Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway / 中国中药杂志

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells / 中国中药杂志

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer: a real-world study from the SEER database / 亚洲男科学杂志(英文版)

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02-1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23-4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92-1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24-6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

Clinical characteristics of IgE-mediated cow's milk protein allergy in children / 中华儿科杂志

Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, β lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23，P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.

Complete androgen blockade vs. medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).@*METHODS@#Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.@*RESULTS@#A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497).@*CONCLUSION@#Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Abuse of Pharmaceutical Drugs and Its Prevention / 法医学杂志

Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and fentanyl, sedative-hypnotics such as benzodiazepines and non-benzodiazepines, and central stimulants such as Ritalin (methylphenidate), Adderall (amphetamine and dextroamphetamine) and modafinil. Abuse of pharmaceutical drugs not only causes direct damage to multiple systems of the body, but also significantly increases risks of mental and physical diseases, imposing a heavy burden on individuals, families and society. Therefore, the prevention and control of pharmaceutical drug abuse are of vital importance. The Chinese government has taken strict administration measures for pharmaceutical drugs with abuse risk. However, confronting endless new drugs and changing abuse trends, it is necessary to further strengthen management and prevention of pharmaceutical drugs, monitor the trend of abuse, establish rapid response mechanisms, popularize relevant knowledge, and develop specific therapeutic drugs and intervention means, in order to promote prevention and treatment of pharmaceutical drug abuse.

Analysis of the effective components and mechanism of Yufang Fangji II for prevention of COVID-19 based on UHPLC-Q-TOF/MS and network pharmacology / 中国临床药理学与治疗学

AIM: The main chemical components of Yufang Fangji II (Hubei Fang) of COVID-19 were studied systematically and combined with network pharmacology to provide a reference for the study of its effective substances. METHODS: Ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) was applied to identify the absorbed components of the prescription in rat plasma. TCMSP database and Swiss Target Prediction data platform were used to predict the target of the identified blood components, and network visualization software Cytoscape 3.7.2 was used draw the association network diagram, and GO enrichment analysis and KEGG pathway enrichment analysis were conducted for the key targets. With the help of CB-Dock online molecular docking platform, the molecular docking of key targets and blood entering compounds was carried out, and the docking combination with good affinity value was displayed by ligplot software to verify the preventive effect of Yufang Fangji II on COVID-19. RESULTS: A total of 52 chemical components identified in the prescription, in which 13 components were absorbed in the rat plasma as the prototype, and they were from Astragalus membranaceus, Atractylodes macrocephala, Saposhnikoviae Radix, Lonicerae Japonicae Flos, and Citri Reticulatae Pericarpium, respectively. These compounds were recognized to act on 17 core targets, including mapk3, TNF and other targets related to inflammation, MPO and other targets related to oxidative stress, VEGFR, KDR and other targets related to vascular endothelium. The results of molecular docking showed that the absorbed components had good binding activity with the key targets. CONCLUSION: Compounds in Yufang Fangji II are involved in regulating inflammation, oxidative stress, vascular and cellular physiological activities, which have preventive effects on COVID-19 through regulating IL-17, PI3K Akt, MAPK and other pathways.

Historical evolution of Salviae Miltiorrhizae Radix et Rhizoma processing methods / 中国中药杂志

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.

Transurethral resection of the prostate is an independent risk factor for biochemical recurrence after radical prostatectomy for prostate cancer / 亚洲男科学杂志(英文版)

