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Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.

Aims: This systematic review and meta‐analysis aimed to evaluate the effects of home‐based telehealth compared with usual care on six‐minute walking distance (6MWD), health‐related quality of life, anxiety and depression in patients with chronic obstructive pulmonary disease. Methods: We identified randomized controlled trials through a systematic multidatabase search. Titles and abstracts were assessed for relevance. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta‐analyses were conducted using Review Manager and Stata. Results: We included 32 randomized controlled trials (n = 5232). Devices used for home‐based telehealth interventions included telephones, videos, and combined devices. The quality of the evidence was downgraded due to high risk of bias, imprecision, and inconsistency. Home‐based telehealth significantly increased 6MWD by 35 m (SD = 30.42) and reduced symptom burden by 3 points (SD = −2.30) on the COPD assessment test compared with usual care. However, no significant differences in anxiety and depression were noted between the home‐based telehealth group and the standard care group. In subgroup analysis, home‐based telehealth significantly improved 6MWD and health status after 6–12 months and >12 months. Conclusion: Low quality evidence showed that home‐based telehealth interventions reduce symptom burden and increase walking distance to a clinically meaningful extent in patients with COPD. However, no effects on depression and anxiety were observed. Summary statement: What is already known about the topic? In the context of chronic obstructive pulmonary disease progression, exacerbation of symptoms results in negative impacts on physical condition and psychological status.The overall effect of telehealth for patients living with chronic obstructive pulmonary disease is unclear based on different results reported in existing studies. What this paper adds? Home‐based telehealth improved the six‐minute walking distance and health status in patients with chronic obstructive pulmonary disease, but it did not improve anxiety and depression.Home‐based telehealth based on combined devices but not telephone or video improved the six‐minute walking distance and health status.Home‐based telehealth significantly improved six‐minute walking distance and health status in the 6–12 months subgroup and the more than 12 months subgroup but not at <6 months. The implications of this paper: Telehealth offers a feasible method to provide long‐term and regular health care to patients with chronic obstructive pulmonary disease living at home.Telehealth can help expand the recognition, accessibility and application of medical care services for patients with chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Fatigue is one of the most common adverse effects of lung cancer, and the efficacy of nonpharmacological interventions on fatigue in lung cancer patients is still unclear. We aimed to assess the effectiveness of nonpharmacological interventions on lung cancer-induced fatigue. A systematic review and meta-analysis were performed on studies retrieved from the PubMed, Embase Ovid, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception to June 2020. A total of 18 of randomized controlled trials with three intervention categories were identified, comprising 1,446 patients. We observed that fatigue was significantly affected by physical therapies (standard mean difference [SMD] = –1.26, 95% confidence intervals [CI]: –2.05 to –0.47, p =.002), but not by exercise interventions (SMD = –0.52, 95% CI: –1.46 to 0.43, p =.29) or education and psychological interventions (SMD = –0.39, 95% CI: –0.92 to 0.14, p =.15). More research with robust methodology is needed to justify these findings. [ABSTRACT FROM AUTHOR]

Aims and objectives: To assess the effects of breathing exercises on postoperative pulmonary complications (PPCs), pulmonary function, 6‐min walk distance (6MWD) and the length of hospital stay (LOS) in lung cancer patients undergoing lung surgery. Background: Lung cancer patients undergoing lung resection have poor pulmonary function and multiple PPCs. Breathing exercises may improve these symptoms. Design: Systematic literature review and meta‐analysis were conducted. Methods: All entries to the following databases were searched up until 20 December 2017: PubMed, EMBASE Ovid, the Cochrane Central Register of Randomized Controlled Trials, Web of Science, Wanfang, Weipu and Chinese National Knowledge Infrastructure databases. Only randomised controlled trials (RCTs) were included in the analysis. Results: A total of sixteen articles including nine articles in Chinese language and seven articles in English met the inclusion criteria. Breathing exercises decreased PPCs, and in addition, the incidence of pneumonia and atelectasis in the postoperative subgroup was reduced. Predicted forced expiratory volume in 1 s (predicted FEV1%), predicted forced vital capacity (predicted FVC%), FVC and FEV1/FVC ratio had improved after breathing exercises, but the changes in FEV1 were not statistically significant. Furthermore, the LOS was significantly decreased, but no improvements were found in 6MWD. Conclusions: The results showed that breathing exercises could improve lung function, decrease the incidence of PPCs and LOS in a sample of lung cancer patients undergoing pulmonary surgery. Relevance to clinical practice: The analysis suggests that breathing exercises should be considered as a respiratory rehabilitation programme for lung cancer patients undergoing lung surgery in clinical practice. [ABSTRACT FROM AUTHOR]

Metal-metal bonding interactions have been employed as an efficient strategy to generate a number of unique gold(I) metallo-macrocycles with fascinating functions. The self-assembly, crystal structure and emission property of novel nest-like tetramer 14, namely, {[Au4(μ-dppm)2(μ-dctp2−)](BF4)2}4 ⋅(CH3CN)2 (dppm=bis(diphenylphosphino)methane, dctp2−= N, N′-bis(dicarbodithioate)-2,11-diaza[3.3]paracyclophane) is reported. The complex has been characterized by single-crystal X-ray diffraction analysis, 1H NMR spectroscopy, 13C NMR spectroscopy, and CSI-MS spectrometry. The aggregate demonstrates the sixteen gold(I) atoms are arranged in a ring with a circumference of 50.011(68) Å generated by AuI⋅⋅⋅AuI attractions. UV/visible and luminescence spectroscopy revealed that this AuI⋅⋅⋅AuI bonded metallo-macrocycle exhibited yellow phosphorescence. [ABSTRACT FROM AUTHOR]

