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 investigate the changes of T lymphocyte subsets in patients with stage Ⅰ and Ⅱ cervical cancer after surgery and their relationship with postoperative lymph node metastasis according to the International Federation of Gynecology and Obstetrics (FIGO) stage (2014) .Methods:A total of 192 patients with FIGO stage ⅠA, ⅠB1, ⅠB2 and ⅡA1 who received radical cervical cancer resection and pelvic lymph node dissection in People's Hospital of Yuechi County of Sichuan Province and West China Guang'an Hospital of Sichuan University from November 2018 to November 2020 were selected for this study. According to FIGO stage, patients were divided into stage Ⅰ group ( n=85) and stage Ⅱ group ( n=107) . The dynamic changes of T lymphocytes subsets in patients with different FIGO stages were compared before and after surgery. Repeated measurement of variance was used to analyze the levels of T lymphocytes subsets in patients of different stages during treatment. Logistic regression was used to analyze the influencing factors of postoperative lymph node metastasis in patients with cervical cancer. Multivariate logistic regression was used to analyze the relationship between T lymphocytes subsets and postoperative lymph node metastasis. Receiver operator characteristic (ROC) curve was used to analyze the predictive efficacy of T lymphocytes level in postoperative lymph node metastasis. Results:The postoperative lymph node metastasis rate in stage Ⅱ patients [32.71% (35/107) ] was higher than that in stage Ⅰ patients [14.12% (12/85) ], with a statistically significant difference ( χ2=8.86, P=0.003) . Compared with the stage Ⅱ group, the levels of CD3 +, CD4 + T lymphocytes and CD4 +/CD8 + ratio were significantly higher in the stage Ⅰ group 1 day before surgery (all P<0.001) , and the level of CD8 + T lymphocytes was significantly lower ( P<0.001) . The levels of CD3 +, CD4 +, CD8 + T lymphocytes and the ratio of CD4 +/CD8 + showed dynamic changes at different stages after surgery. On 1, 7 and 30 days after surgery, the levels of CD3 +, CD4 + T lymphocytes and the ratio of CD4 +/CD8 + in stage Ⅰ group were higher than those in stage Ⅱ group (all P<0.001) , CD8 + T cell levels were lower than those in stage Ⅱ group (all P<0.001) . There were statistically significant differences in T lymphocytes subsets CD3 +, CD4 +, CD8 + and CD4 +/CD8 + time effect, intergroup effect and interaction effect between the two groups (all P<0.001) . Univariate analysis showed that the pathological type ( OR=1.85, 95% CI: 1.14-2.33, P=0.015) , differentiation degree ( OR=1.93, 95% CI: 1.18-2.67, P=0.024) , depth of myometrial invasion ( OR=2.08, 95% CI: 1.26-2.59, P=0.012) , tumor morphology ( OR=2.17, 95% CI: 1.57-2.63, P=0.009) , parametrial invasion ( OR=1.95, 95% CI: 1.43-2.76, P=0.036) and lymphovascular space invasion ( OR=2.03, 95% CI: 1.28-2.57, P=0.021) were the influencing factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate analysis showed that the degree of differentiation ( OR=1.75, 95% CI: 1.08-2.03, P=0.015) , depth of myometrial invasion ( OR=2.30, 95% CI: 1.43-2.84, P=0.021) , parametrial invasion ( OR=2.50, 95% CI: 1.76-2.97, P=0.018) and lymphovascular space invasion ( OR=1.96, 95% CI: 1.03-2.51, P=0.033) were independent factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate logistic regression analysis showed that the levels of CD3 +, CD4 +, CD8 + T cells and the ratio of CD4 +/CD8 + in patients with stage Ⅰ and stage Ⅱ cervical cancer 1 day before surgery were independent influencing factors for postoperative lymph node metastasis (all P<0.05) . ROC curve analysis showed that the areas under the curve of CD3 +, CD4 +, CD8 + T lymphocytes levels and the ratio of CD4 +/CD8 + in stage Ⅰ patients 1 day before surgery for predicting postoperative lymph node metastasis were 0.86, 0.82, 0.83, 0.89, respectively, and those in stage Ⅱ patients were 0.90, 0.93, 0.87, 0.95, respectively. CD4 +/CD8 + ratio was significantly more effective in predicting postoperative lymph node metastasis than other indexes (all P<0.001) . Conclusions:The levels of CD3 +, CD4 + T lymphocytes, and the CD4 +/CD8 + ratio in patients with FIGO stage Ⅰ and Ⅱ cervical cancer are significantly higher in 1-30 days after surgery than before, while the level of CD8 + T lymphocytes is significantly lower than before. There is a significant correlation between T lymphocytes subsets and lymph node metastasis after surgery. In addition, low differentiation, depth of myometrial invasion ≥1/2, parametrial invasion, and lymphovascular space invasion are independent risk factors for postoperative lymph node metastasis.

