This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

OBJECTIVE：To study the pr otective effect of schisandrin A （SA）on CCl 4-induced liver fibrosis model mice and its mechanism. METHODS ：Mice were randomly divided into blank control group ，model group ，silymarin group （positive control，100 mg/kg），SA low-dose and high-dose groups （20，40 mg/kg），with 10 mice in each group. Except for blank control group，other groups were given CCl 4 subcutaneously to induce liver fibrosis model. After successful modeling ，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 6 weeks；blank control group and model group were given constant volume of 0.5％sodium carboxymethyl cellulose solution intragastrically by the same way. HE staining was used to observe the pathological changes of liver tissue in mice. UV spectrophotometry and ELISA assay were adopted to detect the serum levels of liver injury indexes （ALT and AST ）and the contents of inflammatory factors （TNF-α，IL-1β，IL-6）. Western blotting assay was used to detect the expression of NOD like receptor protein 3（NLRP3）/NF-κB and TGF-β/Smad signaling pathway protein. RESULTS ：Compared with blank control group ，obvious pathological changes of liver fibrosis were observed in model group. The serum levels of liver injury indexes and contents of inflammatory factors were significantly increased （P＜0.01）. The expression of NLRP 3，apoptosis associated spot-like protein ，Caspase-1 and IL- 1β，TGF-β1 and ratios ofp-NF-κB p65/NF-κB p65，p-IκBα/IκBα，p-Samd3/Smad3 were increased significantly （P＜0.01）. Compared with model group ，SA could significantly relieve hepatic fibrosis in mice ，reduce serum levels of liver injury indexes and contents of inflammatory factors ，as well as the expression of NLRP 3/NF-κB and TGF-β/Smad signaling pathway protein and phosphorylation level（P＜0.01）. CONCLUSIONS ： SA can effectively relieve liver injury and inflammation of CCl 4-induced hepatic fibrosis model mice ，which may be through the regulation of NLRP 3/NF-κB and TGF-β/Smad3 signaling pathways ，thus inhibiting the process of liver fibrosis.

Objective:To establish a scientific, directional and operable evaluation index system for clinical disciplines, which can meet the needs of discipline construction and is suitable for the evaluation and selection of various disciplines in oncology hospitals, so as to provide decision-making basis for discipline construction.Methods:Literature analysis and in-depth interview were used to draw up the preliminary evaluation index system. The index frame of subject evaluation was compiled, and the expert inquiry paper was compiled, and the index was added, subtracted and modified by Delphi method through two rounds of expert consultation. The index weight was determined by Analytic hierarchy process. Each index was given a specific scoring standard. The evaluation index system was used to test and analyze 22 clinical medical disciplines in the hospital. The total score of each discipline was calculated by weighted summation method. The validity of evaluation was judged by Spearman grade correlation analysis.Results:The clinical discipline evaluation index system consisted of 4 first-class indexes, 10 second-class indexes and 34 third-class indexes. The weights and scoring criteria of each index were determined. 22 disciplines were evaluated by the index system, which was divided into three grades: excellent, medium and poor.Conclusions:The evaluation index system of clinical discipline constructed in this study has high authoritative coefficient of experts, and the P value is less than 0.01.The evaluation results of 22 disciplines are highly correlated with those of experts, and the P value is less than 0.01. It has strong scientific validity and feasibility, and lays a foundation for the widespread application of clinical evaluation.

As one of the main forms of the medical alliance, the specialty alliance functions as a service carrier for hierarchical medical service and resources integration in the region. The authors introduced the exploration and practice of the West China Women′s and Children′s Alliance, the first pediatric specialty alliance in Sichuan, established by the West China Second Hospital of Sichuan University. Based on family doctor contracted services, the West China Women′s and Children′s Alliance took such measures as differentiated functional positioning, assessment of certified physicians, continuous online quality control, construction of referral platforms, and innovative payment mechanisms. Such efforts effectively integrated the three stages of pre-hospital " preventive care" , in-hospital " disease diagnosis and treatment" , and post-hospital " follow-up management" , exploring the homogenization of medical services within the alliance, and forming a pediatric closed-loop health management system, hence improving the primary medical services.

Fluoroquinolones are widely used in clinical practice, but their clinical application in juvenile patients has been controversial.The purpose of this study was to investigate the pharmacokinetic characteristics, indications and adverse reactions of Ciprofloxacin and Levofloxacin in minors.It is shown that the two drugs are effective for infectious diseases and no serious or persistent joint or skeletal muscle injury occurs in minors using the drugs.Hence, in the absence of alternatives, the benefits of Ciprofloxacin or Levofloxacin treatment for minors may outweigh the risks.

