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Ruo Du,1 Ting Zhong,1 Wei-Qiang Zhang,1 Ping Song,1 Wen-Ding Song,1 Yang Zhao,1 Chao-Wang,1 Yi-Qun Tang,3 Xuan Zhang,1,2 Qiang Zhang1,2 1Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 3Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC)-modified sterically stabilized liposomes (SSLs) containing conjugated linoleic acid–paclitaxel (CLA-PTX). The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy- and lipid raft-mediated endocytosis played a key role in the liposomes’ cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84±0.17 µg/g) and 4 hours (1.17±0.28 µg/g) was 2.3- and 2.0-fold higher than that of CLA-PTX solution at 1 hour (0.79±0.06 µg/g) and 4 hours (0.58±0.04 µg/g). The value of the area under the curve for the first 24 hours in the tumors of iRGD-SSL-CLA-PTX-treated mice was significantly higher than that in the SSL-CLA-PTX and CLA-PTX solution-treated groups (P

Background: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown., Methods: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination., Results: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices., Conclusions: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Background: The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring systems orchestrate improvement in predictive accuracy. Methods: 3,212 patients with CAP were recruited to two observational prospective cohort studies. Three bettered scoring systems were derived from the corresponding well-established and extensively used pneumonia-specific severity scoring systems, i.e. pneumonia severity index, minor criteria and CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure, and age ≥65 years) score, with the updating cut-off values for tachypnea and low blood pressure. Cronbach α was employed to determine construct validity. Discrimination was valued by calculating the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). Results: Respiratory rate ≥22/min and systolic blood pressure ≤100 mm Hg were performed better than respiratory rate ≥30/min and hypotension for predicting mortality in the derivation cohort, respectively (AUROC, 0.823 vs 0.519, 0.688 vs 0.622; NRI, 0.61, 0.13). Bettered scoring systems orchestrated higher convergences, indicated by greater Cronbach α and more decrease in Cronbach α if the updating cut-off values were deleted. The six scoring systems agreed well with one another. Bettered- pneumonia severity index, minor criteria and CURB-65 score showed higher associations with severity and mortality rates and demonstrated greater predictive accuracies for mortality compared with the corresponding original systems (AUROC, 0.939 vs 0.883, 0.909 vs 0.871, 0.913 vs 0.859; NRI, 0.113, 0.076, 0.108; respectively). The validation cohort confirmed a similar pattern. Conclusions: Updating cut-off values of severity scoring systems for CAP orchestrate improvement in predictive accuracy, suggesting that it may facilitate the rationalization of clinical triage decision-making and further reduce mortality. The current studies provide the first known prospective evidence of potential benefit of the updating cut-off values of severity scoring systems for CAP in predictive accuracy.Key messagesUpdating cut-off values were performed better for predicting mortality.Bettered scoring systems orchestrated higher convergences.Bettered scoring systems demonstrated greater predictive accuracies for mortality.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with an unclear pathogenesis. This study aimed to elucidate the function and potential mechanisms of TUG1 in IPF progression. Cell viability and migration were detected by CCK-8 and transwell assays. Autophagy, fibrosis, or EMT-related proteins were measured by Western blotting. Pro-inflammatory cytokine levels were assessed by ELISA kits. The subcellular localization of TUG1 was observed by FISH assay. RIP assay detected the interaction between TUG1 and CDC27. TUG1 and CDC27 was up-regulated in TGF-β1-induced RLE-6TN cells. TUG1 depletion suppressed pulmonary fibrosis via attenuating inflammation, EMT, inducing autophagy and inactivating PI3K/Akt/mTOR pathway in vitro and in vivo. TUG1 knockdown prevented CDC27 expression. TUG1 silencing ameliorated pulmonary fibrosis by reducing CDC27 expression and inhibiting PI3K/Akt/mTOR pathway.

Background: Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood., Aim: We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis., Methods: Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe 2+ ), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins., Outcomes: At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe 2+ , and ROS., Results: PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe 2+ , MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death., Clinical Translation: This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction., Strengths and Limitations: In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed., Conclusion: Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis., Competing Interests: None

Objective: To investigate the effect of biflavonoid 4'-O-methylochnaflavone (MF) on palmitic acid-induced endothelial dysfunction in rat cavernous endothelial cells (RCECs)., Methods: The isolated RCECs were commercially available and randomly divided into four groups: normal+BSA group (NC group), palmitic acid (PA) group, MF group, and icariside Ⅱ (ICA Ⅱ) group. The protein expression levels of protein kinase B (PKB/AKT) and endothelial nitric oxide synthase (eNOS) in each group were evaluated via Western blotting. The differences in the intracellular nitric oxide of RCECs treated by MF or ICA Ⅱ were detected by DAF-FM DA that served as a nitric oxide fluorescent probe. Effects of MF and ICA Ⅱ on cell proliferation of PA-stimulated RCECs were determined via CCK-8 assay., Results: The content of nitric oxide in RCECs was significantly increased after the treatment of MF and ICA Ⅱ in comparison with the NC group ( P < 0.05). Moreover, compared with ICA Ⅱ group, MF demonstrated a more obvious effect in promoting nitric oxide production ( P < 0.05). Compared with the NC group, the expression levels of eNOS and AKT in the PA group were significantly decreased, indicating that a model for simulating the high-fat environment in vitro was successfully constructed ( P < 0.05). Meanwhile, the intervention of MF and ICA Ⅱ could effectively increase the expression of eNOS and AKT, suggesting that MF and ICA Ⅱ could promote the recovery of endothelial dysfunction caused by high levels of free fatty acids ( P < 0.05). The results of CCK-8 assays showed that PA could significantly reduce the proli-feration ability of RCECs ( P < 0.05). Furthermore, the decreased cell viability induced by PA was significantly elevated by treatment with ICA Ⅱ and MF ( P < 0.05)., Conclusion: In RCECs, MF and ICA Ⅱ could effectively increase the content of nitric oxide. The down-regulation of the expression of proteins associated with the AKT/eNOS pathway after PA treatment revealed that this pathway was involved in the development of endothelial dysfunction, which could be effectively reversed by MF and ICA Ⅱ. In addition, the cell proliferation ability was significantly decreased following PA treatment, but MF and ICA Ⅱ could restore the above changes. Overall, biflavonoid MF has an obvious repairing effect on PA-stimulated endothelial dysfunction.

Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction. Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay. Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway. Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Tan, Song, Song, Yuan, Xin, Wang, Fang and Guan.)

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level., Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB., Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED., Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fang, Tan, Song, Gu, Pan, Yang, Song, Yuan, Peng, Zhang, Xin, Li and Guan.)

Objective: Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level., Methods: Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL., Results: The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups ( P < 0.001). The incidences had no difference between the VC and OA groups ( P =0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [ OR 0.492 (95% confidence interval 0.288-0.840)]., Conclusion: NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.

The synthesis of lightweight yet strong-ductile materials has been an imperative challenge in alloy design. In this study, the CoCrNi-based medium-entropy alloys (MEAs) with added Al and Si were manufactured by vacuum arc melting furnace subsequently followed by cool rolling and anneal process. The mechanical responses of CoCrNiAl 0.1 Si 0.1 MEAs under quasi-static (1 × 10 -3 s -1 ) tensile strength showed that MEAs had an outstanding balance of yield strength, ultimate tensile strength, and elongation. The yield strength, ultimate tensile strength, and elongation were increased from 480 MPa, 900 MPa, and 58% at 298 K to 700 MPa, 1250 MPa, and 72% at 77 K, respectively. Temperature dependencies of the yield strength and strain hardening were investigated to understand the excellent mechanical performance, considering the contribution of lattice distortions, deformation twins, and microbands. Severe lattice distortions were determined to play a predominant role in the temperature-dependent yield stress. The Peierls barrier height increased with decreasing temperature, owing to thermal vibrations causing the effective width of a dislocation core to decrease. Through the thermodynamic formula, the stacking fault energies were calculated to be 14.12 mJ/m 2 and 8.32 mJ/m 2 at 298 K and 77 K, respectively. In conclusion, the enhanced strength and ductility at cryogenic temperature can be attributed to multiple deformation mechanisms including dislocations, extensive deformation twins, and microbands. The synergistic effect of multiple deformation mechanisms lead to the outstanding mechanical properties of the alloy at room and cryogenic temperature.

Objective: To investigate the effect of simultaneous bone marrow stimulation in the treatment of osteochondral lesions of the talus (OLTs) on arthroscopic repair of anterior talofibular ligament. Methods: The clinical data of 33 patients with ankle instability treated by operation in Sun Yat-Sen Memorial Hospital from January 2018 to December 2019 were retrospectively analyzed. There were 20 males and 13 females with a mean age of (31±9) years. According to the type of surgery, the patients were divided into two groups: ligament repair group (arthroscopic anterior talofibular ligament repair) and bone marrow stimulation group (arthroscopic anterior talofibular ligament repair+talus microfracture). Visual analogue scale (VAS), American Orthopedic Foot And Ankle Society (AOFAS) score, time to return to work and time to return to sport were compared between the two groups. Results: In the ligament repair group, the preoperative VAS score and the AOFAS score was 5.0±1.9 and 72.4±9.0, respectively, and it was 1.1±1.6 and 95.5±5.2 at the last follow-up, respectively. In the bone marrow stimulation group, the preoperative VAS score and the AOFAS score was 5.8±1.9 and 64.8±12.6, respectively, and it was 1.8±1.5 and 93.1±5.6 at the last follow-up, respectively. The scores of VAS and AOFAS were significantly improved in both groups after the operation, but there was no significant difference between the two groups (both P >0.05). There was no significant difference in time to return to work and return to sport between the two groups (both P >0.05). Conclusion: When repairing the anterior talofibular ligament under arthroscopy, simultaneous bone marrow in the treatment of osteochondral lesions of the talus does not affect the postoperative functional recovery and the time to return to work/sport, and satisfactory clinical results also can be obtained.

