Objective To modify the dosage form of Guoganglong Sugar-Coated Tablets,and to investigate the chemical equivalence and pharmacodynamic equivalence between the new and old dosage forms of Guoganglong Tablets.Methods The preparation technology was screened by single-factor exploration with the indexes of hardness and dispersion uniformity,the quality standard was established by thin layer chromatography identification,high performance liquid chromatography(HPLC)content determination and charactertistics chromatograms,the constituents absorbed into blood were analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-Q-TOF-MS),and the pharmacodynamics was evaluated by anti-inflammatory experiment and analgesic experiment in mice model with inflammatory pain.Results The molding process of Guoganglong Dispersible Tablets was determined.A thin layer chromatographic identification method was established.A method for detecting the content of Guoganglong Tablets and the charactertistic chromatograms was established by HPLC,and a total of 15 common peaks were identified,with the similarity of the new-old dosage forms being greater than 0.9.A total of 12 constituents absorbed into blood were identified.Guoganglong Tablets could alleviate swelling degree of toes in mice with inflammatory pain,reduce the levels of interleukin 6(IL-6)in serum,improve spleen index,and increase the thermal pain threshold and acetic acid twisting frequency in mice.Conclusion The prescription process of Guoganglong Dispersible Tablets is stable,the quality standard is feasible,the chemical composition and pharmacological actions between the new and old dosage forms are basically the same,and in terms of certain indexes,Dispersible Tablets of Guoganglongare superior to Sugar-Coated Tablets.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Flagella are the main motility structure of Clostridioides difficile that affects the adhesion, colonization, and virulence of C. difficile in the human gastrointestinal tract. The FliL protein is a single transmembrane protein bound to the flagellar matrix. This study aimed to investigate the effect of the FliL encoding gene flagellar basal body-associated FliL family protein (fliL) on the phenotype of C. difficile. The fliL gene deletion mutant (ΔfliL) and its corresponding complementary strains (: : fliL) were constructed using allele-coupled exchange (ACE) and the standard molecular clone method. The differences in physiological properties such as growth profile, antibiotic sensitivity, pH resistance, motility, and spore production ability between the mutant and wild-type strains (CD630) were investigated. The ΔfliL mutant and the : : fliL complementary strain were successfully constructed. After comparing the phenotypes of strains CD630, ΔfliL, and : : fliL, the results showed that the growth rate and maximum biomass of ΔfliL mutant decreased than that of CD630. The ΔfliL mutant showed increased sensitivity to amoxicillin, ampicillin, and norfloxacin. Its sensitivity to kanamycin and tetracycline antibiotics decreased, and the antibiotic sensitivity partially returned to the level of CD630 strain in the : : fliL strain. Moreover, the motility was significantly reduced in the ΔfliL mutant. Interestingly, the motility of the : : fliL strain significantly increased even when compared to that of the CD630 strain. Furthermore, the pH tolerance of the ΔfliL mutant significantly increased or decreased at pH 5 or 9, respectively. Finally, the sporulation ability of ΔfliL mutant reduced considerably compared to the CD630 strain and recovered in the : : fliL strain. We conclude that the deletion of the fliL gene significantly reduced the swimming motility of C. difficile, suggesting that the fliL gene is essential for the motility of C. difficile. The fliL gene deletion significantly reduced spore production, cell growth rate, tolerance to different antibiotics, acidity, and alkalinity environments of C. difficile. These physiological characteristics are closely related to the survival advantage in the host intestine, which is correlated with its pathogenicity. Thus, we suggested that the function of the fliL gene is closely related to its motility, colonization, environmental tolerance, and spore production ability, which consequently affects the pathogenicity of C. difficile.
Humans ; Clostridioides/metabolism* ; Clostridioides difficile/metabolism* ; Bacterial Proteins/metabolism* ; Virulence ; Anti-Bacterial Agents/metabolism*

Aim To investigate the effect of intestinal cholesterol absorption inhibitor Ezetimibe on lipid accumulation in RAW264.7 cells and identify the underlying mechanism.Method RAW264.7 cells were pretreated with the indicated concentrations of Ezetimibe (0,0.003,0.01 and 0.03 mol·L~(-1))for 24 hours or pretreated with the optimal concentration(0.03 mol·L~(-1))of Ezetimibe for different periods (0,6,12 and 24 h),followed by incubation with 50 mg·L~(-1) oxLDL for 24 hours,then the number of intracellular lipid droplets and lipid content were measured by using oil red O staining and HPLC; the expression of NPC1L1 was measured by Western blot.Results Pretreatment with indicated concentrations of Ezetimibe caused a concentration-dependent inhibition of intracellular lipid accumulation;pretreatment with 0.03 mol·L~(-1) Ezetimibe caused a time-dependent inhibition of intracellular lipid accumulation.It was noted that pretreatment with 0.03 mol·L~(-1) Ezetimibe for 24 hours inhibited CE by about 47%+0.1% compared with control group(oxLDL alone).Immunoblotting results showed that NPC1L1 was expressed in RAW264.7 cells and it was down-regulated after Ezetimibe treatment.Conclusions Ezetimibe causes concentration-dependent and time-dependent inhibition of lipid accumulation in RAW264.7 cells;it also reduces NPC1L1 expression in RAW264.7 cells.

AIM To investigate the relationship between the prevention of probucol against restenosis and functional vascular remodeling after percutaneous transluminal angioplasty(PTA) in rabbits. METHODS New Zealand rabbit thoracic aorta atherosclerosis was induced by 3 5 F balloon catheter injury following a 4 week feeding of high cholesterol diet, and percutaneous transluminal angioplasty(PTA) was performed by using 3 5 F ballon catheter. Probucol(1 g?d -1 ) or vitamin E(400 mg?d -1 ) was administrated one week before PTA. Two weeks after PTA, lumen area,neointima area(NEA),medial area(MA) and NEA/MA were analyzed by computerimage system.The relaxation response of restenotic arteries to acetylcholine and the contractive response to norepinephrine, potassium chloride and serotonin of thoracic aorta rings were measured by bioassay. Nitric oxide of serum was measured by means of biochemical assay.RESULTS After two weeks of PTA, probucol increased lumen area and decreased neointima area significantly. The relaxation response of restenotic arteries to acetylcholine was significantly lower than that of normal arteries〔relaxation percent to acetylcholine (1 ?mol?L -1 ):(18 4?4 0)% vs (63 5?6 4)%, P