This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective The aim of this study was to detect the expression of miR-383-5p in bladder cancer tissues and bladder cancer 5637 cells,BIU-87 cells,TCCSUP cells and HT-1376 cells,and to explore the effects of miR-383-5p on the prolif-eration,invasion,migration and apoptosis of bladder cancer cells by targeting CIP2A.Methods The expression of miR-383-5p was detected by qRT-PCR in human bladder cancer tissues and their corresponding adjacent tissues,5637 cells,BIU-87 cells,TCCSUP cells,HT-1376 cells,human bladder transitional epithelial cells.BIU-87 cells with low miR-383-5p expression were selected for subsequent experiments.BIU-87 cells were divided into the blank group(normal culture),miR-383-5p NC group(negative control,transfected with miR-383-5p negative control),miR-383-5p mimic group(transfected with miR-383-5p mimic),and miR-383-5p mimic+pc-CIP2A group(co-transfected with miR-383-5p mimic and CIP2A overexpression plasmid pc-CIP2A).CCK-8 kit was used to detect the viability of BIU-87 cells in each group;Flow cytometry was used to detect apoptosis of BIU-87 cells;Transwell assay was used to measure cell invasion ability of BIU-87 cells;Scratch assay was used to measure cell migration ability of BIU-87 cells;Western blot was used to determine the expression of proteins related to apoptosis,invasion(MMP-2,MMP-9),and CIP2A/PP2A in BIU-87 cells;The dual luciferase assay was used to verify the targeting relationship between miR-383-5p and CIP2A in BIU-87 cells.Results The expression of miR-383-5p was low in bladder cancer tissues and bladder cancer cells.Compared with the blank group,BIU-87 cells in the miR-383-5p mimic group showed a significant increase the level of miR-383-5p(0.91±0.10 vs.1.67±0.24,P<0.01)and a significant decrease in the expression of CIP2A protein(1.32±0.17 vs.0.45±0.03,P<0.001),the cell viability,invasion,migration abilities,the expression of proteins related to invasion(MMP-2,MMP-9),and the expression of Bcl-2 protein[(100.00±4.36)% vs.(32.15±2.65)% ,(150.20±12.95)vs.(82.35±7.01),(77.91±3.63)% vs.(46.12±2.54)% ,1.02±0.11 vs.0.22±0.04,1.03±0.18 vs.0.21±0.04,1.01±0.14 vs.0.27±0.05,P<0.001];The apoptosis rate,the expression of caspase-3 and Bax proteins related to apoptosis,and PP2A expression were significantly increased[(14.02±2.29)% vs.(38.21±3.20)% ],0.81±0.11 vs.1.78±0.24,0.83±0.12 vs.1.72±0.24,0.27±0.02 vs.0.95±0.16,P<0.001].Compared with the miR-383-5p mimic group,BIU-87 cells in the miR-383-5p mimic+pc-CIP2A group significantly increased the cell viability,invasion,migration abilities,the expression of proteins related to invasion,and the expression of Bcl-2 protein[(32.15±2.65)% vs.(50.18±3.77)% ,(82.35±7.01)% vs.(116.30±13.70),(46.12±2.54)% vs.(58.43±3.15)% ,0.22±0.04 vs.0.60±0.08,0.21±0.04 vs.0.5 8±0.06,0.27±0.05 vs.0.64±0.08,P<0.05];The apoptosis rate,the expression of caspase-3,Bax,and PP2A was signifi-cantly reduced in the miR-383-5p mimic+pc-CIP2A group[(38.21±3.20)% (23.15±2.74)% ,1.78±0.24 vs.1.25±0.21,1.72±0.24 vs.1.23±0.18,0.95±0.16 vs.0.60±0.13,P<0.05].The results of dual luciferase experiments showed a corresponding tar-geting relationship between miR-383-5p and CIP2A.Conclusion Increasing the expression of miR-383-5p can inhibit the prolif-eration,invasion and migration of bladder cancer BIU-87 cells,and enhance the ability of apoptosis,which may be achieved by targe-ted regulation of CIP2A.

