169-0.293). The indirect effect of depression on sleep quality through two pathways, the separate mediating effect value of cognitive fusion was 0.041 (95% CI=0.011-0.074), and the chain mediating effect value of cognitive fusion and sleep beliefs was 0.008(95% CI=0.001-0.020). Conclusion:Depressive symptoms can directly affect sleep quality of depressive disorder adolescents and indirectly through cognitive fusion and sleep beliefs.

Objective To collect and sort out the literature on the clinical medication experience of traditional Chinese medicine(TCM)in the treatment of hepatic precancerous lesions,and to summarize the characteristics of the disease and the treatment ideas by analyzing the rules of its formula,in order to provide instructions for the treatment of precancerous lesions of hepatocellular carcinoma with TCM in terms of medication and experience addition and subtraction.Methods CNKI,VIP,WanFang Data,CBM,PubMed,Web of Science,EMBASE,Cochrane databases were systematically searched,the clinical research and personal experience literature of TCM in the treatment of hepatic precancerous lesions from the establishment of the databases to December 2023 was included,and the prescription information that met the inclusion criteria was extracted.Based on"Traditional Chinese Medicine data Miner(TCM Miner)",the medication database was established to analyze the frequency,properties and flavours of the drugs and meridian tropism.The cluster analysis were conducted by SPSS 25.0 statistical software,and the association rules were analyzed by using Apriori algorithm of SPSS Modeler 14.1,and the complex network analysis of high-frequency drugs was conducted by network module of SPSS Modeler.Results 34 researches including 34 formulas,110 drugs with 291 frequencies and 15 drug efficacy were included.Frequency analysis showed that the top eight types of frequently applied drugs were milkvetch root,largehead atractylodes rhizome,radix salviae miltiorrhhizae,hedyotis,carapax trionycis,zedorgy rhidoray,barbated skullcup herb,redix curcumae.The top three properties in the"four qi"were cold,warm and mild.The top three tastes of the"five flavors"were bitterness,sweetness and acridity.The top four in the frequency of meridian tropism were liver,spleen,kidney and lung.Apriori correlation analysis showed that the core drug pairs was"Hedyotis diffusa+Atractylodes".Complex network analysis showed that the core prescriptions were composed of Atractylodes,Radix Paeoniae Alba,Hedyotis diffusa,Poria cocos,Rhizoma Curcumae,Radix Curcumae Aromaticae,Trionycis Carapax,Radix Astragali,Sparganium stoloniferum,Salvia miltiorrhiza,Scutellaria barbata.Conclusion The TCM treatment of hepatic precancerous lesions should be based on tonifying spleen and nourishing liver,promoting blood circulation and detoxification,and combined with drugs that can promote qi-circulation,clear heat,remove blood-stasis,soften hard masses and resolve hard masses.

OBJECTIVE: To assess the validity and effectiveness of parameter estimation using a time-dependent Weibull proportional hazards model for survival analysis containing partly interval censored data and explore the impact of different covariates on the results of analysis. METHODS: We established a time-dependent Weibull proportional hazards model using the Weibull distribution as the baseline hazard function of the model which incorporated time-varying covariates. Maximum likelihood estimation was employed to estimate the model parameters, which were obtained by optimization of the likelihood function. RESULTS AND CONCLUSION: Numerical simulation results showed that with higher proportions of precise observations across different sample sizes and parameter settings, the proposed model resulted in improved accuracy of parameter estimation with coverage probabilities approximating the theoretical expectation of 95%. As the sample sizes increased, the parameter biases of the model tended to decrease. Experiments with empirical data further validated the effectiveness of the model. Compared with the failure time data for each precisely observed individual, additional interval-censored data helped to obtain more effective estimates of the regression parameters. Comparison with the Cox model that included time-varying covariates further demonstrated the effectiveness of the time-dependent Weibull proportional hazards model for parameter estimation in survival analysis with partly interval censored data.
Proportional Hazards Models ; Survival Analysis ; Likelihood Functions ; Humans ; Computer Simulation ; Time Factors

