Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

Objective:To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia(ITP)and its significance.Methods:Ninety-six children with ITP were enrolled and divided into new diagnosis group(n=40),persistent group(n=30)and chronic group(n=26)according to the course of disease.80 healthy children were selected as the control group.Peripheral blood mononuclear cells(PBMNC)of ITP children and healthy children were isolated and cultured,and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR.The contents of IL-17,IL-23,IL-10 and TGF-β in PBMNC of subjects were determined by ELISA.The correlation between microRNA-3162-3p and platelet count,IL-17,IL-23,IL-10 and TGF-β was analyzed.Results:Compared with the control group,the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreased(P＜0.05),while IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).With the prolongation of the disease course,the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreased(P＜0.05),while the expressions of IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10(r=0.716,0.667),and negatively correlated with IL-17,IL-23,and TGF-β(r=-0.540,-0.641,-0.560).Conclusion:MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP,and is involved in the regulation of Th17/Treg imbalance,which can be used as a potential therapeutic target of ITP.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. Conclusions In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Benign prostatic hyperplasia(BPH) is a common disease in middle-aged and elderly men, with lower urinary tract symptoms as the main manifestation, severely affecting the quality of life of patients. The pathogenesis of BPH is not yet fully understood, and there are still some challenges and limitations in western medicine treatment for BPH. Therefore, finding new and more effective treatment strategies is urgent. In recent years, many basic and clinical studies have confirmed the important role of traditional Chinese medicine in the treatment of BPH. This article reviews the progress of basic and clinical research in the treatment of BPH with traditional Chinese medicine, and believes that basic research mainly focuses on the active ingredients of Chinese medicine [regulating pathways such as NF-E2-related factor 2(Nrf2)/antioxidant response element(ARE), nuclear factor κB(NF-κB), epidermal growth factor receptor(EGFR)/signal transducer and activator of transcription 3(STAT3), phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR), p38 mitogen-activated protein kinase(p38 MAPK)/forkhead box O subtype(FOXO3a), etc.], single Chinese herbs(regulating inflammatory factors, oxidative stress-related proteins, cell cycle-related proteins, and apoptotic factors, etc.), and Chinese herbal compounds and patent medicines [regulating extracellular signal-regulated kinase(ERK1/2), transforming growth factor-β(TGF-β)/Smad, mitogen-activated protein kinase(MAPK), PI3K/Akt, Nrf2, trefoil factor 2(TFF2)/Wnt, interleukin-6(IL-6)/Janus kinase 2(JAK2)/STAT3, hypoxia-inducible factor 1α(HIF-1α)/vascular endothelial growth factor receptor(VEGFR), etc.], and then play a therapeutic role by inhibiting BPH cell proliferation, oxidative stress, inflammatory response, promoting apoptosis, and inhibiting epithelial-mesenchymal transition. Clinical studies mainly focus on internal treatment, external treatment, combined internal and external treatment, and integrated Chinese and western medicine treatment as the main methods, aiming to improve traditional Chinese medicine syndrome scores, prostate symptom scores, residual urine volume, effective bladder volume, sexual quality of life, increase average urine flow rate, maximum urine flow rate, and promote balance of sex hormone secretion. Through this research, it is hoped to provide some reference ideas for clinical research and drug development for BPH.
Prostatic Hyperplasia/metabolism* ; Male ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; NF-E2-Related Factor 2/genetics*

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
Animals ; Mice ; Liver ; Aspartate Aminotransferases ; Bupleurum