Objective:To construct the rpoN gene knockout strain (Δ rpoN) and the complemented strain (CΔ rpoN) of Vibrio vulnificus ( V. vulnificus), and investigate the role of the rpoN gene in regulating bacterial motility and biofilm formation. Methods:The Δ rpoN strain of V. vulnificus was constructed using homologous recombination. Bacterial motility was assessed via swimming assays, and flagellar morphology was observed by transmission electron microscopy. Biofilm formation capacity was evaluated using crystal violet and Congo red staining assays, as well as colony morphology analysis. Real-time quantitative RT-PCR (qRT-PCR) was used to detect mRNA levels of target genes associated with flagellar synthesis and biofilm formation in Δ rpoN and the wild-type strains. Results:The V. vulnificus genome harbored a single rpoN gene, encoding a protein with high amino acid sequence similarity to RpoN homologs in other bacterial species. The Δ rpoN strain was successfully constructed. Compared with the wild-type strain, the Δ rpoN strain exhibited complete loss of motility on soft agar plates, absence of flagellar, and downregulated mRNA levels of flagellar synthesis-related genes. Conclusions:In V. vulnificus, RpoN regulates flagellar assembly by modulating the expression of flagellar synthesis genes, thereby controlling bacterial motility and biofilm formation.

Background::The prevalence of type 2 diabetes mellitus (T2DM) has been rapidly growing in Chinese populations in recent decades, and the shift in eating habits is a key contributing factor to this increase. Eating out of home (EOH) is one of the major shifts in eating habits during this period. However, the influence of EOH on the incidence of T2DM among Chinese urban workers is unknown.Methods::The cross-sectional study involved an analysis of 13,904 urban workers recruited from 11 health examination centers in the major cities of China to explore the relationship between EOH and T2DM between 2013 September and 2016 March.Results::Average weekly EOH frequency ≥10 times was positively associated with increased incidence of T2DM in the sampled population (OR: 1.31 [1.11-1.54], p < 0.01), most notably in participants ≤45 years old (OR: 1.41[1.11-1.80], p < 0.01]) and in males (OR:1.26 [1.06-1.51], p < 0.01). An EOH frequency of 5 times/week appears as a threshold for a significant increase in the odds of T2DM. Weekly EOH frequency ≥5 times was associated with increased odds of T2DM in a dose-response manner in the total population and almost all subgroups ( poverall association < 0.05 and pnonlinearity ≤ 0.05). Conclusion::This study showed that a frequency of EOH (≥5 times/week) was associated with a frequency-dependent increase in the odds of T2DM urban workers in China. More nutrition promotion is needed to improve the eating behavior of Chinese urban workers to reduce T2DM risk.

Objective To evaluate the effectiveness and feasibility of a remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology.Methods A convenient and elderly-friendly mo-bile application(hereinafter referred to as Yaoshiyi APP)was developed,and a remote medication treatment management team consisting of clinical pharmacists from tertiary hospitals,community pharmacists,and community physicians was formed.Patients from communities were selected for practical research,led by pharmacists.Based on the Yaoshiyi APP,patients were subjected to 6 months of medication treatment management practice,and the effectiveness and feasibility of the practice were evaluated.Re-sults The Yaoshiyi APP can be integrated with a variety of medical-grade wearable devices to realize the functions of automati-cally uploading monitoring data,abnormal value reminding,medication reminding,medication consultation,and medication sci-ence popularization.A total of 302 elderly patients with chronic disease at home completed the study.The results showed that phar-macists have identified and intervened in 695 cases of medication-related problems.According to the classification of medication-related problems,the top three were 247 cases(35.5％)of additional treatment,97 cases(14.0％)of unnecessary drug treat-ment,and 93 cases(13.4％)of medication compliance problems.The patient's medication adherence score(Morisky medication adherence scale-8,MMAS-8)increased from(5.85±1.57)at enrollment to(6.74±1.23)6 months after enrollment(P＜0.01).After 6 months of enrollment,the patient's satisfaction with the pharmacist's work reached a score of(4.99±0.08)out of 5.The average reduction in drug costs for patients caused by pharmacists intervening in irrational medication is(20.9±18.0)％.At the end of follow-up,93.4％of patients were proficient in using the Yaoshiyi APP.Conclusion The remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology constructed in this study can ef-fectively improve patient compliance with disease monitoring and medication,ensure rational drug use,reduce medical resource waste,and receive high patient acceptance.

Background::The prevalence of type 2 diabetes mellitus (T2DM) has been rapidly growing in Chinese populations in recent decades, and the shift in eating habits is a key contributing factor to this increase. Eating out of home (EOH) is one of the major shifts in eating habits during this period. However, the influence of EOH on the incidence of T2DM among Chinese urban workers is unknown.Methods::The cross-sectional study involved an analysis of 13,904 urban workers recruited from 11 health examination centers in the major cities of China to explore the relationship between EOH and T2DM between 2013 September and 2016 March.Results::Average weekly EOH frequency ≥10 times was positively associated with increased incidence of T2DM in the sampled population (OR: 1.31 [1.11-1.54], p < 0.01), most notably in participants ≤45 years old (OR: 1.41[1.11-1.80], p < 0.01]) and in males (OR:1.26 [1.06-1.51], p < 0.01). An EOH frequency of 5 times/week appears as a threshold for a significant increase in the odds of T2DM. Weekly EOH frequency ≥5 times was associated with increased odds of T2DM in a dose-response manner in the total population and almost all subgroups ( poverall association < 0.05 and pnonlinearity ≤ 0.05). Conclusion::This study showed that a frequency of EOH (≥5 times/week) was associated with a frequency-dependent increase in the odds of T2DM urban workers in China. More nutrition promotion is needed to improve the eating behavior of Chinese urban workers to reduce T2DM risk.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

