Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective:To study the clinical features and prognostic impact of transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs) combination therapy regimens in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis.Methods:Patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma (HBV) who visited the Affiliated Hospital of Xuzhou Medical University between January 1, 2020, and December 31, 2022, were enrolled. TACE+TKIs +ICIs combination therapy was used to treat all patients. The occurrence and factors influencing cholestasis, as well as the impact on prognosis after combined therapy, were analyzed. The measurement data were compared using a t-test and a non-parametric rank sum test. The count data was compared using the χ2 test. The survival rates were compared using a log-rank test between different groups. Results:A total of 106 cases with HBV-related intermediate-and advanced-stage hepatocellular carcinoma were enrolled. The probabilities of secondary cholestasis within 3 and 6 months, 1, 2, and 3 years after TACE+ICIs+TKIs combination therapy were 9.4%, 12.3%, 14.2%, 24.5%, and 24.5%, respectively. Patients with secondary cholestasis had persistent symptoms and rapid progression. During the treatment course, the median survival time was significantly longer in patients with hepatocellular carcinoma without secondary cholestasis than that of patients with cholestasis (26.9 months vs. 13.7 months, respectively, P < 0.05). Secondary cholestasis, baseline aspartate aminotransferase, and prothrombin activity levels were independent risk factors that affected the survival and prognosis of patients treated with combination therapy. There was no statistically significant difference in the occurrence of other adverse reactions between the two groups with secondary and non-secondary cholestasis during the treatment course (47.5% vs. 43.3%, χ2=0.058, P = 0.810). Conclusion:TACE+ICIs+TKIs therapy combination is relatively common in the treatment of patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Moreover, accelerated disease progression is an independent risk factor affecting the survival and prognosis of patients.

Objective:To establish an in vitro capsular bag model and compare the inhibitory effects of different 360° square-edge intraocular lens (IOL) on lens epithelial cells (LECs) migration. Methods:In vitro capsular bag model with posterior capsule opacification (PCO) was established using Transwell compartment, cell climbing slices, human collagen type Ⅳ, and IOL.The models were divided into Plate-loop HydroSmart group, C-loop HydroSmart group, and C-compensation-loop Hydrophobic group according to the different square-edge IOL implanted.A blank control group was set using the Transwell compartment without IOL.The early PCO pathological manifestations in lens epithelial cell line SRA01/04 cultured in the Transwell compartment were observed with an inverted microscope.The cell morphology in different groups was observed by hematoxylin and eosin staining.The cell counting and cell migration inhibition rate of anterior capsule and posterior capsule were calculated by Transwell assay and cell-exclusion zone assay, respectively. Results:The early pathological characteristics of PCO, such as early Soemmering ring and small Elschnig pearl, could be found in cells in the in vitro capsular bag model after 48-hour culture.The migrating cells in model groups were fibrous.No changes mentioned above were found in blank control group.The number of migrating cells in the anterior capsule of Plate-loop HydroSmart group, C-loop HydroSmart group, C-compensation-loop Hydrophobic group was 18.80±5.53, 24.67±9.80, and 34.47±10.80, respectively, and the number of migrating cells in the optical area of the posterior capsule of the three groups was 56.43±9.00, 162.20±16.38, and 121.30±12.01, respectively.The cell migration inhibition rate in the anterior capsule of Plate-loop HydroSmart group, C-loop HydroSmart group, C-compensation-loop Hydrophobic group was (92.02±1.94)%, (89.76±3.10)%, (86.27±4.54)%, respectively, and the cell migration inhibition rate in optical area of the posterior capsule of the three groups was (91.60±3.65)%, (70.14±5.35)%, (78.43±3.48)%, respectively.The number of migrating cells in the anterior capsule was lower and the cell migration rate inhibition was higher in Plate-loop HydroSmart group than C-compensation-loop Hydrophobic group, with significant differences (both at P<0.05). The number of migrating cells in the optical area of the posterior capsule and the cell migration inhibition rate was greater than those of C-loop HydroSmart group and C-compensation-loop Hydrophobic group, showing statistically significant differences (all at P<0.001). Conclusions:The in vitro capsular bag model can be used in PCO research.Compared with C-loop HydroSmart IOL and C-compensation-loop Hydrophobic IOL, Plate-loop HydroSmart IOL can more effectively inhibit the migration of LECs to the optical area of the posterior capsule.

