OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.

Objective:To explore the equity and driving path of primary healthcare human resource allocation across 31 provinces in China,providing references for optimizing such allocations.Methods:Using data from the 2022 primary healthcare human resources in 31 provinces in China,the Health Resource Density Index(HRDI)was used to measure the equity of primary healthcare human resource allocation.The fuzzy-set Qualitative Comparative Analysis(fsQCA)was applied to construct configurational pathways influencing on allocation patterns.Results:In 2022,the HRDI for primary healthcare human resources in China was 2.349 0 in the East,1.198 6 in the Central region,and 0.775 2 in the West.Configurational analysis revealed three paths that promote high equity:the internal-external balance-driven model(H1),the government-led model(H2),and the economic-demand combined model(H3),with overall consistency and coverage of 0.955 and 0.794,respectively.Seven paths lead to low equity:internal-external constraint models(L1,L2),economic constraint models(L3),and demand constraint models(L4,L5,L6,L7),with overall consistency and coverage of 0.967 and 0.795,respectively.Conclusions:Significant regional disparities exist in the equity of primary healthcare human resource allocation in China.Population density is a critical factor influencing allocation equity.The collaboration of various factors contributes to enhancing the equity of primary healthcare human resources distribution.Therefore,future efforts to enhance equity should focus on promoting inter-regional mobility and resource sharing,while precisely addressing regional shortcomings to achieve high equity in primary healthcare human resource allocation.

Objective:To explore the equity and driving path of primary healthcare human resource allocation across 31 provinces in China,providing references for optimizing such allocations.Methods:Using data from the 2022 primary healthcare human resources in 31 provinces in China,the Health Resource Density Index(HRDI)was used to measure the equity of primary healthcare human resource allocation.The fuzzy-set Qualitative Comparative Analysis(fsQCA)was applied to construct configurational pathways influencing on allocation patterns.Results:In 2022,the HRDI for primary healthcare human resources in China was 2.349 0 in the East,1.198 6 in the Central region,and 0.775 2 in the West.Configurational analysis revealed three paths that promote high equity:the internal-external balance-driven model(H1),the government-led model(H2),and the economic-demand combined model(H3),with overall consistency and coverage of 0.955 and 0.794,respectively.Seven paths lead to low equity:internal-external constraint models(L1,L2),economic constraint models(L3),and demand constraint models(L4,L5,L6,L7),with overall consistency and coverage of 0.967 and 0.795,respectively.Conclusions:Significant regional disparities exist in the equity of primary healthcare human resource allocation in China.Population density is a critical factor influencing allocation equity.The collaboration of various factors contributes to enhancing the equity of primary healthcare human resources distribution.Therefore,future efforts to enhance equity should focus on promoting inter-regional mobility and resource sharing,while precisely addressing regional shortcomings to achieve high equity in primary healthcare human resource allocation.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To investigate the characteristics of gut flora related to dampness syndrome in the population at risk of cerebrovascular disease and to explore their influencing factors.Methods Based on the results of epidemiological investigation of damp syndrome in at-risk population of cerebrovascular disease in Guangdong from October 2021 to February 2023,60 subjects(including 41 at-risk cases of cerebrovascular disease and 19 healthy controls)were included in the study.The identification of dampness syndrome and the risk rating of stroke were carried out for the subjects,and fecal samples were collected.High-throughput 16S rRNA sequencing technology and bioinformatics methods were used to analyze the characteristics of gut flora.Results(1)A total of 53 cases(88.33％)were identified as dampness syndrome.There was significant difference in the quantitative score of dampness syndrome between the risk group and the healthy group,and between the low-,medium-and high-risk groups(P=0.016;P=0.041).(2)There was no statistical difference in the species and abundance of gut flora between the dampness syndrome group and the non-dampness syndrome group.(3)In the population identified as dampness syndrome,there was no significant difference in Alpha diversity between the healthy group and the risk group,but there was significant difference in Beta diversity analysis;LEfSe analysis found that Fusobacterium and Lactobacillus were enriched in the risk group;correlation analysis showed that the differential bacteria were related to the three risk factors of diabetes,dyslipidemia and obesity and carotid intima-media thickness(IMT).(4)In the population identified as dampness syndrome and having the risk of cerebrovascular disease,there was no significant difference in Alpha diversity among three groups with different levels of risks,while significant difference in Beta diversity was observed;LEfSe analysis showed that Acidaminococcaceae,Phascolarctobacterium and Butyricimonas were enriched in the low-risk group,Veillonellaceae was enriched in the medium-risk group,and Ruminococcus 2 and Alloprevotella were enriched in the high-risk group;correlation analysis showed that the differential bacteria were associated with high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),white blood cell count(WBC),and neutrophil count(NEUT).Conclusion In the Guangdong population predominated by dampness syndrome,the severity of dampness syndrome is related to the risk of stroke,and the specific flora associated with sub-clinical atherosclerosis,inflammatory response and lipid metabolism are presented.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.