Objective:To construct the rpoN gene knockout strain (Δ rpoN) and the complemented strain (CΔ rpoN) of Vibrio vulnificus ( V. vulnificus), and investigate the role of the rpoN gene in regulating bacterial motility and biofilm formation. Methods:The Δ rpoN strain of V. vulnificus was constructed using homologous recombination. Bacterial motility was assessed via swimming assays, and flagellar morphology was observed by transmission electron microscopy. Biofilm formation capacity was evaluated using crystal violet and Congo red staining assays, as well as colony morphology analysis. Real-time quantitative RT-PCR (qRT-PCR) was used to detect mRNA levels of target genes associated with flagellar synthesis and biofilm formation in Δ rpoN and the wild-type strains. Results:The V. vulnificus genome harbored a single rpoN gene, encoding a protein with high amino acid sequence similarity to RpoN homologs in other bacterial species. The Δ rpoN strain was successfully constructed. Compared with the wild-type strain, the Δ rpoN strain exhibited complete loss of motility on soft agar plates, absence of flagellar, and downregulated mRNA levels of flagellar synthesis-related genes. Conclusions:In V. vulnificus, RpoN regulates flagellar assembly by modulating the expression of flagellar synthesis genes, thereby controlling bacterial motility and biofilm formation.

Objective To evaluate the effectiveness and feasibility of a remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology.Methods A convenient and elderly-friendly mo-bile application(hereinafter referred to as Yaoshiyi APP)was developed,and a remote medication treatment management team consisting of clinical pharmacists from tertiary hospitals,community pharmacists,and community physicians was formed.Patients from communities were selected for practical research,led by pharmacists.Based on the Yaoshiyi APP,patients were subjected to 6 months of medication treatment management practice,and the effectiveness and feasibility of the practice were evaluated.Re-sults The Yaoshiyi APP can be integrated with a variety of medical-grade wearable devices to realize the functions of automati-cally uploading monitoring data,abnormal value reminding,medication reminding,medication consultation,and medication sci-ence popularization.A total of 302 elderly patients with chronic disease at home completed the study.The results showed that phar-macists have identified and intervened in 695 cases of medication-related problems.According to the classification of medication-related problems,the top three were 247 cases(35.5％)of additional treatment,97 cases(14.0％)of unnecessary drug treat-ment,and 93 cases(13.4％)of medication compliance problems.The patient's medication adherence score(Morisky medication adherence scale-8,MMAS-8)increased from(5.85±1.57)at enrollment to(6.74±1.23)6 months after enrollment(P＜0.01).After 6 months of enrollment,the patient's satisfaction with the pharmacist's work reached a score of(4.99±0.08)out of 5.The average reduction in drug costs for patients caused by pharmacists intervening in irrational medication is(20.9±18.0)％.At the end of follow-up,93.4％of patients were proficient in using the Yaoshiyi APP.Conclusion The remote medication treatment management model for elderly patients with chronic disease at home based on mobile technology constructed in this study can ef-fectively improve patient compliance with disease monitoring and medication,ensure rational drug use,reduce medical resource waste,and receive high patient acceptance.

ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

OBJECTIVE To investigate the current status of pharmaceutical care in medical institutions in China， and provide experience and suggestions for better development of pharmaceutical care. METHODS Questionnaire survey was used to investigate the development of pharmaceutical care in medical institutions in 31 provinces （autonomous regions and municipalities directly） in March 2023， and descriptive analysis and binary logistic regression analysis on the influencing factors of pharmaceutical care were conducted. RESULTS A total of 1 368 questionnaires were sent out， and 1 304 valid questionnaires were collected with the effective recovery rate of 95.32%. Pharmaceutical care was carried out in 671 medical institutions （51.46%）， and the rates of pharmaceutical care in tertiary， secondary， primary and other medical institutions were 74.79%， 27.97% and 7.35%， respectively. The average number of patients receiving pharmaceutical care was 2 638.96 per year， and there were 8.33 pharmacists in each medical institution to carry out pharmaceutical care， among which 93.68% were clinical pharmacists. The main departments covered by pharmaceutical care services included respiratory and critical care medicine， cardiology， intensive care unit， endocrinology， oncology， gastroenterology， obstetrics and gynecology and other departments. There were only 48 medical institutions （7.15%） with additional compensation for pharmaceutical care services. The main experiences of developing pharmaceutical care were to pay attention to talent cultivation and discipline construction， but the main difficulties were serious shortage of staff and qualified talents， low compensation level and low enthusiasm. Grade of medical institutions， the number of pharmacists engaged in clinical pharmacy， the number of qualified clinical pharmacists and the degree of information in the pharmacy department were the main influencing factors for carrying out pharmaceutical care （P＜0.05）. CONCLUSIONS In recent years， pharmaceutical care in Chinese medical institutions has made certain progress， while that of primary medical institutions， secondary medical institutions and other medical institutions should be improved. In the future， it is still necessary to further enhance the implementation of pharmaceutical care， promote personnel training， and attach importance to demonstrating the value of pharmaceutical care， thereby promoting the sustainable and high- quality development of pharmaceutical care.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.