The association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility: a systematic review and meta-analysis.

During recent decades, the association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility remains doubtful. We conducted this meta-analysis to evaluate the association between mutations in USP26 and male infertility according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021225251). PubMed, Web of Science, and Scopus were systematically searched for comparative clinical studies, which were written in English and provided eligible data. Studies were included when they compared USP26 mutations in azoospermic, oligozoospermic, and asthenozoospermic patients with controls with normal sperm parameter values or whose partners had experienced spontaneous pregnancy. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated with random effect models. Overall, twelve studies with 3927 infertility patients and 4648 healthy controls were included. The association between overall USP26 mutations and infertility was not significant (OR = 1.60, 95% CI: 0.51-5.01). For specific mutations, the pooled ORs were 1.65 (95% CI: 1.02-2.69) for cluster mutation (including 370-371insACA, 494T>C, and 1423C>T), 1.80 (95% CI: 0.35-9.15) for c.576G>A, 1.43 (95% CI: 0.79-2.56) for c.1090C>T, and 3.59 (95% CI: 2.30-5.59) for c.1737G>A. Our results suggest that several mutations (cluster mutation, c.1737G>A) may play roles in male infertility, while others (c.576G>A and c.1090C>T) do not show notable associations with male infertility. More high-quality clinical researches are needed for validation.

Development and validation of prognostic scoring in primary intestinal diffuse large B-cell lymphoma: a single-institution study of 184 patients.

BACKGROUND: The incidence of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is much lower than primary gastric DLBCL, and large-scale analyses on the clinical characteristics, molecular features, therapeutic strategies, and risk stratification have been seldomly performed in PI-DLBCL. METHODS: To assess prognostic model development, 107 PI-DLBCL patients diagnosed before 2014 were studied for prognosis factors including different primary involved sites and treatment strategies. For internal validation, a non-random split sample set with 77 PI-DLBCL patients after 2014 was included for validation of the prognosis factors. RESULTS: Patients with an ileocecal lesion presented with better survival time than those with non-ileocecal sites, with surgical resection significantly influencing the prognosis. Non-ileocecal patients who underwent surgery with lymphadenectomy had superior overall survival (OS) and progression-free survival (PFS) compared to those receiving surgery without lymphadenectomy or those not receiving (without) surgery. For ileocecal patients, surgery with or without lymphadenectomy resulted in better OS and PFS than those without surgery. For biomarker analysis, only BCL-2 >50% or Ki67 >80% on tumor cells indicated poor clinical outcome. In multivariate analysis, age, Eastern Cooperative Oncology Group (ECOG) score, and site of origin were independent prognostic factors for inferior OS in PI-DLBCL. A prognosis model was set up based on age, ECOG score, and site of origin, and validated well. CONCLUSIONS: The prognosis in patients with PI-DLBCL with ileocecal involvement showed was better than those with non-ileocecal involvement. Surgical strategy can impact the clinical outcome of PI-DLBCL patients.

[A preliminary pharmacophylogenetic study of Solanaceae medicinal plants containing tropane alkaloids].

The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.

Flavonoids in myocardial ischemia-reperfusion injury: Therapeutic effects and mechanisms.

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients' quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

[Analysis on formula of Mongolian medicine for prevention of COVID-19].

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

The interactions between gut microbiota and bioactive ingredients of traditional Chinese medicines: A review.

In recent years, the interaction between the bioactive ingredients of traditional Chinese medicine (TCM) and gut microbiota has been a focus of many studies. When TCM enters the digestive tract, some bioactive ingredients are not absorbed into the gut well thus leading to low bioavailability. Ingredients of TCM are metabolised, or biotransformed by gut microbiota, thereby producing new bioactive molecules, and promote medicine absorption into the circulation. At the same time, the ingredients of TCM effect the composition and structure of gut microbiota, thereby influencing the remote function of diseased organs / tissues through the systemic action of the gut microbiota. In this review, we summarise the gut microbiota-mediated metabolism of flavonoids, alkaloids, terpenoids, saponins, polysaccharides, phenylpropanoids, and organic acids, along with a discussion on the metabolites formed and the biotransformation pathways involving various enzymes. We also highlight the importance of bioactive ingredients of TCM in regulating gut microbiota.

Robotic thyroidectomy via bilateral axillo-breast approach: Experience and learning curve through initial 220 cases.