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1flox and Cre-ERTM mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood–testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans. [ABSTRACT FROM AUTHOR]

In recent years, with the policy reform of new drug review and approval, China has ushered in a surge of innovative drug development. Based on the Pharnexcloud database and the Pharmcube database, we analyzed the innovative drugs approved for marketing and entered clinical trials in China, sorted out the major research and development (R&D) institutions and enterprises, the distribution of innovative drug target types, and the primary therapeutic areas of the approved innovative drugs, and compared with the global innovative drug R&D landscape. Since 2020, China's innovative drug development has shown a rapid growth trend, with intense competition among biopharmaceutical companies, and the emergence of a number of leading biopharmaceutical enterprises. Popular targets for clinical-stage and approved drugs include protein tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, and others. Oncological diseases are the most active domain for new drug R&D in China, followed by infectious diseases and neurological diseases. Suggestions for future development are proposed to increase policy support, enhance R&D innovation investment, optimize pipeline layout, strengthen international cooperation, and focus on innovative targets. This review provides a reference for pharmaceutical R&D enterprises, scientific researchers, and government administrators. [ABSTRACT FROM AUTHOR]

Stearyl coenzyme A desaturase (SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids. In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant ( scd -/- ) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry (GC-MS) showed that the scd -/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd -/- mammals, the scd -/- zebrafish showed significantly increased fat accumulation in the whole body, especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis. Mechanistically, srebf1 , a gene encoding a transcriptional activator related to adipogenesis, acc1 and acaca , genes involved in fatty acid synthesis, and dgat2 , a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd -/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd -/- mutants could be rescued by ubiquitous transgenic overexpression of scd . In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.

Problem Identification: To investigate the effectiveness of home-based exercise training on exercise capacity, dyspnea, anxiety, depression, and health-related quality of life (HRQOL)., Literature Search: A systematic literature search of the Cochrane Central Register of Randomized Controlled Trials, Embase®, PubMed®, and Web of Science databases was performed for articles published through July 22, 2018., Data Evaluation: The meta-analysis was conducted with Review Manager, version 5.3, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines., Synthesis: 10 articles with a total of 453 patients met the inclusion criteria. Home-based exercise training was found to increase the six-minute walk distance. In addition, anxiety was also improved after the intervention. However, no improvements in dyspnea, depression, or HRQOL were observed., Implications for Research: Home-based exercise training as a nursing intervention for promoting the rehabilitation of patients with lung cancer can be recommended, but more research should be undertaken to determine the most effective exercises and follow-up methods.

Problem Identification: To evaluate the effects of breathing exercises on dyspnea, six-minute walk distance (6MWD), anxiety, and depression in patients with lung cancer., Literature Search: A systematic literature search of the Cochrane Library, Web of Science, Embase®, PubMed®, Weipu, Wanfang, and Chinese National Knowledge Infrastructure databases was performed for publications dated prior to April 6, 2018., Data Evaluation: The meta-analysis was performed using Review Manager and Stata., Synthesis: 15 randomized controlled trials with a total of 870 participants met the inclusion criteria. The findings suggest that breathing exercises have positive effects on dyspnea and 6MWD, but not on anxiety and depression. Subgroup analyses showed that breathing exercises combined with other exercises yield similar beneficial effects on dyspnea and 6MWD. In addition, breathing exercises in the surgery subgroup could significantly improve dyspnea and 6MWD. Dyspnea in the other treatment approaches subgroup was significantly improved, and 6MWD did not increase significantly., Implications for Nursing: Breathing exercises can be considered as a conventional rehabilitation nursing technique in clinical practice, and nurses should be aware of the importance of breathing exercises.

Background/aims: Liver cirrhosis is the end-stage of various liver diseases, which has a poor prognosis and determined by deterioration of hepatic functional capacity and consecutive development of hepatic complications. We investigated the role of IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G gene polymorphisms on the development of liver cirrhosis., Methodology: A 1:2 matched case-control study was conducted, including 266 patients from 302 Military Hospital. Genotyping of IL-10-592 A/C, IL-10-819 C/T and IL-10-1082 A/G were performed in a 384-well plate format on the Sequenom MassARRAY platform., Results: Multivariate regression analyses showed that subjects carrying the IL-10-592 CC variant had a significant increased risk of liver cirrhosis (OR: 1.83, 95% Cl: 1.10-3.03), and IL-0-592 A/C showed a significant increased risk in recessive model (OR: 1.97, 95% CI: 1.15-3.45). We found those carrying IL-10-592 CC genotype had a heavy increased risk of liver cirrhosis in those with positive chronic hepatitis B, with an OR (95% CI) of 2.46 (1.35-4.42), and a significant interaction was observed between the IL-10-592 A/C genotype and chronic hepatitis B infection (P = 0.036). Those carrying IL-10-819 C/T and IL-10-1082 A/G variants had non-significant increased risk of liver cirrhosis., Conclusions: Our study demonstrates that IL-10-592A/C gene polymorphism would enhance the risk for liver cirrhosis, and this gene variant has interaction with chronic hepatitis B infection in Asian population.