Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis.

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

SUCCESSFUL RESOLUTION OF NUTCRACKER SYNDROME WITH 3D PRINTED PEEK EXTRAVASCULAR STENT IN AN ADOLESCENT BOY.

Three-dimensional printed polyetheretherketone (PEEK) extravascular stent was applied to treat a 14-year-old boy with nutcracker syndrome. Digital subtraction angiography revealed a segment of the left renal vein (LRV) with reduced contrast filling immediately before its inflow into the inferior vena cava, and high-pressure gradient. The three-dimensional reconstruction model demonstrated that the LRV and the duodenum were contracted at the aortomesenteric angle, resulting in LRV compression from the abnormal high-level duodenal compartment. When duodenum courses between the abdominal aorta and superior mesenteric artery (duodenal interposition), the LRV entrapment occurs even at <90 aortomesenteric degrees. Three-dimensional printed PEEK extravascular stent was chosen to elevate the superior mesenteric artery and lower the duodenum position, thus relieving LRV compression. This extravascular application has significant advantages over open surgery, endovascular stenting and artificial vessel procedures with expanded polytetrafluoroethylene. It provides better cellular vitality by ensuring soft tissue proliferation. By reducing external acceleration and centrifugal force, a three-dimensional printed PEEK extravascular stent reduces adverse side effects. Such a stent has a distinctive personalized design, good stiffness, and durability that allows blood vessel growth, preventing stent migration and thrombosis. Therefore, it is suitable for both adult and pediatric patients. According to the abdominal ultrasound and multi-slice computed tomography scan, the postoperative follow-up results were satisfactory one year after surgery. The patient felt well, the blood flow in the LRV was not obstructed, and the blood flow velocity was average. The external stent was in place.

Efficacy and safety of 3D printing-assisted percutaneous nephrolithotomy in complex renal calculi.

This study evaluated the efficacy and safety of 3D printing technology combined with percutaneous nephrolithotomy in the treatment of complex renal calculi. Ninety patients with complex renal calculi were randomly divided into a 3D printing group (45 patients) and a control group (45 patients). In the 3D printing group, a patient-specific 1:1 3D printing model was established based on the patient's thin-layer CT scanning data. A 3D printing model was used for preoperative communication between doctors and patients. Preoperative puncture training, channel design, residual stone prediction, and percutaneous nephrolithotomy were performed under the guidance of a 3D printing model and B-ultrasound. The control group was treated with the conventional B-ultrasound-guided puncture method. Results suggest that there was a statistically significant difference between the two groups (P < 0.05). The overall score of the doctor-patient communication objects in the 3D printing group was 19.32 ± 1.57 points, and in the control group, it was 14.51 ± 2.13 points. The operation time of the 3D printing group was 103.21 ± 13.49 min, and that of the control group was 126.12 ± 25.87 min. The calculi clearance rate of the 3D printing group was 96%, while that of the control group was 80%. The incidence of postoperative complications was 6.67% in the 3D printing group and 22.22% in the control group. Compared with traditional percutaneous nephrolithotomy, 3D printing technology combined with percutaneous nephrolithotomy can significantly enhance the effectiveness of doctor-patient communication, shorten operation time, reduce operation bleeding, improve the stone clearance rate, reduce the incidence of complications and shorten the length of hospital stay. The proposed method is thus a safe and effective method to treat complex renal calculi.

3D-Printed Cold Preservation Device in Renal Autotransplantation for the Treatment of a Patient With Renal Artery Stenosis.

Percutaneous transluminal angioplasty (PTRA) is a common treatment method for renal vascular disease (RVD). However, PTRA may not be effective in patients with abnormal vascular disease. Renal autotransplantation (RAT) has been used as an alternative therapy for these diseases. Restrictions due to intracorporeal kidney cold preservation and the renal function of intracorporeal RAT were not as well protected compared with open operation. We developed this technique of 3D-printed polylactide (PLA) cold jackets for laparoscopic complete intracorporeal RAT for the purpose of better protecting the renal function and determining the feasibility of this novel procedure. The procedure was successfully applied to a 51-year-old woman with bilateral renal artery stenosis. The operation time was 5 hours, and blood loss was 200 ml. The patient's blood pressure remained constant throughout the operation, and the pressure was maintained at 120-140/70-90 mmHg without antihypertensive drugs 1 week after the operation. B-ultrasound showed that the blood flow signal of the transplanted kidney was normal and the boundary between the skin and medulla was clear. The patient was discharged 2 weeks after surgery. One year postoperatively, Doppler ultrasound of the autotransplant showed that the transplanted kidney was normal in size and shape. Radionuclide renal dynamic imaging revealed that the glomerular filtration rate (GFR) of the transplanted kidney was 36.9 ml/min. 3D-printed polylactide (PLA) cold jackets for laparoscopic complete intracorporeal RAT are a safe and effective method for the treatment of renal artery stenosis and represent a feasible method for preserving the renal function of severe renal artery stenosis patients; however, the technology is still at the exploratory stage and has room for further improvements.