OBJECTIVE: This study is aim to summarize the experience of robotic thyroidectomy via bilateral axillo-breast approach of our center and also to find out the learning curve of this technique. METHODS: In total 220 initial patients who have undergone robotic thyroidectomy via bilateral axillo-breast approach from May 2015 to September 2017 were involved in this study. The data of operation time, clinical characteristics, surgical outcomes and oncological outcomes were collected. The moving average method is use to explore the learning curve. RESULTS: All patients had undergone robotic thyroidectomy successfully without conversion to other surgical approaches. The mean age of the enrolled subjects was 34.4 ± 7.8 years old, while the sex ratio (male/female) was 38/182. There were 50 benign tumor cases and 170 malignant tumor cases. The mean total operation time was 105.3 ± 37.6 min. Lymph node metastasis was observed in 61 (35.9%) patients. The mean retrieved lymph node count was 5.1 ± 3.8 while the mean metastatic lymph node count was 0.7 ± 1.5. The operation time decreased significantly after about 30-35 cases and formed the plateau. After 80 cases, the operation time significantly decreased again. CONCLUSION: For skilled endocrine surgeons, robotic thyroidectomy has proved to be safe and feasible, which could be applied extensively in patients strictly selected in high-volume centers, with a relatively short learning curve of about 30-35 cases. While the surgeons getting more experienced, this technique would be more efficient.

Endothelial progenitor cells with overexpressing angiotensin-converting enzyme 2 reduce monocrotaline-induced pulmonary arterial hypertension in rats / 基础医学与临床

Objective To investigate the therapeutic effect of endothelial progenitor cells (EPCs) with overex-pressed angiotensin converting enzyme 2(ACE2) on rat model of monocrotaline(MCT) induced pulmonary arterial hypertension (PAH). Methods EPCs were extracted,purified and identified from the very beginning. The lenti-virus vector carrying ACE2 gene was infected with EPCs in order to prepare the ACE2-EPCs. Besides,the expres-sion of ACE2 and proliferation as well as tube function of EPCs were detected before and after the transduction. The SD rat were randomly divided into control group, MCT induced pulmonary arterial hypertension group (PAH group),ACE2 transduction of endothelial progenitor cells group(lenti-ACE2-EPCs group) and endothelial progenitor cells group (EPCs group).The mean pulmonary artery pressure of rats(mPAP) and right ventricular hypertrophy in-dex (RV/LV+S) were determined in third week after the molding;the lung tissue specimens were stained with HE and the pulmonary arterial wall thickness index(TI) as well as area index(AI) were also calculated;The expression levels of ACE2 in lung tissue were detected by Western blot.Results The mPAP,RV/LV+S,TI and AI detected in PAH group in the third week after the molding were signficantly lower than those in control group(P<0.01); The mPAP,RV/LV+S,TI and AI detected in lenti-ACE2-EPCs group in the third week after the molding were markedly lower than those in PAH group and EPCs group (P<0.01); The expression level of ACE2 in lung tissue of lenti-ACE2-EPCs group was significantly higher than that in PAH group (P<0.01);The mPAP,RV/LV+S,TI and AI detected in EPCs group in the third week after the molding were markedly lower than those in PAH group(P<0.01), while higher than that as compared with control group and lenti-ACE2-EPCs group (P<0.01). Conclusions ACE2 overexpression in endothelial progenitor cells(EPCs) can effectively reduce the mean pulmonary arterial pressure in PAH rat models,and the therapeutic effect of ACE2-EPCs is generally better than that of EPCs.

Overexpression of the X-linked ribosomal protein S4 predicts poor prognosis in patients with intrahepatic cholangiocarcinoma.

X-linked ribosomal protein S4 (RPS4X) has previously been reported to be associated with cisplatin resistance and clinical outcome in bladder and ovarian cancer. However, the value of RPS4X as a diagnostic and prognostic marker in intrahepatic cholangiocarcinoma (ICC) has not yet been investigated. The present study evaluated the expression pattern, and diagnostic and prognostic value of RPS4X in patients with ICC. Retrospective analysis was performed for a total of 201 patients with intrahepatic cholangiocarcinoma, and 8 patients with inflammation of the bile duct. Immunohistochemistry was performed using tissue microarrays to characterize the expression profile of RPS4X. Receiver operating characteristic (ROC) curves, the Kaplan-Meier estimator and Cox regression analysis were applied to evaluate the potential diagnostic and prognostic value of RPS4X in ICC. RPS4X was significantly upregulated in ICC tissues compared with the inflamed bile duct tissues. When differentiating ICC from normal controls, ROC analysis of RPS4X gave an area under the curve value of 0.9030 (sensitivity, 82.59%; specificity, 100%). RPS4X expression was significantly positively correlated with serum alkaline phosphatase levels. Survival analysis demonstrated that RPS4X expression levels were an independent prognostic factor for overall survival. Therefore, RPS4X expression levels may serve as a novel diagnostic and prognostic marker in ICC.

Long-term results of small-diameter proximal splenorenal venous shunt: a retrospective study.