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.

BACKGROUND:THZ1,an inhibitor of cyclin-dependent kinase 7,has been shown to inhibit the proliferation of a variety of tumor cells,but whether THZ1 can affect the stemness of glioma stem cells through the Wnt/β-catenin signaling pathway remains unclear.OBJECTIVE:To investigate the effect of THZ1 on stemness of glioma cell U87 and its mechanism.METHODS:U87 adherent cells were cultured to form stem cell mammospheres.The expressions of stemness related proteins were verified by western blot assay.The effect of THZ1 on half maximal inhibitory concentration(IC50)of U87 cells was determined by Cell Counting Kit-8(CCK-8)assays.The effects of THZ1 on proliferation and migration of U87 cells were determined by cell colony-formation assays,cell wound healing assays,and Transwell migration assays.The effect of THZ1 treatment on mammosphere forming rate and mammosphere size of U87 stem cells was analyzed.Stemness associated proteins CD133,ABCG2,Nanog,OCT4,SOX2,epithelial-mesenchymal transformation-related proteins E-cadherin,N-cadherin,Occludin,Snail,and Wnt/β-catenin pathway associated proteins Axin1,β-Catenin,WNT-5A,GSK3β,Cyclind-1,and C-myc were measured by western blot assay.RESULTS AND CONCLUSION:(1)Compared with adherent cells,the expressions of stemness related proteins Nestin,CD133,ABCG2,Nanog,OCT4,and SOX2 were significantly increased.(2)Compared with the control group,THZ1 decreased the proliferation and migration of U87 cells.(3)THZ1 inhibited the mammosphere forming rate and mammosphere size of U87 stem cells.(4)After THZ1 treatment,the expression of N-cadherin and Snail decreased,while the protein expression of E-cadherin and Occludin increased.(5)THZ1 treatment decreased the expression of Wnt/β-catenin pathway related proteins Axin1,β-Catenin,Wnt-5A,GSK3β,Cyclind-1,and C-myc in U87 stem cells.It is concluded that THZ1 can suppress the proliferation and migration of U87 cells,and inhibit the mammosphere forming ability,stemness related protein expression,and epithelial-mesenchymal transformation ability of U87 stem cells by down-regulating the expression of Wnt/β-catenin signaling pathway related molecules.

