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Abstract Background The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. Methods Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. Results In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. Conclusions WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

Background In this study, the chemical properties of Ganoderma applanatum polysaccharides (GAP) were systematically investigated, followed by a comprehensive analysis of their antitumor and antioxidant capabilities.Methods Ultrasonic circulation technology was employed for the extraction of GAP, facilitating the procurement of crude polysaccharides through the Sevag method, dialysis, and sequential alcohol precipitation. The chemical constituents of these polysaccharides were subsequently analyzed utilizing Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry. The antitumor and antioxidant properties of the polysaccharide components were assessed utilizing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and free radical scavenging methods, respectively.Results Gradient ethanol precipitation yielded three principal polysaccharide fractions: GAP-40, GAP-60 and GAP-80. Analysis revealed glucose as the predominant component in these fractions, with average molecular weights determined to be 77.75, 9.25 and 1.03 kDa, respectively. The antitumor activity of GAP-40, GAP-60 and GAP-80 against MCF-7 cells demonstrated both time and concentration dependence. Significantly, GAP-40, at a concentration of 1000 μg/mL over 48 h, presented a notable inhibition rate of 56.77%, outperforming GAP-60 and GAP-80. Furthermore, the antioxidant capacities of GAP-40, GAP-60 and GAP-80 were comparably significant to that of vitamin C, with detailed analysis revealing marked differences in antioxidant activity among the GAP variants. Specifically, GAP-40 exhibited superior efficacy in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals relative to GAP-60 and GAP-80. In contrast, GAP-80 was distinguished by its exceptional hydroxyl radical scavenging capacity, surpassing that of both GAP-40 and GAP-60.Conclusion These results substantiate the potential of GAPs as viable and effective antitumor agents, additionally suggesting their utility as functional foods endowed with antioxidant attributes.

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.

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients.Design: Clinical study protocol, SPIRIT compliant.Setting: Prospective, single-center, randomized, and sham-controlled trial.Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients.Exposures: Intraoral or sham acupuncture.Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the “Drooling Severity and Frequency Scale” and “Functional Oral Intake Scale.” Results : : The results from this study will be published in peer-reviewed journals.Conclusion : : Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

AIM: To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism. METHODS: Male Sprague–Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-β1 (TGF-β1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. RESULTS: Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P

Abstract Cold‐inducible RNA‐binding protein (CIRP) is a damage‐associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen‐free 8–9‐week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and IL‐1β] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription‐polymerase chain reaction, western blotting, and enzyme‐linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF‐α, IL‐6 and IL‐1β proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF‐α, IL‐6, and IL‐1β increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF‐α, IL‐6, and IL‐1β in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.

AbstractBackground: 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.

The fungal genus Nigrospora is known to be a plant pathogen, endophyte, and saprobe, and it is usually isolated from various substrates like soil and air. During the surveys of soil fungi in Hebei Province of China, two isolates of Nigrospora were obtained. A multi-locus phylogeny of combined loci of the 5.8S nuclear ribosomal gene with the two flanking transcribed spacers (ITS), part of the translation elongation factor 1-alpha (tef1), and the beta-tubulin (tub2) loci, in conjunction with morphological characters were used to identify the newly collected isolates. Nigrospora humicola sp. Nov. is described and proposed herein, which differs from its phylogenetically close species N. chinensis and N. globosa by the sequences of ITS, tef1, and tub2.

Six benzophenone derivatives, carneusones A-F (1–6), along with seven known compounds (7–13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 μM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 μM.

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26–30 years, 31–35 years, 36–40 years, 41–45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.

AIM: To explore the effect of intravitreal conbercept in the treatment of chorionic neovascularization(CNV)of macular macula with high myopia. METHODS: Totally 56 patients with high myopia caused by macular angiogenesis in our hospital were retrospectively selected as the research objects from June 2015 to December 2019. According to the treatment methods, patients were divided into the control group and the observation group. The 28 cases(28 eyes)of patients in the control group were treated with the intravitreous injection of Rayzumab, and 28 cases(28 eyes)of patients in the observation group were treated with intravitreal injection of conbercept. After the last treatment, the patients were followed up for 3mo to record the intraocular pressure, the best corrected visual acuity(BCVA)and the incidence of complications. Optical coherence tomography(OCT)was used to measure the thickness of macular fovea retinal(CMT), and horizontal linear scanning of OCT instrument was used to measure the CNV area.RESULTS:After treatment, the visual acuity of patients in the observation group gradually increased, and the improvement of BCVA was significantly higher than that of the control group at the same time point(P

Background: Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation. Objective: The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes. Methods: Glucose uptake was determined using a 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. The phosphorylation levels of proteins involved in the insulin and 5’-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting. Results: We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. PA had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (Tyr632) and protein kinase B (PKB/Akt), but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway in vitro. Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK. Conclusion: PA, an odd-chain SFA, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.

Abstract 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.

