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When an enterprise crosses a long-term development into mature stage, the organizational structure always tend to be rigid, the willingness to improve will decline, and other problems will also follow. How can we overcome the disease of large enterprises, and even avoid the crisis of decline? The answers given by researchers and managers are often related to organizational reform. Li Ning's development process may point out a new idea for the development of enterprises: brand innovation. Based on the theory of organizational life cycle, this paper will analyze the whole process of Li Ning's brand innovation to overcome the decline, in order to provide reference for other enterprises, especially those in the transitional stage.

A highly sensitive temperature and strain sensor based on an antiresonant hollow core fiber (ARHCF) probe with the Vernier effect is proposed and experimentally demonstrated. The ARHCF probe is used as a reference interferometer by sandwiching an ARHCF, which is insensitive to temperature, strain, and refractive index, between a single-mode fiber (SMF) and a polarization-maintaining fiber (PMF). The polarization mode interferometer (PMI), fabricated by splicing a section of PMF with a fiber polarizer at a 45-degree angle, works as a sensing interferometer. The Vernier effect is introduced by connecting the reference interferometer and the PMI in parallel. The experimental results show that by introducing the Vernier effect, the temperature sensitivity is improved from − 1.68 to − 15.7 n m / ∘ C and the strain sensitivity is improved from 5.09 to 47.65 pm/µ ε . The magnification is consistent with the theoretical results. The reference segment of the proposed sensor is not affected by ambient factors, which provides a new strategy and idea for the development of multiparameter sensors based on the Vernier effect.

Purpose: Prostate cancer (PCa) has become the most frequently occurring cancer among western men, due to the rapid progression of tumor, late events will inevitably occur, which leads to poor prognosis of patients. Therefore, it is of great significance to explore the molecular mechanism of tumor progression.Methods: Herein, we conducted a transcriptomic analysis using public database to search for key genes that affect PCa progression. The correlation between gene expression and clinical pathological parameters and patient prognosis were examined, and it was verified in clinical samples. Next, we established cell lines by RNA interference, and studied its biological function by MTS, EdU, colony formation, wound-healing and transwell assay. The impact of gene on tumor growth was examined in nude mice xenograft model. Finally, high-throughput sequencing and signal pathway analysis were used to explore the molecular mechanism of gene action.Results: By combining clinical samples with public databases, we found that NETO2 expression was markedly elevated in tumors especially in metastatic tumors compared with normal tissues, and the expression level of NETO2 was closely associated with the clinical pathological parameters and prognosis of the patients. Functionally, NETO2 drove PCa cell proliferation, migration and invasion in vitro, and promoted growth of PCa cells in vivo. Moreover, through transcriptome high-throughput sequencing and experimental verification, our data demonstrate that NETO2 inhibits PCa cellular senescence via modulating p53-p21 pathway.Conclusions: Our results indicate that NETO2 plays an oncogenic role in PCa, which provides a new idea for clinical diagnosis and treatment of refractory PCa.

Prostate cancer (PCa) is the second cause of death due to malignancy among men, and metastasis is the leading cause of mortality in patients with PCa. MicroRNAs (miRNAs) play important regulatory roles in tumor development and metastasis. Here, we identified 13 miRNAs related to PCa metastasis by bioinformatics analysis. Moreover, we found that miR-671-5p was increased in metastatic PCa tissues, and its high expression indicated poor prognosis of PCa. MiR-671-5p could facilitate PCa cells proliferation, migration, and invasion in vitro and vivo. We confirmed that miR-671-5p directly bound to the 3’ untranslated regions of NFIA mRNA, and NFIA directly bound to the CRYAB promoter. High expression of NFIA and CRYAB negatively correlated with the advanced clinicopathological characteristics and metastasis status of PCa patients. Our study demonstrated that miR-671-5p promoted PCa development and metastasis by suppressing NFIA/ CRYAB axis.

Aim: To construct a survival prediction signature for prostate cancer (PC) based on the RNA N6-methyladenosine (m6A) methylation regulator. Materials & methods: This paper explores the interaction network of differentially expressed m6A RNA methylation regulators in PC by Pearson correlation analysis. Univariate Cox risk regression and LASSO regression analysis were used to construct a predictive signature of PC. Kaplan–Meier survival analysis compared the overall survival of the high- and low-risk groups. Results & Conclusion: We first constructed a prognostic two gene signature for PC based on the m6A RNA methylation regulators MRTTL14 and YTHDF2. The interaction network of m6A RNA methylation regulators in PC was also established.

For the optical fiber sensing system using phase generated carrier (PGC) technology, it is very important to eliminate the nonlinear effect of phase modulation depth (C) fluctuation on the demodulation results in the actual environment. In this paper, an ameliorated phase generated carrier demodulation technique is presented to calculate the C value and suppress its nonlinear influence on the demodulation results. The value of C is calculated out by the fundamental and third harmonic components with the equation fitted by the orthogonal distance regression algorithm. Then the Bessel recursive formula is used to convert the coefficients of each order of Bessel function contained in demodulation result into C values. Finally, the coefficients in demodulation result are removed by the calculated C values. In the experiment, when the C ranges from 1.0 rad to 3.5 rad, the minimum total harmonic distortion and maximum phase amplitude fluctuation of the ameliorated algorithm are 0.09% and 3.58%, which are far superior to the demodulation results of the traditional arctangent algorithm. The experimental results demonstrate that the proposed method can effectively eliminate the error caused by the fluctuation of the C value, which provides a reference for signal processing in practical applications of fiber-optic interferometric sensors.

