Objective: To investigate the efficacy and safety of Liqingtong (LQT) granules in patients with dampness-heat hyperuricemia. Methods: A randomized, double-blind, placebo-controlled pilot trial was conducted at the 983rd Hospital of the Joint Logistic Support Force of the People's Liberation Army from March 15, 2023, to August 10, 2023. In total, 119 participants were enrolled in this trial, and participants were given either LQT granules or placebo for 60 days based on a health education. The primary outcome was serum uric acid (SUA) level, and the secondary outcome was the traditional Chinese medicine (TCM) symptom score, measured on days 0, 30, and 60. Safety indicators, including liver function, kidney function, blood routine, glucose, blood lipid, blood pressure, and heart rate were tested on days 0 and 60 of the trial. The data were analyzed using Prism 9 software, and the significance level was set at P < .05. Results: Among 119 participants, six in the LQT granule group and seven in the placebo group dropped out, and 106 participants completed clinical observation. Baseline information, including SUA levels, TCM symptom scores, and other clinical characteristics, did not differ between the groups. At the end of the trial, compared with baseline values, the SUA levels in the LQT granule group decreased (P < .001), and no significant change was observed in the placebo group (P = .422); compared with the placebo group, the SUA levels decreased in the LQT granule group (P = .001). Compared with baseline values, the total TCM symptom scores in the LQT granule group decreased (P < .001), with no change in the placebo group (P = .136). Safety indicators did not differ significantly between the two groups. Conclusion The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.
Apoptosis ; Autophagy* ; Cell Cycle Checkpoints ; Cell Death ; Colon* ; Colonic Neoplasms* ; Heterografts ; HT29 Cells ; Humans ; Protein Processing, Post-Translational

The immune system is a complex system involving multiple organs,and it is vulnerable to age,gender,environment and other factors.For a variation normal physiological range,it is a great challenge to evaluate drug-induced immunotoxicity in preclinical safety study.Histomorphologic assessment of the immune system is a recognized cornerstone in the identification of immunotoxicity at present.In this paper,the principles of pathological evaluation for immune system,and pathological evaluation for important immune organs including thymus,spleen,lymph nodes are discussed briefly,so that it is intended to assist toxicity pathologists in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system.

Toxicological pathology is a morphological elucidatet ion of tissue damage caused by drug toxicity,including damage type,location,severity grade and prognosis.It provides objective and accurate data to support preclinical drug safety evaluation.Therefore,toxicological pathology plays an important role in drug safety evaluation,and the pathologic data or conclusion often determines the termination or continuation in many drug development projects.In this paper,the characteristic of toxicological pathology,standardized management,the development of new techniques including in situ hybridization,laser scanning cytometry and laser capture microdissection,and related problems in pathology are discussed briefly.

Objective To initially understand the condition of quality of life (QOL) and depression as well as the correlation between them in the stroke inpatients. Methods 56 stroke patients from September 2014 to January 2015 in our hospital were included. Their QOL and depression status were evaluated with Stroke-Specific Quality of Life Scale (SS-QOL) and Self-rating Depression Scale (SDS). The de-pression was as the dependent variable, the score of SS-QOL, gender, age, education background, and the duration of stroke were as the inde-pendent variables, and analyzed with Logistic regression. Results Depression correlated with SS-QOL score (OR=0.955, P<0.05), but not with gender, age, education background, and the duration of stroke (P>0.05). Conclusion The depression status correlated with the QOL of stroke patients, but did not with gender, age, education background and the duration of stroke.

