Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

ObjectiveA qualitative analysis method was established for the composition of Astragali Radix（AR） before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice（ARR）， the structures of their major compounds were deduced and identified， and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the samples of AR and ARR in positive and negative ion modes， respectively. The compounds were analyzed and identified through self-constructed databases， literature， and reference standards， etc. And the data were analyzed by chemometrics， in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR， including 41 flavonoids， 19 terpenoids， 26 organic acids， 8 amino acids， 5 nucleotides， 5 carbohydrates and 19 other compounds. Among them， there were 95 common components in both， 18 unique components in AR， and 10 unique components in ARR. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying， and a total of 26 constituents with differences in the content were screened out， including L-canavanine， L-pyroglutamic acid， L-phenylalanine， cis-caffeic acid， and malonylastragaloside Ⅰ. Among them， 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids， terpenoids， and organic acids， and analyzes the components with significant differences in content between the two in combination with chemometrics， and the differential components are dominated by amino acids， organic acids and terpenoids， which can provide reference for the subsequent quality control and material basis research.

ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription （ZJYP） in Goto-Kakizaki （GK） rats with early-stage diabetic kidney disease （DKD）. MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding， with fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1 and urinary albumin/creatinine ratio （ACR） ≥ 30 mg·g^-1 used as model criteria. After successful modeling， DKD rats were randomly divided into five groups （n=10 in each group）： the model group， the western medicine group treated with dapagliflozin （1.0 mg·kg^-1·d^-1）， low-， medium-， and high-dose ZJYP groups （4.9， 9.9， 19.9 g·kg^-1·d^-1 by gavage）. Ten Wistar rats served as normal controls， with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR， FBG， body weight， and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect miRNA-27a， Wnt， and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group， the FBG levels in DKD rats of the model group increased significantly at 0， 2， 4， 6， and 8 weeks of drug intervention （P<0.05）， and urinary ACR increased significantly at 0， 4， 8 weeks （P<0.05）. Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix， slight thickening of the basement membrane， and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a， Wnt， and β-catenin were significantly higher in the model group than in the normal group （P<0.05）. Renal Wnt and β-catenin protein levels were also significantly higher in the model group （P<0.05）. After drug intervention， the FBG levels in the low-， medium-， and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks （P<0.05）. The urinary ACR also showed a dose-dependent decrease in the low-， medium-， and high-dose ZJYP groups， but the differences were not statistically significant. There were no significant differences in liver function， renal function， renal index， or routine blood lipid test results among the low-， medium-， and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group， with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a， Wnt， and β-catenin were significantly lower in the high-dose ZJYP group （P<0.05）， and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group （P<0.05）. The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group， but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats， thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.

OBJECTIVE To study the fingerprint of Denghong buyang huanwu granules （DBHG）， screen the quality markers， and establish the method for content determination of active ingredients. METHODS HPLC method was adopted. The fingerprints of 10 batches of DBHG （S1-S10） were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）， and similarity evaluation was also performed. Traditional Chinese medicine pieces attribution analysis， cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were conducted for common peaks， and quality biomarkers were screened based on variable importance projection （VIP） values＞1. The contents of 10 batches of samples were determined by the same HPLC method， such as salidroside， tyrosol， calycosin-7-O-beta-D-glucoside， scutellarin and calycosin. RESULTS A total of 25 common peaks were obtained in the fingerprints for 10 batches of samples and 6 common peaks were identified， i.e. salidroside， tyrosol， paeoniflorin， calycosin-7-O-beta-D-glucoside， scutellarin， calycosin. Their similarities were greater than 0.9， and 10 common peaks of them were unique components of Erigeron breviscapus. DBHG could be clustered into 2 categories by using CA and PCA； S4-S5， and S7 could be clustered into one category and other samples could be clustered into one category. The corresponding components of peaks 16 （scutellarin）， 12， 15 （calycosin-7-O-beta-D-glucoside）， 13 （paeoniflorin）， and 14 were quality markers. The average contents of salidroside， tyrosol， calycosin-7-O-beta-D-glucoside， scutellarin and calycosin were 1.64， 0.45， 0.31， 0.73， 0.15 mg/g in 10 batches of samples. CONCLUSIONS HPLC fingerprint for DBHG and a method for determining the contents of five active ingredients including salidroside are successfully established. Five quality markers have been screened. It can be used for the quality control of the preparation.

Objective:To optimize the dispensing method of national drug standard substances and develop a novel adjustable quantitative dispensing device for improving dispensing efficiency and production quality.Methods:Stain-less steel was used to fabricate an adjustable volume tank and a matching scraper for dispensing powder samples of fixed volume.Results:31 types of uniform powder samples,including chemicals and pharmaceutical excipients,were dispensed using the dispensing device.It showed a small test fluctuation range,high accuracy,and consistent effectiveness among different samples.The dispensing efficiency was improved by 147％compared to the conventional method of single-weight dispensing using a balance.Conclusion:The device can significantly reduce dispensing time,increase production efficiency,and meet the dispensing specifications for drug standard substances,which brings remarkable convenience and value to the production and preparation of drug standard substances.

