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.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Objectives: To elucidate the potential mechanisms of electroacupuncture (EA) in restoring detrusor-bladder neck dyssynergia (DBND) following suprasacral spinal cord injury (SSCI). Methods: A total of 52 specific pathogen-free (SPF) grade famale Sprague-Dawley (SD) rats (10 – 12 weeks, 250 – 280 g) were randomly assigned to either a sham group (n = 12) or a spinal cord injury model group (n = 40). In the model group, DBND was induced through Hassan Shaker spinal cord transection at T10 level, with 24 rats meeting inclusion criteria and subsequently randomized into DBND group (n = 12) and EA intervention group (DBND + EA group, n = 12). After spinal shock recovery (day 19 after modeling), DBND + EA group received EA treatment at Ciliao (BL32), Zhongji (RN3), and Sanyinjiao (SP6) acupoints for 20 min per session at 10/50 Hz frequencies, once daily for 10 d. Sham and DBND groups received anesthesia only without EA intervention. On day 29 post-modeling, all rats underwent urodynamic assessments, followed by hematoxylin and eosin (HE) staining, tandem mass tag (TMT) proteomics, and Western blot (WB) analysis of detrusor and bladder neck tissues. Differentially expressed proteins (DEPs) were defined as proteins with P < 0.05, unique peptides ≥ 2, and fold change > 1.2 or < 0.83. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using KOBAS 3.0 (P < 0.01), and protein-protein interaction (PPI) networks were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.5 and Cytoscape 3.9.1. Results: Compared with sham group, DBND group showed significantly elevated leak point pressure (LPP) and maximum cystometric capacity (MCC) (both P < 0.01). EA treatment significantly reduced both LPP and MCC compared with DBND group (P < 0.01 and P < 0.05, respectively). HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation. TMT proteomics identified 30 overlapping DEPs in detrusor and 59 overlapping DEPs in bladder neck when comparing DBND + EA/DBND groups with sham group. In detrusor tissue, KEGG analysis revealed 10 significantly enriched pathways (P < 0.01), including mitogen-activated protein kinase (MAPK) signaling pathway. PPI analysis showed 22 of 30 DEPs were interconnected. In bladder neck tissue, 14 pathways were significantly enriched (P < 0.01), including relaxin signaling pathway, with 51 of 59 DEPs showing interconnections. Both TMT and WB validations demonstrated that compared with sham controls, DBND rats exhibited upregulated collagen type IV alpha 2 chain (Col4a2) and downregulated guanine nucleotide-binding protein G(z) subunit alpha (Gnaz) in detrusor tissue, while EA treatment normalized both proteins (both P < 0.05). In bladder neck tissue, DBND rats showed decreased expression of smoothelin (Smtn) and calcium-activated potassium channel subunit beta-1 (Kcnmb1) compared with sham controls (both P < 0.01), which were both upregulated following EA treatment (P < 0.01 and P < 0.05, respectively). Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms. In detrusor tissue, EA modulates contraction via extracellular matrix remodeling, cyclic adenosine monophosphate (cAMP) signaling pathway regulation, and enhanced adenosine triphosphate (ATP) biosynthesis mediated by neurotransmitters. In bladder neck tissue, EA promotes relaxation by maintaining contractile phenotypes, reducing fibrosis, suppressing smooth muscle excitation, and regulating presynaptic neurotransmitter release. These findings provide mechanistic insights into EA's therapeutic role in managing DBND.

ObjectiveTo observe the clinical effectiveness and potential mechanism of combined tongue three-needle acupuncture and acupoint application on Lianquan （CV 23） for patients with dysphagia after ischemic stroke. MethodsA prospective study was conducted on 160 patients with post-stroke dysphagia， who were randomly divided into a treatment group and a control group， with 80 cases in each group. The control group received conventional rehabilitation training， while the treatment group received tongue three-needle acupuncture combined with acupoint application on Lianquan （CV 23） on the basis of conventional rehabilitation training， for 4 weeks in both groups. We compared the clinical effectivenss of both groups after treatment， and assessed the swallowing function including videofluoroscopic swallowing study （VFSS）， standardized swallowing assessment （SSA） and functional oral intake scale （FIOS）， swallowing contrast test including hyoid maximum displacement （HmaxD）， pharyngeal transit time （PTT）， and upper esophageal sphincter （UES） opening， surface electromyography （sEMG） test including maximum amplitude and swallowing duration as well as swallowing quality of life questionnaire （SWAL-QOL） score of the patients in both groups before treatment， after 2 weeks and 4 weeks of treatment， respectively. ResultsThe total effective rate in treatment group was 82.50% （66/80）， significantly higher than 66.25% （53/80） in control group （P＜0.05）. The VFSS， and FOIS scores， UES opening rate and HmaxD， sEMG maximal amplitude values， and SWAL-QOL scores were increased in both groups after 2 weeks and 4 weeks of treatment compared with the values before treatment （P＜0.05）， while SSA scores， PTT， and swallowing duration were decreased compared within group before treatment （P＜0.05）. VFSS and FOIS scores， UES opening rate and HmaxD， sEMG maximal amplitude values， and SWAL-QOL scores after 2 and 4 weeks of treatment in the treatment group were higher （P＜0.05）， while SSA scores， PTT， and swallowing duration were lower （P＜0.05） than those in the control group at the same time. ConclusionCombined tongue three-needle acupuncture and acupoint application on Lianquan （CV 23） for patients with dysphagia after ischemic stroke can significantly improve swallowing activities， and its mechanism of action may be related to the improvement of the contraction ability and coordination of swallowing-related muscle groups.