Objective To investigate the clinical efficacy of Jia Yi Formula(composed of Trionycis Carapax,Ranunculi Ternati Radix,Pinelliae Rhizoma Praeparatum,Trichosanthis Pericarpium,Poria,Curcumae Radix,Fritillariae Thunbergii Bulbus,and Albiziae Cortex)in improving anxiety symptoms of patients with hyperthyroidism(HT).Methods A total of 84 HT patients with yin deficiency with internal heat and phlegm blended with stasis syndrome accompanied by anxiety were enrolled from the Endocrinology Outpatient and Inpatient Departments of The Affiliated Guangzhou Traditional Chinese Medicine Hospital of Guangzhou University of Chinese Medicine between February and December of 2024.Patients were randomly divided into treatment group and control group(n=42 each)using a random number table.Both groups received conventional therapy,while the control group additionally received oral methimazole,and the treatment group received Jia Yi Formula and methimazole.The treatment duration was 12 weeks for both groups.Changes in Hamilton Anxiety Scale(HAMA)scores,traditional Chinese medicine(TCM)syndrome scores,and serum thyroid hormone levels[free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)]were observed.The improvement in anxiety status,TCM syndrome efficacy,and drug safety were evaluated.Results(1)In terms of TCM syndrome improvement,the total effective rate was 92.86％(39/42)in the treatment group versus 71.43％(30/42)in the control group.Intergroup comparison(by Mann-Whitney U test)showed that the TCM syndrome improvement in the treatment group was superior to the control group(P＜0.05).(2)For anxiety improvement,the total effective rate was 83.33％(38/42)in the treatment group versus 69.05％(29/42)in the control group.Intergroup comparison(by Mann-Whitney U test)showed that the anxiety improvement in the treatment group was superior to the control group(P＜0.01).(3)After treatment,both groups showed significant reductions in HAMA scores and TCM syndrome scores(P＜0.01),with greater reductions observed in the treatment group(P＜0.01).(4)Thyroid hormone levels(FT3,FT4,TSH)were significantly improved in both groups(P＜0.01),with FT3 and TSH showing greater improvement in the treatment group(P＜0.05 or P＜0.01),while FT4 improvement did not differ significantly between groups(P＞0.05).(5)The incidence of adverse reactions was 4.76％(2/42)in the treatment group and 7.14％(3/42)in the control group.Intergroup comparison(by Fisher's exact test)showed that the difference was not statistically significant(P＞0.05).Conclusion Jia Yi Formula demonstrates significant efficacy in improving anxiety,clinical symptoms,and thyroid function in HT patients with yin deficiency with internal heat and phlegm blended with stasis syndrome,showing superior benefits when used together with methimazole compared to methimazole alone.

BACKGROUND:THZ1,an inhibitor of cyclin-dependent kinase 7,has been shown to inhibit the proliferation of a variety of tumor cells,but whether THZ1 can affect the stemness of glioma stem cells through the Wnt/β-catenin signaling pathway remains unclear.OBJECTIVE:To investigate the effect of THZ1 on stemness of glioma cell U87 and its mechanism.METHODS:U87 adherent cells were cultured to form stem cell mammospheres.The expressions of stemness related proteins were verified by western blot assay.The effect of THZ1 on half maximal inhibitory concentration(IC50)of U87 cells was determined by Cell Counting Kit-8(CCK-8)assays.The effects of THZ1 on proliferation and migration of U87 cells were determined by cell colony-formation assays,cell wound healing assays,and Transwell migration assays.The effect of THZ1 treatment on mammosphere forming rate and mammosphere size of U87 stem cells was analyzed.Stemness associated proteins CD133,ABCG2,Nanog,OCT4,SOX2,epithelial-mesenchymal transformation-related proteins E-cadherin,N-cadherin,Occludin,Snail,and Wnt/β-catenin pathway associated proteins Axin1,β-Catenin,WNT-5A,GSK3β,Cyclind-1,and C-myc were measured by western blot assay.RESULTS AND CONCLUSION:(1)Compared with adherent cells,the expressions of stemness related proteins Nestin,CD133,ABCG2,Nanog,OCT4,and SOX2 were significantly increased.(2)Compared with the control group,THZ1 decreased the proliferation and migration of U87 cells.(3)THZ1 inhibited the mammosphere forming rate and mammosphere size of U87 stem cells.(4)After THZ1 treatment,the expression of N-cadherin and Snail decreased,while the protein expression of E-cadherin and Occludin increased.(5)THZ1 treatment decreased the expression of Wnt/β-catenin pathway related proteins Axin1,β-Catenin,Wnt-5A,GSK3β,Cyclind-1,and C-myc in U87 stem cells.It is concluded that THZ1 can suppress the proliferation and migration of U87 cells,and inhibit the mammosphere forming ability,stemness related protein expression,and epithelial-mesenchymal transformation ability of U87 stem cells by down-regulating the expression of Wnt/β-catenin signaling pathway related molecules.