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH).Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated.Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased.Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

Abstract Background Alisol A-24-acetate (AA-24-a) is one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., which possesses multiple biological activities, including a hypoglycemic effect. Whether AA-24-a is a hypoglycemic-active compound of A. orientale (Sam.) Juz. is unclear. The present study aimed to clarify the effect and potential mechanism of action of AA-24-a on glucose uptake in C2C12 myotubes. Method Effects of AA-24-a on glucose uptake and GLUT4 translocation to the plasma membrane were evaluated. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. To determine the underlying mechanism, the phosphorylation levels of proteins involved in the insulin and 5′-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined using western blotting. Furthermore, specific inhibitors of key enzymes in AMPK signaling pathway were used to examine the role of these kinases in the AA-24-a-induced glucose uptake and GLUT4 translocation. Results We found that AA-24-a significantly promoted glucose uptake and GLUT4 translocation in C2C12 myotubes. AA-24-a increased the phosphorylation of AMPK, but had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/AKT). In addition, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the AKT substrate of 160 kDa (AS160), two proteins that act downstream of AMPK, was upregulated. Compound C, an AMPK inhibitor, blocked AA-24-a–induced AMPK pathway activation and reversed AA-24-a–induced glucose uptake and GLUT4 translocation to the plasma membrane, indicating that AA-24-a promotes glucose metabolism via the AMPK pathway in vitro. STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, also attenuated AA-24-a–induced glucose uptake and GLUT4 translocation. Moreover, STO-609 weakened AA-24-a-induced phosphorylation of AMPK, p38 MAPK and AS160. Conclusions These results indicate that AA-24-a isolated from A. orientale (Sam.) Juz. significantly enhances glucose uptake via the CaMKKβ-AMPK-p38 MAPK/AS160 pathway.

Water deficit is one of the main limiting factors for apple growth and production. Root architecture plays an important role in drought tolerance of plants. However, little is known about the molecular basis of root system in apple trees under drought. In this study, we compared root morphology of two widely used rootstocks of apple (R3 and Malus sieversii) under drought. Our results suggested that M. sieversii is more tolerant to drought than R3, since M. sieversii had a higher ratio of root to shoot as well as root hydraulic conductivity under long-term drought conditions. We then performed whole-genome transcriptomic analysis to figure out the molecular basis of root responses in M. sieversii under drought. It was found that genes involved in transcription regulation, signaling or biosynthesis of hormones, and oxidative stress were differentially expressed under drought. Consistent with the gene expression profile, roots of M. sieversii had higher activities of peroxidase (POD) and superoxide dismutase (SOD) under drought, as well as higher content of abscisic acid (ABA) and lower content of auxin. Taken together, our results revealed the physiological and transcriptomic analyses of M. sieversii roots in response to drought.

Objective: Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D). In this study, we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers. Methods: We conducted a cross-sectional analysis of 26,008 Chinese male workers in an occupational cohort study from 2011 to 2013. We assessed metal exposure and alcohol consumption at baseline in these workers who were aged ≥20 years. Based on occupations which were categorized according to measured urine metal levels, multiple logistic regression analyses were used to evaluate the independent and joint effects of metal and alcohol exposure on the risk of T2D and prediabetes. Results: Risks of T2D (Ptrend = 0.001) and prediabetes (Ptrend = 0.001) were significantly elevated with increasing number of standard drinks per week, years of drinking, and lifetime alcohol consumption. An adjusted odds ratio (OR) of 6.1 (95% confidence interval [CI]: 4.8–7.8) was observed for the smelting/refining workers (highest metal exposure levels) who had the highest lifetime alcohol consumption (>873 kg) (Pinteraction = 0.018), whereas no statistically significant joint effect was found for prediabetes (Pinteraction = 0.515). Conclusions: Both exposures to metal and heavy alcohol intake were associated with the risk of diabetes in this large cohort of male workers. There was a strong interaction between these two exposures in affecting diabetes risk that needs to be confirmed in future studies. Keywords: Metals, Alcohol, Type 2 diabetes, Prediabetes, Interaction

Abstract Background Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. Methods The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype–genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype–phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). Results Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic‐onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. Conclusion It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss‐of‐function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH.

Ubiquitylation is a form of post-translational modification of proteins that can alter localization, functionality, degradation, or transcriptional activity within a cell. E2 ubiquitin-conjugating enzyme (UBC) and E3 ubiquitin ligases are the primary determinants of substrate specificity in the context of ubiquitin conjugation. Multiubiquitination modifies target proteins for 26S proteasome degradation, while monoubiquitination controls protein activation and localization. At present, research on the monoubiquitination, especially histone monoubiquitination, has mostly focused on model plants with relatively few on crop species. In this study, we identified 91 UBC-like genes in soybean. The chromosomal localization, phylogenetic relationships, gene structures, and putative cis-acting elements were evaluated. Furthermore, the tissue-specific expression patterns of UBC Class I genes under drought stress were also investigated. Among Class I genes, GmUBC9 induction in response to drought stress was evident, and so this gene was selected for further analysis. GmUBC9 localized to the nucleus and endoplasmic reticulum. The overexpression of GmUBC9 in Arabidopsis led to enhanced tolerance for drought conditions across a range of stages of development, while overexpression in soybean hairy roots similarly led to improvements in tolerance for drought conditions, increased proline content, and reduced MDA content in soybean seedlings compared to wild type plants. HISTONE MONOUBIQUITINATION 2 (HUB2), an E3-like protein involved in histone H2B ubiquitylation (H2Bub1), was found to interact with GmUBC9 through Y2H analysis and BiFC assays in Arabidopsis and soybean. Under drought conditions, the level of H2Bub1 increased, and transcription of drought response genes was activated in GmUBC9 transgenic Arabidopsis and soybean. In addition, GmUBC9 transgenic Arabidopsis and soybean showed a late-flowering phenotype and had increased expression levels of the flowering related genes FLC and MAF4. These findings indicate that GmUBC9 is important for drought stress response and regulation of flowering time in soybean.