Prostate cancer (PCa) has become the most frequently occurring cancer among western men according to the latest report, and patients’ prognosis is often poor in the event of tumor progression, therefore, many researches are devoted to exploring the molecular mechanism of PCa metastasis. MicroRNAs (miRNA) have proved to play an important role in this process. In present study, by combining clinical samples with public databases, we found that miR-629-5p increased to varying degrees in primary localized PCa tissues and metastatic PCa tissues compared with adjacent normal tissues, and bioinformatics analysis suggested that high level of miR-629-5p was related to poor prognosis. Functionally, miR-629-5p drove PCa cell proliferation, migration and invasion in vitro, and promoted growth of PCa cells in vivo. Moreover, A-kinase Anchor Protein 13 (AKAP13) was screened as a direct target of miR-629-5p, that expression was negatively correlated with the malignant phenotype of tumor cells. In the end, through verification in clinical specimens, we found that AKAP13 could be independently used as a clinical prognostic indicator. Overall, the present study indicates that miR-629-5p plays an oncogenic role in PCa by targeting AKAP13, which provides a new idea for clinical diagnosis and treatment of complex refractory PCa.

Erectile dysfunction (ED) is a common ageing male's disease, and vascular ED accounts for the largest proportion of all types of ED. One of the mechanisms of vascular ED in the clinic is arterial insufficiency, which mainly caused by atherosclerosis, trauma and surgical. Moreover, oxidative stress damage after tissue ischemia usually aggravated the progress of ED. As a new way of acellular therapy, mesenchymal stem cell‐derived exosomes (MSC‐Exos) have great potential in ED treatment. In the current study, we have explored the mechanism of MSC‐Exos therapy in a rat model of internal iliac artery injury‐induced ED. Compared with intracavernous (IC) injection of phosphate‐buffered saline after artery injury, of note, we observed that both mesenchymal stem cells (MSCs) and MSC‐Exos through IC injection could improve the erectile function to varying degrees. More specifically, IC injection MSC‐Exos could promote cavernous sinus endothelial formation, reduce the organization oxidative stress damage, and improve the nitric oxide synthase and smooth muscle content in the corpus cavernosum. With similar potency compared with the stem cell therapy and other unique advantages, IC injection of MSC‐ Exos could be an effective treatment to ameliorate erectile function in a rat model of arterial injury.

To predict survival outcomes for individual patients with clinical T1 high-grade (T1HG) bladder cancer (BC), data from the Surveillance Epidemiology and End Results (SEER) database were analyzed in the present study. The data of 6,980 cases of T1HG BC between 2004 and 2014 were obtained from the SEER database. Uni- and multivariate Cox analyses were performed to identify significant prognostic factors. Subsequently, prognostic nomograms for predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were constructed based on the SEER database. Clinical information from the SEER database was divided into internal and external groups and used to validate the nomograms. In addition, calibration plot diagrams and concordance indices (C-indices) were used to verify the predictive performance of the nomogram. A total of 6,980 patients were randomly allocated to the training cohort (n=4,886) or the validation cohort (n=2094). Univariate and multivariate Cox analyses indicated that age, ethnicity, tumor size, marital status, radiation and surgical status were independent prognostic factors. These characteristics were used to establish nomograms. The C-indices for OS and CSS rate predictions for the training cohort were 0.707 (95% CI, 0.693-0.721) and 0.700 (95% CI, 0.679-0.721), respectively. Internal and external calibration plot diagrams exhibited an excellent consistency between actual survival rates and nomogram predictions, particularly for 3- and 5-year OS and CSS. The significant prognostic factors in patients with T1HG BC were age, ethnicity, marital status, tumor size, status of surgery and use of radiation. In the present study, a nomogram was developed that may serve as an effective and convenient evaluation tool to help surgeons perform individualized survival evaluations and mortality risk determination for patients with T1HG BC.

Purpose Sexual functioning is an important factor influencing quality of life. Mounting evidence suggests that both male and female patients with epilepsy (PWE) have an increased risk of developing sexual dysfunction (SD). The aim of this meta-analysis was to quantify the association between epilepsy and the risk of SD. Methods PubMed, Embase, and Cochrane Library database were systematically searched to identify the pertinent studies focusing on the association between epilepsy and SD. Relative risk (RR) for SD with 95% confidence interval (CI) was calculated. The overall quality of the evidence was generated by applying the GRADE-profiler. This meta-analysis was registered on the PROSPERO (ID: CRD42018103572, http://www.crd.york.ac.uk/PROSPERO ). Results Nine studies (3 cross-sectional, 5 case-control, and 1 cohort) were included in this meta-analysis, for a total of 1556 subjects and 599 cases of epilepsy. Synthetic results demonstrated that epilepsy was associated with an increased risk of female SD (6 studies, pooled RR = 2.69, 95%CI: 1.48–4.89, P = 0.001; heterogeneity: I2 = 88.9%, P Conclusions Epilepsy is significantly associated with an increased risk of SD in both sexes. These findings suggest that both clinicians and patients should recognize that epilepsy has a potential hazardous effect on sexual functioning.