Objective To observe the changes of the peripheral blood T helper (Th)17 cells/regulatory T cells (Treg) ratio in patients with anti‐tuberculosis drug‐induced liver injury ,and to explore the relationship between Th17/Treg ratio and liver function . Methods Ninety inpatients with the diagnosis of secondary pulmonary tuberculosis (TB) from Affiliated Hospital of Zunyi Medical College from Feb .2013 to Mar .2015 were included in this study .All these patients had normal base line liver function .After 2 weeks of anti‐TB chemotherapy ,21 patients with alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ≥2 × upper limit of normal (ULN) were defined as TB with liver injure group ,the other 69 patients with ALT and/or AST<2 × ULN were defined as TB with non‐liver injured group .Before treatment and two weeks after anti‐TB therapy ,the peripheral blood Th17/Treg ratios and liver functions of all patients in both groups were detected in order to compare the changes of Th17/Treg ratios pre and post anti‐TB chemotherapy and to explore the relationship between Th17/Treg ratio and ALT/AST levels .Student′s t test was used for statistical analysis ,and Pearson correlation analysis was used for correlation test .Results Before treatment ,there was no statistical significance of Th17 ,Treg and Th17/Treg ratio between groups (P> 0 .05) .The Th17 levels in TB with liver injured group ([2 .522 ± 0 .388]/mL vs [2 .075 ± 0 .369]/mL ,t=3 .633 ,P<0 .01) and TB with non‐liver injured group ([2 .326 ± 0 .348]/mL vs [1 .929 ± 0 .402]/mL ,t= 6 .468 , P< 0 .01) ,and Th17/Treg ratios in both groups(0.618±0.104vs0.489±0.107,t=3.553,P<0.01 ;0.554±0.108vs0.450±0.098,t=6 .353 ,P<0 .01) were all increased after anti‐TB chemotherapy ,with statistically significant differences . However ,there was no statistical significance of Treg levels pre and post anti‐treatment in both groups (both P>0 .05) .The Th17 level and Th17/Treg ratio in TB with liver injured group were significantly higher than those in TB with non‐liver injured group (t= 2 .203 , P< 0 .05 and t= 2 .345 , P< 0 .05 , respectively) .In liver injured group ,the Th17/Treg ratio was positively correlated with ALT level (r=0 .849 ,P=0 .044) ,but not with AST level (P>0 .05) .Conclusion The changes of Th17/Treg ratio are related with anti‐TB drug‐induced liver injury in patients with secondary pulmonary tuberculosis .

Objective To express the capsid proteins of WU polyomavirus(WUPyV) for research and find antigen for diagnostic value. Methods Coding sequences of capsid proteins of WU polyomavirus by PCR were cloned in prokaryotic expression vector PGEX-20T. Recombinant plasmids were transformed into E. coli BL21(DE3) and induced by IPTG for proteins expression. Recombinant proteins were identified by Western blot. Results SDS-PAGE proved that recombinant proteins showed three bands with molecular relative mass of 69×103, 63×103 and 56×103. The recombinant proteins were recognized by anti-GST McAb. The antigenicity was tested by Western blot using 16 WU polyomavirus positive and 70 negative sera. Conclusion Recombinant VP1, VP2 and VP3 expressed in E. coli can combine with WUPyV-Ab and have good antigenicity. They can be used for further research.

Objctive:To investigate the immunohistochemical and morphological characteristics of the papillary thyroid microcarcinoma(PTM) ,and differential diagnosis of the related disease.Methods:The morphological characteristics of 223 patients with PTM were observed under light microscope.Seventy-four cases of PTM and 32 cases of proliferative lesion of thyroid were observed under light microscope with stains of hematoxylin and eosin and immunohistochemical staining.The antibody included CK19,MC,Galectin-3 and CD56.Results:Eighty-six cases were follicular-patterned and 31 cases nuclear features were untypical in 223 cases of PTM.The positive expression rates of CK19、MC、 Galectin-3、CD56 were 100.0%,98.6%,98.6% and 4.1% in 74 cases of PTM,and were 37.5%,12.5%,18.8%,68.8% in proliferative lesion of thyroid,respectively.Conclusion:Some cases of PTM show a follicular-patterned and the nuclear features.It is untypical compared with classical papillary thyroid carcinoma.It can be differentiated from proliferative lesion with absence of envelope,obviously various and unusually proliferated follicular cells,sclerotic stroma,neoplastic follicles among the collagen and normal follicles.The wide and intensive expression of CK19,Galectin-3,and the negative expression of CD56 are extremely useful in the diagnosis of PTM,four-marker panel with CK19,Galectin-3,MC and CD56 can improve the specificity and accuracy of the differential diagnosis of PTM.

OBJECTIVETo observe the clinical efficacy of shensong yangxin capsule (SYC) on ventricular premature beat (VPB) differentiated in TCM as palpitation of Qi-yin deficiency syndrome or Xin collateral stagnation syndrome, and cardiovascular autonomic nervous function in patients with coronary heart disease (CHD).

METHODSThe randomized, double-blind, parallel contrast method was adopted, patients were randomly assigned by 3:1 ratio into two groups. One hundred and sixty-five patients in SYC treated group and 56 in the control group (treated with Xinlvning tablet), and the therapeutic course for both groups was 4 weeks.

RESULTSThe clinical efficacy on VPB and in improving TCM syndromes was better in SYC group than that in the control group (P < 0.01). After treatment, the heart rate variability (HRV) and QT dispersion in the two groups were improved in a certain degree. The changes of SDNN, SDANN, SDNN Index and PNN50 in the two groups were significantly different (P < 0.05, P < 0.01), the efficacy in the treated group was superior to that in the control group.

CONCLUSIONSYC has definite effect on VPB and TCM Syndromes, it can obviously meliorate the activity of cardiovascular autonomic nervous system in the patients with CHD.

Adult ; Aged ; Autonomic Nervous System ; drug effects ; physiopathology ; Capsules ; Coronary Disease ; complications ; drug therapy ; Double-Blind Method ; Drug Administration Schedule ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart ; innervation ; Humans ; Male ; Middle Aged ; Phytotherapy ; Ventricular Premature Complexes ; drug therapy ; etiology