Guided by the theory of "fire and original qi are restricted"， it is believed that original qi depletion is the root of the cutaneous immune-related adverse events （cirAEs） related to immune checkpoint inhibitors （ICIs）， and the yin fire exuberance is the branch. Among them， original qi depletion is the internal foundation of the disease， while the drug toxicity of ICIs harming original qi is the initiating factor， and exuberant yin fire is the key pathogenesis. In clinical practice， the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction （补中益气汤） can be used to activate transportation of middle jiao （焦） and promote ascent and dispersion of clear yang， thereby restoring the balance of qi and fire， and medicinals such as Huangqin （Radix Scutellariae）， Huanglian （Rhizoma Coptidis） and Huangbai （Cortex Phellodendri Chinensis） can be supplementetd to clear and drain yin fire. At the same time， considering the accompanying symptoms such as dampness-stasis and fluids depletion， the methods of removing dampness and dispelling stasis， supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.

ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula （芪术抗癌方， QZKAF） for the treatment of colorectal cancer （CRC）. MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC， and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation （GO） and Kyoto Encyclopedia of Genomes （KEGG） pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group， the model group， the 5-fluorouracil （5-Fu） group， and the QZKAF low-， medium-， and high-dose groups， with 8 mice in each group. Except for the sham operation group， the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling， while the QZKAF low-， medium-， and high-dose groups were given 2.925， 5.85， and 11.7 g/（kg·d） of QZKAF by gastric gavage， respectively， and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day， all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining， and the protein expression of protein tyrosine phosphatase nonreceptor type 1 （PTPN1）， vinculin， integrin subunit αν， integrin subunit β3， and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin， kaempferol， apigenin， luteolin， baicalein and ursolic acid. There were 212 targets of action， and the ranked top three were prostaglandin endoperoxide synthase 1 （PTGS1）， prostaglandin endoperoxide synthase 2 （PTGS2）， and PTPN1， which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， focal adhesion and adhesion junction. Molecular docking results： except for PTGS1 with better binding activity to quercetin， kaempferol， and apigenin （binding energy ≥-7.0 kcal/mol）， PTGS1 showed strong binding activity to lignans， baicalein， ursolic acid， as well as PTGS2 and PTPN1 to the six core active ingredients （binding energy ＜-7.0 kcal/mol）. Experimental validation results： the protein expression of PTPN1， vinculin， integrin subunit αν， integrin subunit β3 in the colon tumor tissues of mice in the model group significantly increased， and the expression of E-cadherin significantly decreased compared to those in the sham operation group （P＜0.05）. Compared to those in the model group， the mass of the in situ tumors was reduced， and the number of hepatic metastasis nodules decreased in the high- and medium-dose QZKAF groups （P＜0.05）； the expression levels of PTNP1， vinculin， integrin subunit αν， integrin subunit β3 and E-cadherin in all QZKAF groups and 5-Fu group showed different degrees of retracement， and the changes of the indicators in all QZKAF groups showed a certain degree of dose-dependence （P＜0.05）. HE staining showed that the nuclei of tumor cells in the model group were mostly schizophrenic， and there were different degrees of nuclear fragmentation of tumor cells in all QZKAF groups with more in the medium- and high-dose groups. ConclusionQZKAF could inhibit the growth of in situ tumors and liver metastasis of CRC. Its mechanism might be related to the regulation of tumor cell-cell and tumor cell-extracellular matrix adhesion by PTPN1.

OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P＜0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P＜0.01 or P＜0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

OBJECTIVE: Antiretroviral drugs covered by medical insurance have been gradually used by people living with human immunodeficiency virus (PLWH) in recent years in China. This study aimed to analyze their willingness to pay (WTP) for antiretroviral drugs. METHODS: A mixed-methods study design involving a cross-sectional survey and in-depth interviews was conducted. A cross-sectional survey was performed to collect data on the general characteristics, economic status, antiretroviral therapy (ART) status, and WTP of PLWH in 18 Chinese cities from August 2022 to February 2023. Multivariate logistic regression was used to analyze the factors associated with WTP. Representatives of PLWH were interviewed via in-depth interviews, and the data were thematically analyzed. RESULTS: Among the 941 PLWH, 271 (28.80%) were willing to pay for antiretroviral drugs covered by medical insurance. For basic medical insurance for urban and rural residents, PLWH with the following characteristics were more willing to pay: an educational level of senior high school or technical secondary school, having an undergraduate degree or higher, frequently working away from their hometowns, and homosexual transmission. Off-farm workers and recipients of government medical aid were more unwilling to pay. For basic medical insurance for urban employees, PLWH with the following characteristics were more willing to pay: frequently working away from their hometowns; homosexual transmission; personal annual income ≥ 100,000 CNY; and adverse events of antiretroviral drugs. The main reasons for PLWH's WTP for antiretroviral drugs covered by medical insurance were that the drugs had fewer adverse events and were easier to administer. The main reasons for PLWH's unwillingness to pay were financial difficulties and privacy concerns. CONCLUSION Nearly one-third of PLWH are willing to pay for antiretroviral drugs covered by medical insurance. In the future, PLWH with a high WTP can be guided to use these drugs.
Humans ; HIV Infections/economics* ; China ; Male ; Female ; Adult ; Cross-Sectional Studies ; Middle Aged ; Anti-Retroviral Agents/economics* ; Cities ; Insurance, Health/economics* ; Young Adult

ObjectiveThis paper analyzed the punishment situation of unlicensed medical practice in recent 7 years in Jinshan District of Shanghai， then suggested the countermeasures to prevent and combat unlicensed medical practice in the future. MethodsA total of 190 cases of unlicensed medical practice from 2016 to 2022 were investigated. The basic situation of the punishment，legal basis，subject distribution，clue source and individual characteristics were analyzed. ResultsThe case-filing number of unlicensed medical practice showed a decreasing trend，but the amount of fines increased obviously. The clues of investigation and punishment of unlicensed medicine practice were mainly found by inspection（32.11%） and transferred from other departments（28.42%）， while the number of complaints and clues reported from grassroots increased year by year. Medical and dental were the two major unlicensed practice，accounting for 35.79% and 33.16%， respectively. In addition， unlicensed medical cosmetology practice was increasing year by year. 78.62% of the unlicensed medical practioners are immigrants， 62.76% of them aged between 31 and 50 years old， among them 70.34% are men， and 62.76% of them have a fixed place. ConclusionThough the prevention and crack-down on unlicensed medical practice has achieved significant achievements，it is still necessary to enhance the responsibility of local administration，strengthen the inspection，investigate and deal with cases jointly by multiple departments，and implement the comprehensive supervision mechanism of the health care industry.