On the basis of web databases, 111 compounds with nephrotoxicity and 90 compounds without nephrotoxicity were collected as data set of nephrotoxicity discrimination model, 39 compounds with tubular necrosis and 39 compounds without tubular necrosis were collected as data set of tubular necrosis discrimination model. The 6 122 molecular descriptors, including physicochemical, charge distribution and geometrical descriptors were calculated to characterize the molecular structure of the above-mentioned compounds. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to select molecular descriptors. Two models with high accuracy were built based on the support vector machine (SVM) approach, respectively. Accuracy, sensitivity, specificity and matthew's correlation coefficient of the two models were all above 70%. By using 22 nephrotoxicity compounds of Chinese medicine, the nephrotoxicity discrimination model was further verified with an accuracy of 72.73%. Using the tubular necrosis discrimination model, 10 potential compounds which can cause tubular necrosis were screened from the positive results of nephrotoxicity discrimination model, 6 of them have been verified by literatures. The results demonstrated that the discrimination models can be applied to screen nephrotoxic compounds from Chinese medicinal materials, and they also offer a new research idea for the further studies on the mechanism of nephrotoxicity.
Drugs, Chinese Herbal ; toxicity ; Nephrons ; drug effects ; Support Vector Machine ; Toxicity Tests ; instrumentation ; methods

In this study, based on web database, 324 neurotoxic compounds and 234 non-neurotoxic compounds were selected as a data set for neurotoxicity discriminative model. 6 122 molecular descriptors, including charge distribution, physicochemical and geometrical descriptors,were calculated to characterize the molecular structure of neurotoxic compounds. The combination of Cfs Subset Evaluation and Best First-D1-N5 searching was used to select molecular descriptors. A discrimination model with high accuracy was built based on the support vector machine (SVM) approach. Meanwhile, the model accuracy, sensitivity and specificity were all above 80%. Besides, 30 traditional Chinese medicine compositions with neurotoxicity were set as external validation to further verify the model accuracy,with anaccuracy of 73.333%. Using the model, 13 potential neurotoxic compounds were screened from Sophorae subprostrate Radix,4 of them were verified by literatures. The results demonstrated that the discrimination model can be applied to screen neurotoxic compounds from Chinese medicinal materials.
Computer Simulation ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; methods ; Models, Theoretical ; Neurotoxins ; analysis ; chemistry ; Reproducibility of Results ; Support Vector Machine

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

This article introduces the independent experiment and social investigation activities in the course of medication analy- sis set up for strengthening students' comprehensive abilities.These activities create a good study atmosphere for enhancing stu- dents' ability to do research and their humanistic qualities.

Objective: To investigate the status and identify the influencing factors of smoking among residents in Shaoxing City, Zhejiang Province, so as to provide insights into tobacco control. Methods: Permanent residents aged 15 to 69 years in Shaoxing City were recruited using the stratified multistage random sampling method from June to December 2022, and smoking behaviors and health literacy were collected using the National Questionnaire for Surveillance on Healthy Literacy in Chinese Residents. Factors affecting smoking were identified using a multivariable logistic regression model. Results: Totally 4 156 questionnaires were allocated, and 4 055 valid questionnaires were recovered, with an effective recovery rate of 97.57%. There were 1 899 men (46.83%), 2 073 residents in rural areas (51.12%), and 3 256 married residents (80.30%). There were 805 smokers, and the rate of smoking was 19.85%. Multivariable logistic regression analysis showed that male (OR=169.861, 95%CI: 92.335-312.481), age (25-<35 years, OR=8.768, 95%CI: 2.964-25.937; 35-<45 years, OR=9.271, 95%CI: 3.077-27.933; 45-<55 years, OR=10.467, 95%CI: 3.498-31.327; 55-<65 years, OR=8.880, 95%CI: 2.964-26.608; 65-69 years, OR=6.115, 95%CI: 1.992-18.774), marital status (divorced, OR=2.035, 95%CI: 1.260-3.287; widowed, OR=2.317, 95%CI: 1.337-4.016), educational level (illiterate or semi-literate, OR=2.724, 95%CI: 1.515-4.898; primary school, OR=2.734, 95%CI: 1.823-4.100; junior high school, OR=2.003, 95%CI: 1.423-2.820; high school/vocational high school /technical secondary school, OR=1.625, 95%CI: 1.148-2.299), self-rated health status (general, OR=0.788, 95%CI: 0.623-0.996; relatively poor, OR=0.343, 95%CI: 0.191-0.617) and lack of basic health skills (OR=1.290, 95%CI: 1.007-1.653) were associated with smoking. Conclusions The smoking rate among residents in Shaoxing City is relatively low, and might be influenced by gender, age, marital status, educational level, self-rated health status, and basic health skills.