Background: The objective of this study is to examine the effectiveness and safety of electroacupuncture (EA) in the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI)., Methods: All potential studies will be retrieved from the electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, CBM, and China National Knowledge Infrastructure from origin of each database up to January 31, 2020. Additionally, we will check other resources, such as Google scholar, dissertations, conference proceedings, and reference lists of included studies. No language and publication date limitations will be considered in the literature resources search. All randomized controlled trials using EA for the treatment of UI in patients with SCI will be included. Two independent investigators will perform study selection, data extraction and study quality assessment. If any conflicts occur, we will invite a third investigator to solve them. Cochrane risk of bias will be used for study quality assessment, and RevMan 5.3 software will be employed for statistical analysis., Results: This study will summarize the most recent evidence to assess the effectiveness and safety of EA for the treatment of UI in patients with SCI., Conclusion: The results of this study will provide helpful evidence to determine whether EA is effective and safety for the treatment of UI in patients with SCI or not., Prospero Registration Number: PROSPERO CRD42020165562.

Background: This systematic review will assess the effectiveness and safety neuromuscular electrical stimulation (NMES) for cancer pain (CP) in children with osteosarcoma., Methods: This systematic review protocol will retrieve the following electronic databases from inception to June 1 in Cochrane Library, MEDLINE, EMBASE, Web of Science, Scopus, CNKI, and VIP database. Manual head-searching of reference lists and conference proceedings will be performed to further examine the articles of interest. No restrictions will be applied to language and publication status. We will utilize a 3-stage approach to scan titles, abstracts, and full-text studies against all eligibility criteria, and collect data from included trials. Study quality will be evaluated by the Cochrane Risk of Bias Tool. If possible, we will narratively summarize study results and carry out meta-analysis., Results: This study will recapitulate the present high quality trials to appraise the effectiveness and safety of NMES for CP in children with osteosarcoma., Conclusion: The findings of this study will present evidence to determine whether NMES is effective and safe for CP in children with osteosarcoma.

Background: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis., Methods: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices., Results: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices., Conclusions: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.

Background: Post-stroke shoulder-hand syndrome (PSSHS) is one of the most common sequelae in patients with stroke. Previous studies have reported that extracorporeal shock wave (EPSW) has been used to treat this condition effectively. However, its conclusions are still inconsistent. Therefore, this study will provide evidence to systematically assess the effectiveness and safety of EPSW for the treatment of PSSHS., Methods: We will comprehensively search relevant randomized controlled trials (RCTs) assessing the effectiveness and safety of EPSW for the treatment of PSSHS in the following databases from their start to February 1, 2020 without language and publication date limitations: Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, PsycINFO, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. For trials that meet all inclusion criteria, 2 researchers will independently extract the data from them and appraise study quality by Cochrane risk of bias. Any differences will be solved by discussion with the help of another researcher. All data will be performed and analyzed using RevMan 5.3 software., Results: We will summarize up-to-date high quality RCTs to evaluate the effectiveness and safety of EPSW for the treatment of PSSHS., Conclusions: This study will provide a comprehensive evidence summary to determine whether EPSW is effective and safety for the treatment of PSSHS or not., Prospero Registration Number: PROSPERO CRD42020175630.

Background: This study will explore the efficacy and safety of intrathecal baclofen bolus (IBB) on neuropathic pain (NPP) in patients with spinal cord injury (SCI)., Methods: All potential literatures of IBB on NPP in patients with SCI will be searched from the following electronic databases from inauguration to the January 31, 2020: PUBMED, EMBASE, Cochrane Library, Web of Science, Chinese Scientific Journal Database Information, WANGFANG, and China National Knowledge Infrastructure. In addition, we will search other sources, such as dissertations and reference lists of included trials. There are no restrictions of language and publication status in searching all literature sources. The quality of each eligible trial will be assessed using Cochrane risk of bias tool, and publication bias will be checked using a funnel plot and Egger test. Statistical analysis will be conducted using RevMan 5.3 software., Results: This study will scrutinize the efficacy and safety of IBB on NPP in patients with SCI through pain intensity of NPP, spasticity, walking ability, health-related quality of life, duration of stay at hospital (days), incidence of adverse event, and mortality rate., Conclusions: The findings of this study will present helpful evidence to judge whether IBB is effective on NPP in patients with SCI or not., Study Registration Number: INPLASY202040192.

Background: The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS items to develop a weighted ESS scoring system improve the accuracy of the AHI prediction? It is warranted to explore the intriguing hypotheses., Methods: Seven hundred fifty-six adult patients with suspicion of obstructive sleep apnoea syndrome (OSAS) were prospectively recruited to a derivation cohort. This was tested against a prospective validation cohort of 810 adult patients with suspected OSAS. Each ESS item's increased odds ratio for the corresponding AHI was calculated using univariate logistic regression. The receiver operating characteristic curves were created and the areas under the curves (AUCs) were calculated to illustrate and compare the accuracy of the indices., Results: The higher the ESS item-score, the closer the relationship with the corresponding AHI. The odds ratios decreased as a result of the increased AHI. The ESS items were of unequal weight in predicting the corresponding AHI and a weighted ESS was developed. The coincidence rates with the corresponding AHI, body mass indices, and neck circumferences rose as the scores increased, whereas nocturnal nadir oxygen saturations decreased, and the weighted ESS was more strongly associated with these indices, compared with the ESS. The capability in predicting the patients without OSAS or with severe OSAS was strong, especially the latter, and the weighted ESS orchestrated manifest improvement in screening the patients with simple snoring. The patterns of sensitivities, specificities, and Youden's indices of the four ranks of weighted ESS for predicting the corresponding AHI were better than those of the ESS, and the AUCs of weighted ESS were greater than the corresponding areas of ESS in the two cohorts., Conclusions: The weighted ESS orchestrated significant improvement in predicting the AHI, indicating that the capability in predicting the patients without OSAS or with severe OSAS was strong, which might have implications for clinical triage decisions to prioritize patients for polysomnography.

The objective of this study was to explore the diagnostic value of the bronchoalveolar lavage fluid galactomannan (BALF GM) test for chronic respiratory disease with pulmonary aspergillosis and to establish the optimal cutoff value. Samples from a total of 309 chronic respiratory disease patients seen at the respiratory medicine department of Peking University Shenzhen Hospital from September 2016 to September 2019 were analyzed. According to the diagnostic criteria, we divided the patients into a case group ( n  = 79, comprising 25 proven cases and 54 probable cases) and a control group ( n  = 230). Bronchoalveolar lavage fluid was collected, and the BALF GM test results were analyzed. A nonparametric rank sum test showed that the mean rank of the case group was 255.30, which was higher than that of the control group (120.55). The Z-value was -11.567 ( P = 0.000), indicating that the general distributions of BALF GM differed between the two groups. A BALF GM cutoff value of 0.88 showed the highest diagnostic efficacy for pulmonary aspergillosis. The sensitivity, specificity, positive predictive value, and negative predictive value were 77.2%, 93%, 79.2%, and 92.2%, respectively. As the cutoff value increased, the specificity and sensitivity of the BALF GM test increased and decreased, respectively. The BALF GM test can be used confirm the diagnosis of patients with pulmonary aspergillosis and chronic respiratory disease. The optimum BALF GM cutoff value is 0.88., (Copyright © 2020 American Society for Microbiology.)

Humanacellular dermal matrix (HADM) is widely used in the field of burn wound repair and tissue engineering plastic surgery. HADM is manufactored by physical and chemical decellular process to remove the antigenic components that might cause immune rejection in dermis.The extracellular matrix of three-dimensional cell scaffold structure with collagen fibers had been used for wound repair and tissue regeneration, while HADM characterized with low absorption rate after implantation and strong ability to induce angiogenesis in host tissue. Studies reported that after the HADM was implanted into the patient, the host cells, such as fibroblasts and myofibroblasts, as well as lymphocytes, macrophages, granulocytes and mast cells, rapidly infiltrated the graft. The connective tissue and neovascularization were then formed within the HADM three-dimensional cell scaffold, the lymphatic system also appears after vascular reconstruction. Traditional urethral reconstruction using autologous skin flaps has some defects, such as complexity of the technology, risk of necrosis of the skin flaps after transplantation, and failure to achieve functional repair of the urethral epithelium. It has been reported that using HADM to reconstruct the urethra in patients with urethral stricture, hypospadias and bladder-vaginal fistula, showed promising results. Others have reported the experience of using HADM to repair and reconstruct congenital classic bladder exstrophy. HADM has also been used for tissue repair in patients with penile skin defect caused by Fonier's gangrene and hidradenitis suppurativa, and implanted under Bucks' fascia to enlarge the penis. The report of HADM implantation for treating premature ejaculation also deserves attention. Researchers found that HADM implantation can form a tissue barrier between the skin and corpus cavernosum, which can effectively reduce penile sensitivity and treat premature ejaculation. The safety and effectiveness of HADM implantation in the treatment of premature ejaculation need to be further standardized by data from multi-center, large-sample clinical studies. In summary, HADM is the extracellular matrix and three-dimensional cell scaffold of human dermis. As a new type of tissue repair material, new blood vessels are formed actively after implantation, which shows good histocompatibility. HADM has shown increasingly broad application prospects in treatment of genitourinary diseases including penis, urethra and bladder diseases. HADM has also been used in the treatment of premature ejaculation in recent clinical studies, and its long-term safety and efficacy need to be further investigated.

Background: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis., Methods: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO 2 /FiO 2  ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others., Results: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm., Conclusions: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.

It is not clear whether the IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified or even be modified to orchestrate improvements in predicting mortality.A retrospective cohort study of 1230 CAP patients was performed to simplify and to modify the scoring system by excluding 4 noncontributory or infrequent variables (leukopenia, hypothermia, hypotension, and thrombocytopenia) and by excluding these variables and then adding age ≥65 years, respectively. The simplification and modification were tested against a prospective 2-center validation cohort of 1409 adults with CAP.The increasing numbers of IDSA/ATS, simplified, and modified minor criteria present in the retrospective cohort were positively associated with the mortality, showing significant increased odds ratios for mortality of 2.711, 4.095, and 3.755, respectively. The validation cohort confirmed a similar pattern. The sensitivity, specificity, positive predictive value, and Youden index of modified minor criteria for mortality prediction were the best pattern in the retrospective cohort. High values of corresponding indices were confirmed in the validation cohort. The highest accuracy of the modified version for predicting mortality in the retrospective cohort was illustrated by the highest area under the receiver operating characteristic curve of 0.925 (descending order: modified, simplified, and IDSA/ATS minor criteria). The validation cohort confirmed a similar paradigm.The IDSA/ATS minor criteria could be simplified to 5 variables and then be modified to orchestrate improvements in predicting mortality in CAP patients. The modified version best predicted mortality. These were more suitable for clinic and emergency department.

