Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway / 中国中药杂志

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.

Real world study on characteristics of Maixuekang Capsules combined with traditional Chinese medicines in treating nephrotic syndrome / 中国中药杂志

To analyze the clinical characteristics of Maixuekang Capsules combined with traditional Chinese medicines in the treatment of patients with nephrotic syndrome,and provide references for improving rationality of clinical drug use. Based on the database of hospital information system(HIS) in 15 hospitals in China,the electrical medical records of the patients diagnosed as nephrotic syndrome and treated with Maixuekang Capsules were collected. Their diagnostic information and characteristics of combined traditional Chinese medicines were analyzed by using association rules. The results showed that 1 588 patients of nephrotic syndrome who used Maixuekang Capsules were often complicated with hypertension(863 cases,accounting for 7. 54%),anemia(551 cases,accounting for 4. 81%),and coronary heart disease(349 cases,accounting for 3. 05%). Maixuekang Capsules were mainly combined with Tabellae Rhei et Natrii Bicarbonatis,Baining Capsules,tanshinone,Ganmao Qingre Granule,Shuxuening Injection in treating nephrotic syndrome. The results indicated that in the real world,Maixuekang Capsules was mainly used in combination with traditional Chinese medicines such as blood-activating and stasis-removing agents,pathogens eliminating and supporting healthy Qi agents,digestants,anti-bacterial and anti-inflammatory agents,wind-dispersing and antipyretic agents for patients with nephropathy. By the pharmacological effect,it was suitable for nephropathy patients based on combined diagnosis. The association rules of combination were specific,and can provide reference for subsequent studies and rational clinical medication of traditional Chinese medicines.

Complex network analysis on Shenxiong glucose injection in combined use with Chinese and Western medicine for cerebral infarction in real world study / 中国中药杂志

In order to analyze Shenxiong glucose injection in combined use with other medicines for cerebral infarction in real world, the basic information, Chinese and western medicine diagnosis information, doctors'advice information, and laboratory checking information for the patients with Shenxiong glucose injection in treatment of cerebral infarction were extracted from the hospital information system (HIS) of sixteen 3A hospitals. Apriori Algorithm was used to establish models, and Clementine 12.0 was used for correlation analysis. Then complex network was established to analyze the combined drug use and visualize the results. A total of 635 patients were included in the study, among which 599 patients (94.33%) showed superior effect. Shenxiong glucose injection was often used with platelet suppressant drug, neuroprotective agent, lipid regulating agents, free radical scavenger, vitamins and Chinese medicine blood activating and stasis eliminating agent in the treatment of cerebral infarction. In the patients with superior effect, neuroprotective agent and free radical scavengers were also used based on the combined use with Aspirin, hypolipidemic drugs and blood activating and stasis removing agents, highlighting the rain protection strategies. Shenxiong glucose injection in combined use with Chinese and western medicines for cerebral infarction complied with the latest clinical practice guideline on the treatment of cerebral infarction, and the application of neuroprotective agent was propitious to improve the therapeutic effect.

Clinical features analysis of Qingkailing injection for adolescent patients based on real world HIS / 中国中药杂志

To explore the clinical application features of Qingkailing injection for adolescent patients. This study was based on the information from the hospitalized patients in 1998-2011 in HIS (hospital information system) of 16 tertiary hospitals in China. 615 adolescent patients with Qingkailing injection were used to investigate the clinical characteristics of Qingkailing injection. Apriori algorithm was adopted to establish the model, and Clementine 12.0 was used for correlation analysis. The results showed that male patients (355 cases) were more than female patients (243 cases); the age of the most patients was under 14 years old, with an average age of 9.40 years old; the hospital stay was most of 4-7 d; the patients were mostly concentrated in pediatrics, mainly including upper respiratory tract infection; outpatient admission to the majority (451 cases, accounting for 75.54%). The traditional Chinese medicine (TCM) syndrome mainly included phlegm-dampness internal resistance (38.46%), Qi and Yin Deficiency (11.54%), Liver qi stagnation (15.38%), and Yang deficiency syndrome (11.54%); the highest admission rate was during Slight Cold (13.01%). In combined application, the most common western medicine pair was Cephalosporin injection+vitamin C (with supporting rate of 24.6%) and the most common TCM pair was Shuanghuanglian+Ganmao Qingre granules (with supporting rate of 4.065%). The most common 3 western medicines in combined use were Potassium chloride injection+Cephalosporin injection+vitamin C (supporting rate of 15.93%); while the most common three Chinese medicines were Shuanghuanglian+Yunnan Baiyao+Ganmao Qingre granules (supporting rate of 1.138%). Qingkailing injection was also widely used in adolescent patients; the diagnosis and use were basically in line with the instructions; men were slightly more than women; age of onset, solar terms and TCM syndromes were highly consistent. Qingkailing injection was mainly combined with western medicines in combined drug use, and Chinese medicines were also available. Combined drug use was more reasonable. Based on the results of the real world HIS, Qingkailing injection could provide the idea and reference for regulating the medication in adolescent patients.