Abstract Porcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that causes watery diarrhea in piglets. Little is known regarding the alteration of the gut microbiota in PDCoV‐induced diarrhea piglets. In this study, 5‐day‐old piglets were experimentally infected with PDCoV strain CH‐01, and all piglets developed typical clinical disease, characterized by acute and severe watery diarrhea. Histologic lesions were limited to the villous epithelium of the duodenum and ileum. Gut microbiota profiles in the colon and feces of piglets inoculated with PDCoV were investigated using 16S rRNA sequencing. The results showed that PDCoV infection reduced bacterial diversity and significantly altered the composition of the microbiota from the phylum to the genus level in the colon and feces of piglets. Firmicutes (phylum), Lactobacillaceae (family), and Lactobacillus (genus) were significantly increased (p

Objective: To observe whether urethral injection of chemokine (c-c motif) ligand 7 (CCL7) and overexpressing CC receptor 1 (CCR1) in mesenchymal stem cells (MSCs) can promote their homing and engraftment to the injured tissue, and improve the recovery of simulated birth injury-induced stress urinary incontinence (SUI) in rats.Methods: Female rats underwent a dual injury consisting of vaginal distension (VD) and pudendal nerve crush (PNC) to induce SUI. Bone marrow-derived MSCs were transduced with lentivirus carrying CCR1 (MSC-CCR1) and green fluorescent protein (GFP). Forty virgin Sprague–Dawley rats were evenly distributed into four groups: sham SUI + MSC-CCR1+CCL7, SUI + MSCs, SUI + MSC-CCR1, and SUI + MSC-CCR1+CCL7 group. The engrafted MSCs in urethra were quantified. Another three groups of rats, including sham SUI + sham MSC-CCR1+CCL7 treatment, SUI + sham MSC-CCR1+CCL7 treatment, and SUI + MSC-CCR1+CCL7 treatment group, were used to evaluate the functional recovery by testing external urethral sphincter electromyography (EUS EMG), pudendal nerve motor branch potentials (PNMBP), and leak point pressure (LPP) 1 week after injury and injection. Urethra and vagina were harvested for histological examination.Results: The SUI + MSC-CCR1+CCL7 group received intravenous injection of CCR1-overexpressing MSCs and local injection of CCL7 after simulated birth injury had the most engraftment of MSCs to the injured tissues and best functional recovery from SUI compared to other groups. Histological examination showed a partial repair in the SUI + MSC-CCR1+CCL7 group.Conclusions: Our study demonstrated combined treatment with CCR1-overexpressing MSCs and CCL7 can increase engraftment of MSCs and promote the functional recovery of simulated birth trauma-induced SUI in rats, which could be a new therapeutic strategy for SUI.

Abstract Background Mesenchymal stromal cells (MSCs) were originally characterized by the ability to differentiate into different mesenchymal lineages in vitro, and their immunomodulatory and trophic functions have recently aroused significant interest in the application of MSCs in cell-based regenerative medicine. However, a major problem in clinical practice is the replicative senescence of MSCs, which limits the cell proliferation potential of MSCs after large-scale expansion. Telomeric zinc finger-associated protein (TZAP), a novel specific telomere-binding protein, was recently found to stimulate telomere trimming and prevent excessive telomere elongation. The aim of this study was to elucidate the role of TZAP in regulating MSCs senescence, differentiation and proliferation. Method Primary porcine mesenchymal stromal cells (pMSCs) were isolated from the bone marrow of Tibet minipigs by a noninvasive method in combination with frequent medium changes (FMCs). The deterioration of the pMSCs’ proliferation capacity and their resultant entry into senescence were analyzed by using CCK8 and EdU incorporation assays, SA-β-gal staining and comparisons of the expression levels of cellular senescence markers (p16INK14 and p21) in pMSC cell lines with TZAP overexpression or knockout. The effects of TZAP overexpression or knockout on the differentiation potential of pMSCs were assessed by alizarin red S staining after osteogenic induction or by oil red O staining after adipogenic induction. The effect of TZAP overexpression and the involvement of the p53 signaling pathway were evaluated by detecting changes in ARF, MDM2, P53 and P21 protein levels in pMSCs. Results TZAP levels were significantly elevated in late-passage pMSCs compared to those in early-passage pMSCs. We also observed significantly increased levels of the senescence markers p16INK4A and p21. Overexpression of TZAP reduced the differentiation potential of the cells, leading to premature senescence in early-passage pMSCs, while knockout of TZAP led to the opposite phenotype in late-passage pMSCs. Furthermore, overexpression of TZAP activated the P53 pathway (ARF-MDM2-P53-P21WAF/CDKN1A) in vitro. TZAP also downregulated the expression levels of PPARγ and Cebpα, two key modulators of adipogenesis. Conclusions This study demonstrates that the level of TZAP is closely related to differentiation potential in pMSCs and affects cellular senescence outcomes via the p53 pathway. Therefore, attenuation of intracellular TZAP levels could be a new strategy for improving the efficiency of pMSCs in cell therapy and tissue engineering applications.