Objective To assess whether radiotherapy (RT) for prostate cancer (PCa) was a risk factor for secondary bladder cancer (BLCa) through a meta-analysis. Materials and methods The MEDLINE, Embase, and the Cochrane Library were systematically searched for all studies investigating the risk of BLCa in patients with RT. The association between RT and risk of BLCa was summarized using hazard ratio with a 95%CI. The protocol for this meta-analysis is available from PROSPERO (CRD42018090075). Results Overall, 619,479 participants (age: 57-79 years) were included from 15 studies, 206,852 of whom were patients who received RT. Synthesis of results indicated that RT was significantly associated with an increased risk of BLCa compared with the risk in those who received radical prostatectomy or non-RT (overall HR=1.6, 95%CI: 1.33-1.92, P

Purpose: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. Results: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers’ levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469–9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774–8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315–5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017–1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. Conclusions: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.

To evaluate the efficiency of an energy density of 0.05mj/mm2 of low intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) patients.A total of 45 ED patients met the inclusion criteria, including 7 PDE5i responders and 38 nonresponders. All the patients have already been delivered 10000 shockwaves of total seven treatment points twice a week for 4 weeks. Simultaneously, questionnaires of International Index of Erectile Function-Erectile Function (IIEF-EF), Erectile Hard Score (EHS) and Minimal Clinical Important Differences (MCID) were evaluated for the efficiency and safety at 8th and 16th weeks.The changes in the IIEF-EF score by MCID suggested that Li-ESWT treatment was effective in 22 PDE5i nonresponders patients (58%) at 8th week. Then at 16th week the number of patients who were effectively treated increased to 27 (71%). Among PDE5i responders, 5 patients (71%) were effective base on MCID at 16th week. Among PDE5i nonresponders 22 patients (58%) achieved erection hard enough for vaginal penetration and increased to 27 (71%) patients at 16th week (EHS ≥3). Moreover, even 3 patients achieved EHS 4 in PDE5i nonresponders at 16th week. Among PDE5i responders, 4 of 7 patients reached EHS of 4 from EHS 3 at 16th week. Apart from this, Li-ESWT treatment was also effective in 9 patients (24%) in PDE5i nonresponders without follow-up PDE5i.Energy flux density (EFD) of 0.05 of Li-ESWT could improve the erectile function of ED patients with PDE5i response. In addition, EFD of 0.05 of Li-ESWT treatment could turn PDE5i nonresponders to responders.

The prostate stem cell antigen (PSCA), as a predominantly prostate-specific marker, is overexpressed in most prostate cancer specimens, is positively correlated with prostate cancer androgen independence, and has the potential to be treated with castration-resistant prostate cancer (CRPC) as a gene therapy target. Using the typical androgen deprivation therapy, most tumors will progress to CRPC, as well as develop into neuroendocrine prostate cancer (NEPC) characterized by the expression of neuroendocrine markers such as enolase 2 (NSE). Our study was aimed at investigating the expressions of PSCA and NSE and the relationship between the two markers, as well as the correlation between the PSCA and NSE expressions and the clinicopathological parameters in prostate cancer specimens from 118 patients by using immunohistochemistry. Our results demonstrated that the PSCA and NSE protein expressions did not correlate with the prostate cancer patients’ age or the hormone therapy but showed a significant correlation with the pathological tumor stage of prostate cancer, the Gleason score, and the presence of metastasis. There is a positive association between PSCA and NSE but a negative one between the prostate-specific antigen (PSA) and PSCA or between PSA and NSE. High PSCA and NSE expressions correlated with a poor prognosis in prostate cancer patients. PSCA may play an important role in the progression of neuroendocrine prostate cancer (NEPC).

Background It has been shown that sexual dysfunction (SD) is highly prevalent among patients with chronic renal failure (CRF), and starting renal replacement therapy may even increase it. However, SD is an infrequently reported problem in these treated patients. Aim To investigate the prevalence of SD among patients with CRF undergoing renal replacement therapy, by a meta-analysis method. Methods PubMed, Embase, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with CRF receiving renal replacement therapy from January 2000 to April 2020. Relative risk (RR) with 95% CIs was used for analysis to assess the risk of SD in patients with CRF receiving renal replacement therapy. The cross-sectional study quality methodology checklist was used for the cross-sectional study. The methodologic quality of the case-control and cohort studies was assessed with the Newcastle-Ottawa Scale. Data were pooled for the random-effect model. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. Outcomes The prevalence of SD among patients with CRF receiving renal replacement therapy was summarized using pooled RR and 95% CI. Results This meta-analysis included 3,725 participants from 10 studies. Of these, 737 were patients with CRF receiving renal replacement therapy. The mean age of participants ranged from 32.75 to 56.1 years. Based on the random-effect model, synthesis of results demonstrated that the prevalence of SD was significantly increased among patients with CRF receiving renal replacement therapy in women (RR = 2.07, 95% CI: 1.47–2.91, P = .000; heterogeneity: I2 = 78.7%, P = .000) and in men (RR = 2.95, 95% CI: 2.16–4.02, P = .000; heterogeneity: I2 = 86.1%, P = .000). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. Clinical Implications Patients with CRF receiving renal replacement therapy had a significantly increased risk of SD, which suggests that clinicians should evaluate sexual function, when managing patients with CRF receiving renal replacement therapy. Strengths and Limitations This is the first study to explore the prevalence of SD among patients with CRF undergoing renal replacement therapy based on all available epidemiologic studies. However, all included studies were an observational design, which may downgrade this evidence. Conclusion The prevalence of SD is significantly increased among patients with CRF receiving renal replacement therapy. More research studies are warranted to clarify the relationship.

