Oxytocinergic neurons, but not oxytocin, are crucial for male penile erection.

The cumulative evidence suggests that oxytocin is involved in the male sexual behaviors. However, no significant sexual impairments were observed in oxytocin gene knock-out (KO) mice, suggesting that oxytocin is not necessary for sexual behavior in male mice. To better understand the role of oxytocin in male erection, two types of oxytocin gene KO mice were created. In the first type, the oxytocin gene was deleted in the zygote, while in the second type, the oxytocin gene was mutated in adulthood by injecting the CRISPR/Cas9 AAVs. The results showed that disrupting the oxytocin gene at either the embryonic or adult stage did not affect erection, indicating that oxytocin is not necessary for penile erection. Pharmacologically, injecting oxytocin receptor agonist Carbetocin into the VTA of the oxytocin gene KO mice still evoked penile erection. By employing the Oxt-Ires-Cre mice, we found that specifically activating oxytocinergic neurons through chemogenetics strongly induced penile erection, while inhibiting these neurons blocked the erection responses. Furthermore, ablating PVN oxytocinergic neurons abolished the male erection response. In conclusion, although the neuropeptide oxytocin is not essential for male erection, the activity of oxytocinergic neurons is required. Our results might reflect the redundancy in the central nerve system in the sense that many signals contribute to the activation of oxytocinergic neurons to evoke penile erection during sexual behaviors.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

Icaritin and intratumoral injection of CpG treatment synergistically promote T cell infiltration and antitumor immune response in mice.

The development of combination therapy that can modulate the tumor immunosuppressive microenvironment is highly desirable for cancer immunotherapy. Icaritin (ICT), a hydrolytic product of icariin from genus Epimedium, has been used as an anti-cancer immunoregulatory agent for many types of cancers. Herein, we design a novel therapeutic strategy for mice melanoma that combines systemic administration of icaritin with intratumoral injection of unmethylated cytosine-guanine oligodeoxynucleotide (CpG). Icaritin induces tumor cell apoptosis and increases tumor immunogenicity. The combination of icaritin with CpG synergistically suppresses tumor growth and significantly prolonged survival time of B16F10 melanoma bearing mice. importantly, the anti-tumor effects of this combination strategy are associated with the reversing of immunosuppressive microenvironment through increased recruitment of functional DCs and tumor-associated macrophages (TAM) in tumors, leading to the infiltration of cytotoxic CD8+ T cells expressing elevated levels of IFN-γ and TNF-α. Furthermore, the combination of icaritin with CpG augments the anti-tumor immune response to anti-PD-1/CTLA-4 immune checkpoint blockade treatment. These results support the combination of icaritin with CpG as a novel strategy to elicit effective T cell-mediated antitumor immune response.

Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Understanding Responses of Soil Microbiome to the Nitrogen and Phosphorus Addition in Metasequoia glyptostroboides Plantations of Different Ages.

Nitrogen (N) and phosphorus (P) have significant effects on soil microbial community diversity, composition, and function. Also, trees of different life stages have different fertilization requirements. In this study, we designed three N additions and three P levels (5 years of experimental treatment) at two Metasequoia glyptostroboides plantations of different ages (young, 6 years old; middle mature, 24 years old) to understand how different addition levels of N and P affect the soil microbiome. Here, the N fertilization of M. glyptostroboides plantation land (5 years of experimental treatment) significantly enriched microbes (e.g., Lysobacter, Luteimonas, and Rhodanobacter) involved in nitrification, denitrification, and P-starvation response regulation, which might further lead to the decreasing in alpha diversity (especially in 6YMP soil). The P addition could impact the genes involved in inorganic P-solubilization and organic P-mineralization by increasing soil AP and TP. Moreover, the functional differences in the soil microbiomes were identified between the 6YMP and 24YMP soil. This study provides valuable information that improves our understanding on the effects of N and P input on the belowground soil microbial community and functional characteristics in plantations of different stand ages.

Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Systematic Evaluation of the Effect of Bedside Ward Round Checklist on Clinical Outcomes of Critical Patients.