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea and induces proinflammatory cytokine responses in piglets. Our previous research showed that the specific-pathogen-free (SPF) chicks exhibited mild diarrhea and low fecal viral shedding, along with cecum lesions after PDCoV infection. Disturbances in the homeostasis of the gut microbiota have been associated with various diseases. We aimed to explore the effects of PDCoV infection on chick gut microbiota, short-chain fatty acid (SCFAs) production, and inflammatory cytokine expression in chicks, and also to investigate the relationship between gut microbiota and SCFAs or inflammatory cytokine expression of the PDCoV-infected chicks. Results obtained using 16S rRNA sequencing showed that infection with PDCoV strain HNZK-02 significantly altered the composition of chick gut microbiota, with the reduced abundance of Eisenbergiella and Anaerotruncus genera at 5 days post-inoculation (dpi) (P < 0.05), and an increased abundance of Alistipes genus at 17 dpi (P < 0.05). The production of SCFAs in the cecum of PDCoV HNZK-02–infected chicks, including acetic acid, propionic acid, and butyric acid, decreased in all cases. The expression of inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-10) was increased in the cecum tissue and serum of the PDCoV HNZK-02–infected chicks when detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Further analysis showed significant correlation between bacterial genera and SCFAs or inflammatory cytokines expression in cecum of the PDCoV infected chicks. These findings might provide new insight into the pathology and physiology of PDCoV in chicks.

Objective To analyze the types and characteristics of nystagmus in patients with positional vertigo who were ineffective by particle repositioning maneuver (PRM) and had negative findings in MRI, and try to explore drug treatment and prevention programme. Methods A total of 43 patients with positional nystagmus were randomly treated with clonazepam or flunarizine hydrochloride. The therapeutic effect at acute phase was evaluated by comparing maximum slow phase velocity (SPV) before and after treatment. Among all patients, 21 patients with frequent attacks in recent 2 months were randomly divided into flunarizine hydrochloride prophylaxis treatment group (prophylaxis group) and blank control group (control group), followed up and recorded the average attack days of vertigo per month (days of single attack × number of attacks). The preventive effect of flunarizine hydrochloride was analyzed. Results Among 43 patients, 29 cases met the diagnostic criteria of definite and probable vestibular migraine. The main types of nystagmus were horizontal apogeotropic nystagmus (23 cases, 53.49% ), horizontal geotropic nystagmus (3 cases, 6.98% ), downbeat nystagmus (4 cases, 9.30% ) and mixed nystagmus (13 cases, 30.23%). Nystagmus lasted a longer time and lacked the characteristics of crescendo-decrescendo. After 3 d of treatment, the maximum SPV [2.40 (0.00, 17.15) °/s] of clonazepam group was significantly reduced, and the therapeutic effect at acute phase was better compared with flunarizine hydrochloride group [18.85 (1.58, 35.75) °/s; Z = -2.284, P = 0.022]. After 2 months, the average attack days of vertigo per month in prophylaxis group [1 (0, 2) d] was significantly reduced in comparison with control group [3.50 (1.50, 6.50) d; Z = -2.096, P = 0.036). Conclusions Positional vertigo with ineffective PRM and negative findings in MRI may be related to abnormal central function. After excluding the relevant contraindications, clonazepam can relieve vertigo and nystagmus in the acute phase, especially in vestibular migraine patients. For patients with frequent attacks, flunarizine hydrochloride maybe an available preventive treatment. DOI: 10.3969/j.issn.1672-6731.2019.02.003

Abstract 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 PaO2/FiO2 ≤ 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.

Abstract Background Data on the prevalence of insomnia symptoms in medical outpatient clinics in China are lacking. This study examined the prevalence of insomnia symptoms and their socio-demographic correlates in patients treated at medical outpatient clinics affiliated with four general hospitals in Guangzhou, a large metropolis in southern China. Method A total of 4399 patients were consecutively invited to participate in the study. Data on insomnia and its socio-demographic correlates were collected with standardized questionnaires. Results The prevalence of any type of insomnia symptoms was 22.1% (95% confidence interval (CI): 20.9–23.3%); the prevalence of difficulty initiating sleep was 14.3%, difficulty maintaining sleep was 16.2%, and early morning awakening was 12.4%. Only 17.5% of the patients suffering from insomnia received sleeping pills. Multiple logistic regression analysis revealed that male gender, education level, rural residence, and being unemployed or retired were negatively associated with insomnia symptoms, while lacking health insurance, older age and more severe depressive symptoms were positively associated with insomnia symptoms. Conclusions Insomnia symptoms are common in patients attending medical outpatient clinics in Guangzhou. Increasing awareness of sleep hygiene measures, regular screening and psychosocial and pharmacological interventions for insomnia are needed in China. Trial registration ChiCTR-INR-16008066. Registered 8 March 2016.