Drug combination characteristics of Shenxiong glucose injection in treating ischemic cerebrovascular disease in real world / 中国中药杂志

To analyze the clinical drug use characteristics of Shenxiong glucose injection in the treatment of ischemic cerebrovascular disease. From hospital information system (HIS) of 19 hospitals over China, the basic information of patients with Shenxiong glucose injection for ischemic cerebrovascular disease, traditional Chinese medicine and Western medicine diagnosis information, order information, and laboratory examination information were extracted. Then Apriori algorithm was used to construct the model, and the association analysis was performed by using Clementine 12 to analyze the clinical drug use characteristics of Shenxiong glucose injection in the real world. A total of 411 kinds of Western medicines and 110 kinds of traditional Chinese medicines were included in 784 cases of drug combination. In the drug combination, aspirin had the highest frequency in Western medicine, which was used in 515 cases (65.69%); Ginkgo biloba extract had the highest frequency in Chinese medicine, which was used in 121 cases (15.43%). Atorvastatin+aspirin (association rules of 10.15%) was the most common Western medicine pairs; atorvastatin+clopidogrel+aspirin (association support 5.56%) was the most common triple Western medicine therapy, often combined with antibiotics and blood stasis drugs in use. Results showed that Shenxiong glucose injection was often combined with antiplatelet drugs and blood stasis drugs in the treatment of ischemic cerebrovascular disease clinically, contributing to the enhancement of platelet aggregation and blood stasis. The incompatibility of combined application of drugs shall be noted to ensure the clinical medication safety and efficacy of the combined drug use.

Analysis of drug combination characteristics of Qingkailing injection for treating abnormal inflammatory factors in real world / 中国中药杂志

To analyze the drug combination characteristics of Qingkailing injection for treating abnormal inflammatory factors such as elevated white blood cells and C reactive protein in real world. The patients with Qingkailing injection for abnormal C reactive proteins and abnormal white blood cells were extracted from hospital information system (HIS) of 16 Class 3A hospitals. Then the basic information, traditional Chinese medicine and Western medicine diagnostic information, doctor's advice information, and laboratory information were analyzed; Apriori algorithm was used to construct the models, and Clementine 12.0 was used for correlation analysis to analyze the clinical medication rules and drug combination characteristics in the patients with Qingkailing injection for treatment of elevated C reactive protein and white blood cells in the real world. The results of the study showed that when Qingkailing injection was combined with one kind of western medicine and traditional Chinese medicine in treatment of patients with abnormal C reactive protein, vitamin C (159 cases, 74.30%) and Tanreqing injection (71 cases, 33.18%) were most frequently used; when it was combined with 2 kinds of traditional Chinese medicines, Xueshuantong injection plus Tanreqing injection (support degree 10.75%) were most frequently used. When Qingkailing injection was combined with one kind of western medicine and traditional Chinese medicine in treatment of patients with abnormal white blood cells, vitamin C (596 cases, 56.02%) and Ganmao Qingre granules (247 cases, 23.21%) were most frequently used; when it was combined with 2 kinds of traditional Chinese medicines, Shuanghuanglian+Ganmao Qingre granules (support degree 5.26%) were most frequently used. In the patients with abnormal C-reactive protein and white blood cells, its combinations with antibiotics and nutritional support agents were most common from the pharmacological perspective, indicating that in the treatment of abnormal C-reactive protein, white blood cells and other increased inflammatory indicators, Qingkailing injection was most frequently combined with antibiotic drugs to achieve synergistic effect.