Objective: To systematically evaluate the effect of bedside ward round checklists on the clinical outcomes of critical patients and thus provide a scientific and rational basis for decision-making in its clinical application. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang databases were searched to collect the literature studies about randomized controlled trials (RCTs) and cohort studies involving the effect of bedside ward round checklists on the clinical outcomes of critical patients, and the retrieval time limit was from the establishment of the database to August 2019. After two researchers independently screened the literature studies, extracted the literature data, and evaluated the risk of bias in included studies, meta-analysis was carried out by using Stata 12.0 software. Results: Two RCTs and nine cohort studies were included in this study. The results of meta-analysis showed that compared with the ordinary bedside ward round, the application of checklist in bedside ward round could shorten the ICU hospitalization time (standardized mean difference (SMD) = - 0.37, 95% CI (- 0.78, 0.04), P ≤ 0.001) and mechanical ventilation time (SMD = - 0.24, 95% CI (- 0.44, -0.04), P = 0.037) and reduce the incidence of ventilator-associated pneumonia (VAP) (SMD = 0.61, 95% CI (0.38, 0.99), P = 0.057) in critical patients. However, there were no significant differences in central venous catheter (CVC) retention time and incidence and mortality of deep venous thrombosis (DVT) between ordinary ward round and bedside ward round checklist. Conclusion: The existing evidence shows that compared with the ordinary ward round, the application of bedside ward round checklists can shorten ICU hospitalization time and mechanical ventilation time and reduce VAP incidence and ICU mortality in critical patients. However, due to the limitations of the quality of the included studies, the above conclusions need to be verified with more high-quality studies.

Icaritin promotes tumor T-cell infiltration and induces antitumor immunity in mice.

Icaritin, a hydrolytic product of icariin isolated from traditional Chinese herbal medicine genus Epimedium, has many pharmacological and biological activities. Here, we show that icaritin can effectively decrease tumor burden of murine B16F10 melanoma and MC38 colorectal tumors in a T-cell dependent manner. The treatment effects are associated with increased CD8 T-cell infiltration and increased effector memory T-cell frequency. In vivo depletion of CD8 T cell using an anti-CD8 monoclonal antibody abolished the antitumor effect, which supports the critical role of CD8 T cells during icaritin treatment. By analyzing immune cells in the tumor tissue, we found reduced frequency of CD11b+ Gr1+ myeloid-derived suppression cells (MDSCs) infiltration and downregulation of PD-L1 expression on MDSCs after icaritin treatment. This was not limited to MDSCs, as icaritin also decreased the expression of PD-L1 on neutrophils. Importantly, the combination of anti-PD-1/CTLA-4 and icaritin significantly enhances antitumor ability and increases the efficacy of either treatment alone. Our findings reveal that icaritin induces antitumor immunity in a CD8 T-cell-dependent way and justify further investigation of combining immune checkpoint therapy to icaritin-based antitumor therapy.

Improvement of telescope resolution using a diffractive phase modulater.

Metasurface, fluorescent microscopy and scanning near-field optical microscopy can improve the resolution of microscopes remarkably, while the resolution of the telescope remains unimproved constrained by its giant objective lenses and distant targets. Here we put forward a way to raise the resolution of telescopes simply by adding a binary optical thin surface around its focal plane. Simulation results show that the surface can raise the image quality in the Cassegrain and Kepler telescope. By nano-lathe, we fabricated a designed binary surface and experiment it in the Kepler telescope. The results are consistent with those of simulation results. More details of the calibrated target are resolvable on the image plane after applying the binary optical surface. It proves that the binary optic surface can make contribute to the resolution of the telescope, thus is beneficial in astronomy, military surveillance field.

Carbon fabric supported 3D cobalt oxides/hydroxide nanosheet network as cathode for flexible all-solid-state asymmetric supercapacitor.

Owing to a lack of electroactive sites and poor conductivity, Co oxides/hydroxides nanosheet network electrodes usually show low experimental capacity, hardly meeting the demand for high energy density needed for an asymmetric supercapacitor. Herein, we demonstrate a surface capacity enhancement of a 3D cobalt oxides/hydroxides nanosheet network cathode through a simple cyclic voltammetry electro-deposition method. By optimizing the electro-deposition parameters, the as-prepared Co oxides/hydroxides nanosheet network electrode delivers a significantly high capacity of 427 C g-1 at the current density of 1 A g-1 and excellent rate ability of 79.8% at the current density of 10 A g-1, as well as outstanding cycling life. A detailed voltammetric analysis using the power-law relationship and Trasatti's method shows that both the large surface area, high pore volume and polycrystalline nature contribute to the enhancement of the surface capacity. In addition, the assembled asymmetric all-solid-state supercapacitor also presents a volume energy density of 2.78 mW h cm-3 at a power density of 14 mW cm-3 and excellent cycling stability. In addition, our prepared asymmetric supercapacitor shows super flexibility and was used to light up a heart-shaped logo. This work may provide valuable insights into the design and fabrication of electrode materials with improved capacity and rate ability.