Objective:Taking Inflammatory Bowel Disease(IBD)patients as an example,to explore the impact of disparities in regional outpatient security policies on medication reimbursement benefits for patients,and to provide insights for promoting the reform and development of equal outpatient security policy.Methods:39 cities from 9 provinces in China were selected as research samples to analyze the types,coverage,and benefits of their outpatient security policies.Indicators such as the individual out-of-pocket ratio,deductible,and specified reimbursement rate were used to simulate the actual reimbursement ratio for IBD patients using negotiated drugs.Results:Under the general outpatient coordination policy,the average actual reimbursement rate for medications in IBD patients was 26.36%for residents and 36.47%for employees.Under the outpatient chronic and special disease policy,the average actual reimbursement rate was 42.49%for residents and 50.94%for employees,while patients receiving drug treatment under the outpatient special drug policy have an average actual reimbursement rate of 51.62%(for residents)and 64.92%(for employees).Conclusion:Under China's outpatient security policies,there are significant disparities in reimbursement benefits for IBD patients across different regions.Therefore,it is recommended to strengthen the coordination of outpatient security policies across regions,optimize policy design,and provide patients with more equitable and accessible medical coverage.

Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.

Objective:Taking Inflammatory Bowel Disease(IBD)patients as an example,to explore the impact of disparities in regional outpatient security policies on medication reimbursement benefits for patients,and to provide insights for promoting the reform and development of equal outpatient security policy.Methods:39 cities from 9 provinces in China were selected as research samples to analyze the types,coverage,and benefits of their outpatient security policies.Indicators such as the individual out-of-pocket ratio,deductible,and specified reimbursement rate were used to simulate the actual reimbursement ratio for IBD patients using negotiated drugs.Results:Under the general outpatient coordination policy,the average actual reimbursement rate for medications in IBD patients was 26.36%for residents and 36.47%for employees.Under the outpatient chronic and special disease policy,the average actual reimbursement rate was 42.49%for residents and 50.94%for employees,while patients receiving drug treatment under the outpatient special drug policy have an average actual reimbursement rate of 51.62%(for residents)and 64.92%(for employees).Conclusion:Under China's outpatient security policies,there are significant disparities in reimbursement benefits for IBD patients across different regions.Therefore,it is recommended to strengthen the coordination of outpatient security policies across regions,optimize policy design,and provide patients with more equitable and accessible medical coverage.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective The aim of this study was to detect the expression of miR-383-5p in bladder cancer tissues and bladder cancer 5637 cells,BIU-87 cells,TCCSUP cells and HT-1376 cells,and to explore the effects of miR-383-5p on the prolif-eration,invasion,migration and apoptosis of bladder cancer cells by targeting CIP2A.Methods The expression of miR-383-5p was detected by qRT-PCR in human bladder cancer tissues and their corresponding adjacent tissues,5637 cells,BIU-87 cells,TCCSUP cells,HT-1376 cells,human bladder transitional epithelial cells.BIU-87 cells with low miR-383-5p expression were selected for subsequent experiments.BIU-87 cells were divided into the blank group(normal culture),miR-383-5p NC group(negative control,transfected with miR-383-5p negative control),miR-383-5p mimic group(transfected with miR-383-5p mimic),and miR-383-5p mimic+pc-CIP2A group(co-transfected with miR-383-5p mimic and CIP2A overexpression plasmid pc-CIP2A).CCK-8 kit was used to detect the viability of BIU-87 cells in each group;Flow cytometry was used to detect apoptosis of BIU-87 cells;Transwell assay was used to measure cell invasion ability of BIU-87 cells;Scratch assay was used to measure cell migration ability of BIU-87 cells;Western blot was used to determine the expression of proteins related to apoptosis,invasion(MMP-2,MMP-9),and CIP2A/PP2A in BIU-87 cells;The dual luciferase assay was used to verify the targeting relationship between miR-383-5p and CIP2A in BIU-87 cells.Results The expression of miR-383-5p was low in bladder cancer tissues and bladder cancer cells.Compared with the blank group,BIU-87 cells in the miR-383-5p mimic group showed a significant increase the level of miR-383-5p(0.91±0.10 vs.1.67±0.24,P<0.01)and a significant decrease in the expression of CIP2A protein(1.32±0.17 vs.0.45±0.03,P<0.001),the cell viability,invasion,migration abilities,the expression of proteins related to invasion(MMP-2,MMP-9),and the expression of Bcl-2 protein[(100.00±4.36)% vs.(32.15±2.65)% ,(150.20±12.95)vs.(82.35±7.01),(77.91±3.63)% vs.(46.12±2.54)% ,1.02±0.11 vs.0.22±0.04,1.03±0.18 vs.0.21±0.04,1.01±0.14 vs.0.27±0.05,P<0.001];The apoptosis rate,the expression of caspase-3 and Bax proteins related to apoptosis,and PP2A expression were significantly increased[(14.02±2.29)% vs.(38.21±3.20)% ],0.81±0.11 vs.1.78±0.24,0.83±0.12 vs.1.72±0.24,0.27±0.02 vs.0.95±0.16,P<0.001].Compared with the miR-383-5p mimic group,BIU-87 cells in the miR-383-5p mimic+pc-CIP2A group significantly increased the cell viability,invasion,migration abilities,the expression of proteins related to invasion,and the expression of Bcl-2 protein[(32.15±2.65)% vs.(50.18±3.77)% ,(82.35±7.01)% vs.(116.30±13.70),(46.12±2.54)% vs.(58.43±3.15)% ,0.22±0.04 vs.0.60±0.08,0.21±0.04 vs.0.5 8±0.06,0.27±0.05 vs.0.64±0.08,P<0.05];The apoptosis rate,the expression of caspase-3,Bax,and PP2A was signifi-cantly reduced in the miR-383-5p mimic+pc-CIP2A group[(38.21±3.20)% (23.15±2.74)% ,1.78±0.24 vs.1.25±0.21,1.72±0.24 vs.1.23±0.18,0.95±0.16 vs.0.60±0.13,P<0.05].The results of dual luciferase experiments showed a corresponding tar-geting relationship between miR-383-5p and CIP2A.Conclusion Increasing the expression of miR-383-5p can inhibit the prolif-eration,invasion and migration of bladder cancer BIU-87 cells,and enhance the ability of apoptosis,which may be achieved by targe-ted regulation of CIP2A.

