Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review.

OBJECTIVE: To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. PATIENTS AND METHODS: We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live-birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. RESULTS: Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle-stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live-born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. CONCLUSIONS: The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work.

Sirt3 overexpression alleviates hyperglycemia-induced vascular inflammation through regulating redox balance, cell survival, and AMPK-mediated mitochondrial homeostasis.

Context: Sirtuin-3 (Sirt3), a NAD-dependent deacetylase, has been reported to be involved in many biological processes.Objective: The present study aimed to investigate the effect and mechanism of Sirt3 on diabetic mice and human umbilical vein endothelial cells (HUVECs) under high glucose (HG) condition.Materials and methods: HUVECs were cultured under HG and inflammation pathway was determined via qPCR, western blots, and immunofluorescence.Results: Sirt3 expression was reduced in the progression of diabetic nephropathy. Overexpression of Sirt3 sustains renal function and retard the development of diabetic nephropathy. Mechanistically, Sirt3 overexpression attenuated hyperglycemia-mediated endothelial cells apoptosis in kidney. Besides, Sirt3 overexpression repressed oxidative injury and blocked caspase-9-related apoptosis pathway. Moreover, we found that Sirt3 overexpression was associated with AMPK activation and the latter elevates PGC1α-related mitochondrial protective system, especially mitochondrial autophagy. Loss of opa1 and/or inhibition of AMPK could depress mitochondrial autophagy and exacerbates mitochondrial function, finally contributing to the death of human renal mesangial cells.Conclusions: Our results demonstrated the beneficial effects of Sirt3 in the progression of diabetic nephropathy. Increased Sirt3-activated AMPK pathway, augments PGC1α-related mitochondrial protective system, sustained redox balance and closed caspase-9-involved apoptosis pathway in the setting of diabetic nephropathy.

FBXW7 expression is associated with prognosis and chemotherapeutic outcome in Chinese patients with gastric adenocarcinoma.

BACKGROUND: FBXW7, a component of the Skp-Cullin1-F-box, mediates target protein recognition. It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and Notch degradation. There are few studies, particularly involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression. METHODS: Our study aimed to evaluate the value of FBXW7 as a clinical marker in gastric adenocarcinoma (GC) patients including a subset treated with postoperative chemotherapy. Quantitative reverse transcription PCR (qRT-PCR) assay was used to measure FBXW7 transcript levels in tumors paired with normal gastric tissue in 24 gastric adenocarcinoma patients. Subsequently, 546 additional GC samples were evaluated from patients that underwent radical gastrectomy, including 118 early stage cases(Stage I) and 428 advanced stage cases (Stages II or III). Amongst the advanced stage patient cases evaluated, 347 received postoperative adjuvant chemotherapy. All 546 gastric adenocarcinoma cases were then evaluated by tissue microarray and immunohistochemistry (IHC) for FBXW7 expression. Clinicopathological features and diagnoses were confirmed by histopathologic evaluation and review of clinical data. Overall survival (OS) was then evaluated in the 546 gastric cancer patients. RESULTS: By immunohistologic evaluation, low expression of FBXW7 in primary gastric cancer significantly correlated with poor differentiation of tumor cells. Moreover, low FBXW7 expression was associated with worse survival as well as worse adjuvant chemotherapy response. CONCLUSION: Our findings suggest that FBXW7 may serve as an important predictor in chemotherapeutic responses.

Obesity-Associated Anxiety Is Prevalent among College Students and Alleviated by Calorie Restriction.

Anxiety is a common disorder among college students, especially those with obesity. Obesity contributes to metabolic disorders and disturbs the neural functions, further leading to anxiety. In this cross-sectional study, we aimed to determine the association between obesity and anxiety among college students and identified the potential factors for obesity-associated anxiety. We evaluated the intervention effects of calorie restriction on anxiety. Self-reported questionnaires were distributed to 1381 college students from January to March in 2021. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were classified into anxiety and non-anxiety groups according to their STAI scores. Chi-squared test and logistic regression were used to analyze the potential factors. We found that 383 college students exhibited anxiety, accounting for 30.1% among all included college students, which was higher than the global average. The association between anxiety and obesity was observed among college students (p = 0.009), especially in males (p = 0.007). We identified that pre-obesity (p = 0.012), unhealthy calorie intake (p = 0.001), dieting (p = 0.003) and high academic year (p = 0.006) as the risk factors for anxiety and found that the long sleep duration was a protective factor for anxiety (p < 0.001). We found that more obese students showed an improvement of anxiety than the underweight students after calorie restriction (p < 0.001). Collectively, our findings suggest that obesity-associated anxiety is prevalent among the college students and could be alleviated by moderate calorie restriction. It is necessary for students to receive anxiety management in their college life. Additionally, the proper calorie restriction should be promoted to help students protect against obesity and obesity-associated anxiety.

Sema3C promotes hepatic metastasis and predicts poor prognosis in gastric adenocarcinoma.