BACKGROUND An association between inflammatory bowel diseases (IBD) and increased susceptibility to sexual dysfunction (SD) was reported in a number of studies. METHOD MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all relevant studies reporting the sexual function in IBD patients. Relative risk (RR) with a 95% confidence interval (CI) was used to summarize the association between IBD and risk of SD. Subgroup and sensitivity analyses were applied to detect potential bias. RESULTS Overall, 351,668 male individuals and 1309 female individuals (the mean age ranged from 33.6 years to 52.4 years) were included from 8 studies (of which 4 studies provided the outcomes of both sexes). Synthesis of results revealed that IBD was significantly associated with an elevated risk of SD in male subjects (7 studies, RR = 1.41, 95% CI, 1.09-1.81, P = 0.008; heterogeneity: I2 = 80.2%, P < 0.001) and female subjects (5 studies, RR = 1.76, 95% CI, 1.28-2.42, P < 0.001; heterogeneity: I2 = 69.6%, P = 0.011). Stratified analysis by the mean age of the individuals indicated that patients with IBD with a relatively young age (male: younger than 50 years; female: younger than 40 years) exhibited a significantly increased odds of SD. Sensitivity analyses showed that no single study dominated the overall combined RR. CONCLUSION Evidence from this meta-analysis revealed that both male and female patients with IBD have a significantly increased risk of SD, which should remind both gastroenterologists and urologists to be aware of the potential hazardous effect of IBD for developing SD.

Introduction It has been reported that multiple sclerosis (MS) would increase the susceptibility to female sexual dysfunction (FSD). Aim To assess whether MS was a risk factor for FSD through a comprehensive literature review and meta-analysis. Methods MEDLINE (PubMed), Embase, Cochrane Library, and PsychINFO databases were systematically searched for all studies reporting sexual function in women with MS. The protocol for this meta-analysis is available from PROSPERO (CRD42018094392). Main Outcome Measures The association between MS and risk of FSD was summarized using relative risk or standard mean differences with 95% CI. Subgroup and sensitivity analyses were conducted to detect potential bias. Results Overall, 1,485 women participants (the mean age ranged from 29.15 to 45.89 years) were included from 9 studies (4 cross-sectional and 5 case-control studies); 826 of them were patients with MS, with a mean disease duration from 2.7 to 16.51 years. Synthesis of results revealed that MS was significantly associated with an increased risk of FSD (relative risk 1.87, 95% CI 1.25–2.78, P = .002; heterogeneity: I 2 = 89.0%, P < .001). Women with MS had significantly lower values in total Female Sexual Function Index scores as compared with healthy controls (standard mean differences –2.41,95% CI −3.87 to −0.96, P = .017; heterogeneity: I 2 = 97.2%, P = .001). The grading of recommendations assessment, development, and evaluation–relevant outcomes revealed that the absolute effect of MS on FSD was 434 more per 1000 (from 125 more to 888 more); and the overall quality of the evidence was judged as low. Clinical Implications The present meta-analysis indicates that women patients with MS have a significant elevated risk of sexual dysfunction, which should raise awareness of the potential association between MS and FSD by both neurologists and urologists. Strengths & Limitations This the first study to summarize all available evidence for combining the odds on the association between MS and the risk of developing FSD. However, all the included studies were observational design, which may downgrade this evidence. Conclusion Results of this meta-analysis revealed a potential hazardous effect of MS for developing FSD. High-quality stringently controlled studies with large sample size are still warranted to validate this relationship.

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs‐derived EVs (MSC‐EVs) treatment in a pre‐clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC‐EVs (administration via renal‐arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC‐EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor‐β1 induced fibration. Due to MSC‐EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC‐EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.

5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains unclear. Therefore, the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate cancer. We searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed, Embase, Medline, and Cochrane Library databases. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were accepted to evaluate the association between 5-ARI and the risk of prostate cancer. Synthetic results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer (RR = 0.74; 95% CI: 0.66–0.82; P < 0.001). Subgroup analyses further revealed that 5-ARI reduction of the incidence of prostate cancer was limited to low-grade (Gleason score 2–6; RR = 0.68; 95% CI: 0.57–0.81; P < 0.001) and intermediate-grade tumors (Gleason score 7; RR = 0.81; 95% CI: 0.67–0.97; P = 0.023), but not high-grade tumors (Gleason score >7; RR = 1.19; 95% CI: 0.98–1.43; P = 0.069). The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality (RR = 1.0; 95% CI: 0.95–1.05; P = 0.916). In addition, it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors (RR = 0.58; 95% CI: 0.43–0.78; P < 0.001).

Previous studies investigating the risk of erectile dysfunction (ED) among patients with gout have produced inconsistent evidence. Therefore, the aim of this meta-analysis was to investigate the relationship between gout and the risk of ED. The Embase, Medline, Scopus, Web of Science and Cochrane Library databases were searched for all studies assessing the risk of ED in patients with gout. Relative risks (RR) and corresponding 95% confidence intervals (CI) were adopted to estimate the association between gout and the risk of ED. Sensitivity analyses were applied to evaluate the robustness of results. Overall, 355,761 participants were included from 8 studies (3 cross-sectional and 5 cohort studies). Of these, 85,067 were patients with gout. Synthesis results showed patients with gout had a 1.2-fold higher risk of ED than individual without gout (RR 1.20, 95% CI 1.10–1.31, P

Objective To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.

Objective. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.