Objective To establish evaluation indicators of nutrition care ability for carrying out oral feeding by caregivers of patients with post-stroke dysphagia (PSD) so as to provide references for nursing staff in evaluation of the nutritional care ability of caregivers and for the targeted health education. Methods Based on the caregiver skill model proposed by Farran et al,literature review and analysis,semi-structured interview,Delphi expert inquiry,analysis with the Analytic Hierarchy Process and pre-survey were conducted to establish a pool of evaluation indicators for nutrition care ability in carrying out oral feeding by caregivers of patients with PSD and to determine the weights of indicators. Results The two rounds of inquiry questionnaires achieved effective response rates of 90.00％ and 100.00％,respectively. The expert authority coefficients were at 0.869 and 0.910,and the coefficients of variation ranged 0.035 to 0.162 and 0.025 to 0.078 for the first and second rounds. The Kendall coordination coefficients were between 0.205 and 0.276 for the first round and between 0.278 and 0.364 for the second round (P<0.01). Based on expert consultations,the evaluation indicators were finalised,comprising 6 primary indicators and 38 secondary indicators,with consistency coefficients of each level indicator is less than 0.05. The primary indicators consisted of the knowledge of oral feeding nutrition care,attitude of oral feeding nutrition care,care skills,personal qualities of the caregiver,management of own emotions,and management of family and social resources. Conclusion The evaluation indicators for nutrition care ability to carry out oral feeding by caregivers of patients with PSD has been established. They are scientifically sound and rational,with strong practicality,and are able to provide a reference for nursing staff in evaluation of the nutrition care ability of caregivers and the health education.

Objective To establish evaluation indicators of nutrition care ability for carrying out oral feeding by caregivers of patients with post-stroke dysphagia (PSD) so as to provide references for nursing staff in evaluation of the nutritional care ability of caregivers and for the targeted health education. Methods Based on the caregiver skill model proposed by Farran et al,literature review and analysis,semi-structured interview,Delphi expert inquiry,analysis with the Analytic Hierarchy Process and pre-survey were conducted to establish a pool of evaluation indicators for nutrition care ability in carrying out oral feeding by caregivers of patients with PSD and to determine the weights of indicators. Results The two rounds of inquiry questionnaires achieved effective response rates of 90.00％ and 100.00％,respectively. The expert authority coefficients were at 0.869 and 0.910,and the coefficients of variation ranged 0.035 to 0.162 and 0.025 to 0.078 for the first and second rounds. The Kendall coordination coefficients were between 0.205 and 0.276 for the first round and between 0.278 and 0.364 for the second round (P<0.01). Based on expert consultations,the evaluation indicators were finalised,comprising 6 primary indicators and 38 secondary indicators,with consistency coefficients of each level indicator is less than 0.05. The primary indicators consisted of the knowledge of oral feeding nutrition care,attitude of oral feeding nutrition care,care skills,personal qualities of the caregiver,management of own emotions,and management of family and social resources. Conclusion The evaluation indicators for nutrition care ability to carry out oral feeding by caregivers of patients with PSD has been established. They are scientifically sound and rational,with strong practicality,and are able to provide a reference for nursing staff in evaluation of the nutrition care ability of caregivers and the health education.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.