Background/Aims: The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. Methods: A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. Results: In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Objective: To analyze the related factors of postoperative complications after laparoscopic assisted D2 radical resection for advanced gastric cancer. Methods: From August 2015 to July 2017, 80 patients with advanced gastric cancer admitted to the First Hospital of Jiaxing were selected.All the patients were treated with laparoscopic-assisted D2 radical resection, and the risk factors related to postoperative complications were analyzed by logistic regression analysis model. Results: There were 33 cases (41.25%) with postoperative system complications, 19 cases (23.75%) with complications of level Ⅱ and above; 15 cases (18.75%) with postoperative local complications, among them 12 cases (15.00%) appeared level Ⅱ and above local complications.The number of concomitant diseases and age were related risk factors for systemic complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=1.982, 95%CI: 2.183-34.405, OR=6.587, 95%CI: 1.738-23.495, all P<0.05). The preoperative neoadjuvant chemotherapy, reconstruction method and age were the risk factors for local complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=8.273, 95%CI: 4.982-35.394, OR=12.304, 95%CI: 2.384-88.921, OR=6.365, 95%CI: 2.183-21.384, all P<0.05). Conclusion Treatment of advanced gastric cancer patients with laparoscopic D2 radical mastectomy, attention should be paid to control the patients' age, preoperative neoadjuvant chemotherapy, reconstruction mode, associated disease and other related risk factors.In order to ensure the safety of patients and to avoid postoperative complications.

Fever and abdominal pain are common symptoms and could be main manifestations in patients with autoinflammatory diseases.A 48-year-old female patient was admitted with recurrent fever and abdominal pain for 9 years.Serum level of inflammatory markers synchronously fluctuated with fever,and returned to normal when fever subsided.The periodic episodes of fever occurred every 1 to 4 months and failed to respond to empirical antibiotics.Whole exome sequencing showed heterozygous mutation of NOD2 gene q902k,leading to the final diagnosis of autoinflammatory disease.Corticosteroid and tripterygiumglycosides were effective for the disease remission.

We constructed the CAP2NC prokaryotic expression vector of HIV-1 NL4-3 strain and obtained relatively pure CAP2NC protein by optimizing its purification conditions to explore its in vitro self-assembly conditions. Primers were designed according to the CAP2NC DNA sequence of HIV-1 NL4-3 strain. The target gene was amplified by PCR and cloned into prokaryotic expression vector pTO-T7. Then the recombinant strain was transformed into Escherichia coli BL21 (DE3). IPTG induced protein expression, then the protein was purified by hydrophobic chromatography. SDS-PAGE and Western blotting were performed to analyze the target protein, and the biological activity of the antigen was identified through ELISA. The self-assembly of CAP2NC protein was analyzed by transmission electron microscopy and gel filtration chromatography. The protein had good reaction with the specific antibodies of p24 and formed different structures in various conditions. When 10% yeast RNA was added to the protein complex, the recombinant protein only formed into a tubular structure, which was similar to the self-assembled structure of the HIV-1 virus capsid. The results showed that the HIV-1 CAP2NC protein had in vitro self-assembly activity, and the RNA affected the structure of CAP2NC protein assembly. The protein can be used as a simple and effective molecular model to study its structure, and then it can provide a reference for the study of HIV immature virus particles.

Objective To document the etiologies of seizures in children admitted to the pediatric observation unit of an inen r city hospital in Chian .Me thods A ot tal of 975 children ( aged 1 month to 18 years old) admitted to the pediatric observation unit of Guangzhou Women adn Children′s Medical Center between October,2013 and October,2014 with seizures were evaluated restrospectively.Results A total of 975 patients were included in this study.The causes of seizures were febrile seizures ( 588 cases,60.3%) , epilepsy( 163 cases, 16.7%) , and benign inaf ntile convulsions associated with mild gasrt oenteritis ( 111 cases,11.4%) .The main causes of seizures for children less than one year old were febrile seizures ( 75 cases,34.1%) and epilepsy(75 cases,34.1%),following by the intracranial infection(22 cases,10.0%). Febrile seizures also predominated the causes of seizures among children between one and six years old(487 cases, 70.3%),whereas benign infantile convulsions associated with mild gastroenteritis accounting for 14.0%(97 cases) of all causes.Meanwhile, the leading causes of seizures for children of six years or older were febrile seizures(26 cases,41.9%) and epilepsy(20 cases,32.3%).Conclusion Febrile seizures is the leading cause of seizures among children.Contrast to previous studies,the proportions of epilepsy and benign infantile convulsions associated with mild gastroenteritis are increasing,while the proportion of intracranial infection is reducing.Rapid assessment and accurately identifying the etiology play an important role in the management of seizures.

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.
Calcium-Binding Proteins ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Chromatin Assembly and Disassembly ; physiology ; DNA Helicases ; genetics ; metabolism ; HeLa Cells ; Humans ; Multiprotein Complexes ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; physiology ; Transcription, Genetic ; physiology ; YY1 Transcription Factor ; genetics ; metabolism