Neuropeptide (NP) F is a homolog of vertebrate neuropeptide Y, and mounting evidence suggests that it may play a role in innate immunity in addition to its function in invertebrate neurobiology. However, so far, there have been few reports on the immunological properties of crustacean NPs. Here, we cloned a neuropeptide FII gene, naming it SpNPFII, from the mud crab Scylla paramamosain. The full-length cDNA sequence of SpNPFII was 551 bp, encoding 124 amino acids. Structural prediction suggested that the SpNPFII mature peptide mainly formed an α-helix. SpNPFII was predominately expressed in male crab gonadal tissues, with the highest expression in the anterior vas deferens and seminal vesicle. The expression level of SpNPFII changed significantly under challenge by lipopolysaccharide (LPS) or Vibrio alginolyticus. After bioinformatic analysis, a truncated 45-amino acid peptide derived from SpNPFII and having potent antimicrobial activity was identified and named Sp-NPFin. Sp-NPFin exerted strong, broad-spectrum antibacterial (minimum inhibitory concentration [MIC] ranged from 1.5 to 12 μM) and antimildew activity (MIC ranged from 1.5 to 48 μM), a low fungicidal concentration (e.g., minimum bactericidal concentration [MBC] for Fusarium oxysporum was 1.5 to 3 μM) and rapid bactericidal kinetic (killed all bacteria within 1 to 6 h). Sp-NPFin could bind to several microbial surface components (e.g. LPS, lipoteichoic acid, peptidoglycan and glucan), and induce significant damage to microbial membranes and cause leakage of cell contents in a concentration-dependent manner. Confocal microscopy indicated that Sp-NPFin was localized at microbial surfaces. In addition, Sp-NPFin exhibited no cytotoxicity to primary cultured crab hemocytes and mammalian cells, and in vivo study demonstrated that it could significantly improve the survival rate of S. paramamosain under the challenge of V. alginolyticus. Taken together, SpNPFII might play a role in the immune system of S. paramamosain, and its truncated peptide, Sp-NPFin, would be a promising antibacterial and antimildew agent with broad application prospects in the fields of aquaculture, veterinary practices and medicine.

A Correction to this paper has been published: https://doi.org/10.1038/s41416-020-01258-w

Background: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. Aims: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. Methods/Results: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt. The expression of ERK1/2, p38, JNK, and Akt was not altered by melatonin. PD98059 and melatonin alone, and especially in combination, significantly inhibited cell proliferation. The changes included G1 and G2/M phase arrest of the cell cycle, and a downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4 (related to the G1 phase) and of cyclin B1 and CDK1 (related to the G2/M phase) as measured by flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Furthermore, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Co-immunoprecipitation further confirmed that there was an interaction between p-ERK1/2 and cyclin D1, CDK4, cyclin B1, or CDK1, which was blunted in the presence of melatonin or PD98059. Conclusion: These findings suggest that melatonin's antiproliferative action is mediated by inhibition of the ERK1/2 signaling pathway rather than the p38, JNK, or Akt pathways.

Polyvinyl alcohol (PVA)/polyethylene glycol diacrylate (PEGDA)/Agar/sulfuric acid (H2SO4) hydrogels with triple-network (TN) structure were successfully fabricated using a facile radiation-assistant method. The as prepared PVA/PEGDA/Agar/H2SO4 hydrogels are highly conductive, transparent and self-healing, which are demonstrated as a strain sensor to monitor human activity and an ionic cable to transmit signal. Sulfuric acid plays important roles in this synthesis strategy, which increases the conductive ability, transparency and water retention capacity of the hydrogel. This work proposed a facile method to fabricate physically and chemically cross-linked ion conducting hydrogels, which are promising candidates in flexible electronics.

Teleost fish are the most primitive bony vertebrates that contain immunoglobulin (Ig). Although teleost Ig is known to be important during tetrapod evolution and comparative immunology, little is known about the genomic organization of the immunoglobulin heavy-chain (IgH) locus. Here, three Ig isotype classes, IgM, IgD and IgT, were firstly identified in dojo loach (Misgurnus anguillicaudatus), and the IgH locus covering τ, μ and δ genes was also illustrated. Variable (V) gene segments lie upstream of two tandem diversity (D), joining (J) and constant (C) clusters and the genomic organization of the IgH locus presented as Vn-Dn-Jn-Cτ-Dn-Jn-Cμ-Cδ, similar to some other teleost fish. However, unlike some other teleost fish, ten VH, ten D and nine J genes were observed in this locus, which suggest teleost Igs might be conserved and diverse. Thus, it would be interesting to determine how Igs divide among themselves in immune response to different antigens. To address this hypothesis, we have developed three models by bath infection with parasitic, bacterial and fungal pathogens, respectively. We found that IgM, IgD and IgT were highly upregulated in the head kidney and spleen after infection with Ichthyophthirius multifiliis (Ich), suggesting that the three Igs might participate in the systemic immune responses to Ich. Moreover, the high expression of IgT in mucosal tissue, such as skin or gills, appeared after being infected with three different pathogens infection, respectively, in which the expression of IgT increased more rapidly in response to Ich infection. Interestingly, the expression of IgD showed a higher increase in spleen and head kidney being challenged with fungi, suggesting that IgD might play an important role in antifungal infection.