Objective To understand the capacity of technical support institutions for occupational disease prevention and treatment in Ningxia Hui Autonomous Region (hereinafter referred as "Ningxia"). Methods The basic data of 26 technical support institutions for occupational disease prevention and treatment in Ningxia in 2023 were collected through the "National Management Platform for Technical Support Institutions for Occupational Disease Prevention and Treatment". The status of these institutions was investigated, and their qualifications, human resources, equipment allocation, and testing capacities were analyzed. Results Among the 26 technical support institutions for occupational disease prevention and treatment in Ningxia, all were qualified occupational disease surveillance institutes, eight were qualified occupational hazard factor monitoring institutes, two were qualified occupational medical examination institutes, one was a qualified occupational diagnosis institute, one was a qualified occupational treatment institute, four were qualified for radiological health technical services, and one was qualified for occupational health technical services. A total of 168 professionals engaged in occupational diseases prevention and treatment, with the majority holding a bachelor degree and junior professional titles, accounting for 66.1% and 40.5%, respectively. The technical support institutions for occupational disease prevention and treatment of the district level,city level and county level of Ningxia were provided with 121, 68 and 32 instruments and equipment respectively on average,and the number of testing items of occupational hazard factors which the institutions of aforementioned levels are 50.0,17.0 and 1.3 respectively. Conclusion The technical support institutions for occupational disease prevention and treatment in Ningxia show insufficient qualifications and capacities, inadequate professional staff, imbalanced talent structure, incomplete equipment allocation, weak testing capacity, and an underdeveloped support system.

Objective Traditional Chinese medicine(TCM)has precise traits and advantages in the scientific prevention and remedy practice of diabetic gastroparesis(DGP).The review gathered and reviewed the research on the therapy of DGP with TCM in current years.It was once located that it performed an essential function by regulating Cajal interstitial cells,enteric nervous system,gastrointestinal hormones and gut microbiota.The research development of the mechanism and effect of TCM in the treatment of DGP were respectively reviewed from the above factors,providing thoughts and scientific foundation for the prevention and treatment of DGP.

The UV cross-linking immunoprecipitation (CLIP) technique was first established in 2003. Sequences of target RNAs and binding sites of specific RNA-binding proteins (RBPs) were identified within the entire transcriptome by UV cross-linking, immunoprecipitation, reverse transcription, and subsequent high-throughput sequencing. Over the last 20 years, CLIP has been continuously modified and improved. Advanced operability and accuracy have extended its application category. Currently, the widely used CLIP technologies include high-throughput sequencing with crosslinking-immunoprecipitation (HITS-CLIP), photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP), individual nucleotide resolution CLIP (iCLIP), enhanced CLIP (eCLIP), infrared-CLIP (irCLIP), etc. HITS-CLIP combines high-throughput sequencing with UV cross-linking immunoprecipitation. The 254 nm UV cross-linking and RNAase digestion steps allow the technology to capture transient intracellular RBP-RNA interactions. However, there are limitations in the efficiency of UV cross-linking, with low resolution and high intrinsic background noise. For PAR-CLIP, photoactivatable ribonucleoside was incorporated into RNA molecules, and RBP cross-linked with RNA by 365 nm UV light to improve cross-linking efficiency and resolution. Cross-linking mediated single-base mutations provide more accurate binding site information and reduce interference from background sequences. Long-term alternative nucleotide incorporation, on the other hand, can be cytotoxic and may skew experimental results. iCLIP can identify RBP-RNA cross-linking sites at the single nucleotide level through cDNA circularization and subsequent re-linearization steps, but it has more experimental procedures, and partial cDNAs lost in the circularization step are inevitable. eCLIP discards the radioisotope labeling procedure and reduces RNA loss by ligating adaptors in two separate steps, greatly improving the library-building efficiency, and reducing bias associated with PCR amplification; however, the efficiency of immunoprecipitation cannot be visually assessed at the early stage of the experiment. The irCLIP technique replaces radioisotopes with infrared dyes and greatly reduces the initial number of cells required for the experiment; however, an infrared imaging scanner is essential for the irCLIP application. To address more particular scientific issues, derivative CLIP-related techniques such as PAPERCLIP, cTag-PAPERCLIP, hiCLIP, and tiCLIP have also been developed in recent years. In practice, the aforementioned CLIP approaches have their advantages and disadvantages. When deciding on a technical strategy, we should take into account our experimental objectives and conditions, such as whether we need to precisely define the RNA site for binding to RBP; whether we have the necessary experimental conditions for working with radioisotopes or performing infrared imaging; the amount of initial sample size, and so on. In addition, the CLIP technique has a relatively large number of procedures and can be divided into several successive experimental modules. We can try to combine modules from different mainstream CLIP technologies to meet our experimental requirements, which also gives us more opportunities to improve and refine them and to build more targeted derivative CLIP technologies according to our research objectives.