Objective To establish and evaluate a talent training system for hospital information pharmacists based on a competency model,thereby enhancing refined management of pharmaceutical affairs in hospitals and promoting high-quality development of pharmacy services.Methods The current development status of hospital information pharmacists at home and abroad was examined.A competency model for hospital information pharmacist positions was established using methods such as behavioral event interviews.In conjunction with this model,training course outlines addressing knowledge and capability requirements were developed.National skill training classes for hospital information pharmacists were conducted using innovative teaching methods like scenario simulation and case discussion.Training effectiveness was evaluated by tracking participants'work performance and scientific research achievements in the field of pharmaceutical information through questionnaire surveys before and after the training.Results The hospital information pharmacist positions competency model was constructed in four parts:knowledge,experience,skills,and personal traits.Based on this model,a training system for hospital information pharmacists was established,which included setting job responsibilities and performance indicators,establishing a pharmacy information department system,designing a series of training courses and publishing textbooks,founding national training classes,creating a specialized question bank,and developing a digital pharmacy network platform.The project team tracked the work performance and scientific research achievements of participants before and after training,using the national hospital information pharmacist training class hosted by the Guangdong Pharmaceutical Association as an example.From 2018 to 2024,a total of 465 information pharmacists from 298 hospitals across 28 provinces and cities were trained over seven sessions.Questionnaires were sent to participants who had completed at least one year since graduation,and 236 valid responses were received.Of these,169(71.6% )participants reported playing a major role in pharmacy informatization projects after the training,and 65(27.5% )participants published papers,applied for projects,or filed for patents after the training,with the majority related to pharmacy automation and informatization.Conclusion A competency model for hospital information pharmacist positions was constructed and applied nationwide,achieving favorable results.

IgG4-related disease (IgG4-RD) involving the ureter manifested as a ureteral tumor is rare. This paper reports a case of a female patient who was found with a mass at the left ureteropelvic junction for one week during physical examination. Urinary ultrasound and MRI showed a 3 cm mass at the left ureteropelvic junction with hydronephrosis, and the serum level of IgG4 was elevated. B-ultrasonic guided biopsy of the mass was performed. Histopathological findings showed lymphoplasmic infiltration and the ratio of IgG4/IgG positive cells>0.5. We finally diagnosed IgG4-RD and started using glucocorticoid for her treatment. One month later, CT-scan revealed that the tumor became smaller and the serum IgG4 decreased to the normal range.

Ectopic prostate is rare.This paper reports a case of a male patient who was found a mass in the pelvis for 20 days during physical examination.Urinary ultrasound, CT scan and MRI showed a pelvic mass that was about 4 cm×5 cm in size.Serum total prostate specific antigen (tPSA) was 6.09 ng/ml, and free PSA (fPSA) was 1.97 ng/ml. B-ultrasonic guided biopsy of the prostate and the mass was performed. Pathological findings suggest benign prostatic hyperplasia, weakly positive P504S and positive 34βE12. Pelvic mass is the prostate tissue with negative P504S and positive 34βE12. Finally, the ectopic prostate was diagnosed. Although it is rare, ectopic prostate should also be considered as a differential diagnosis of the pelvic tumor.

Objective To investigate the factors influencing rapid neurological improvement(RNI)after mechani-cal thrombectomy(MT)in patients with acute anterior circulation ischemic stroke(AACIS),and to construct a predictive scoring model for RNI.Methods A retrospective study was conducted on 312 AAIS patients treated with MT at the South-west Hospital and the Zigong Third People's Hospital from January 2017 to October 2021.Univariate analysis and multi-variate logistic regression analysis were performed to identify the independent factors influencing RNI.A scoring model for RNI prediction was established by assigning scores to significant variables in multivariate analysis.The prediction value was evalu-ated using the receiver operating characteristic(ROC)curve.Results Among the 312 AACIS patients,159(50.96%)dem-onstrated RNI.Multivariate logistic regression analysis showed that history of diabetes mellitus[odds ratio(OR)=0.518;95%confidence interval(CI)0.290-0.926;P=0.027]and Van Swieten score(3-4 points)(OR=0.537;95%CI 0.294-0.981;P=0.043)were independent risk factors for RNI in AACIS patients after MT.However,mTICI(grade 2b or 3)was an inde-pendent protective factor for RNI in patients with AACIS(OR=3.912;95%CI 1.706-8.982;P=0.001).The area under the ROC curve of the predictive scoring model was 0.628(95%CI 0.565-0.690;P<0.001).The optimal cut-off value was 3 points,the sensitivity was 68.39%,and the specificity was 52.98%.Conclusion The predictive scoring model consisting of history of diabetes mellitus,preoperative Van Swieten score,and postoperative mTICI grade is valuable in predicting RNI in patients with AACIS after MT.