Objective To optimize the formula of Dahuang Xiaoshi decoction components based on its hepatoprotective activity and evaluate their efficacy.Methods The Wistar rats were randomly divided into blank group,model group,ursodeoxycholic acid group(positive group),and orthogonal groups of Dahuang Xiaoshi decoction components.The acute liver injury model induced by alpha-napthyl-i sothiocyanate(ANIT)was used to optimize the allocation ratio of Dahuang Xiaoshi decoction components by taking liver function indicators as an index and combining with multiple statistical methods.The additional Wistar rats were taken to induce liver injury and optimize the compatible dosage of Natrii Sulfas(0,1,2,4 g)in Dahuang Xiaoshi decoction components based on the biological signs and liver function biochemical indicators.On this basis,the Wistar rats were randomly divided into blank group,model group,ursodeoxycholic acid group and different dosages(low,medium and high)of the Zhibaihuang components group.The liver protective effect of Zhibaihuang components was systematically evaluated through the general biological signs,liver function biochemical indicators,lipid peroxide indicators,liver pathological examination and bile transport-related indicators.Results Dahuang Xiaoshi decoction components optimized by orthogonal and multiple statistics could improve the biological signs and ameliorate the biochemical abnormalities in rats with liver injury.Dahuang Xiaoshi decoction components combined with different dosages of Natrii Sulfas could slow down the mass loss of ANIT-induced acute liver injury rats(P＜0.01 or P＜0.05)and recall the abnormally elevated serum liver function enzyme activities(P＜0.01 or P＜0.05).Except for alkaline phosphatase(ALP),there was no statistical difference in regulating other liver function enzyme activity between different allocations of Natrii Sulfas.After comprehensive consideration,its composition was optimized to the Zhibaihuang components without Natrii Sulfas.Further pharmacodynamic evaluation results showed that the optimized Zhibaihuang components could improve their abnormal biological signs(P＜0.01 or P＜0.05),decrease the serum liver function enzyme activity(P＜0.01 or P＜0.05)and the levels of T-BiL and TG(P＜0.05),and restore the levels of hepatic lipid peroxide(P＜0.01 or P＜0.05),repair liver pathological injury,adjust the expression of bile transport proteins(P＜0.05),and thus exert good liver protective activity.Conclusion The optimized Dahuang Xiaoshi decoction components,Zhibaihuang components,was obtained through orthogonal,multiple statistics and univariate investigation.It could improve the abnormal biological signs of animals,protect the liver and reduce enzymes,resist lipid peroxidation,restore abnormal metabolic indicators,and repair liver pathological injury,which provides a reference for its further clinical application and development.

【Objective】 To analyze the composition of urinary calculi in Longnan, Gansu province, and the relationship between the composition and clinical characteristics of patients, so as to provide reference for the prevention and treatment of this disease. 【Methods】 The composition of 500 cases of urinary calculi hospitalized in our department during Apr. 2021 and Feb.2023 were analyzed using the infrared spectrum stone composition analyzer. The clinical characteristics of the patients were evaluated and analyzed. 【Results】 The male-to-female ration of patients was 2.70∶1. Most patients aged 21 to 60 years (437, 87.4%). Most cases were ureteral calculi (72.8%), followed by renal calculi (22.2%), and bladder calculi (5.0%). There were 166 cases of calcium oxalate calculi, 293 cases of calcium oxalate + carbonated apatite calculi, 24 cases of calcium oxalate + carbonated apatite + hydroxyl apatite calculi, 4 cases of calcium oxalate + calcium bicarbonate calculi, 7 cases of urate calculi, 6 cases of carbonated apatite + struvite calculi. Oxalate calculi were the most common in all age groups, and urate calculi were the most common in the 21 to 40 age group. Calcium oxalate calculi were most common in the ureter (127, 76.5%), significantly higher than in other sites (χ²=3.222, P=0.020). Calcium oxalate + calcium hydrogen phosphate calculi was the least common in the bladder, significantly different from the other parts (χ²=2.092, P=0.037). Magnesium ammonium phosphate hexahydrate and/or calcium carbonate or calcium oxalate calculi were the most common in the kidney (50.0%), significantly different from the other parts (χ²=9.448, P=0.007). 【Conclusion】 In Longnan area, the incidence of urinary calculi is significantly higher in male than in female. Ureteral calculi are mainly composed of calcium oxalate + carbonated apatite and calcium oxalate. According to different risk factors, individual prevention programs should be developed.

Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limited.In this study,an improved approach that integrates offline two-dimensional liquid chromatography(2D LC)separation,precursor ion list,library screening,and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C.sinensis.Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides.A library containing the potential 400 dipeptides was created,and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity.To identify dipeptides,the type and connection sequence of amino acids were determined according to the product ions.Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07.Ultimately,170 dipeptides were identified or tentatively characterized from C.sinensis,and most are reported for the first time in this species herein.In addition,the identified dipeptides were also applied for discrimination among the three Cordyceps species,and 11 markers were identified.The obtained results provide a deeper understanding of the chemical basis of C.sinensis.

Objective:To look for the problems faced in the construction of the tele-critical care system, explore the framework of construction of the tele-critical care system, and verify the application effects of the established tele-critical care system.Methods:Through literature review and on-site investigation and demonstration, the causes affecting the construction of the tele-critical care system were explored. Through on-site investigation of the actual situation of the critical care department in relevant hospitals, arguing and choosing intended intensive care unit (ICU) and cooperative third-party communication and equipment companies, and through the Internet of Things and 5G communication technology, a tele-critical care system with the core hospital of the group as the center and the member institutes within the group as the nodes was built. Via the established tele-critical care system, activities such as tele-monitoring, visual remote ward rounds, remote consultation, remote teaching were carried out to verify the functions of the system.Results:The insufficient cognition of relevant personnel, tele-medicine practice certification requirements, information security issues and the barriers of equipment information integration were the main causes affecting the construction of tele-critical care system. There were five parts in the tele-critical care system architecture foundations, including bed unit equipment and audio and video information collection system, lossless and secure transmission of collected information, real-time display of information in the remote center, real-time staff interaction between the centre and the nodal hospitals, and information cloud storage. It has been verified that patients' diagnostic and treatment information can be transmitted safely, losslessly and in real-time by a special line through private 5G network. Through this system, real-time and stable upload of audio and video information of patients and application information of monitors, ventilators and infusion work stations can be achieved; combined with tele-conference connections to conduct two-way communication with local medical staff, real-time tele-monitoring, visual remote ward rounds, remote consultation, remote teaching and other functions can be achieved.Conclusion:The tele-critical care system we established is feasible to construct within the medical group and can safely and effectively realize the functions of real-time tele-monitoring, visual remote ward rounds, remote consultation, and remote teaching.

Objective:To investigate the risk factors of acute pancreatitis (AP) complicated with thrombotic diseases.Methods:Clinical data of 5 223 patients with AP admitted to the General Hospital of Ningxia Medical University from January 2015 to September 2020 were retrospectively analyzed. They were divided into thrombosis group and non-thrombosis group according to whether they were complicated with thrombotic diseases. The following data were recorded: gender, age, past history, time of onset, etiology, severity grade of AP, BISAP score, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer(D-D), fibrinogen(FIB), white blood cell count(WBC), platelet count (PLT), lactate dehydrogenase (LDH), blood glucose level, with or without hypoalbuminemia, hypertriglyceridemia and hypercholesterolemia, date of diagnosis, location of thrombus, clinical manifestations and anticoagulant therapy. Univariate and Logistic multivariate regression analysis were used to analyze the risk factors of AP complicated with thrombotic diseases. The receiver operating characteristic (ROC) curve was drawn, the area under the curve (AUC) was calculated, and the efficacy of independent risk factors in predicting AP complicated with thrombotic diseases was evaluated.Results:46(0.88%) of 5 223 patients with AP were complicated with thrombosis, which occurred 8.50(2.00-15.00) days after the onset of AP; the age of onset was 66 (52-74) years; the patients with thrombotic diseases were mostly SAP patients (23/46, 50%); the most common type was deep venous thrombosis in lower extremity (19/46, 41.3%); 37 patients (80.4%) received regular anticoagulant treatment after finding thrombus, and no bleeding was found during hospitalization. Univariate analysis showed that the age of patients with thrombosis was higher than that of patients without thrombosis, APTT value was prolonged, D-D value was increased, WBC was decreased and SAP was more in AP severity, the number of patients with BISAP score ≥3 was increased significantly, and the differences were statistically significant ( P<0.05). Multivariate logistic regression analysis showed that AP severity ( OR=3.017, 95% CI 1.799-5.061, P<0.001) and age ( OR=1.029, 95% CI 1.000-1.059, P=0.049) were independent risk factors for AP patients complicated with thrombosis. The AUC of AP severity and age in predicting AP complicated with thrombotic diseases were 0.714 and 0.625, respectively. The sensitivity was 67.4% and 47.8%, and the specificity was 70.6% and 77.9%, respectively. Conclusions:The severity grade and age of AP were independent risk factors for AP complicated with thrombotic diseases. Early vigilance and clinical intervention should be given.