Objectives: The individual 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is not clear whether the combinations of predictive findings might imply diverse severities or different mortalities., Methods: A prospective two centre cohort study was performed of 385 severe CAP patients fulfilling three or more IDSA/ATS minor criteria amongst 1430 patients., Results: Hospital mortality rose sharply from 5.7%, 9.9%, and 16.5%, respectively, for patients with none of three predictive findings most strongly associated to mortality (PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia), one of those, and two of those to 38.6% for patients with all those (p<0.001). The number of three predictive findings present had a significantly increased odds ratio for mortality of 2.796 (p<0.001), and had the degree of positive association with sequential organ failure assessment scores at 72hours, incurring significantly longer hospital stay and higher costs., Conclusions: Different combinations of 2007 IDSA/ATS minor criteria for severe CAP were associated to diverse severities and different mortalities. The combination of PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia predicted more severity and higher mortality compared with others., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We retrospectively evaluated the clinical outcome of penile prosthesis implantation (PPI) in Chinese patients with severe erectile dysfunction (SED). From July 2000 to December 2011, 224 patients (mean age: 35.9±11.8 years, range: 20-75 years) with SED underwent PPI by experienced surgeon according to standard PPI procedure at our centre. A malleable prosthesis (AMS 650) was implanted in 45 cases (20.1%), and a three-piece inflatable prosthesis (AMS 700 CXM or AMS 700 CXR) was implanted in 179 cases (79.9%). Surgical outcomes, including postoperative complications, clinical efficacy and couple satisfaction, were evaluated over than 6 months postoperatively using medical record abstraction, IIEF-5, quality of life (QoL) scores, and the patient/partner sexual satisfaction score proposed by Bhojwani et al. Of the 224 patients eligible for the study, 201 subjects (89.7%) completed follow-up. All of patients could perform sexual intercourse post PPI with the mean postoperative IIEF-5 and QoL scores were 20.02±2.32 and 5.28±0.76, respectively, which were significantly improved compared with the preoperative scores (6.29±1.5 and 2.13±0.84, P<0.01). Of the 201 men, mechanical malfunction occurred in four cases (2.0%) and three cases were re-implanted new device, and two cases (1.0%) developed a mild curvature of the penis. Scrotal erosion with infection occurred in one case with diabetes mellitus (0.5%) and required complete removal of the implanted AMS 700 CXM. Satisfactory sexual intercourse at least twice per month was reported by 178 men (88.6%), and overall satisfaction with the PPI surgery was reported by 89.0% of men and 82.5% of partners. Patient satisfaction in the three-piece inflatable prosthesis group was higher than in the malleable prosthesis group (P<0.05). Satisfaction, however, between the types of prostheses, did not differ in the partner survey. PPI is a safe and effective treatment option for Chinese patients with SED and experienced surgeon perform PPI according to standard PPI procedure could reduce the postoperative complications of PPI and could improve patient satisfaction ratio and QoL.

In the title complex, (C2H7N2)2[Mn(C14H6N2O4)2]·7H2O, the Mn(II) atom is coordinated by four N atoms and four O atoms from two 1,10-phenanthroline-2,9-dicarboxyl-ate ligands in a distorted dodeca-hedral geometry. The double negative charge is balanced by two ethanamidinium cations. A three-dimensional supra-molecular structure is formed through N-H⋯O and O-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.553 (2) Å].

In the title compound, [Cd(C(10)H(7)N(6))(2)(H(2)O)(2)], the Cd(II) atom lies on an inversion centre and is coordinated by four N atoms from 5-[4-(1H-imidazol-1-yl)phen-yl]tetra-zol-1-ide ligands and two O atoms from the coordinated water mol-ecules in an octa-hedral arrangement. The complex polymeric chains are inter-connected via inter-molecular water O-H⋯N hydrogen bonds into a three-dimensional network.

The title mol-ecule, C(13)H(8)N(4), is is essentially planar [r.m.s. deviation for all non-H atoms = 0.025 (3) Å]. In the crystal, mol-ecules are connected through one weak bifurcated N-H⋯(N,N) hydrogen bond and three π-π stacking inter-actions between pyridine and imidazole rings [centroid-centroid distance = 3.631 (8) Å] and between pyridine and benzene rings [centroid-centroid distances = 3.675 (5) and 3.666 (2) Å].

In the title compound, C(10)H(8)N(6), the tetra-zole and benzene rings are close to being coplanar [dihedral angle = 9.90 (16)°], but the imidazole ring is rotated 37.18 (09)° out of the benzene plane. In the crystal, mol-ecules are connected through tetra-zole-imidazole N-H⋯N hydrogen bonds, giving rise to zigzag chains, which extend along [010].

In the title complex polymer, [Sr(C(10)H(7)N(6))(2)(H(2)O)(2)](n), the Sr(II) atom lies on an inversion centre and is coordinated by four N atoms from two bidentate bridging trans-related 5-[4-(1H-imidazol-1-yl)phen-yl]tetra-zolide ligands [Sr-N = 2.387 (4) Å for the tetrazolide moiety and Sr-N = 2.273 (5) Å for the imidazole moiety], and by two O atoms from water mol-ecules [Sr-O = 2.464 (4) Å], giving a distorted octa-hedral coordination. Pairs of ligand bridges link the complex units, forming chains which extend along [111] and are inter-associated through O(water)-H⋯N hydrogen bonds, giving a two-dimensional network structure parallel to (001). Weak π-π stacking inter-actions between the benzene and imidazole rings are also present [minimum ring centroid separation = 3.691 (4) Å].