Bacteriophage Protects Against Aerococcus viridans Infection in a Murine Mastitis Model.

Bovine mastitis, an inflammatory disease that occurs frequently in early lactation or the dry period, is primarily caused by bacterial infections. There is growing evidence that Aerococcus viridans (A. viridans) is becoming an important cause of bovine mastitis. The treatment of bovine mastitis is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. On the other hand, bacteriophages present a promising alternative treatment strategy. The object of this study was to evaluate the potential of a previously isolated A. viridans phage vB_AviM_AVP (AVP) as an anti-mastitis agent in an experimental A. viridans-induced murine mastitis model. A. viridans N14 was isolated from the milk of clinical bovine mastitis and used to establish a mastitis model in mice. We demonstrated that administration of phage AVP significantly reduced colony formation by A. viridans and alleviated damage to breast tissue. In addition, reduced inflammation was indicated by decreased levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and myeloperoxidase (MPO) activity in the phage-treated group compared to those in the phosphate buffered saline (PBS)-treated group. To the best of our knowledge, this report is the first to show the potential use of phages as a treatment for A. viridans-induced mastitis.

3D-Printed PEEK Extravascular Stent in the Treatment of Nutcracker Syndrome: Imaging Evaluation and Short-Term Clinical Outcome.

Minimally invasive options are safe and reliable alternatives for the treatment of nutcracker syndrome (NCS). After continued efforts, our team successfully devised a new and effective therapeutic method: 3D-printed extravascular stenting of the left renal vein. From December 2017 to May 2019, 28 patients (25 men and 3 women) from different parts of China between 18 and 37 years old (mean, 23.6 years) diagnosed with NCS were admitted for laparoscopic 3D-printed extravascular stenting treatment. The post-operative follow-up duration was 6-24 months (median, 16.3 months). Technical success of the operation was achieved in all patients. After treatment, the NCS symptoms all patients resolved or improved during the follow-up period, without relapse. Most symptoms, including macro-/microhematuria, proteinuria, and flank/abdominal pain, tended to resolve within 3-6 months after the surgery; other symptoms, such as left-sided varicocele, also showed varying degrees of improvement at different times post-operatively. Perioperative complications were noted in two patients, including transient and mild lymphatic leakage, without any adverse effects. All extravascular stents were visualized on computed tomography and Doppler ultrasound scans, and no migration or any side effects occurred during the entire follow-up period. Compared to endovascular stenting or polytetrafluoroethylene artificial vessel procedures, 3D-printed polyetheretherketone extravascular stenting has more advantages in terms of stent design and rigidity and approach rationality while successfully preventing stent migration and thrombosis. Therefore, this method may serve as an accurate and effective treatment for NCS patients.

A minimally invasive alternative for the treatment of nutcracker syndrome using individualized three-dimensional printed extravascular titanium stents.

BACKGROUND: This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications. METHOD: The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV's primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 µm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed. RESULTS: The mean duration of surgery was 75 ±â€Š9 min, and the mean blood loss was 20 ±â€Š5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7°â€Š±â€Š4.3° to 48.0°â€Š±â€Š8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ±â€Š0.5 to 1.3 ±â€Š0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ±â€Š3.3 to 18.5 ±â€Š3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery. CONCLUSION: The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.

MDR1 gene polymorphisms and imatinib response in chronic myeloid leukemia: a meta-analysis.

