Objective To investigate the clinical efficacy of Zhikang Capsules plus Compound Huangbai Lotion for retention enema in the treatment of patients with mild to moderate distal ulcerative colitis(UC)of damp-heat in large intestine type,and to observe their effects on the serum levels of pro-inflammatory cytokines of tumor necrosis factor α(TNF-α),interleukin 6(IL-6)and C-reactive protein(CRP).Methods A total of 110 patients with mild to moderate distal UC of damp-heat in large intestine type who were treated in the Outpatient Clinics and Wards of the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine from October 2022 to December 2023 were randomly divided into an observation group and a control group according to random number table method,with 55 patients in each group.The control group was given retention enema with 1 g of Xilei Powder and 50 mL of Compound Huangbai Lotion before going to bed every night,while the observation group was given retention enema with 2.4 g of Zhikang Capsules and 50 mL of Compound Huangbai Lotion before going to bed every night The course of treatment for the two groups covered 14 days.The changes in the serum inflammation factors,coagulation function indicators,traditional Chinese medicine(TCM)syndrome scores,and the Inflammatory Bowel Disease Quality of Life Questionnaire(IBDQ)scores in the two groups were observed before and after treatment.After treatment,the clinical efficacy and drug safety in the two groups were evaluated.Results(1)After 14 days of treatment,the total effective rate of the observation group was 90.91％(50/55)and that of the control group was 80.00％(44/55),and the intergroup comparison(tested by rank sum test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammation factors of TNF-α,IL-6,and CRP patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the prothrombin time(PT)and fibrinogen(FIB)of the two groups of patients were improved compared with those before treatment(P＜0.05),while the improvement of thrombin time(TT)and activated partial thromboplastin time(APTT)were not obvious when compared with those before treatment(P＞0.05);the comparison between the two groups showed that the improvement of PT and FIB in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the scores of TCM symptoms of diarrhea,mucous-purulent and bloody stool,tenesmus,scorching sensation of the anus in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)After treatment,the scores of IBDQ items of general symptoms,intestinal symptoms,social functioning,emotional role functioning in the two groups were increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the treatment,no obvious adverse reactions occurred in the two groups,with higher safety.Conclusion Zhikang Capsules plus Compound Huangbai Lotion for retention enema are effective and safe in treating mild to moderate distal UC of damp-heat in large intestine type.The therapy can effectively control the illness of UC,alleviate the clinical symptoms and negative emotions,improve the inflammatory response and coagulation function,and enhance the quality of life of the patients.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
Aconitine/pharmacology* ; Analgesics/pharmacology* ; Animals ; Pharmaceutical Preparations ; Rats ; Rats, Sprague-Dawley

A serumal metabonomics method based on UPLC/Q-TOF-MS was established to investigate the mechanism of Schisandra chinensis to treating diabetic nephropathy. The diabetic model was established by feeding with high-fat and high-sucrose chow and streptozotocin intraperitoneal injection. After intragastric administration for 12 weeks, the content of protein and creatinine in rat urine was detected. The results showed that Schisandra chinensis could reduce the content of protein in urine of diabetic rat ( p<0 . 05 ) and ameliorate the condition of diabetic nephropathy. The serum metabolic profiling was analysed by using UPLC/Q-TOF-MS and partial least squares-discriminated analysis ( PLS-DA) was used for data analysis. The score of PLS-DA showed that there was significant difference among the metabolic profile of control group, model group and Schisandra chinensis group ( WWZ ) . Potential biomarkers of Schisandra chinensis ameliorating diabetic nephropathy were selected by orthogonal partial least squares ( OPLS)-DA model. According to the results of OPLS-DA, the MS/MS data of each compound which provided greater contribution to separation of each group were searched from the HMDB databases. Seven endogenous metabolites were identified as potential biomarkers such as xanthurenic acid, palmitic amide, oleamide, uric acid, 5-hydroxyhexanoic acid, p-cresol sulfate, and p-cresol glucuronide. The results revealed that Schisandra chinensis mainly affected the pathways of tryptophan metabolism, gut microbiota metabolism, purine metabolism and fatty acid metabolism to treating type 2 diabetes mellitus. The gut microbiota metabolism and purine metabolism was an important pathway on diabetic nephropathy.

EphA7 is one of the most important members of the Eph family .It is a key regulatory factor of cell adhesion and repulsion ,it also contributes to establish men ,maintain ance and tissue remodeling in cell mor-phology .In recent years ,its function in tumors has been revealed gradually .It plays a variety of roles in different tumors.The overexpression of EphA7 can be detected in acute leukemia ,glioblastomamultiforme,lung cancer and hepatic carcinoma ,which suggests EphA 7 may be involved in the development of these tumors .While in colon cancer,prostate cancer,follicular lymphoma and gastric cancer ,a significant reduction of EphA7 expression with promoter hypermethylation is discovered ,which suggests EphA 7 play a tumor suppressor role in these tumors .E-ven though the function of EphA 7 is still under exploration , EphA7 and tumor development are inextricably linked,it may have roles in the pathogenesis and development of these carcinomas .