ObjectiveTo investigate the feasibility of Legacy pedicle screw system plus minimally invasive technique in treatment of Tile type C pelvic fracture and evaluate its therapeutic effects.MethodsFrom January 2008 to March 2010, 12 patients with closed Tile type C pelvic fractures were treated with Legacy pedicle screw system plus minimally invasive technique.There were seven males and five females, at age range of 21-60 years (average 39.6 years).All patients had sacrum fractures of the posterior pelvic rings.The anterior pelvic ring fractures included unilateral ischiadic ramus fractures in four patients and bilateral ischiadic ramus fractures in eight.Three patients were combined with shock.The anterior pelvic rings were fixed with minimally invasive reconstruction plates and the posterior pelvic rings fixed with minimally invasive technique plus Legacy pedicle screw system.ResultsThe operation lasted for average 90 minutes (range, 80-110 minutes) , with average intraoperative blood loss of 105 ml (range, 80-150 ml).All patients were followed up for average 18 months (range, 6-32 months), which showed that all patients got satisfactory reductions and that the fractures were healed at one stage, with average period of 11.5 weeks (range, 9-13 weeks).There occurred no infections, failures of internal fixations or nerve injuries.According to improved Lindahl standard of pelvic injury function assessment, the result was excellent in 10 patients and good in two, with average score of 78.6 points.Conclusions Under master of the surgical indications, Legacy pedicle screw system plus minimally invasive technique takes advantages of minor trauma, less intraoperative fluoroscopy, short operation time, good curative resuhs and few complications in treatment of Tile type C pelvic fractures by fixation of the posterior pelvic rings and reconstruction of the anterior pelvic rings.

Objective To evaluate the efficiency of normal sacral nerve root transposition in repair of the sacral plexus root avulsion. Methods A total of 30 adult SD rats were chosen and divided into three groups,ie,group A(the sciatic nerve received no repair),group B(the autologous sacral plexus root nerve was bridged with the right L6 nerve root by the translocation of the left L6)and group C (the right L5 nerve root nerve was bridged by the translocation of the left L6),10 rats per group.The left side of the rats was used as the control side and the right one as the experimental side.Twelve weeks after operation,the rats in each group were selected for the histomorphological observation of the nerves under the microscope and the electron microscope.The models were evaluated by observing the survival rates of the rats,BBB scores,electron microscope weight and muscle fiber CSA(cross section area)of double biceps femoris,triceps surae and tibial muscle. Results Twelve weeks after operation,the BBB scores in groups B and C was higher than that in group A,with statistical difference(P<0.01)between three groups.A remarkable improvement was found in the ratio of weight and muscle fiber CSA of double biceps femoris,triceps surse and tibial muscle.The repair efficiency in the group C was better than that in the group B.In the group B,the biceps femoris,triceps surae and tibial muscle recovered at different degrees.The biceps femoris recovered the best,when a great deal of myelinated nerve fiber regeneration was observed under the microscope and the electromicroscope.Electromyography revealed the volatility in the muscles of three groups,with larger peak value for the proximal biceps femoris and the triceps muscle but smaller peak value for the distal anterior tibial muscle. Conclusions L6 transposition combined with auto-graft of nerve root or without the auto-graft can reconstruct the partial function of the sciatic nerve in the paraplegia rats,when the latter has the better effect.

Objective To assess longitudinal segmental myocardial strain and displacement of left ventricle (LV) in patients with dual chamber pacing (DDD) using velocity vector imaging (VVI) and to explore the clinical application value of VVI in assessing left ventricular motion.Methods A total of 23 patients before and after DDD pacemaker implantation were enrolled in this study.The peak systolic strain and displacement of ventricular segments were measured with VVI and compared before and after pacemaker implantation.Results Compared to the values at the baseline,the strain and displacement of lateral,interventricular septum,anterior and posterior wall of LV in patients with pacing were significantly decreased.The strain,displacement of basal and mid segments with pacing were decreased as well(P＜0.01).The left ventricular strain and displacement in patients with pacing were significantly decreased than those of patients at the baseline(P＜0.05).Left ventricular longitudinal displacement before and after DDD pacing was significantly decreased from basal,mid to apical segments.But no significant difference was found in longitudinal strain from basal,mid to apical segments of LV.Conclusions (1) Left ventricular strain and displacement in patients with pacing were different between those before and after DDD pacing.(2) VVI can accurately assess left ventricular strain and displacement in patients with DDD pacing,and can become a powerful mean to assess the regional myocardial function.

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry

Acetaminophen ; metabolism ; Animals ; Cells, Cultured ; Drug Interactions ; Flavonoids ; metabolism ; Hepatocytes ; metabolism ; Humans