Attempting a Laparoscopic Approach in Patients Undergoing Left-Sided Colorectal Surgery Who Have Had a Previous Laparotomy: Is it Feasible?

BACKGROUND: The feasibility of a laparoscopic approach in patients who have had a prior laparotomy (PL) remains controversial. We hypothesized that laparoscopic colorectal resection was safe and feasible in patients with previous open abdominal surgery. METHODS: A retrospective review (2007-2015) of all patients undergoing laparoscopic resection for sigmoid and rectal adenocarcinoma with or without prior midline laparotomy (NPL) was performed. Primary endpoints included conversion and perioperative morbidity. Secondary endpoints included length of stay and perioperative outcomes. Demographics, surgical history, oncologic staging, and short-term outcomes were reviewed. RESULTS: We identified 211 patients, of whom 33 (15.6%) had a prior laparotomy. Significantly more patients in the PL group were female (76.2 vs. 52.8%, p = 0.004). Patients with PL were of similar age to NPL patients (69.3 vs. 62.5, p = 0.09), and comorbidities, tumor staging, and neoadjuvant therapy were comparable between groups (all p > 0.05). Additional trocar placement was significantly higher in PL group (33.3 vs. 17.4%, p = 0.03), while conversion rate did not reach statistical significance (24.2 vs. 12.9%, p = 0.08). The postoperative complication rate was comparable between PL and NPL patients (33.3 vs. 25.3%, respectively, p = 0.2). CONCLUSIONS: Prior laparotomy should not be a contraindication to patients undergoing laparoscopic colorectal surgery, though surgeons should anticipate a higher likelihood of conversion to open.

"Candy cane syndrome:" an underappreciated cause of abdominal pain and nausea after Roux-en-Y gastric bypass surgery.

BACKGROUND: "Candy cane" syndrome (a blind afferent Roux limb at the gastrojejunostomy) has been implicated as a cause of abdominal pain, nausea, and emesis after Roux-n-Y gastric bypass (RYGB) but remains poorly described. OBJECTIVES: To report that "candy cane" syndrome is real and can be treated effectively with revisional bariatric surgery SETTING: All patients underwent "candy cane" resection at University Hospitals of Cleveland. METHODS: All patients who underwent resection of the "candy cane" between January 2011 and July 2015 were included. All had preoperative workup to identify "candy cane" syndrome. Demographic data; pre-, peri-, and postoperative symptoms; data regarding hospitalization; and postoperative weight loss were assessed through retrospective chart review. Data were analyzed using Student's t test and χ2 analysis where appropriate. RESULTS: Nineteen patients had resection of the "candy cane" (94% female, mean age 50±11 yr), within 3 to 11 years after initial RYGB. Primary presenting symptoms were epigastric abdominal pain (68%) and nausea/vomiting (32%), particularly with fibrous foods and meats. On upper gastrointestinal study and endoscopy, the afferent blind limb was the most direct outlet from the gastrojejunostomy. Only patients with these preoperative findings were deemed to have "candy cane" syndrome. Eighteen (94%) cases were completed laparoscopically. Length of the "candy cane" ranged from 3 to 22 cm. Median length of stay was 1 day. After resection, 18 (94%) patients had complete resolution of their symptoms (P<.001). Mean body mass index decreased from 33.9±6.1 kg/m2 preoperatively to 31.7±5.6 kg/m2 at 6 months (17.4% excess weight loss) and 30.5±6.9 kg/m2 at 1 year (25.7% excess weight loss). The average length of latest follow-up was 20.7 months. CONCLUSION: "Candy cane" syndrome is a real phenomenon that can be managed safely with excellent outcomes with resection of the blind afferent limb. A thorough diagnostic workup is paramount to proper identification of this syndrome. Surgeons should minimize the size of the blind afferent loop left at the time of initial RYGB.

Evaluating surgical management and outcomes of colovaginal fistulas.

BACKGROUND: Colovaginal fistula is a rare condition associated with significant morbidity. The literature characterizing colovaginal fistula repair is sparse. We present our institution's experience treating colovaginal fistulas. METHODS: A retrospective review of all patients surgically treated for colovaginal fistula between 2005 and 2015 was performed. Patient demographics, intra-operative details, and post-operative outcomes were reviewed. RESULTS: We identified 27 patients with a mean age of 71 (±13) and BMI of 30 (±9). The most common etiology for fistula was diverticulitis (n = 24, 89%). A laparoscopic approach was initiated in 19 patients (70%) and an open approach for 8 (30%) with 8 patients converted from laparoscopy to open (42%). At a mean follow-up of 18 months (±21), there were no recurrences. CONCLUSION: We present one of the largest series of the surgical management of colovaginal fistulas. Although our conversion rate was high, we recommend a laparoscopic approach be utilized when feasible.

