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 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 compare the clinical comprehensive value of 15 Chinese patent medicines for the treatment of chronic hepatitis B， in order to provide reference for clinical rational drug use. METHODS According to the Management Guidelines for Clinical Comprehensive Evaluation of Pharmaceuticals （2021 Version for Trial Implementation）， systematic literature review， meta-analysis and other related data analysis methods were used to perform qualitative and quantitative analysis for the safety， efficacy， economy， suitability， accessibility and innovation of 15 Chinese patent medicines. RESULTS In terms of safety， most of the adverse drug reactions of chronic hepatitis B Chinese patent medicines before the market were unobserved or unclear； post-marketing safety took nucleoside analogs as the intermediate bridge for meta-analysis， there was no significant difference in the incidence of adverse drug reactions among the combined regimens of Chinese patent medicines （P＞0.05）， except that the combination regimen of Fuzheng huayu capsule， Compound yiganling capsules versus combination regimen of Jiuwei gantai capsules showed statistically significant differences （P＜0.05）. In terms of effectiveness， the results of network meta-analysis showed that most Chinese patent medicines， such as Fuzheng huayu capsules combined regimens， had no significant differences in effective rate， HBeAg negative conversion rate and HBV-DNA negative conversion rate （P＞0.05）； however， in reducing the liver elastic hardness value， the combined regimen of Dangfei liganning tablet （capsule） was better than the other combined regimens （P＜0.05）. In terms of economy， the highest cost was the Shuganning injection， and the lowest was Hepatitis B qingre jiedu granules. In terms of suitability， most of the medicines were capsules， tablets and granules， which only needed to be sealed to store and taken orally or taken with boiling water. Compared with injections and some similar products that required strict control of storage temperature， its suitability was better. In terms of accessibility， from the perspective of drug price and affordability， Shuganning injection had the highest average daily cost， the number of days that needed to be borne by the average daily wage was the highest； the average daily cost of Compound yiganling tablets was the lowest， and the number of days required to be borne by the average daily wage was the lowest. From the perspective of availability， Compound biejia ruangan tablets， Dangfei liganning capsules and Wuzhi granules were easier to obtain. In terms of innovation， the 15 Chinese patent medicines included in the study were all domestically produced medicines with a relatively long-term theoretical basis of traditional Chinese medicine and experience in human medicine， and had good industrial innovation. Among them， Compound huayu tablets （capsules） and Anluo huaxian pills were protected varieties of traditional Chinese medicine； Fuzheng huayu tablets （capsules） with more patents had 6 valid patents， all of which were patents for invention. CONCLUSIONS Wuzhi capsule， Sedum sarmentosum granules， Compound yiganling tablets， Rhubarb buchong pills and Dangfei liganning capsules have high clinical comprehensive value.

ObjectiveTo explore the effect and mechanism of Zuojinwan （ZJW） in the treatment of ulcerative colitis （UC） through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking， the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group， a model group， a sulfasalazine group （300 mg·kg^-1）， and low-， medium-， and high-dose ZJW groups （1.82， 3.64， 7.28 g·kg^-1）. The UC model was induced by dextran sulfate sodium （DSS）， and oral administration of drugs began on the third day of modeling， lasting for 7 days. The general condition of mice was observed daily， and the disease activity index （DAI） was evaluated. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group， the model group had shortened colon length （P<0.01）， increased DAI scores， spleen index， colon tissue pathology scores， and levels of TNF-α and IL-6 in serum （P<0.05， P<0.01）， increased PI3K， phosphorylated Akt （p-Akt）， and B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax） expression in colon tissue （P<0.05， P<0.01）， and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）. Compared with the model group， the ZJW groups showed significant improvement in UC symptoms， relieved colon tissue pathological damage， downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum （P<0.01）， inhibited expression of PI3K， p-Akt， and Bax proteins in colon tissue （P<0.05， P<0.01）， and increased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）， with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC， and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
Mice ; Humans ; Animals ; Tumor-Associated Macrophages/metabolism* ; Carcinoma, Squamous Cell ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms ; GTP-Binding Proteins/metabolism* ; Head and Neck Neoplasms ; Ubiquitin-Protein Ligases/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; RGS Proteins/metabolism* ; Kinesins/metabolism* ; Repressor Proteins/metabolism*

Objective:To learn about the awareness, education status and willingness of iodine deficiency disorders (IDD) among elementary school students in Guizhou Province, and to provide a scientific basis for exploring intervention strategies for health education of iodine deficiency in the future.Methods:From June 2021 to May 2022, each IDD monitoring county was selected from the east, south, west, north and middle directions of Guizhou Province, and one elementary school was selected from each county. All students in two classes of Grade 5 and Grade 6 were selected in whole groups to conduct on-site questionnaire surveys in the form of anonymous examinations. The survey mainly included general demographic information and IDD awareness, education status and willingness, and binary logistic regression was used to analyze the relevant influencing factors.Results:A total of 1 259 elementary school students in Guizhou Province were investigated, the rates of awareness of IDD, acceptance of IDD publicity and education, and willingness to accept IDD publicity and education among elementary school students were 37.7% (1 900/5 036), 25.1% (316/1 259) and 69.6% (876/1 259), respectively. By binary logistic regression analysis, gender, residence, grade and father's education level were the influencing factors of pupils' awareness of iodine deficiency ( P < 0.05); residence, age and father's education level were the influential factors of elementary school students receiving iodine deficiency education ( P < 0.05); gender, residence, ethnicity and whether the child was the only child or not were the influential factors of elementary school students' willingness to accept IDD education ( P < 0.05). Conclusions:The elementary school students in Guizhou Province have insufficient knowledge about IDD. The publicity and education for iodine deficiency prevention is limited, and the students' willingness to learn is not high. The publicity, education and intervention for iodine deficiency prevention among elementary school students should be comprehensively strengthened.