OBJECTIVE: Semaphorin 3C (Sema3C) may regulate tumor metastasis and prognosis. We determined the biological roles of Sema3C in the hepatic metastasis of gastric adenocarcinoma and evaluated its clinical significance as a potential biomarker. METHODS: Sema3C expression in gastric cancer (GC) cell lines and tissues was measured using RT-qPCR and western blotting. Moreover, Sema3C functions were analyzed using Transwell assays and in vitro metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of Sema3C on the prognosis of 80 randomly selected patients with GC was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in GC tissues. RESULTS: Sema3C expression was significantly upregulated in highly metastatic GC cell lines and tissues. Additionally, Sema3C promoted invasion, migration and hepatic metastasis in GC cells. Moreover, Sema3C expression was positively correlated with clinicopathological features in GC and paired hepatic metastatic tissues, and Sema3C expression was an independent prognostic factor. Finally, Sema3C expression was associated with node metastasis, hepatic metastasis and EMT marker expression. CONCLUSIONS: Sema3C may play roles in regulating the EMT and metastasis of gastric adenocarcinoma, highlighting its potential use as a prognostic factor for hepatic metastasis and poor prognosis in gastric adenocarcinoma.

Hsa_circ_0024093 accelerates VSMC proliferation via miR-4677-3p/miR-889-3p/USP9X/YAP1 axis in in vitro model of lower extremity ASO.

Arteriosclerosis obliterans (ASO) of the lower extremities is identified as a kind of cardiovascular disease with aberrant proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Accumulating studies have demonstrated the vital role of Yes1-associated transcriptional regulator (YAP1) in VSMCs, while its upstream regulatory mechanism in VSMCs in ASO of the lower extremities needs to be further elucidated. Herein, hsa_circ_0024093, a circular RNA (circRNA) from YAP1, was identified to positively regulate the protein level of YAP1 in VSMCs. Functionally, silencing of hsa_circ_0024093 obviously impeded cell proliferation and migration and promoted apoptosis in VSMCs in the in vitro model of ASO of the lower extremities. Mechanistically, it was found that hsa_circ_0024093 could regulate the expression of USP9X, which further induced YAP1 deubiquitination to stabilize YAP1 protein. In depth, it was revealed from mechanism experiments that hsa_circ_0024093 sequestered miR-889-3p or miR-4677-3p to enhance USP9X expression. Further, rescue assays validated that hsa_circ_0024093 regulated the miR-4677-3p/miR-889-3p/USP9X axis to accelerate the proliferation and migration of VSMCs in the in vitro model of ASO of the lower extremities. These findings may provide a novel perspective for better understanding of ASO of the lower extremities.

Exosomes Derived from Human Induced Pluripotent Stem Cells-Endothelia Cells Promotes Postnatal Angiogenesis in Mice Bearing Ischemic Limbs.

Induced pluripotent stem cell (iPSC) derived endothelial cells (ECs) is a novel therapeutic option for ischemic diseases. Although the detailed mechanism of this novel therapy remains unknown, emerging evidence has demonstrated that exosomes derived from hiPSC-ECs play a critical role in this approach. In this study, we first isolated and characterized the exosomes from iPSCs-ECs (hiPSC-EC-Exo) and determined the functional roles of hiPSC-EC-Exo in neovascularization and the underlying mechanism. Further, we evaluated the effect of exosomes derived from hiPS-ECs on promoting angiogenesis in a mouse model bearing ischemic limbs. Our results showed that miR-199b-5p, an miRNA highly associated with angiogenesis, is significantly upregulated during the differentiation of hiPSC-ECs. Mechanically, our studies found that hiPSC-ECs expressing miR-199b-5p significantly promote cell migration, proliferation and tube formation through Jagged-1-dependent upregulation of VEGFR2 in HUVECs. Similarly, coculture of hiPSC-ECs-Exo with HUVECs also resulted in a significant improvement in HUVEC migration, proliferation, and tube formation, suggesting that exosome-mediated cell-cell communication in a paracrine manner may serve as a fundamental mechanism for iPSC-EC-based treatment. Consequently, we found that the transfer of hiPSC-ECs enriched with miR-199b-5p significantly enhanced micro-vessel density and blood perfusion in ischemic limbs in vivo. Taken together, our studies were the first to demonstrate that transfer of hiPSC-ECs-Exo is a promising approach to treat ischemic injury via the mechanism of promoting neovascularization.

MiR-130b attenuates vascular inflammation via negatively regulating tumor progression locus 2 (Tpl2) expression.

Endothelial cell (EC) activation and dysfunction have been linked to a wide variety of vascular inflammatory diseases. However, the role of microRNAs in EC activation and inflammation remains largely unknown. In this study, we found that miR-130b was significantly decreased in human umbilical vein endothelial cells (HUVECs) after lipopolysaccharides (LPS) treatment. Forced expression of miR-130b inhibited the LPS-induced activation of extracellular signal-regulated kinase (ERK) and the inflammatory genes expression, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Furthermore, we identified that tumor progression locus 2 (Tpl2) is a direct target of miR-130b. Finally, in vivo overexpression of miR-130b via miR-130b agomir attenuates acute lung vascular inflammation in the LPS-induced sepsis mouse model. Taken together, our data demonstrated that miR-130b represses vascular inflammation via targeting Tpl2, suggesting that miR-130b mimics might be a promising therapeutic strategy for treatment of vascular inflammatory diseases.