Abstract Background Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide association study (GWAS) of plasma NFL in Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI-1) cohort to identify novel variants associated with AD. Methods This study included 179 cognitively healthy controls (HC), 176 patients with mild cognitive impairment (MCI), and 172 patients with AD. All subjects were restricted to non-Hispanic Caucasian derived from the ADNI cohort and met all quality control (QC) criteria. Association of plasma NFL with the genetic variants was assessed using PLINK with an additive genetic model, i.e.dose-dependent effect of the minor alleles. The influence of a genetic variant associated with plasma NFL (rs7943454) on brain structure was further assessed using PLINK with a linear regression model. Results The minor allele (T) of rs7943454 in leucine zipper protein 2 gene (LUZP2) was associated with higher plasma NFL at suggestive levels (P = 1.39 × 10− 6) in a dose-dependent fashion. In contrast, the minor allele (G) of rs640476 near GABRB2 was associated with lower plasma NFL at suggestive levels (P = 6.71 × 10− 6) in a dose-dependent effect in all diagnostic groups except the MCI group. Furthermore, the minor allele (T) of rs7943454 within LUZP2 increased the onset risk of AD (odds ratio = 1.547, confidence interval 95% = 1.018–2.351) and was associated with atrophy of right middle temporal gyrus in the whole cohort in the longitudinal study (P = 0.0234). Conclusion GWAS found the associations of two single nucleotide polymorphisms (rs7943454 and rs640476) with plasma NFL at suggestive levels. Rs7943454 in LUZP2 was associated with the onset risk of AD and atrophy of right middle temporal gyrusin the whole cohort. Using an endophenotype-based approach, we identified rs7943454 as a new AD risk locus.

Abstract Background The purpose of this study was to evaluate the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum infections in infertile men that consulted our outpatient departments using a novel simultaneous amplification testing (SAT) that is RNA-detection based. The possible impact of C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections on semen parameters was also noted in the present study. Methods A total of 2607 males that were diagnosed with infertility were included in this study. C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections were detected in the urine samples using SAT method. Related data, including semen parameters and age as well as C. trachomatis, N. gonorrhoeae, M. genitalium and U. urealyticum infections were collected and analyzed. Results A total of 51 and 1418 urine samples were found positive for M. genitalium RNA and U. urealyticum RNA, respectively, while the prevalence of C. trachomatis and N. gonorrhoeae was relatively lower. Men with positive M. genitalium RNA and U. urealyticum RNA had higher sperm DNA fragmentation index (DFI) while the comparisons of other semen parameters yielded nonsignificant results between the RNA positive and negative group. A multivariate linear regression analysis revealed that U. urealyticum and M. genitalium infections posed significant factors of DFI (adjusted R2 = 46.2%). Conclusions Our study suggested a relative high prevalence of U. urealyticum and M. genitalium infection based on this novel SAT detection method. U. urealyticum and M. genitalium infection could possibly impair male fertility potential through promoting sperm DNA damage.

Objective To summarize the experience of endoscopic surgery by transsphenoidal approach for repairing cerebrospinal fluid (CSF) rhinorrhea after pituitary adenoma resection. Methods Clinical data, operation skills and follow-up data of 16 cases of persistent CSF rhinorrhea after pituitary adenoma resection from March 2009 to July 2014 were retrospectively analyzed. Results All patients were repaired by endoscopic transsphenoidal approach, 13 cases (13/16) were successful by one reparative surgery, 2 cases (2/16) were successful by the second repairment, and one case (1/16) was failed by several endoscopic surgeries, but was successfully repaired by craniotomy. One case presented intracranial infection after surgery, and recovered after taking ceftriaxone. After postoperative follow-up for 6 months to 2 years (average 12 months), no tumor recurrence or CSF rhinorrhea recurrence occurred. Conclusions Endoscopic transsphenoidal approach for repairing CSF rhinorrhea after pituitary adenoma resection was safe and effective. It can be widely used in clinic. DOI: 10.3969/j.issn.1672-6731.2017.06.012