Biochemical recurrence (BCR) is important for measuring the oncological outcomes of patients who undergo radical prostatectomy (RP). Whether transurethral resection of the prostate (TURP) has negative postoperative effects on oncological outcomes remains controversial. The primary aim of our retrospective study was to determine whether a history of TURP could affect the postoperative BCR rate. We retrospectively reviewed patients with prostate cancer (PCa) who had undergone RP between January 2009 and October 2017. Clinical data on age, prostate volume, serum prostate-specific antigen levels (PSA), biopsy Gleason score (GS), metastasis stage (TNM), D'Amico classification, and American Society of Anesthesiologists (ASA) classification were collected. Statistical analyses including Cox proportional hazard models and sensitivity analyses which included propensity score matching, were performed, and the inverse-probability-of-treatment-weighted estimator and standardized mortality ratio-weighted estimator were determined. We included 1083 patients, of which 118 had a history of TURP. Before matching, the non-TURP group differed from the TURP group with respect to GS (P= 0.047), prostate volume (mean: 45.19 vs 36.00 ml, P < 0.001), and PSA level (mean: 29.41 vs 15.11 ng ml-1, P= 0.001). After adjusting for age, PSA level, T stage, N stage, M stage, and GS, the TURP group showed higher risk of BCR (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.13-3.94, P= 0.004). After matching (ratio 1:4), patients who underwent TURP were still more likely to develop BCR according to the adjusted propensity score (HR: 2.00, 95% CI: 1.05-3.79, P= 0.034). Among patients with PCa, those with a history of TURP were more likely to develop BCR after RP.

Clinical Efficacy of Dahuang Zhuyu Decoction for Oral Administration and Enema on Severe Acute Pancreatitis with Syndromes of Blood Stasis, Toxin and Its Effect on Serum Inflammatory Factors / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of Dahuang Zhuyu decoction for oral administration and enema on severe acute pancreatitis with syndromes of blood stasis and toxin and its effect on serum inflammatory factors. Method::Sixty eight patients with severe acute pancreatitis with syndromes of blood stasis and toxin who were admitted in Henan Provincial People's Hospital from September 2017 to December 2018 were randomly divided into treatment group (34 cases) and control group (34 cases). The control group was treated with western medicine. The treatment group was treated with Dahuang Zhuyu decoction for oral administattion and enema in addition to the therapy of the control group. Both groups were treated for 7 days. Before and after treatment, abdominal pain, bloating, nausea and vomiting were scored separately, serum amylase (AMS), lipase (LPS), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were detected, and abdominal pain disappearance time, bloating disappearance time and exhaust recovery time were recorded. Result::After treatment, the abdominal pain score, abdominal distension score, nausea and vomiting score, serum AMS, LPS, IL-6 and TNF-α were lower than those before treatment (P<0.05), and those in treatment group was lower than those in control group (P<0.05). After treatment, IL-10 level in both groups was higher than those before treatment (P<0.05), and that in treatment group was higher than that in control group (P<0.05). The disappearance time of abdominal pain, the disappearance time of abdominal distension and the recovery time of exhaust were shorter in treatment group than in control group (P<0.05). The total effective rate of the treatment group was higher than that of the control group (P<0.05). Conclusion::Dahuang Zhuyu decoction for oral administration and enema for severe acute pancreatitis with syndromes of blood stasis and toxin can alleviate clinical symptoms, reduce amylase and lipase levels, inhibit the expression of pro-inflammatory factors, promote the expression of anti-inflammatory factors, restore intestinal function, and improve clinical efficacy.

Effect of Cinobufacin injection combined with chemotherapy on serum tumor markers and immune function in elderly patients with colorectal cancer / 中国医师进修杂志