BACKGROUND: MDR1 gene polymorphisms were demonstrated to be associated with interindividual variability of imatinib response for chronic myeloid leukemia (CML) patients in several studies; however, the results have been inconclusive. MATERIALS & METHODS: To clarify the effect of common MDR1 variants on clinical response to imatinib, we performed a meta-analysis to quantify the accumulated information from genetic association studies. After a thorough search of the published literature, we undertook a meta-analysis to evaluate the effect of MDR1 C1236T, G2677T and C3435T polymorphisms on imatinib response. RESULTS: Our pooled data showed a significant association between MDR1 C1236T polymorphism and the increasing risk of imatinib resistance in Asian CML patients. However, no significant association was found for the MDR1 G2677T or C3435T polymorphisms in an Asian CML population as well as a Caucasian CML population. CONCLUSION: The synonymous MDR1 C1236T polymorphism might be a risk factor for nonoptimal clinical response to imatinib in Asian CML patients.

Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis.

INTRODUCTION: Accumulating evidences indicate that microRNA-21(miR-21) show significant high concentration in plasma of gastric cancer (GC) patients compared to normal individuals, suggesting that it may be a useful novel diagnostic biomarker for gastric cancer. Therefore, we aimed to assess the potential diagnostic value of miR-21 for gastric cancer in this study. METHODS: Literature database including PubMed, Embase, the Cochrane Library, Web of Science, Ovid, SciVerse, Science Direct, Scopus, BioMed Central, Biosis previews,Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang DATA were searched for publications concerning the diagnostic value of miR-21 for GC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Then, data were retrieved from any qualified article hits and subject to meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2) test. RESULTS: Five studies with a total 251 GC patients and 184 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score$13). The summary estimates revealed that the pooled sensitivity is 66.5% (95% confidence interval (CI): 55.0%-76.3%) and the specificity is 83.1% (95% CI: 69.4%-91.5%). In addition, the area under the summary ROC curve (AUC) is 0.80. CONCLUSION: The current evidence suggests that miR-21 has potential diagnostic value with a moderate sensitivity and specificity for GC. More prospective studies on the diagnostic value of miR-21 for GC are needed in the future.

Diagnostic value of bladder tumor fibronectin in patients with bladder tumor: a systematic review with meta-analysis.

OBJECTIVES: Bladder tumor fibronectin (BTF) has been related as a promising biomarker for the early diagnosis of bladder tumor. The meta-analysis was used to establish the diagnostic value of bladder tumor fibronectin in diagnosing bladder tumor. METHODS: Relevant literatures evaluating the value of BTF in the diagnosis of bladder tumor were searched in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Data. Summary estimates were used to evaluate the value of BTF in the diagnosis of bladder tumor by using the Meta-DiSc and STATA 11.0 statistical software. RESULTS: The meta-analysis included 5 studies (649 patients, 291 controls). The summary estimates revealed that the pooled sensitivity was 81% (95% confidence interval [CI]: 74%-85.1%) and specificity was 80% (95%CI 74%-84%). In addition, the area under the summary ROC curve (AUC) was 0.86 (95%CI 0.82-0.89). CONCLUSION: BTF is a potential marker for the diagnosis of bladder tumor, and more prospective studies are needed in the future.

Vascular endothelial growth factor polymorphisms and risk of Alzheimer's disease: a meta-analysis.

There were conflicting results about whether promoter polymorphisms (-2578C/A, -1154G/A) of vascular endothelial growth factor (VEGF) gene is a risk factor of Alzheimer's disease (AD). To determine the relationship between them, a meta-analysis is needed urgently. We searched all the reports about VEGF promoter polymorphisms (-2578C/A, -1154G/A) and AD risk from PubMed, Web of Science, Cochrane Collaboration and Google Scholar database for the period up to 1 August, 2012. A total of 7 studies were included in this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated applying fixed or random effects models. There was no significant association between VEGF -2578C/A polymorphisms and AD risk in all gene models (OR=1.08, 95% CI=0.94-1.23 for A vs. C; OR=1.19, 95% CI=0.89-1.59 for AA vs. CC; OR=1.15, 95% CI=0.91-1.45 for AA vs. CC+CA; OR=1.11, 95% CI=0.98-1.25 for AA+CA vs. CC). Similar results were provided in subgroup analysis by ethnicity. For the VEGF -1154G/A polymorphisms, lack of an association was also found (A vs. G: OR=0.89, 95% CI=0.79-1.01; AA vs. GG: OR=0.82, 95% CI=0.62-1.08; AA vs. GA+GG: OR=0.89, 95% CI=0.68-1.16; AA+AG vs. GG: OR=0.85, 95% CI=0.72-1.00). Conclusively, the result of this meta-analysis suggested that VEGF promoter polymorphisms (-2578C/A, -1154G/A) might not contribute to the susceptibility of AD.