Real world analysis to explore clinical features of Shenxiong glucose injection combined with other medications / 中国中药杂志

To explore the real world clinical medication and combination characteristics of Shenxiong glucose injection. The basic information of patients with Shenxiong glucose injection, traditional Chinese and western medicine diagnosis information, doctor advice information and laboratory test information from the hospital information system(HIS) of 19 tertiary hospitals in China. Apriori algorithm was adopted to establish the models, and Clementine 12.0 was used for correlation analysis to analyze the real world clinical medication and combination characteristics of Shenxiong glucose injection. Among 8 316 patients in the study, 523 kinds of western medicine and 148 kinds of traditional Chinese medicine(TCM) were used. In combined application, the single western medicine with highest use frequency was aspirin(1 908 cases, 22.94%), and single Chinese medicine with highest use frequency was Shuxuetong injection (771 cases, 9.27%); the most common TCM pair was Xianling Gubao capsule+Lugua Duotai injection(rules support degree was 2.55%), and the most common western medicine pair was aspirin+atorvastatin(degree of association rules was 10.15%). They were often used in combination with antibiotics, blood-activating and stasis-dissolving prescription, and adrenal cortical hormone drugs. Shenxiong glucose injection was often used in combination with antiplatelet drugs and blood-activating and stasis-dissolving prescription in clinical application to enhance the effects of anti-platelet aggregation and blood-activating and stasis-dissolving; it was often used in combination with antibiotics to treat cor pulmonale, and incompatibility shall be noticed to ensure efficacy enhancement under the premise of clinical medication safety.

Establishment and drug susceptibility test of isoniazid resistant Mycobacterium smegmatis / 药学学报

With the emergence of drug resistant tuberculosis, it is very urgent to find novel anti-tuberculosis drugs, especially novel anti-drug-resistant tuberculosis drugs. Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis, the development of evaluation of drug effect is severely impeded. In order to solve these issues, non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism. The inhA is one of a target of isoniazid (INH) overexpression or mutation of this gene in Mycobacterium tuberculosis conferring resistant to INH. A recombinant plasmid bearing inhA was constructed and electroporated into Mycobacterium smegmatis, using shuttle expression vector pMV261. Transformants were induced to express a protein of inhA, identified by SDS-PAGE. Results show that Mycobacterium smegmatis containing inhA plasmids exhibited 100-fold or greater increased resistance to INH, but it conferred no increased resistance to others first-line anti-tuberculosis drugs. Resazurin microtiter assay plate testing of Mycobacterium smegmatis susceptibility to drugs is a rapid, simple, and inexpensive method and could decrease color background of drugs by detecting fluorescence. It will be benefit for high-throughout screening of drugs of anti-isoniazid-resistant Mycobacteria.

Establishment and application of a screening anti-HIV-1 drug model targeted nuclear trafficking of virus RNA / 药学学报

The HIV-1 Rev protein facilitates nuclear export of unspliced and singly spliced viral transcripts containing RRE RNA through the CRM1 export pathway. Inhibition of Rev-mediated RNA nuclear export can arrest HIV-1 transcriptional process, which clearly, reveals a target for anti-HIV drug development. In this work, a cell-based assay has been established for screening anti-HIV compounds targeting the Rev-mediated RNA nuclear export. This assay utilized a codon-optimized green fluorescent protein (GFP) as reporter gene, which expression is in a Rev-dependent manner. Any compound that inhibits the Rev-mediated RNA nuclear export is identified by reducing emission of GFP. The Z' score of this model is 0.8220. Three thousands compounds were screened and the positive rate was 9.3% with a cutoff at 50% inhibition. IMB7C7, one of the positive compounds, efficiently inhibits viral production from HIV-1 infected cells.

Establishment and application of a high-throughput screening assay for premature activation of HIV-1 precursors / 药学学报

Strict regulation of HIV-1 PR function is critical for efficient production of mature viral particles. During viral protein expression and viral assembly, HIV-1 PR located within Gag-Pol precursor must be inactive to prevent premature cytoplasmic processing of the viral Gag and Gag-Pol precursors. Premature activation of HIV-1 precursors leads to major defects in viral assembly and production of viral particles. A cell-level premature activation of HIV-1 precursors assay using bioluminescence resonance energy transfer (BRET) was established. Three thousand compounds were screened to evaluate this assay. The results showed that the assay is sensitive, specific and stable (Z' factor is 0.905).