In the title compound, [Mn(C(10)H(7)N(6))(2)(H(2)O)(4)]·2H(2)O, the Mn(2+) lies on a twofold rotation axis and is six-coordinated by two N atoms from the cis-related monodentate 5-[4-(imidazol-1-yl)phen-yl]tetra-zolide ligands and four O atoms from the coordinated water mol-ecules. The complex mol-ecules are connected via water O-H⋯O and O-H⋯N hydrogen bonds and weak π-π stacking inter-actions between the benzene rings [minimum ring centroid separation = 3.750 (6) Å] into a three-dimensional polymeric structure. The imidazolyl group of the ligand is partially disordered over two sets of sites with refined occupancies of 0.531 (7):0.469 (7).

In the title compound, [Co(C(10)H(7)N(2)O(2))(2)(H(2)O)(4)], the Co(II) atom lies on an inversion centre and displays a slightly distorted octa-hedral geometry. The coordination sphere is defined by two mutually trans N atoms from two 4-(imidazol-1-yl)benzoate ligands and the O atoms from four water mol-ecules. The crystal structure is stabilized by O-H⋯O hydrogen bonds.

In the title compound, [Co(C(7)H(7)N(2)O(4))(2)(H(2)O)(2)]·3H(2)O, the Co(II) cation, located on an inversion center, is N,O-chelated by two 5-carboxy-2-ethyl-1H-imidazole-4-carboxylate anions and further coordinated by two water mol-ecules in a distorted octa-hedral geometry. Only one carboxy group of the anion is deprotonated, and the two carboxyl groups of the same anion are linked via an intra-molecular O-H⋯O hydrogen bond. One of the lattice water mol-ecules is located on an inversion center, its H atom equally disordered over two positions. One of H atoms of another lattice water mol-ecules is also equally disordered over two sites. Water H atoms and the amino H atom all are involved in an inter-molecular hydrogen-bonded network in the crystal.

In the title complex, [Cd(C(8)H(9)N(2)O(4))(2)(H(2)O)(2)]·2C(3)H(7)NO, the six-coordinate Cd(II) ion is in a slightly distorted octa-hedral environment, defined by two O atoms from two coordinated water mol-ecules and two carboxyl-ate O atoms and two N atoms from two N,O-bidentate 5-carb-oxy-2-propyl-1H-imidazole-4-carboxyl-ate ligands. In the crystal, complex mol-ecules and dimethyl-formamide solvent mol-ecules are linked by O-H⋯O and N-H⋯O hydrogen bonds into a two-dimensional supra-molecular structure. The propyl groups of the ligands are disordered over two conformations with refined occupancies of 0.680 (7) and 0.320 (7).

The title compound, [Sr(C(10)H(6)NO(2))(2)(H(2)O)(2)](n), contains an eight-coordinate Sr(II) ion displaying a distorted square-anti-prismatic geometry, two quinoline-3-carboxyl-ate ligands and two terminal water mol-ecules. The Sr(II) atom is surrounded by six carboxyl-ate O atoms from four separate quinoline-3-carboxyl-ate ligands and two O atoms from two coordinated water mol-ecules. The bridging carboxyl-ate O atoms [Sr-O = 2.498 (3) and 2.495 (3) Å] link Sr(II) atoms, forming a chain substructure extending along the c axis. The chains are linked by O-H⋯N and O-H⋯O hydrogen bonds, giving a three-dimensional framework structure.

In this study, we investigated the safety and efficacy of a poly acid-co-glycolide biodegradable scaffold (Maxpol-T) coated by autologous fibroblasts (AF) for penile girth enlargement in small penis syndrome (SPS). Eighty patients with SPS were enrolled in a clinical study at 2 medical centers; 69 patients completed the study protocol. Scrotal skin was harvested under local anesthesia, and AFs were cultured and seeded on a Maxpol-T scaffold; the cografted scaffold was implanted under the Buck's fascia of penile shaft via a circumcising incision. Patients were followed up at 1, 3, and 6 months to evaluate penile girth changes. Patient satisfaction was assessed via Visual Analogue Scale and scored on the International Index of Erectile Function-5 (IIEF-5). Mean preoperative penile girth in the flaccid and erect state was 8.18 ± 0.83 cm and 10.26 ± 1.22 cm, respectively. At the 6-month postoperative follow-up, mean penile girth in the flaccid and erect state was increased to 12.19 ± 1.27 cm and 13.18 ± 1.31 cm, respectively (P < .001 for change in both flaccid and erect state). Sixty-five patients (94.2%) reported satisfaction with the procedure. Among them, 4 cases (5.8%) were dissatisfied, 7 cases (10.1%) were satisfied, 26 cases (37.7%) were very satisfied, and 32 cases (46.4%) were extremely satisfied. All men maintained IIEF-5 scores of more than 22. Complications included prolonged subcutaneous edema in 3 patients (4.3%) and pinpoint erosion at the suture area in 3 patients (4.3%). Implantation of autologous fibroblasts seeded on a Maxpol-T collagen scaffold holds promise as a safe and novel technique for penile girth enhancement in patients with SPS.