Objective:To investigate the short-term effect of Cinobufacin injection combined with chemotherapy on elderly patients with colorectal cancer and its influence on tumor markers and immune function.Methods:Sixty-two elderly patients with colorectal cancer admitted to Xinchang Branch of Zhejiang Hospital of Traditional Chinese Medicine from January 2015 to December 2017 were randomly divided into observation group (31 cases) and control group (31 cases). Patients in the control group were treated with chemotherapy, while those in the observation group were treated with Cinobufacin injection on the basis of the control group. Two treatment of 21 d was as a cycle, continuous chemotherapy 2-4 cycles. The short-term therapeutic effect, Karnofsky function state score (KPS score), serum tumor markers, immune function and side effects of the two groups were compared before and after treatment.Results:After treatment, the total effective rate of the observation group was 77.42%(24/31), and was higher than that of the control group 48.39%(15/31), there was significant difference ( χ2=5.599, P<0.05). The KPS scores of the observation group was higher than that of the control group [(87.48 ± 6.57) scores vs. (80.20 ± 6.12) scores], there was significant difference ( t=4.514, P<0.05). The levels of serum cancer antigen 19-9(CA19-9), carbohydrate antigen 724(CA724) and carcino-embryonic antigen (CEA) in the observation group were lower than those in the control group [(3.59 ± 1.02) kU/L vs. (6.98 ± 1.37) kU/L, (7.38 ± 1.87) μg/L vs.(9.82 ± 1.42) μg/L, (12.27 ± 2.36) μg/L vs.(16.57 ± 3.24) μg/L], there were significant differences ( t=11.051, 9.042, 10.624, P<0.05). The levels of CD 3+, CD 4+ and CD 4+/CD 8+ in the observation group were higher than those in the control group [(58.97 ± 3.72)% vs. (47.31 ± 2.98)%, (38.85 ± 3.25)% vs. (30.19 ± 2.71)%, 1.59 ± 0.18 vs. 0.89 ± 0.14], there were significant differences ( t=13.620, 11.394, 17.091, P<0.05). The incidence of side effects in the observation group was lower than that in the control group ( P<0.05). Conclusions:Cinobufacin injection combined with chemotherapy can improve the quality of life of elderly patients with colorectal cancer in the near future, reduce the levels of serum CA19-9, CA724 and CEA, improve the immune function of patients, and have fewer side effects.

Anti-tumor effect and mechanisms of shikonin on gliomas / 国际肿瘤学杂志

Shikonin has anti-tumor activity,and it not only can inhibit the proliferation,migration and infiltration of glioma cells,but also induce necroptosis of glioma cells via promoting the production of reactive oxygen species.Shikonin combined with endoplasmic reticulum stress inhibitors or regulatory tactics of microRNA expression may further enhance its killing effect on gliomas.Shikonin armed by nanoparticles shows increased targetability to gliomas.Shikonin combined with tumor-targeted therapeutic drugs or chemotherapeutic drugs is expected to overcome the drug resistance of glioma cells.

Toll-like receptor 10 (TLR10) exhibits suppressive effects on inflammation of prostate epithelial cells / 亚洲男科学杂志(英文版)

Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were downregulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were involved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.

Effects of CXC-chemokine Receptor 7 Expression in Endothelial Progenitor Cells on Angiogenesis after Cerebral Ischemia-reperfusion Injury / 中国康复理论与实践

Objective:To explore the effect of upregulating CXC-chemokine receptor 7 (CXCR7) in endothelial progenitor cells (EPCs) on angiogenesis after cerebral ischemia-reperfusion injury. Methods:EPCs were isolated and cultured from human umbilical cord blood and identified. Then, the EPCs were transfected with CXCR7 overexpression lentiviral vector, and the expression of CXCR7 was identified with real-time PCR and Western blotting. The tube-like structure formation and apoptosis of EPCs under oxidized low density lipoprotein (ox-LDL) were detected with tube-like structure formation test and Annexin V/PI staining. Cerebral ischemia-reperfusion injury model in rats was established, and the qualified model rats were randomly divided into three groups after 24 hours reperfusion: PBS group (n = 12) was injected with phosphate buffers through tail vein, control group (n = 12) was injected the EPCs infected with control lentiviral vector, and CXCR7 group (n = 12) was injected with EPCs infected with CXCR7 overexpression lentiviral vector. Neurological function scores were determined seven and 14 days after transplantation. The cerebral infarct volume was measured, the number of GFP-positive cells in the ischemic site and the density of capillary were observed. Results:The expression of CXCR7 in EPCs increased after transfection (P < 0.01). Overexpression of CXCR7 improved tube formation and reduced apoptosis of EPCs under ox-LDL (P < 0.05). Compared with PBS and control groups , neurological function improved in CXCR7 group, with less infarct volume, more GFP-positive cells and density of capillary (P < 0.05). Conclusion:Up-regulating CXCR7 can improve the survival and angiogenesis of EPCs, and improve the repair of cerebral ischemia-reperfusion injury.

Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in Kidney Transplant Recipients: A Network Meta-Analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>Background</b>Mineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies.</p><p><b>Methods</b>We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence.</p><p><b>Results</b>A total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best.</p><p><b>Conclusions</b>Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.</p>

Improvement of continence with preservation of pelvic stabilized structure in patients undergoing robot-assisted laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective To investigate the effect of pelvic floor stabilized structure preservation (PPSS) during robot-assisted laparoscopic radical prostatectomy (RARP)on postoperative continence recovery.Methods From October 2017 to April 2018,86 patients with prostatic cancer who underwent traditional RARP and RARP plus PPSS were included.There were 31 patients in non-PPSS group and 55 patients in PPSS group.In non-PPSS group,patients age was (68.48 ± 7.79) years old,BMI was (24.79 ± 3.05) kg/m2,median prostate volume was 63.54 (53.00-99.36) cm3,clinic T-stage T1-T2,T3,T4 accounted for 49.39％,22.58％,6.45％ and ISUP grade 1,2,3,4,5 accounted for 22.58％,22.81％,12.90％,12.90％,19.35％ respectively.In PPSS group,patients age was (69.53 ± 6.81)years old,BMI was (23.95 ± 3.03) kg/m2,median prostate volume was 73.39 (54.88-94.23) cm3,clinic T-stage T1-T2,T3,T4 accounted for 72.73％,7.27％,3.64％ and ISUP grade 1,2,3,4,5 accounted for 21.82％,18.18％,23.64％,18.18％,10.91％ respectively.The preoperative PSA,BMI,clinical T-stage,ISUP grade,and postoperative hospital days had no significant differences (P ＞ 0.05)between the two groups.Both groups were operated via transperitoneal approach.In the non PPSS group,endo-pelvic fascia and pubic prostate ligament was cut,and dorsal vessel complex was ligated.In PPSS group,the partial endo-pelvic fascia was bluntly pushed to the pelvic wall to preserve tendon arch,and pubic prostate ligament also was preserved without suturing and ligating dorsal vascular complex.The catheter was removed 7 d after RARP.The continence recovery were compared between the two groups,including pad number on the day of I,7,14,30,90 and ICI-Q-SF scores on the day of 30 and 90 after catheter removal.Results There was no significant difference in pad numbers used between the two groups on the day of 1,7,14,30 after catheter removal.On the 90th day,the proportions of using pad ≥4 in PPSS group were significantly lower than those in non-PPSS group (1.89％ vs.20.69％,P =0.004).No significant difference was found in ICI-Q-SF scores on the 30th and 90th day between the two groups.Univariate analysis showed that PPSS group used less pads than non-PPSS group on the 90th day [OR =0.07(95％ CI 0.01-0.65),P =0.019];T3 patients used more pads than T1-T2 patients [OR =9.19 (95％ CI 1.32-63.87),P =0.025].After adjusting for age,ISUP grading,T staging,and PSA,multivariate regression analysis showed that the risk of using pad ≥ 4 in PPSS group compared with non-PPSS group was 0.46,0.34,0.27,0.25,and 0.03 on the day of 1,7,14,30 and 90 after catheter removal,respectively.The PPSS approach didn't increase the risk of positive surgical margin.Conclusions Preservation of pelvic stabilized structure in RARP is very efficient in term of continence rate after RARP,and it does not increase the risk of positive surgical margin.