Using Modified Frailty Index to Predict Safe Discharge Within 48 Hours of Ileostomy Closure.

BACKGROUND: Enhanced recovery pathways allow for safe discharge and optimal outcomes within 48 hours after ileostomy closure. Unfortunately, some patients undergoing ileostomy closure have prolonged hospital stays. We have shown previously that the Modified Frailty Index can help predict patients who will fail early discharge after laparoscopic colorectal surgery. OBJECTIVE: The purpose of this study was to use the Modified Frailty Index to identify patients who were safe for early discharge after ileostomy closure. DESIGN: This was a retrospective review. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Patients who underwent ileostomy closure (2006-2015) were stratified into early (≤48 hours) and late discharge groups. MAIN OUTCOME MEASURES: The Modified Frailty Index, morbidity, and readmission rates were measured. RESULTS: A total of 272 patients undergoing ileostomy closure were evaluated. Overall length of stay was 3.64 days (±3.23 days), with 114 patients (42%) discharged within 48 hours. Sex, age, and ASA scores were similar between early and later discharge groups (p > 0.2). Univariate logistic regression demonstrated that a Modified Frailty Index score of 0 was associated with early discharge (p = 0.03), whereas a Modified Frailty Index score ≤1 and ≤2 were not. There was no significant association between the Modified Frailty Index and complication or readmission rates. Postoperative complications occurred in 39 patients (14.3%), and 1 patient died secondary to an anastomotic leak. Fifteen patients (5.5%) were readmitted within 30 days. Readmission rate within 30 days was 3.2%, with a Modified Frailty Index score of 0, 6.1% for a Modified Frailty Index score of <1, and 5.9% for a Modified Frailty Index score of <2, for which there was not an association based on univariate logistic regression (Modified Frailty Index = 0, p = 0.13; <1, p = 0.55; <2, p = 0.53). LIMITATIONS: The study was limited by nature of being a retrospective review. CONCLUSIONS: Patients undergoing ileostomy closure with a Modified Frailty Index score of 0 are associated with higher rates of discharge within 48 hours of ileostomy closure surgery than those with a higher Modified Frailty Index, without higher readmission rates. This information can be helpful to better manage patient and resource use expectations for the duration of inpatient recovery.

Alvimopan in the setting of colorectal resection with an ostomy: To use or not to use?

BACKGROUND: Postoperative ileus (POI) is a major cause of morbidity, increased length of stay (LOS) and hospital cost after colorectal surgery. Alvimopan is a µ-opioid antagonist used to accelerate upper and lower gastrointestinal function after bowel resection. We hypothesized that alvimopan would reduce LOS in patients undergoing colorectal resection with stoma, a situation that has not been evaluated. METHODS: A retrospective review (2010-2015) identified 58 patients who underwent colorectal resection for benign or malignant disease with stoma creation and received alvimopan. They were case-matched to 58 non-alvimopan patients based on age, BMI, baseline comorbidities, stoma type created and surgical approach. We compared overall LOS, incidence of POI and other postoperative complications. RESULTS: There were equal numbers of laparoscopic (N = 18) and open resections (N = 40) in the alvimopan group and non-alvimopan group. There were also equal numbers of patients with an ileostomy (N = 37) or colostomy (N = 21) in each group. Overall, 41 patients underwent resection for malignant disease in the alvimopan group compared to 37 in the non-alvimopan group. There was a significant reduction in median LOS overall (alvimopan 5 (4-7) versus control 6 (4.75-9.25) days, P = 0.03). While the 6-day median LOS was similar for patients undergoing ileostomy creation (P = 0.25), alvimopan patients had a 3-day decreased median LOS that approached statistical significance (P = 0.06). The overall 30-day complication rate was higher in the control group (41.4 vs. 51.7%, P = 0.26), but the readmission rate within 30 days was higher in the alvimopan group (19 vs. 13.8%, P = 0.45). Neither of these differences reached statistically significance. CONCLUSION: The use of alvimopan in patients undergoing colorectal resection with stoma is associated with a significantly shorter LOS, but the increased readmission rate warrants further study. Based on these data, alvimopan should be evaluated in a controlled setting for patients undergoing colorectal resection with colostomy creation.

Comparative analysis of biologic versus synthetic mesh outcomes in contaminated hernia repairs.