In this study, we characterized sporadically occurring sclerotium rot caused by Sclerotium rolfsii in Chinese chive (Allium tuberosum Roth.) in farm fields in Sacheon, Korea. The initial symptom of the disease was water-soaked, which progressed to rotting, wilting, blighting, and eventually death. Further, mycelial mats spread over the lesions near the soil line, and sclerotia formed on the scaly stem and leaves. The sclerotia were globoid, 1~3 mm, and white to brown. The optimum temperature for growth and sclerotia formation on potato dextrose agar (PDA) was 30℃. The diameter of the hypae ranged from 4 to 8 µm. Clamp connection was observed on PDA medium after 5 days of incubation. Based on the mycological characteristics, internal transcribed spacer sequence analysis, and pathogenicity test, the causal agent was identified as Sclerotium rolfsii Saccardo. This is the first report of sclerotium rot in Chinese chive caused by S. rolfsii in Korea.

This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction (ED) and lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS). The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 (IIEF-5) scores ≤21 and International Prostate Symptom Score (IPSS) ≥10 points, were enrolled and randomly divided into Group A (168 cases; doxazosin GITS 4 mg once daily plus sildenafil 25-100 mg on demand) and Group B (82 cases; sildenafil 25-100 mg on demand). Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life (QoL) questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.

The title compound, C(13)H(9)NO(4), crystallizes in a zwitterionic form with the pyridine N atom protonated and the carboxyl OH group deprotonated. The benzene and pyridinium rings are inclined with a dihedral angle of 31.42 (14)° between them. A previous report of this stucture claims, we believe incorrectly, that neither of the carboxyl-ate groups is deprotonated [Zhang et al. (2010 ▶). Acta Cryst. E66, o2928-o2928]. In the crystal, inter-molecular O-H⋯O, N-H⋯O and weak C-H⋯O hydrogen-bonding inter-actions link adjacent mol-ecules into a three-dimensional supra-molecular network.

In the title compound, [Zn(C(12)H(9)O(2))(2)(C(12)H(12)N(2))]·0.5H(2)O, the water mol-ecule lies on a twofold rotation axis. The Zn(II) atom is coordinated by three O atoms from two 1-naphthyl-acetate ligands, one monodentate and the other asymmetric bidentate chelate, and two N atoms from a 5,5'-dimethyl-2,2'-bipyridine ligand, giving an irregular environment. In the crystal, the complex mol-ecules are inter-linked through the water mol-ecule by O-H⋯O(carboxyl-ate) hydrogen bonds, together with weak C-H⋯O and bipyridine ring π-π stacking inter-actions [ring centroid separation = 3.761 (2) Å], giving a two-dimensional network structure.

In the centrosymmetric dinuclear anions of the title bimetallic complex, {[Mg(H(2)O)(6)][Cu(2)(C(8)H(2)NO(7))(2)]·2H(2)O}(n), each Cu(II) ion is strongly coordinated by four O atoms in a distorted square-planar geometry. Two of these O atoms belong to phenolate groups and the other two to carboxylate groups from 5-nitro-2-oxidoisophthalate (L1) trianions, derived from 5-nitrobenzene-1,2,3-tricarboxylic acid (O(2)N-H(3)L). The phenolate O atoms bridge the two Cu(II) ions in the anion. In addition, each Cu(II) cation interacts weakly with a symmetry-related carboxylate O atom of an adjacent L1 ligand, giving a square-pyramidal coordination geometry. The copper residue forms a ladder-like linear coordination polymer via L1 ligands. The [Mg(H(2)O)(6)](2+) cations sit on centres of inversion. The polymeric anions, cations and free water molecules are self-assembled into a three-dimensional supramolecular network via O-H···O hydrogen bonds.

In the title compound, [Co(C(8)H(5)Cl(2)O(3))(C(12)H(12)N(2))], the Co(II) atom, lying on a twofold rotation axis, is coordinated by four O atoms from two chelating 2,4-dichloro-phen-oxy-acetate ligands and two N atoms from a 5,5'-dimethyl-2,2'-bipyridine ligand, displaying a distorted octa-hedral geometry. A three-dimensional supra-molecular structure is formed through inter-molecular C-H⋯O hydrogen bonds and π-π stacking inter-actions between the pyridine and benzene rings [centroid-centroid distance = 3.779 (2) Å].

In the title compound, C(7)H(8)N(2)O(4)·H(2)O, the imidazole N atom is protonated and one of the carboxyl-ate groups is deprontonated, forming a zwitterion. The two carboxyl groups are are approximately coplanar with the imidazole ring [O-C-C-C torsion angles = -176.8 (2) and 2.9 (4)° for one group and -4.6 (3) and 176.4 (2)° for the other] and have an intra-molecular O-H⋯O hydrogen bond between them. The water mol-ecule is linked to the organic mol-ecules via an N-H⋯O hydrogen bonds. Inter-molecular O-H⋯O and N-H⋯O hydrogen bonds are found in the crystal structure.