The vacuolar proton pump ATPase (V-H+-ATPase), which is a multi-subunit membrane protein complex, plays a major role in the activation of ion and nutrient transport and has been suggested to be involved in several physiological processes, such as cell expansion and salt tolerance. In this study, three genes encoding V-H+-ATPase subunits B (ScVHA-B, GenBank: JF826506), C (ScVHA-C, GenBank: JF826507) and H (ScVHA-H, GenBank: JF826508) were isolated from the halophyte Suaeda corniculata. The transcript levels of ScVHA-B, ScVHA-C and ScVHA-H were increased by salt, drought and saline-alkali treatments. V-H+-ATPase activity was also examined under salt, drought and saline-alkali stresses. The results showed that V-H+-ATPase activity was correlated with salt, drought and saline-alkali stress. Furthermore, V-H+-ATPase subunits B, C and H (ScVHA-B, ScVHA-C and ScVHA-H) from S. corniculata were introduced separately into the alfalfa genome. The transgenic alfalfa was verified by Southern and Northern blot analysis. During salt and saline-alkali stresses, transgenic lines carrying the B, C and H subunits had higher germination rates than the wild type (WT). More free proline, higher superoxide dismutase (SOD) activity and lower malondialdehyde (MDA) levels were detected in the transgenic plants under salt and saline-alkali treatments. Moreover, the ScVHA-B transgenic lines showed greater tolerance to salt and saline-alkali stresses than the WT. These results suggest that overexpression of ScVHA-B, ScVHA-C and ScVHA-H improves tolerance to salt and saline-alkali stresses in transgenic alfalfa.

When an electron is incident from a Weyl material to an insulator and totally reflected, it suffers a reflection group delay and a reflection shift (Goos–Hänchen and/or Imbert–Fedorov shifts). We found the group delay is negative for half of the incident states. The negative group delay does not mean the electron is bounced back before its injection, but is an effective acceleration of the electron near the interface induced by self-interference. The reflection shift orients circulating the points at which the surface-bulk state transition occurs. The reflection shift and the group delay cause velocity correction of the bound states in the Weyl material sandwiched by two insulators. The velocity correction features induced by the negative group delay were verified by a tight-binding calculation, in which the concept of group delay is not used.

In order to avoid unexpected damage of structural specimens in the test, at the beginning, a signal with small amplitude is adopted to input the shake table device to gain the transfer function and corresponding drive signal, and then a strong earthquake output can be reproduced by amplifying the drive signal proportionally. However, as there are obvious nonlinearities inherent in the shake table device and structural specimen under strong earthquakes, errors inevitably exist in the replayed and amplified earthquake output if the linear transfer function and the drive signal, which are obtained by the small amplitude input, are adopted, and the desired output signal cannot accurately be achieved. Considering this point, several typical structural experiments are introduced and analyzed in this paper to study the earthquake output accuracy of the large-scale shake table test, such as inertia and elastic specimens, large-span floor, isolated building, high-speed railway station, bridge piers, and collision of adjacent multispan bridges. The transfer function of the shake table device and structural specimen is described. The energy-time history (energy-TH) index can assess the accuracy of the shake table on the strong earthquake output in the aspect of specimens other than signals themselves. The double parameter performance table is established based on this energy-TH index. More attention should be paid to energy and amplitude for the reproduction of strong earthquakes, and the accuracy details of signal reproduction should not be too strict.

Background Hyperprolactinaemia is a common adverse effect of antipsychotics (APs). The results of Peony-Glycyrrhiza decoction (PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials (RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia.Methods English (PubMed, Embase, Cochrane Library, PsycINFO) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PICOS—Participants: adult patients with schizophrenia; Intervention: PGD plus APs; Comparison: APs plus placebo or AP monotherapy; Outcomes: efficacy and safety; Study design: RCTs. The weighted mean difference (WMD) and risk ratio (RR) along with their 95% CIs were calculated using Review Manager (RevMan) V.5.3 software.Results Five RCTs (n=450) were included and analysed. Two RCTs (n=140) were double-blind and four RCTs (n=409) reported ‘random’ assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group (n=380, WMD: −32.69 ng/mL (95% CI −41.66 to 23.72), p

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 ≤ 250 mm Hg, confusion and uraemia), one of those, and two of those to 38.6% for patients with all those (p

In northern China, the soil-born diseases of wheat have been getting more and more serious under a new farming system that returns maize straw to the field. In order to investigate the allelopathy of the decomposed maize straw products on three soil-born diseases of wheat, culture dish and pot experiments were conducted and the compounds in the products were identified by gas chromatography-mass spectrometry (GC-MS). Culture dish experiments showed that the mycelial growth, sclerotia formation amount and total weight of Rhizoctonia cerealis were promoted at concentrations of 0.03, 0.06 and 0.12 g mL−1 and inhibited at concentration of 0.48 g mL−1 of the decomposed products. No significant effects were found of the product concentrations on average weight of the sclerotia. Mycelial growth of Gaeumannomyces graminis was promoted at almost all concentrations except the highest one. Mycelial growth and spore germination of Bipolaris sorokiniana were significantly inhibited by all concentrations of the decomposed products, with enhanced inhibition effects along with the increased concentrations. The length, number and dry weight of roots together with the root superoxide dismutase activity were promoted by the lowest concentration (0.03 g mL−1), with a synthetic effect index of 0.012, and inhibited by other concentrations. The ion leakage of roots was increased and the root peroxidase activity of roots was lowered by all the treatments. Pot experiments revealed that occurrence of the sharp eyespot was reduced by 0.03 and 0.06 g mL−1 of decomposed products after irrigation. However, the incidence rates and disease indexes were significantly increased by 0.12, 0.24 and 0.48 g mL−1 of decomposed products. The results indicated that incidence rates and disease indexes of the take-all were significantly promoted after being irrigated with the decomposed products, while occurrences of the common rot didn't change, significantly. GC-MS results showed that the compounds of the decomposed products included organic acids, esters, hydrocarbons, amides and aldehydes, with the proportions 25.26, 24.01, 17.22, 14.39 and 7.73%, respectively. Further analysis investigated that the allelochemicals identified in straw decomposed products contained p-hydroxybenzoic acid (9.21%), dibutyl phthalate (6.94%), 3-phenyl-2-acrylic (5.06%), 4-hydroxy-3,5-dimethoxybenzoic acid (2.26%), hexanoic acid (1.73%), 8-octadecenoic acid (1.06%), 3-(4-hydroxy-3-methoxy-phenyl)-2-propenoic acid (1.04%), 4-hydroxy-3-methoxy-benzoic acid (0.94%) and salicylic acid (0.94%).