AIM: To investigate recurrent variceal hemorrhage and long-term survival rates of patients treated with partial proximal splenorenal venous shunt. METHODS: Patients with variceal hemorrhage who were treated with small-diameter proximal splenorenal venous shunt in Ruijin Hospital between 1996 and 2009 were included in this study. Shunt diameter was determined before operation using Duplex Doppler ultrasonography. Peri-operative and long-term results in term of rehemorrhage, encephalopathy and mortality were followed up. RESULTS: Ninety-eight patients with Child A and B variceal hemorrhage received small-diameter proximal splenorenal venous shunt with a diameter of 7-10 mm. After operation, the patients' mean free portal pressure (P < 0.01) and the flow rate of main portal vein (P < 0.01) decreased significantly compared with that before operation. The rates of rebleeding and mortality were 6.12% (6 cases) and 2.04% (2 cases), respectively. Ninety-one patients were followed up for 7 mo-14 years (median, 48.57 mo). Long-term rates of rehemorrhage and encephalopathy were 4.40% (4 cases) and 3.30% (3 cases), respectively. Thirteen patients (14.29%) died mainly due to progressive hepatic dysfunction. Five- and ten-year survival rates were 82.12% and 71.24%, respectively. CONCLUSION: Small-diameter proximal splenorenal venous shunt affords protection against variceal rehemorrhage with a low occurrence of encephalopathy in patients with normal liver function.

[The retrospective analysis of surgical outcome of portal hypertension].

OBJECTIVE: To retrospectively analyze the surgical outcome of portal hypertension and explore the risk-factors of long-term survival after operation. METHODS: The data of 149 patients (male 119, female 30, aged from 19 to 73 years old) with portal hypertension treated surgically from January 1996 to October 2007 was collected. Among these patients, there were 110 patients for Child A and 39 patients for Child B according to Child-Pugh classification. According to different surgical modality, all patients were divided into devascularization group (n = 85) and shunting group (n = 64). RESULTS: The follow-up rate was 78.8% and the average follow-up time was (46.3 +/- 30.4) months. The overall survival rates of 1-, 3-, 5- and 10-years were 95.6%, 88.7%, 83.4% and 65.1% respectively. Meanwhile the survival rates of 1-, 3-, 5- and 10-years in devascularization group and in shunting group were 95.4%, 87.7%, 80.6%, 56.3% and 95.8%, 90.1%, 86.8%, 72.6% respectively. There was no significant difference in survival rate between these two groups (P > 0.05). Child-Pugh classification has been the most important risk-factor that could influence long-term survival after operation by analysis of COX regression and it showed that the long-term survival time in Child A was longer than in Child B. The re-hemorrhage rates of 1-, 3- and 5-years in shunting group would be much better than in devascularization group. The rate of postoperative encephalopathy in devascularization group and shunting group was 6.9% and 6.1% respectively and there was no significant difference (P > 0.05). The portal venous pressure and flow of portal vein decreased significantly after shunting operation (P < 0.05). CONCLUSIONS: The mainly sole risk-factor of long-term survival for portal hypertension has been the classification of Child-Pugh, not surgical procedure. The individualized proximal splenorenal shunt is much better than devascularization in controlling variceal hemorrhage.

[A clinical study on splanchnic hemodynamic changes after orthotopic liver transplantation for patients with portal hypertension].

OBJECTIVE: To study the regularity of splanchnic hemodynamic changes after orthotopic liver transplantation (OLT) for patients with portal hypertension. At the same time, effect of such changes on splenomegaly, hypersplenism, collateral circulation and the postoperative liver function was discussed. METHODS: Between June 2002 and October 2005, 173 liver transplantations were performed. In 38 patients with portal hypertension undergoing OLT, the following parameters were measured before surgery and subsequently at 1, 3, 5, 7 days, 1, 6 months and 1, 2, 3 years after operation by using Color Doppler sonography: portal blood flow mean velocity (PBV), portal blood flow volume (PBF), hepatic artery resistance indexes (HA-RI) and spleen size. The same parameters were measured in 8 patients with acute liver failure and 20 healthy controls. Meanwhile to observe liver function and varicose vein of esophagus. RESULTS: In cirrhotics, PBV and PBF increased immediately after transplantation [from (13.7 +/- 4.2) cm/s to (58.4 +/- 25.2) cm/s and from (958 +/- 445) ml/min to (3024 +/- 1207) ml/min respectively, P < 0.05]. HA-RI also augmented [from (0.65 +/- 0.11) to (0.74 +/- 0.12), P < 0.05]. PBV returned to normal values after 6 months, PBF returned to normal value after 2 years. Spleen size decreased significantly, but splenomegaly persisted after 3 years. In addition the esophagogastric varix ameliorated significantly. CONCLUSIONS: Abnormal splanchnic hemodynamic changes for patients with portal hypertension still will long-term exist after OLT, but does not effect recovery of hypersplenism, esophagogastric varix and liver function.

Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma.

AIM: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. METHODS: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. RESULTS: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4+ and CD8+ T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. CONCLUSION: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor.