The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective:To investigate the clinical effect of magnetic stimulation combined with moxibustion on mild to moderate overactive bladder(OAB)and sexual function in women.Methods:We enrolled 80 female patients with mild to moderate OAB in this study and equally randomized them into a control and an experimental group,the former treated by magnetic stimulation and the latter by magnetic stimulation combined with moxibustion,both for 8 weeks.We obtained from the patients their OAB syndrome scores(OABSS),72-hour urination diary(72-h UD)scores,International Consultation on Incontinence Questionnaire-Overactive Bladder(ICIQ-OAB)scores and female sexual function indexes(FSFI),and compared them between the two groups before and after interven-tion.Results:A total of 77 patients completed the study,37 in the control and 40 in the experimental group.There were no statisti-cally significant differences in the baseline data between the two groups(P＞0.05).Compared with the baseline,the experimental group showed significant improvement after treatment in the OABSS(7.54±1.12 vs 4.46±0.96),72-h urine volume([126.40±46.04]vs[216.63±38.26]ml),urination frequency(15.55±3.21 vs 8.03±1.40),ICIQ-OAB score(10.25±1.15 vs 6.32±1.07)and FSFI(20.00±12.40 vs 33.30±21.00)(all P＜0.05),even more significantly than in the control group(OABSS:4.46±0.96 vs 5.59±0.90;72-h urine volume:[216.63±38.26]vs[173.41±15.55]ml;urination frequency:8.03±1.40 vs 9.90±1.49;ICIQ-OAB score:6.32±1.07 vs 7.89±0.77;FSFI:33.30±21.00 vs 30.40±10.40)(all P＜0.01).Conclu-sion:Magnetic stimulation combined with moxibustion can improve the symptoms of mild to moderate overactive bladder and improve sexual function in females.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective:To explore the construction and application of the evaluation system for ideological and political education in clinical medicine courses based on analytic hierarchy process (AHP) and fuzzy comprehensive evaluation (FCE) models.Methods:The evaluation system for ideological and political education in clinical medicine courses was constructed based on AHP and FCE models in the Yaahp software. Ideological and political education checklist teaching that places equal emphasis on medical ethics and skill was implemented in internal medicine course taken by 185 students in The First Affiliated Hospital of Xi'an Jiaotong University. At the end of the course, the evaluation system was used to obtain quantitative comprehensive evaluation results.Results:Based on AHP and FCE models, the evaluation system for ideological and political education in clinical medicine courses was established. The goal was education of students with both medical ethics and skill, the criteria included teachers' ethics, curriculum design, students' experience and development assessment, and thirteen alternatives were used in the system. The implementation effect of ideological and political education in internal medicine course of the first semester in the 2020-2021 academic year was evaluated by the evaluation system. The quantitative comprehensive evaluation score was 4.080 (range 1-5), which showed that the ideological and political education checklist teaching with equal emphasis on medical ethics and skill achieved good educating effect.Conclusion:The evaluation system for the implementation effect of ideological and political education in clinical medicine courses can be constructed based on the AHP and FCE models. The evaluation system is scientific, quantitative, comprehensive, and improvable.

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC₅₀ value of 6.35 μmol·L^-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1β, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal ; Inflammation/metabolism* ; Lipids ; Liver ; Mice ; NF-E2-Related Factor 2/metabolism* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Oxidative Stress ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*

The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.

Objective To evaluate the effect of a deep learning reconstruction (DLR) method on the visibility of contrast-enhanced CT images of the biliary system by comparing it with different iterative reconstruction algorithms including the adaptive iterative dose reduction 3D (AIDR 3D) algorithm,forward projected model based iterative reconstruction solution (FIRST),and filtered back projection (FBP) algorithm. Methods A total of 30 patients subjected to abdominal contrast-enhanced CT and diagnosed with dilatation of common bile duct or extrahepatic bile duct were retrospectively included in this study.The images of the portal phase were reconstructed via four different algorithms (FBP,AIDR 3D,FIRST,and DLR).Signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the dilated bile duct,liver parenchyma,measurable bile duct lesions,and image noise were compared between the four datasets.In subjective analyses,two radiologists independently scored the image quality (best:4 points,second:3 points;third:2 points;fourth:1 point) of the four datasets based on the noise and image visual quality of the biliary system.The Friedman and the Bonferroni-Dunn post-hoc tests were performed for comparison. Results The DLR images (bile duct:4.42±0.87;liver parenchyma:3.78±1.47) yielded higher CNR than the FBP (bile duct:2.21±1.02,P<0.001;liver parenchyma:1.43±1.29,P<0.001),AIDR 3D (bile duct:2.81±0.91,P=0.024;liver parenchyma:2.39±1.94,P=0.278),and FIRST (bile duct:2.51±1.24,P<0.001;liver parenchyma:2.45±1.81,P=0.003) images.Furthermore,the DLR images had higher SNR (bile duct:1.39±0.85,liver parenchyma:9.75±1.90) than the FBP (bile duct:0.86±0.63,P<0.001;liver parenchyma:3.31±1.12,P<0.001) and FIRST (bile duct:1.01±0.61,P=0.013;liver parenchyma:5.73±1.37,P<0.001) images,and showed lower noise (10.51±3.53) than the FBP(4.10±3.92,P<0.001),AIDR 3D (15.72±2.41,P=0.032),and FIRST (17.20±3.82,P<0.001) images.SNR and CNR showed no significant differences between FIRST and AIDR 3D images (all P>0.05).DLR images [4(4,4)] obtained higher score than FPB [1(1,1),P<0.001],AIDR3D[3 (2,3),P=0.029],and FIRST[2 (2,3),P<0.001] images. Conclusion DLR algorithm improved the subjective and objective quality of the contrast-enhanced CT image of the biliary system.
Biliary Tract ; Deep Learning ; Humans ; Imaging, Three-Dimensional ; Radiographic Image Interpretation, Computer-Assisted/methods* ; Retrospective Studies ; Tomography, X-Ray Computed/methods*

Tripterygium hypoglaucum (Levl.) Hutch, a traditional Chinese medicinal herb with a long history of use, is widely distributed in China. One of its main active components, celastrol, has great potential to be developed into anti-cancer and anti-obesity drugs. Although it exhibits strong pharmacological activities, there is a lack of sustainable sources of celastrol and its derivatives, making it crucial to develop novel sources of these drugs through synthetic biology. The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases. Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases (CYP450s). Here, we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast. Through substrate supplementation and in vitro enzyme analysis, ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid, which is considered a vital step in the biosynthesis of celastrol, and will lay a foundation for further analysis of its biosynthetic pathway.
Anti-Obesity Agents ; Cytochrome P-450 Enzyme System/metabolism* ; Pentacyclic Triterpenes ; Squalene/analogs & derivatives* ; Tripterygium/metabolism* ; Triterpenes/metabolism*