Implication of serum steroid receptor coactivator-3 level for lumbar bone mineral density and bone turnover in postmenopausal women / 中国组织工程研究

BACKGROUND: Steroid receptor coactivator-3 (SRC-3) is a member of the steroid receptor coactivator family,and it can promote proliferation and differentiation in human osteoblasts by modulating estrogen receptor activity. Previous studies have reported that allelic variation at the SRC-3 locus is significantly positively correlated with the lumbar bone mineral density in Caucasian men, but the relationship between SRC-3 and bone metabolism in postmenopausal women remains unknown.OBJECTIVE: To investigate the level of serum SRC-3 in postmenopausal women and its association with bone mineral density and bone turnover markers.METHODS: Fifty-five women with postmenopausal osteoporosis and 35 healthy postmenopausal women were recruited, and their serum levels of SRC-3, 25-hydroxyvitamin D, osteocalcin and procollagen I N-terminal peptide, beta C-terminal telopeptide of type I collagen were detected. The bone mineral density of L1-4 vertebrae and femoral neck were measured by dual-energy X-ray absorptiometry.RESULTS AND CONCLUSION: Serum SRC-3 level in postmenopausal women with osteoporosis was remarkably lower than that in healthy individuals. In addition, the serum SRC-3 level was positively correlated with lumbar bone mineral density, and negatively correlated with procollagen I N-terminal peptide and osteocalcin in postmenopausal women with osteoporosis. These results indicate that low serum SRC-3 level may be involved in the pathogenesis of postmenopausal osteoporosis and play a pivotal role in bone turnover.

Effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases / 中国生化药物杂志

Objective To investigate the effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases. Methods 116 cases of patients with upper gastrointestinal bleeding and cardiovascular disease as research subjects. 86 cases of patients used antiplatelet drugs (drug group), 30 cases didn't use antiplatelet drugs (non-drug group). In the drug group, 30 patients with aspirin alone (group A), 24 patients with clopidogrel alone (group B) and 32 patients with aspirin and clopidogrel (group C) . Compared the upper gastrointestinal bleeding in each group of patients. Results The incidence of abdominal pain in the drug group was significantly lower than non-drug group (P<0.05). However, there was no significant difference in the incidence of bloating, nausea, vomiting, acid reflux compared with non - drug group. There were no significant differences in the endoscopic manifestations of gastrointestinal bleeding between the drug group and the non-drug group. The incidence of severe gastrointestinal bleeding in the drug group was 47.67%, significantly higher than that in the non-drug group (26.67%)(P<0.05). A, B, C three groups of patients with severe gastrointestinal bleeding rate and bleeding patterns were no significant difference. There was no significant difference in the total effective rate of gastrointestinal bleeding between the drug group and the non-drug group. Conclusion Antiplatelet drugs may increase the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases, but aspirin and clopidogrel alone or in combination had no significant effect on the degree of gastrointestinal bleeding.

Effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases / 中国生化药物杂志

Objective To investigate the effects of aspirin and clopidogrel on the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases. Methods 116 cases of patients with upper gastrointestinal bleeding and cardiovascular disease as research subjects. 86 cases of patients used antiplatelet drugs (drug group), 30 cases didn't use antiplatelet drugs (non-drug group). In the drug group, 30 patients with aspirin alone (group A), 24 patients with clopidogrel alone (group B) and 32 patients with aspirin and clopidogrel (group C) . Compared the upper gastrointestinal bleeding in each group of patients. Results The incidence of abdominal pain in the drug group was significantly lower than non-drug group (P<0.05). However, there was no significant difference in the incidence of bloating, nausea, vomiting, acid reflux compared with non - drug group. There were no significant differences in the endoscopic manifestations of gastrointestinal bleeding between the drug group and the non-drug group. The incidence of severe gastrointestinal bleeding in the drug group was 47.67%, significantly higher than that in the non-drug group (26.67%)(P<0.05). A, B, C three groups of patients with severe gastrointestinal bleeding rate and bleeding patterns were no significant difference. There was no significant difference in the total effective rate of gastrointestinal bleeding between the drug group and the non-drug group. Conclusion Antiplatelet drugs may increase the risk of upper gastrointestinal bleeding in patients with cardiovascular and cerebrovascular diseases, but aspirin and clopidogrel alone or in combination had no significant effect on the degree of gastrointestinal bleeding.