BACKGROUND: Contaminated operative fields pose significant challenges for surgeons performing ventral hernia repair. Although biologic meshes have been utilized increasingly in these fields, recent evidence suggests that synthetic meshes represent a viable option. We analyzed the outcomes of biologic and synthetic mesh utilized in patients undergoing major ventral hernia repair in clean-contaminated/contaminated fields. METHODS: We conducted a multicenter, retrospective review of patients undergoing open ventral hernia repair in clean-contaminated/contaminated fields using biologic or synthetic mesh. Patient and hernia details were characterized. Primary outcomes included 90-day surgical site event, surgical site infection, and hernia recurrence. RESULTS: A total of 126 patients undergoing major ventral hernia repair in clean-contaminated/contaminated fields (69 biologic and 57 synthetic meshes) were analyzed. Groups were similar in both patient and hernia characteristics. There were 13 (22.8%) surgical site events in the synthetic cohort compared to 29 (42.0%) in the biologic cohort, P = .024. Similarly, surgical site infections were less frequent in the synthetic group, with 7 (12.3%) vs 22 (31.9%), P = .01. With a mean follow-up of 20 months, there were more recurrences in the biologic group: 15 (26.3%) vs 4 (8.9%) in the synthetic group, P = .039. CONCLUSION: The choice of mesh for clean-contaminated/contaminated ventral hernia repair remains debatable. We demonstrated that using synthetic sublay mesh resulted in a significantly lower wound morbidity and more durable outcomes versus a similar cohort of biologic repairs. This is likely secondary to improved bacterial clearance and faster integration of macroporous synthetics. Overall, our findings not only support suitability of synthetic mesh in contaminated settings but also challenge the purported advantage of biologics in clean-contaminated/contaminated ventral hernia repairs.

Effectiveness of Valsartan/Amlodipine Single-pill Combination in Hypertensive Patients With Excess Body Weight: Subanalysis of China Status II.

Obesity is a major global health concern and is associated with hypertension. However, there is a lack of studies evaluating the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy. To evaluate this effectiveness and its association with obese categories, we performed a prespecified subanalysis and a post hoc analysis of patients from China status II study. In this subanalysis, 11,289 and 11,182 patients stratified by body mass index (BMI) and waist circumference (WC), respectively, were included. Significant mean sitting systolic and diastolic blood pressure (BP) reductions from baseline were observed at week 8 across all BMI and WC subgroups (P < 0.001). The percentages of patients achieving BP control were 65.2%, 62.8%, and 64.5% (men 64.5% and women 64.4%) in the overweight, obesity, and abdominal obesity subgroups, respectively. The positive association between BP control and obese categories could only be found in subgroups stratified by BMI other than WC. Our study demonstrated the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy, and its effectiveness was better associated with BMI than WC.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis.

BACKGROUND: Some studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent. OBJECTIVE: In order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension. METHODS: Eligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models. RESULTS: Regarding the GSTM1 null/present genotype, 14 case-control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case-control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected. CONCLUSION: This meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.

Interaction between the movement protein of barley yellow dwarf virus and the cell nuclear envelope: role of a putative amphiphilic alpha-helix at the N-terminus of the movement protein.

The open reading frame 4 (ORF 4) gene product of barley yellow dwarf virus (BYDV) may act as a movement protein (MP) by assisting the transport of viral genomic RNA across the nuclear envelope (NE) of host plant cells. To investigate interactions between BYDV MP and the NE, wild-type and mutant open reading frame (ORF 4)-green fluorescent protein (GFP) fusion cistrons were expressed in insect cells. A fusion protein expressed by the wild-type ORF 4-GFP cistron associated with the NE and caused protrusions from its surface. The fusion protein expressed by the mutant ORF 4-GFP cistron lacked a putative amphiphilic alpha-helix at its N-terminus and although associating with the NE, showed decreased levels of protrusions. A peptide homologue of this putative alpha-helix induced an increase of 7 degrees C in the phase transition temperature of dimyrystoyl phosphatidylserine (DMPS) membranes, accompanied by a decrease in membrane fluidity, but exhibited no significant interaction with either dimyristoyl phosphatidylcholine (DMPC) or dimyristoyl phosphatidylethanolamine (DMPE) membranes. These results strongly support the view that BYDV MP may interact with the NE to help transport viral genomic RNA into the nuclear compartment. This function of BYDV MP appears to involve protrusions on the surface of the NE and may require the presence of an N-terminal amphiphilic alpha-helix, which is speculated to destabilize membranes, thereby assisting the entry of BYDV-GAV into the nuclear compartment.