In the title complex, {[Na(C(7)H(7)N(2)O(4))(H(2)O)(2)]·H(2)O}(n), the Na(I) atom exhibits a distorted octa-hedral geometry and is six-coordinated in an NO(5) environment. The equatorial plane is defined by three O atoms and one N atom from two distinct 5-carb-oxy-2-ethyl-1H-imidazole-4-carboxyl-ate (H(2)EIDC) ligands and one coordinated water mol-ecule, and the apical sites are occupied by one carboxyl O atom from one H(2)EIDC ligand and one O atom from the other coordinated water mol-ecule. The Na(I) atoms are linked by H(2)EIDC ligands, generating an infinite double chain along the a axis. These chains are further connected via O-H⋯O and N-H⋯O hydrogen bonds into a three-dimensional supra-molecular network.

In the title complex, [Co(C(8)H(9)N(2)O(4))(2)(H(2)O)(2)]·3.5H(2)O, the Co(II) cation is six-coordinated by two H(2)pimda(-) ligands (H(3)pimda is 2-propyl-1H-imidazole-4,5-carboxylic acid) and two water mol-ecules in a distorted octa-hedral environment. The crystal structures features a three-dimensional network stabilized by extensive O-H⋯O and N-H⋯O hydrogen bonds. The propyl groups of the ligands are disordered over two sets of sites with refined occupancies of 0.673 (8):0.327 (8) and 0.621 (17):0.379 (17). One of the water mol-ecules is located on a site with half-occupancy.

In the title complex, [Co(C(8)H(9)N(2)O(4))(2)(H(2)O)(2)]·2C(3)H(7)NO, the Co(II) cation (site symmetry ) is six-coordinated by two 5-carb-oxy-2-propyl-1H-imidazole-4-carboxyl-ate ligands and two water mol-ecules in a distorted octa-hedral environment. In the crystal structure, the complex mol-ecules and dimethyl-formamide solvent mol-ecules are linked by extensive O-H⋯O and N-H⋯O hydrogen bonding into sheets lying parallel to (21).

In the title complex, [Ca(C(10)H(6)NO(2))(2)(H(2)O)(2)](n), the Ca(II) ion is eight-coordinated by six carboxyl-ate O atoms from four separate quinoline-3-carboxyl-ate ligands, two of which are bidentate chelate and two bridging, and two water mol-ecules in a distorted square-anti-prismatic geometry. The bridging groups form a polymeric chain substructure extending along the c axis, the chains being connected by coordinated-water O-H⋯N and O-H⋯O(carboxyl-ate) hydrogen bonds into a three-dimensional framework structure.

In the title compound, [Ni(H(2)O)(6)](C(16)H(12)O(6))·H(2)O, the Ni(II) cation is located on a mirror plane and is coordinated by six water mol-ecules, two of which are also located on the mirror plane, in a distorted octa-hedral geometry. The 4,4'-(1,2-dihy-droxy-ethane-1,2-di-yl)dibenzoate anion is centrosymmetric with the mid-point of the central ethane C-C bond located on an inversion center. The uncoordinated water mol-ecule is located on a mirror plane. Extensive O-H⋯O hydrogen bonding is present in the crystal structure.

Objective: To study the curative effect of operation to flatfoot deformity with concurrent spinal disease in children., Methods: A retrospective survey was performed in 8 flatfoot patients with concurrent spinal disease from January 2004 to January 2008. Every case received special operative treatment. After casting, achilles tendon prolongation, reefing or tendon transfer, rehabilitation therapy was performed sequentially. Radiographs and clinical outcomes were evaluated during the follow-up., Results: Six patients were followed up. There were 2 feet in 1 female and 7 feet in 5 males. The complications included tethered cord syndrome (n = 1), T12-S1 vertebral canal arachnoid cyst (n = 1), cerebral palsy and scoliosis (n = 1) and scoliosis and spinal bifida occult (n = 3). The average age was 8.4 (4 - 14) years old and the average follow-up time 22 (14 - 64) months. All cases were satisfied with the appearance and function according to Maryland foot score. Five were excellent, 2 good and 2 fair postoperatively versus 2 fair and 7 failed preoperatively. The total excellent and good rate was 77.8%. In the early stage after tendon transfer in 4 patients, the lateral view of height arch, talus-first metatarsal angle, calcaneus-navicular-first metatarsal angle and talonavicular coverage angle improved. Yet it lost the improved angle and reverted to the pre-operative state. No degenerative change was detected in tarsus joints during the long follow-up., Conclusion: The special and sequential surgical procedure may be an effective regimen in the treatment of flatfoot deformity with concurrent spinal disease in children.

In the title complex, [Cu(C(8)H(9)N(2)O(4))(2)(H(2)O)(2)]·2C(3)H(7)NO, the Cu(II) ion, lying on an inversion center, is six-coordinated in a slightly distorted octa-hedral geometry. Two N atoms and two O atoms from two H(2)pimda (H(3)pimda is 2-propyl-1H-4,5-dicarb-oxy-lic acid) ligands are in the equatorial plane. The axial positions are occupied by two O atoms from two water mol-ecules. A two-dimensional supra-molecular network parallel to (001) is constructed by N-H⋯O and O-H⋯O hydrogen bonds. An intra-molecular O-H⋯O hydrogen bond is also observed.