The aim of this study was to evaluate whether polycystic ovary syndrome (PCOS) is a risk factor for female sexual dysfunction (FSD) by conducting a systematic review and meta-analysis. The databases PubMed, EMBASE and the Cochrane Library were searched for relevant studies. The association between PCOS and risk of FSD was assessed by relative risk or standard mean differences with 95% confidence interval. The protocol for this meta-analysis is available from PROSPERO (CRD42018102247). Overall, 2626 participants (mean age 25–36 years) were included from 10 studies (five cross-sectional and five case-control studies), 1163 of whom were women with PCOS. The pooled results from eight included studies providing the number of cases revealed no significant association between PCOS and increased risk of FSD (RR = 1.09, 95% CI 0.9 to 1.32; heterogeneity: I2 = 11.0%). The combined overall standard mean difference from five studies reporting Female Sexual Function Index (FSFI) scores showed that patients with PCOS had similar values in total FSFI scores compared with healthy controls (standard mean difference = –0.03, 95% CI –0.12 to 0.05; heterogeneity: I2 = 0.0%). Sensitivity analyses yielded similar results. This meta-analysis suggests no direct association between PCOS and risk of FSD. Well-controlled trials with large sample sizes, however, are needed to validate this evidence.

Background Mounting evidence has emerged suggesting that patients with Parkinson’s disease (PD) are susceptible to sexual dysfunction (SD). Aim To better clarify the relationship between PD and SD. Methods PubMed, Embase, Cochrane Library database, and PsychINFO database were systematically searched for pertinent studies evaluating sexual function in the patients with PD. This systematic review and meta-analysis have been registered on PROSPERO (ID: CRD42018108714; http://www.crd.york.ac.uk/PROSPERO). Outcomes The association between PD and SD was assessed using relative risk (RR) with 95% CI. The quality of evidence was ranked by the GRADE profiler. Results 11 observational studies met the predefined criteria for inclusion, enrolling 30,150 subjects from both the PD group and healthy control group (mean age 54.6–75.1 years). Synthesis results revealed that PD was associated with an elevated risk of SD in males (7 studies; 1.79; 95% CI = 1.26–2.54, P = .001; heterogeneity: I2 = 73.2%, P < .001). However, when restricted to female subjects, the combined RR from 3 eligible studies suggested a lack of significant association between PD and SD (RR = 1.3, 95% CI = 0.64–2.61, P = .469; heterogeneity: I2 = 80.0%, P = .007). The GRADE profiler indicated the overall quality of the evidence was low in studies including males and very low in studies including females. Clinical Implications The current meta-analysis indicated that men with PD were more likely to experience SD than those without PD. In female subjects, however, PD seemed to not be associated with a high prevalence of SD compared with healthy controls. Based on these findings, patients with PD should be routinely assessed for sexual functioning, especially males. Strengths & Limitations This is the first systematic review and meta-analysis of the association between PD and the risks of SD in both males and females. However, substantial heterogeneities were detected across the included studies. Conclusion A hazardous effect of PD for developing SD was detected in men but not in women. As a result, sexual function assessment and appropriate therapy are recommended for men with PD in clinical practice.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease. Mounting evidence shows that male patients with COPD have an increased risk of developing erectile dysfunction (ED). The aim of this meta-analysis was to assess the relationship between COPD and the risk of ED. To identify relevant studies, the PubMed, Cochrane Library and Embase databases, Chinese Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI) were systematically searched up to September 2018. Relative risks (RR) and corresponding 95% confidence intervals (CI) were used to estimate the strength of association between COPD and the risk of ED by using random-effects models. Finally, four studies (three cross-sectional, one cohort study) involving 58,307 participants were included. Synthesis results demonstrated that patients with COPD was not significantly associated with an increased overall prevalence of ED (RR = 1.31, 95% CI: 0.95–1.81, P = 0.099) compared to the healthy controls. However, the subgroup analyses showed that the prevalence of moderate ED (RR = 2.44, 95% CI: 1.29–4.59, P = 0.006) and severe ED (RR = 2.77, 95% CI: 1.57–4.94, P = 0.001) were significantly higher in patients with COPD. Evidence from this meta-analysis revealed that patients with COPD had a significantly increased susceptibility to moderate and severe ED, which should remind both clinicians and patients to be aware of the potential hazardous effect of COPD for developing ED.

To investigate whether radiotherapy for prostate cancer increases the risk of therapy-related rectal cancer and colon cancer. A systematic literature search was carried out using the Medline (PubMed), EMBASE, and the Cochrane Library to identify studies examining the association between radiotherapy for prostate cancer and secondary colorectal cancer (rectal cancer and colon cancer) published before March 19, 2018. The risk of second colorectal cancer after radiotherapy was summarized using unadjusted odds ratio (OR) and adjusted hazard ratio (HR) with their 95% confidence interval (CI). Subgroup and sensitivity analyses were conducted to detect potential bias and heterogeneity. After study selection, 16 reports were retrieved for analysis. When patients received radiotherapy compared with those unexposed to radiation, there was an increased risk of the rectal cancer (OR 1.37, 95%CI 1.01 to 1.85), but not colon cancer. According to adjusted HR, there was an increased risk of the rectal cancer (HR 1.64, 95%CI 1.39 to 1.94), and colon cancer (HR 1.33, 95%CI 1.02 to 1.76). The OR for rectal cancer showed an increased risk with longer latent period (5 years lag time versus 10 years lag time, OR: 1.56 versus 2.22). Brachytherapy had no association with second cancer across all analyses. Radiotherapy was associated with an increased risk of subsequent rectal cancer compared with patients unexposed to radiation. Colon may be free from the damage of radiation. Brachytherapy had no association with second rectal cancer or colon cancer.

