Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Objective To establish the fingerprint of Jianggui granules, and evaluate it by chemometrics. Methods The fingerprint of Jianggui granules was established by HPLC. Similarity evaluation system of chromatographic fingerprint of TCM （2012 edition） was used to evaluate the similarity evaluation. Then, the quality of the drug was assessed by cluster analysis （CA）, principal components analysis （PCA） and partial least squares discriminant analysis （PLS-DA）. Results The characteristic fingerprint of Jianggui granules was established and 18 common peaks were verified. Five chromatographic peaks were identified，i.e. Puerarin, glycyrrhizin, cinnamic acid, cinnamaldehyde and ammonium glycyrrhizinate. The similarities of samples were >0.9. Results of CA showed that 14 batches of samples could be classified into two categories：S1 and S4 were grouped into one category；others were grouped into the other category. The results of PCA showed that the cumulative contribution rate of the first two principal components was 96.61%. The results of OPLS-DA showed that the eleven peaks with VIP value >1 were puerarin （peak 8）, glycyrrhizin （peak 14）, cinnamaldehyde （peak 17） and ammonium glycyrrhizinate （peak 18）. Conclusion HPLC fingerprint of Jianggui granules was established. The established method was accurate and reliable，which could be used in quality evaluation of Jianggui granules.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x（1）（ t+1）=1.16e 0.04t， x（1）（ t+1）=1.04e 0.12t and x（1）（ t+1）=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.

Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x（1）（ t+1）=1.16e 0.04t， x（1）（ t+1）=1.04e 0.12t and x（1）（ t+1）=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.

Objective To explore the effect of intestinal nitrates on the growth of Klebsiella pneumoniae and its regulatory mechanisms. Methods K. pneumoniae strains with nitrate reductase narG and narZ single or double gene knockout or with NarXL gene knockout were constructed and observed for both aerobic and anaerobic growth in the presence of KNO3 using an automated bacterial growth analyzer and a spectrophotometer, respectively. The mRNA expressions of narG and narZ in K. pneumoniae in anaerobic cultures in the presence of KNO3 and the effect of the binary regulatory system NarXL on their expresisons were detected using qRT-PCR. Electrophoretic mobility shift assays (EMSA) and MST analysis were performed to explore the specific regulatory mechanisms of NarXL in sensing and utilizing nitrates. Competitive experiments were conducted to examine anaerobic growth advantages of narG and narZ gene knockout strains of K. pneumoniae in the presence of KNO3. Results The presence of KNO3 in anaerobic conditions, but not in aerobic conditions, promoted bacterial growth more effectively in the wild-type K. pneumoniae strain than in the narXL gene knockout strain. In anaerobic conditions, the narXL gene knockout strain showed significantly lowered mRNA expressions of narG and narZ (P<0.0001). EMSA and MST experiments demonstrated that the NarXL regulator could directly bind to narG and narZ promoter regions. The wild-type K. pneumoniae strain in anaerobic cultures showed significantly increased expressions of narG and narZ mRNAs in the presence of KNO3 (P<0.01), and narG gene knockout resulted in significantly attenuated anaerobic growth and competitive growth abilities of K. pneumoniae in the presence of KNO3 (P<0.01). Conclusion The binary regulatory system NarXL of K. pneumoniae can sense changes in intestinal nitrate concentration and directly regulate the expression of nitrate reductase genes narG and narZ to promote bacterial growth.

Objective To explore the effect of intestinal nitrates on the growth of Klebsiella pneumoniae and its regulatory mechanisms. Methods K. pneumoniae strains with nitrate reductase narG and narZ single or double gene knockout or with NarXL gene knockout were constructed and observed for both aerobic and anaerobic growth in the presence of KNO3 using an automated bacterial growth analyzer and a spectrophotometer, respectively. The mRNA expressions of narG and narZ in K. pneumoniae in anaerobic cultures in the presence of KNO3 and the effect of the binary regulatory system NarXL on their expresisons were detected using qRT-PCR. Electrophoretic mobility shift assays (EMSA) and MST analysis were performed to explore the specific regulatory mechanisms of NarXL in sensing and utilizing nitrates. Competitive experiments were conducted to examine anaerobic growth advantages of narG and narZ gene knockout strains of K. pneumoniae in the presence of KNO3. Results The presence of KNO3 in anaerobic conditions, but not in aerobic conditions, promoted bacterial growth more effectively in the wild-type K. pneumoniae strain than in the narXL gene knockout strain. In anaerobic conditions, the narXL gene knockout strain showed significantly lowered mRNA expressions of narG and narZ (P<0.0001). EMSA and MST experiments demonstrated that the NarXL regulator could directly bind to narG and narZ promoter regions. The wild-type K. pneumoniae strain in anaerobic cultures showed significantly increased expressions of narG and narZ mRNAs in the presence of KNO3 (P<0.01), and narG gene knockout resulted in significantly attenuated anaerobic growth and competitive growth abilities of K. pneumoniae in the presence of KNO3 (P<0.01). Conclusion The binary regulatory system NarXL of K. pneumoniae can sense changes in intestinal nitrate concentration and directly regulate the expression of nitrate reductase genes narG and narZ to promote bacterial growth.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective Based on gender differences,this paper discusses the characteristics of facial color diagnosis in male and female patients with metaplastic chronic atrophic gastritis(CAG),and explores the pathological mechanism of different gender patients from the perspective of TCM pathogenesis,so as to provide personalized reference for TCM prevention and treatment of metaplastic CAG.Methods In this study,the complexion information of patients with chronic non atrophic gastritis(CNG)and CAG was collected by MT-BX-01 four-diagnostic instrument.The color colorimetric characteristics of male and female metaplastic CAG patients and CNG patients were analyzed by case-control study.Results In female patients,the L value and a value of liver region in CAG with mild intestinal metaplasia(IM)group,moderate and severe IM were significantly lower than those in CNG group(P<0.05).In male patients,the L value of spleen region in CAG with moderate and severe IM group was significantly higher than that in CNG group(P<0.05).Conclusion There is a certain gender difference in the facial color characteristics of patients with metaplastic CAG.The facial chromaticity value of female patients with metaplastic CAG changes most significantly in the liver area,while that of male patients mainly in the spleen area.It is suggested that the incidence of female metaplastic CAG is mostly related to liver,while that of male is mostly related to spleen,which provides a personalized method for clinical diagnosis and treatment of metaplastic CAG based on gender differences.