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:To investigate the oral health knowledge awareness, attitude and behavior of children in endemic fluorosis areas of Guizhou Province, and evaluate the effectiveness of health education, so as to provide a scientific basis for improving oral health.Methods:In September 2020, 6 counties (cities and districts) were selected as survey sites from the historical fluorosis medium and severe areas in Guizhou Province. One township/village primary school was selected from each survey site to carry out health education activities for one school year. A questionnaire survey was conducted among students from grades 1 to 6 to analyze the changes in children's oral health knowledge, attitude, and behavior before and after health education and their influencing factors.Results:Before and after health education, the awareness rate of children's oral health knowledge increased from 79.22% (7 744/9 775) to 94.38% (9 169/9 715), the recognition rate of children's importance of oral health increased from 89.26% (3 490/3 910) to 95.88% (3 726/3 886), and the formation rate of children's oral health behavior increased from 62.59% (6 118/9 775) to 80.38% (7 809/9 715), with an increase of 15.16, 6.62 and 17.79 percentage points, respectively, the differences were statistically significant (χ 2 = 975.62, 15.17, 756.29, P < 0.001). The analysis of influencing factors showed that whether to stay, gender, and ethnic characteristics could significantly affect the overall score ( t = - 3.94, - 3.86, - 3.62, P < 0.001). Conclusion:The implementation of oral health education in endemic fluorosis areas in Guizhou Province has significantly improved the health knowledge, attitude and behavior of oral health among children in endemic fluorosis areas.

Objective:To investigate the awareness of iodine deficiency disorders prevention and control knowledge among residents in Guiyang City, as well as the behavioral and attitude characteristics of iodized salt consumption, and to determine the focus and direction of future health education on iodine deficiency disorders.Methods:From 0 : 00 to 24 : 00 on May 15, 2021 (the National Day for Prevention and Control of Iodine Deficiency Disorders), through the "Guizhou Disease Control" WeChat official account, the questionnaire was randomly distributed to the residents of Guiyang City who paid attention to the official account in the form of award-winning contest and returned. The survey content included general demographic data, iodine deficiency disorders prevention and control knowledge among residents and the behaviors and attitudes towards iodized salt consumption. The awareness rate of iodine deficiency disorders prevention and control knowledge among residents and the correct rate of their behaviors and attitudes towards iodized salt consumption were calculated.Results:A total of 3 078 valid questionnaires were collected in this survey. The awareness rate of iodine deficiency disorders prevention and control knowledge among residents was 51.3% (9 467/18 468), with a score of (51.26 ± 14.30) points; the correct rate of behavior and attitude towards iodized salt consumption was 93.0% (11 446/12 312), with a score of (92.97 ± 13.13) points. There was a statistically significant difference in the awareness rate of iodine deficiency disorders prevention and control knowledge among residents of different age groups (χ 2 = 23.03, P < 0.001). There were statistically significant differences in the correct rates of behavior and attitude towards iodized salt consumption among residents of different ages, ethnic groups, and professions (χ 2 = 9.66, 4.88, 24.73, P < 0.05), with lower correct rates in the ≥61 years old group, Han minority people and students. The main channels for obtaining knowledge on iodine deficiency disorders prevention and control were promotional materials (59.3%, 1 825/3 078), newspapers and magazines (56.8%, 1 747/3 078), television (56.6%, 1 743/3 078), and the internet (56.2%, 1 731/3 078). Conclusions:The correct rate of behavior and attitude towards iodized salt consumption among residents in Guiyang City is relatively high, but the awareness rate of iodine deficiency disorders prevention and control knowledge is low. We should strengthen health education for residents, especially the elderly, ethnic minorities, and students, and attach importance to promoting the safety of iodized salt and the necessity of long-term iodine supplementation.