Objective To assess the value of emergency interventional embolization in treating traumatic spleen rupture. Methods A total of 74 patients with traumatic spleen rupture, who were encountered at authors’ hospital during the period from July 2007 to July 2013, were enrolled in this study. The clinical data were retrospectively analyzed. The patients were divided into embolization group (n = 38) and surgery group (n = 36). Interventional splenic artery embolization was carried out in the patients of the embolization group, and surgical repair was employed in the patients of the surgery group. The operation time, the amount of blood loss during the procedure, the hospitalization days, the preservation rate of the spleen and the occurrence of procedure- related adverse events were recorded, and the results were compared between the two groups. Results No significant difference in the operation time existed between the two groups (P = 0.061). The amount of blood loss during the procedure, the hospitalization days and the occurrence of procedure- related adverse events in the embolization group were significantly lower than those in the surgery group (P < 0.05), while the preservation rate of the spleen of the embolization group was significantly higher than that of the surgery group (P = 0.026). Conclusion Emergency interventional embolization is a safe procedure for the treatment of traumatic spleen rupture, this technique can improve the preservation rate of the spleen when compared with traditional surgical repair treatment.

Chinese Society of Medical Science Research Administration Association has been established for 28 years.In order to make Chinese Society of Medical Science Research Administration Association better play the role,strengthen communication and guidance,the author made an investigation and analysis on Local Medical Association Medical Research Management special committee of current situation.With the increasing research investment from government,efficient research outputs need science research personnel and higher comprehensive quality of research and management personnel.Establish and improve local medical science research management special committee by means of positive organizational building and rich academic exchange and professional training to promote medical research management team construction.

Objective To explore the clinical significance of second transurethral resection (TUR) in patients with T1 urothelial cell carcinoma of the bladder.Methods The 142 cases with urothelial carcinoma were recruited.All patients underwent transurethral resection of bladder tumor (TURBT) and were diagnosed as stage T1 urothelial carcinoma of the bladder.The 68 of 142 cases underwent second TUR after the initial surgery.Tumor recurrence rate,progression rate and recurrence-free survival were compared.Results There were no statistical differences in age,gender,follow-up time,number of tumors,size of tumors or grade of tumors between patients with and without second TUR.Of the 68 cases that underwent second TUR,25 cases (36.8%) had residual tumor and 6 of them (8.8%) had muscle-invasive bladder cancer.After an average observation for 26.8 months,patients who underwent second TUR showed lower recurrence rate,higher recurrence-free rate and longer recurrence-free survival than patients without second TUR [37.1% vs.58.1%,x2=5.962,P=0.015;41% vs.35.1%,x2=8.502,P=0.004;21 months vs.12 months,U= 1584,P= 0.002].While the progression rate showed no statistical difference between them (14.5% vs.25.7%,x2 =2.570,P=0.109).Conclusions Second TUR provides an effective way to completely excise tumor.Second TUR is beneficial to the decrease of recurrence rate and improvement of recurrence-free survival.However,its effect on tumor progression needs further discussion.

ObjectiveTo evaluate the clinical effecacy and safety of transurethral enucleation of submucosal bladder leiomyoma.MethodsAnalyze retrospectively the clinical data of 6 patients (2 male,4 female) of submucosal bladder leiomyoma. The mean age was 59 years (range 32- 78). The clinical manifestations included dysuresia in 3 cases, irritative bladder in 1 case, gross hematuria in 1 caes, and no clinical symptoms in 1 case. The mean course was 23 months (range 1 week-4 years). All the bladder tumors were indicated by ultrasonography, CT scan and cystoscopy, while 4 cases of bladder filling defects were showed by intravenous urogram. Before the tranaurethral enucleation of the bladder tumor, a deep needle biopsy and pathological examination were carried out to confirm the diagnosis of bladder leiomyoma. For the relatively small lateral leiomyomas, holium laser enucleation was carried out, while for the big ones, resectoscope enucleation was used to remove the mass. Biopsys were performed after complete removal of the tumor.ResultsTransurethral enucleation of 6 cases of submucosal bladder tumors were successful without any postoperative complication. All patients regained normal urination, and lower urinary tract irritation was relieved obviously and hematuria disappeared. No tumor recurrence or metastasis was found during the follow-up of 4 to 158 months.ConclusionsCystoscopy and transurethral biopsy are the most important methods for the diagnosis of submucosal bladder leiomyoma. The transurethral enucleation is a feasible and safe surgical technique for such patients with excellent results.