Objective We aimed to investigate the effects of electroacupuncture at"Zusanli"(ST36)and"Taichong"(LR3)on gastrointestinal motility,gastrointestinal hormones,and brain-gut axis in rats with functional dyspepsia(FD).Methods 48 SD rats were randomly divided into a normal control group,a model group,a cisapride group,and an electroacupuncture group,with 12 rats in each group.A mild tail pinch stimulation combined with intermittent food deprivation was used to establish the FD rat model.Body mass,food intake,and sucrose preference rate were recorded before and after modeling to verify the success of the FD model.After modeling,the normal control group and the model group received no intervention;the cisapride group rats were administered cisapride[0.4 g/(kg·d)]by intragastric perfusion for 6 consecutive days as one course of treatment,with a rest day between each course;the electroacupuncture group rats received electroacupuncture stimulation at bilateral"Zusanli"and"Taichong"(DC,dense-sparse wave,2/100 Hz,2-5 mA.Electricity was applied for 30 min),with stimulation every 24 h for 6 consecutive times as one course of treatment,with a rest day between each course.After two courses of treatment,samples were collected to compare gastrointestinal motility indices,blood levels of gastrointestinal hormones[motilin,gastrin,serotonin(5-HT),nitric oxide(NO)],serum and tissue levels of endogenous brain-gut peptides[cholecystokinin(CCK),calcitonin gene-related peptide(CGRP),neuropeptide Y(NPY)]in the hypothalamus,gastric antrum,duodenum,colon,and protein expressions of ghrelin and substance P in the hypothalamus,spinal cord,gastric antrum,and colon.Results Body mass,food intake,and sucrose preference rate were lower of the model rats than those of the normal rats(P<0.05).Compared with the model group,rats in the electroacupuncture group and cisapride group had(i)lower gastric residual rates,higher rates of small intestinal propulsion and gastric slow wave main frequency and power(P<0.05);(ii)levels of motilin,gastrin,and 5-HT increased,while NO level decreased(P<0.05);(iii)serum CCK content increased,while CGRP and NPY levels decreased(P<0.05);(iv)CCK protein positive expression increased,while CGRP and NPY protein positive expression decreased in the hypothalamus,gastric antrum,duodenum(P<0.05);(v)ghrelin protein expressions increased,and substance P protein expression decreased in the hypothalamus,spinal cord,gastric antrum,and colon(P<0.05).There were no significant differences in these indicators between the electroacupuncture group and the cisapride group.Conclusion Electroacupuncture at"Zusanli"and"Taichong"can effectively alleviate gastrointestinal motility disorders in FD rats,regulate gastrointestinal hormone levels,reverse abnormal brain-gut peptide expression,and regulate brain-gut interaction balance.

OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1（Jagged1）/Hes family BHLH transcription factor 1（Hes1） signaling pathway. MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE^-/- high-fat diet for four weeks， and they were randomly divided into the model group， Xuefu Zhuyu capsule group， and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules （0.728 g·kg^-1·d^-1）， and the atorvastatin group was intragastrically given atorvastatin tablet （6.07 mg·kg^-1·d^-1）. The normal group and the model group were given equal volume of the deionized water by intragastric administration， and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin （HE） staining， and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry， and serum levels of tumor necrosis factor （TNF）-α， interleukin（IL）-1β， transforming growth factor （TGF）-β₁， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The relative mRNA expressions of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， Notch1， Jagged1， and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The relative protein expression of iNOS， Arg-1， Notch1， Jagged1， and Hes1 in aortic tissue was detected by Western blot. ResultCompared with the normal group， the model group had significant aortic plaque and lipid deposition， and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased （P<0.01）. The expression level of anti-inflammatory cytokine TGF-β₁ showed a downward trend， but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased （P<0.01）. The protein expression of Arg-1 was decreased （P<0.01）， and the mRNA expression of related pathway molecule Jagged1， as well as the protein expressions of Notch1， Jagged1， and Hes1 were increased in the model group （P<0.05， P<0.01）. Compared with those in the model group， the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group， and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β₁ was increased （P<0.05）， and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased （P<0.01）. The mRNA and protein expressions of Arg-1 were increased （P<0.05， P<0.01）. Furthermore， the mRNA and protein expressions of Notch1， Jagged1， and Hes1 were decreased （P<0.01）. ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis， alleviate inflammation， inhibit M1 macrophages， and promote the expression of M2 macrophages， and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.