BackgroundTumor necrosis factor (TNF)-α variant is closely linked to sepsis syndrome and mortality after severe trauma. We aimed to identify feature genes associated with the TNF rs1800629 A allele in trauma patients and help to direct them toward alternative successful treatment. MethodsIn this study, we used 58 sets of gene expression data from Gene Expression Omnibus to predict the feature genes associated with the TNF rs1800629 A allele in trauma patients. We applied support vector machine (SVM) classifier model for classification prediction combining with leave-one-out cross validation method. Functional annotation of feature genes was carried out to study the biological function using database for annotation, visualization, and integrated discovery (DAVID). ResultsA total of 133 feature genes were screened out and was well differentiated in the training set (14 patients with variant, 15 with wild type). Moreover, SVM classifier peaked in predictive accuracy with 100% correct rate in training set and 86.2% in testing set. Interestingly, functional annotation showed that feature genes, such as HMOX1 (heme oxygenase (decycling) 1) and RPS7 (ribosomal protein S7) were mainly enriched in terms of cell proliferation and ribosome. ConclusionHMOX1 and RPS7 may be key feature genes associated with the TNF rs1800629 A allele and may play a crucial role in the inflammatory response in trauma patients. Moreover, the cell proliferation and ribosome pathway may contribute to the progression of severe trauma. A total of 133 feature genes were screened out in training set.SVM classifier peaked at 100% and 86.2% correct rate in training and validation sets.Feature genes were mainly enriched in cell proliferation and ribosome pathway.

Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and adenoma vs. CRC, were identified using the Wilcoxon test method in R respectively. The interactive network of DEGs was constructed to select the significant modules using the Pearson's correlation. Meanwhile, transcriptional network of DEGs was also constructed using the g: Profiler. Totally, 2,741 DEGs in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs. CRC were identified. Moreover, function analysis of DEGs in each group showed FcR-mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in module 6, and Jak-STAT signaling pathway in module 19 were also enriched. Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT, SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development. Therapy targeting on the functions of these key genes might provide novel perspective for CRC treatment.

The polymeric immunoglobulin receptor (pIgR) is an essential component of the mucosal immune system in jawed vertebrates including teleost fish, which mediate transepithelial transport of secretory immunoglobulins (sIgs) to protect organisms against environmental pathogens. In this study, we firstly cloned and identified the pIgR from dojo loach (Misgurnus anguillicaudatus). The full-length cDNA of Ma-pIgR was of 1145 bp, containing an open reading frame (ORF) of 1101 bp encoded a predicted protein of 336 amino acids. The structure of Ma-pIgR is comprised of a signal peptide, a transmembrane region, an intracellular region and an extracellular region with two Ig-like domains (ILDs), which are similar to their counterparts described in other teleosts. Multiple sequence alignment and phylogenetic analysis showed the dojo loach is closely related to the fish family Cyprinidae. The transcriptional level of Ma-pIgR was detected by quantitative real-time PCR (qRT-PCR) in different tissues and high expression was found in liver, skin, kidney, eye, fin and gills. Two infection models of the loach with bacteria (Aeromonas hydrophila) and parasite (Ichthyophthirius multifiliis) were constructed for the first time. Histological studies showed the goblet cells in skin significantly increased and the ratio of gill length to width also significantly changed after challenged with A.hydrophila. Both challenge experiments resulted in the significant up-regulated expression of Ma-pIgR not only in kidney and spleen, but also in skin and gills. Our results suggest that pIgR may play an important role in skin and gill mucosal immunity to protect the loach against bacteria and parasite.

The complement component 3 (C3) is a central component of complement system. All three pathways converge at formation of C3 convertases and share the terminal pathways of membrane attack complex (MAC) formation. In this study, three isoforms of C3 were discovered in Misgurnus anguillicaudatus, named “C3-1”, “C3-2” and “C3-3”, respectively. The full-length of C3-1 cDNA sequence was firstly identified and analyzed from dojo loach (Misgurnus anguillicaudatus). The Ma-C3-1 cDNA sequence comprised of 4509 bp encoding 1454 amino acids with a putative signal peptide of 20 amino acid residues. The deduced amino acid sequence showed that Ma-C3-1 has conserved residues and domain, which are known to be crucial for C3 function. Interestingly, an amino acid substitution of the highly conserved GCGEQ was discovered in Ma-C3-1. Phylogenetic analysis showed that Ma-C3-1 was closely related to Cyprinidae. The mRNA expression levels of three isoforms of C3 were detected in kidney, eye, spleen, gonad, heart, fin ray, gut, muscle, brain, gill, skin, blood and liver. The expression of Ma-C3-1 and Ma-C3-3 were mainly detected in liver, followed by spleen, gonad. However, the high expression of Ma-C3-2 was found in kidney, followed by blood and gonad. The morphological changes of gill and skin, and the expression pattern of these three isoforms C3 molecular following the infection with Aeromonas hydrophila were investigated. The mRNA expression levels of three C3 isoforms were up-regulated in the gill, skin, liver and spleen after infection with A.hydrophila. Similarly, challenge experiments resulted in significant up-regulated expression of other complement-relevant genes in gill, liver and skin, such as C4, C5, C8b, especially at 24 h and 36 h. These results suggest that complement system might play an important role not only in liver, but also in the mucosal tissues as gill and skin of teleost fish.

The purpose of this study was to identify critical genes associated with septic multiple trauma by comparing peripheral whole blood samples from multiple trauma patients with and without sepsis. A microarray data set was downloaded from the Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36 from multiple trauma patients with sepsis and 34 from multiple trauma patients without sepsis (as a control set). The data were preprocessed, and differentially expressed genes (DEGs) were then screened for using packages of the R language. Functional analysis of DEGs was performed with DAVID. Interaction networks were then established for the most up- and down-regulated genes using HitPredict. Pathway-enrichment analysis was conducted for genes in the networks using WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down-regulated) and MMP8 (up-regulated) presented the largest fold-changes, and interaction networks were established for these genes. Further analysis revealed that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase inhibitor, clade F, member 2), which interact with PLAU, play important roles in the pathway of the component and coagulation cascade. We hypothesize that PLAU is a major regulator of the component and coagulation cascade, and down-regulation of PLAU results in dysfunction of the pathway, causing sepsis.