The purpose of this study was to investigate the effect of four fluorescent dyes, True Blue (TB), Fluoro-Gold (FG), Fluoro-Ruby (FR), and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), in retrograde tracing of rat spinal motor neurons. We transected the muscle branch of the rat femoral nerve and applied each tracer to the proximal stump in single labeling experiments, or combinations of tracers (FG-DiI and TB-DiI) in double labeling experiments. In the single labeling experiments, significantly fewer labeled motor neurons were observed after FR labeling than after TB, FG, or DiI, 3 days after tracer application. By 1 week, there were no significant differences in the number of labeled neurons between the four groups. In the double-labeling experiment, the number of double-labeled neurons in the FG-DiI group was not significantly different from that in the TB-DiI group 1 week after tracer application. Our findings indicate that TB, FG, and DiI have similar labeling efficacies in the retrograde labeling of spinal motor neurons in the rat femoral nerve when used alone. Furthermore, combinations of DiI and TB or FG are similarly effective. Therefore, of the dyes studied, TB, FG and DiI, and combinations of DiI with TB or FG, are the most suitable for retrograde labeling studies of motor neurons in the rat femoral nerve.

AIM:To analyze the composition, distribution and characteristics of the elderly primary ocular tumors. METHODS: This was a retrospective study and all 504 cases with primary ocular tumors aged 60 years or older were collected in Shanxi Eye Hospital, during the year 2000-2012. The onset age, location and pathological pattern were analyzed.RESULTS: There were 346 cases of benign ocular tumors(68.7%), and 158 cases of malignancy(31.3%).Papillomas was the most common type of the benign with 83 cases(16.5%), followed by a variety of inflammatory cysts and lesions with 69 cases(13.7%)and 64 cases(12.7%)respectively. Among malignant tumors cases, eyelid basal cell carcinoma originated from epithelial was the most common with 72 cases(14.3%), followed by skin appendages sources malignant tumors with 39 cases(7.7%). Concerning the location of ocular tumors, there were 282 cases of eyelid tumor(56.0%)occupied the first position followed by conjunctival tumor with 157 cases(31.2%). CONCLUSION: The prevalence and type of primary ocular tumor in elderly people are significant differences from the general population and children's, and the proportion of malignant tumors tended to increase along with the increase of age.

Salinity is one of the most serious factors limiting the productivity of agricultural crops, with adverse effects on germination, plant vigor, and crop yield. This salinity may be natural or induced by agricultural activities such as irrigation or the use of certain types of fertilizer. The most detrimental effect of salinity stress is the accumulation of Na+ and Cl− ions in tissues of plants exposed to soils with high NaCl concentrations. The entry of both Na+ and Cl− into the cells causes severe ion imbalance, and excess uptake might cause significant physiological disorder(s). High Na+ concentration inhibits the uptake of K+, which is an element for plant growth and development that results in lower productivity and may even lead to death. The genetic analyses revealed K+ and Na+ transport systems such as SOS1, which belong to the CBL gene family and play a key role in the transport of Na+ from the roots to the aerial parts in the Arabidopsis plant. In this review, we mainly discuss the roles of alkaline cations K+ and Na+, Ion homeostasis-transport determinants, and their regulation. Moreover, we tried to give a synthetic overview of soil salinity, its effects on plants, and tolerance mechanisms to withstand stress.