[Application of laparoscopic function-preservation proximal gastrectomy in the treatment of early gastric cancer].

OBJECTIVE: To discuss the safety and feasibility in the preservation to hepatic branch of vagus nerve by the side-to-side tubular gastroesophageal anastomosis within the laparoscopic radical proximal gastrectomy for early gastric cancer(EGC). METHODS: Retrospective analysis on the intraoperative and postoperative data of 7 EGC patients receiving laparoscopic radical proximal gastrectomy from January 2014 to January 2015 was carried out. All the patients underwent the preservation of hepatic branch of the vagus nerve by side-to-side tubular gastroesophagreal anastomosis. RESULTS: All the 7 patients completed operations successfully without conversion to open surgery. The mean operative time was (213.1 ± 22.1) minute, the mean reconstruction time was (56.9 ± 11.6) minute, and the mean blood loss was (38.6 ± 28.1) ml. Postoperative time to flatus was (2.4 ± 0.5) day, and postoperative hospital stay was (9.3 ± 0.9) day. No operation-related complications were observed. No severe malnutrition, no recurrence or death, and no severe esophageal reflux during follow-up period were found. CONCLUSION: The preservation of hepatic branch of the vagus nerve by side-to-side tubular gastroesophagreal anastomosis within laparoscopic radical proximal gastrectomy for ECG is safe and feasible.

[Function preserving gastrectomy].

Under the premise of radical resection in the treatment, it is of great significance to preserve partial gastric function so that the early gastric cancer (EGC) patients' postoperative quality of life (QOL) can be improved. In the patients with EGC in the upper third of the stomach, the emphasis is on the prevention of reflux esophagitis caused by bile and gastric juice reflux. Pylorus-preserving gastrectomy (PPG) is applicable to the patients with EGC in the middle third of the stomach. In the patients with EGC in the lower third of the stomach, distal gastrectomy (DG) is performed in general. Various anastomosis ways are applied to reduce the negative impact of pylorus resection after DG. Furthermore, it should also be considered that reasonable vagal nerves preservation and lymph node dissection are both important for function preserving gastrectomy of EGC. Rational use of laparoscopy-assisted gastrectomy has advantages of lower invasiveness, faster recovery, etc. And the amplification effect of laparoscope can contribute to preserving nerves and gastric function.

Sarcomatoid carcinoma of the stomach: A case report and literature review.

Sarcomatoid carcinoma of the stomach is a rare type of malignant tumor, characterized by distinct cellular morphology. This type of tumor is even more rare in giant size. The present study reports a case of giant sarcomatoid carcinoma, which developed in the distal stomach. A 49-year-old male underwent medical investigation for gastrointestinal hemorrhage. Endoscopic examination, computed tomography (CT) and positron emission tomography-CT scan identified a giant neoplasm, which involved the gastric antrum and body, gallbladder and hepatic flexure of the colon. Surgery was performed to excise the tumor, which was ~14×13×8 cm in size. A diagnosis of sarcomatoid carcinoma was made since the tumor was positive for epithelial markers, even within the mesenchymal elements. To the best of our knowledge, only 5 cases of sarcomatoid carcinoma of the stomach have been previously reported, and a tumor that has been able to be resected despite such a large size has never been reported.

Heterogeneity of c-Met expression in Chinese gastric cancer patients.

c-Met is an attractive target for gastric cancer (GC) therapy, and detection of c-Met expression is critical for diagnosis. The aims of this study were to quantify the heterogeneous expression of c-Met in GC and to explore its impact on diagnosis. The expression of c-Met in 199 tumor fragments derived from 47 GC patients was evaluated by immunohistochemistry. In parallel, copy numbers of MET were determined by fluorescence in situ hybridization. Expression of c-Met was observed in 22 patients, and 18 (81.8%) of 22 were heterogeneous; but the incidence rate of heterogeneity was not significantly different among patient subgroups with various degrees of c-Met expression. MET copies were increased in 4 patients. Two represented polysomy, and 2 were caused by amplification. Expression of c-Met in MET-amplified tumors was homogeneous. In conclusion, heterogeneity of c-Met expression was widely observed in GC but was not associated with the extent of expression.

[Research progression of translational medicine in gastric cancer].

Gastric cancer is one of the most common malignant tumors which is a great threat to human health. In recent years, the reform of surgical mordalities and the optimization of radiation and chemotherapy is still far from reducing morbidity and mortality of gastric cancer. As a new research pattern, translational medicine has emerged in various clinical subjects, which leads to remarkable effects. In this paper, the definition and development of translational medicine, molecular markers and drug treatment of gastric cancer will be discussed and the feasibility of translational medicine in the treatment of gastric cancer will be explained. In our opinion, the intervention of translational medicine could change the current situation that scientific researches is severely disconnected with clinical practice and increase the detection rate of gastric cancer and the effective rate of adjuvant therapy after surgery to improve the prognosis of patients with gastric cancer.