Potassium iron hexacyanoferrate/polyacrylamide nanohybrid hydrogel (PB/PAM-gel) was successfully synthesized via a convenient one-pot gamma radiation route. The as-prepared PB/PAM-gel has compact internal three-dimensional porous structures with well-dispersed PB nanowires, which exhibit good elasticity and excellent swelling performance. The adsorption experiments reveal that the PB/PAM-gel can rapidly and selectively adsorb Cs[Formula: see text] from the solution in a wide range of pH. The maximum adsorption capacity reaches 131[Formula: see text]mg[Formula: see text]g[Formula: see text]. This nanohybrid hydrogel is very stable and can be easily separated from the solution after adsorption. It can be applied as a potential adsorbent for Cs[Formula: see text] removal from radioactive wastewater.

This is a bioinformatic study designed to investigate the time-course expression changes of microRNAs (miRNAs) after spinal cord injury (SCI).To investigate the mechanism of SCI self-repair at miRNAs level and target genes level.SCI results in loss of sensory and locomotor function, and SCI self-repair might provide clinical therapies; however, the mechanism of SCI self-repair remains unclear.The miRNA expression profile (GSE19890) of adult female Wistar brown rats (Rattus norvegicus) in SCI (laminectony and contusion), sham (laminectony but no contusion), and control (untreated) groups was downloaded from Gene Expression Omnibus. Totally, 35 chips were available, including five controls, five SCI-1-day, five SCI-3-day, five SCI-7-day, five sham-1-day, five sham-3-day, and five sham-7-day. Betr and limma package were used to screen time-course differentially expressed miRNAs (DEmiRNAs), followed by Bayesian hierarchical clustering (BHC), synergetic and functional enrichment analysis through BHC and cluster Profiler packages, respectively. Furthermore, STRING database and Cytoscape software were used to construct interaction networks between time-course DEmiRNAs, and GenCLip2.0 software was applied to pathway enrichment for key genes associated with nervous system.Totally, 68 time-course DEmiRNAs were identified and divided into 15 BHC clusters. Then, 100 time-course DEmiRNA pairs with synergetic function were identified, and time-course DEmiRNAs and target genes interaction networks were constructed, in which 10 genes (AKT1, VEGFA, CTNNB1, IGF1, APP, PTEN, CDC42, BDNF, SOD2, and IFNG) with highest degrees were found. Furthermore, key genes were significantly enriched in neurotrophin signaling pathway.After SCI, miRNAs might collectively regulate target genes, facilitating or inhibiting self-repair. Modulation of these miRNAs might provide novel therapies for SCI treatment.N/A.

Objective To compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision. Methods We systematically searched Medline via PubMed, Embase, CNKI and the Cochrane Library Center Register to identify randomized controlled trials up to March 2018. Effect estimates were performed in random effect models. Mean neonate infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean heart rate were conducted to assessed the effect of analgesia. We found that the EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI 1.27–6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly higher than EMLA group, OR = 0.03, 95% CI 0.00–0.24, P = 0.001. The analysis did not show any significant differences in mean heart rate and the risk of edema and erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88–44.30, P = 0.06 & OR = 0.40, 95% CI 0.15–1.07, P = 0.07 & OR = 7.33, 95% CI 0.84–64.07, P = 0.07). Conclusion Based on the pooled results from the included studies, we found that DPNB was significantly more effective in pain relief as indicated by mean NIPS score than EMLA in infants during circumcision. However, use of DPNB significantly increased the risk of hematoma.

Multiple trauma can induce sepsis and organ failure, even threaten people’s lives. To further study the mechanisms of multiple trauma, we analyzed microarray of GSE5760. GSE5760 was downloaded from the Gene Expression Omnibus including a total of 58 peripheral blood transcriptome from patients without (WT, n = 30) and carrying (MUT, n = 28) the tumor necrosis factor (TNF) rs1800629 A variant. The differentially expressed genes (DEGs) were screened using the limma package in R and the Benjamin and Hochberg method in a multi-test package. Then, functional enrichment analysis of DEGs was performed. Also, transcription factors significantly related to DEGs were searched using WebGestalt and interaction network of transcription factors and DEGs were constructed using STRING online software. Furthermore, pathway enrichment analysis for the DEGs in the interaction network was conducted using KO-Based Annotation System (KOBAS). We screened 39 DEGs including 27 upregulated and 12 downregulated genes. The enriched functions were associated with biological process (BP) (such as response to hypoxia, P value = 0.039803), cell components (CC) (such as mitochondrial part, P value = 0.043857), and molecular function (MF) (such as structural constituent of ribosome, P value = 0.008735). Besides, RPS7 and RPL17 were associated with ribosome and participated in ribosome pathway. PPP2R2B was related to mitochondrion. KCNMA1, ALAS2 and SOCS3 were associated with hypoxia. Moreover, transcription factors of LEF1, CHX10, ELK1, SP1, and MAZ were significantly related to DEGs. RPS7, RPL17, PPP2R2B, KCNMA1, ALAS2, and SOCS3 might relate to multiple trauma. And TNF-α mutation could cause sepsis in patients with multiple trauma by changing the expression of these genes.