It is essential to develop effective methods for the quality control of the traditional medicine with multiple components. However, few researches on the quality control have been conducted to interpret the holistic characteristics of the traditional medicine in terms of dissolution/release. In this study, the multi-component release kinetics of Traditional Chinese Medicine (TCM) dosage forms was characterized and mapped by multivariate analysis techniques in the field of “-omics”. The Liuweidihuang pill was used as a model formulation. The multi-component release kinetics of the concentrated and water-honeyed Liuweidihuang pills at rotation speeds of 50 and 100 rpm were analyzed by chemomic release kinetic theory and modified LC/MS/MS method. Mass features of 103 (concentrated pills) and 101 (water-honeyed pills) were selected with a linear correlation coefficient ≥0.99 between mass responses and concentrations. To compose the chemomic standard spectrum, the relative abundance of both mass features was no less than 1% as compared with an internal standard. The correlation coefficients between six samples of various solutions were in line with analytical requirements of precision (r≥0.985). The score plots of principal component analysis showed that the concentrated Liuweidihuang pills presented better chemomic release reproducibility than the water-honeyed pills. Conversely, the impact of rotation speed on the chemomic release was less obvious. The heat maps of hierarchical clustering analysis did not show significant changes in individual clusters of mass features along different time intervals, reflecting the release integrity of the mass features. Therefore, both multivariate analysis methods, the principal component analysis and the hierarchical clustering analysis, seemed to be effective techniques to demonstrate the multiple component release performance of TCM. The research provided the basis of a new strategy for the quality control procedures of the dissolution/release for the traditional medicine and multi-component natural products to address increasing regulatory requirements and scrutiny across the world.

AIM: To observe the effects of porous polyethylene(Medpor)as a spacer graft in the reconstruction of large areas eyelid defect after the operation of malignant tumors of lower eyelids.METHODS: Nineteen cases(19 eyes)of malignant tumors of lower eyelid underwent the eyelid reconstruction were selected. Medpor lower eyelid inserts implantation were used to replace tarsal joint sliding conjunctival flap and pedicle flap, and repaired full-thickness lower eyelid defects then underwent eyelid reconstruction. RESULTS: Appearance of eyelids and functional improvements were satisfactory with no stimulation on the eyeball and no effect on the visual function. Implants is with no absorption, shift, exclusion or infection and no tumor recurrence in all cases during the follow up for 6-36mo.CONCLUSION: Medpor lower eyelid inserts implantation can instead tarsal plate for the reconstruction of medium to large areas lower eyelid defect, which is easy performing with rare complications. It is an ideal alternatives of tarsal plate.

Osmanthus fragrans, or “RiXiangGui”, is an ornamental, woody, evergreen plant that is cultivated widely because it blooms recurrently and emits a strong fragrance. Recently, the germplasm resources, classification, and aroma compositions of O. fragrans have been investigated. However, the molecular mechanisms of the floral scent formation and regulation have remained largely unknown. To obtain a global perspective on the molecular mechanism of the aroma formation during blooming, nine RNA Sequencing (RNA-Seq) libraries were constructed from three flowering stages: The initial, full, and final flowering stage. In short, a total of 523,961,310 high-quality clean reads were assembled into 136,611unigenes, with an average sequence length of 792 bp. About 47.43% of the unigenes (64,795) could be annotated in the NCBI non-redundant protein database. A number of candidate genes were identified in the terpenoid metabolic pathways and 1327 transcription factors (TFs), which showed differential expression patterns among the floral scent formation stages, were also identified, especially OfMYB1, OfMYB6, OfWRKY1, and OfWRKY3, which could play critical roles in the floral scent formation. These results indicated that the floral scent formation of O. fragrans was a very complex process which involved a large number of TFs. This study provides reliable resources for further studies of the O.fragrans floral scent formation.

AIM: To compare the optometric examination results of myopic young children between those diagnosed in the period from 1998 to 2000 and those diagnosed in the period from 2008 to 2010; and to find out the causes of myopia and factors that worsen the condition, and suggest methods of its prevention and treatment.METHODS: This study was a retrospective case study. We randomly selected sample from out-patient department register of cases and divided them into two main groups, ‘ten year before group'(TYBG)(1998/2000 year cases)and ‘ten years later group'(2008/2010 year cases)(TYLG). Each group was further subdivided into three sub-groups by age: under-six years old children group(CG), seven-twelve years old primary-school group(PSG)and thirteen-eighteen years old middle-school group(MSG). The optometric examination results were statistically analyzed.RESULTS: The difference of the mean dioptre between the TYBG and TYLG was strongly statistically significant, also forward-lead trend of age when children suffered from myopia was found(P<0.01). There was a significant increase of dioptre among PSG and MSG in TYLG compared to TYBG(PCONCLUSION: Our study shows that the age of getting myopia was forward lead, the dioptre increases by 1.00 degree and the prevalence of myopia is increasing gradually. This situation may due to the modern life style and changes of living standard of the population. Therefore, prevention of myopia should concentrate more on younger children at kindergarten and primary school stage students.

In the title three-dimensional coordination polymer, [Cd(N3)2(C8H10N4)]n, the coordination geometry around the CdII atom is distorted octahedral. The CdII atom is coordinated by two N atoms from two cis-positioned bridging 1,2-bis(imidazol-1-yl)ethane (bime) ligands and four N atoms from four azide anions. Each azide ligand acts in an end-on bridging coordination mode. The azide ligands and CdII atoms form a one-dimensional zigzag chain constructed from four-membered [Cd(N3)2]n metallacycles extending along the a axis. These inorganic chains are connected with four other chains via bridging bime ligands to form a three-dimensional coordination network.

This paper is concerned with the finite-time synchronization problem for two different chaotic systems with parameter uncertainties. Using finite-time control approach and robust control method, an adaptive synchronization scheme is proposed to make the synchronization errors of the systems with parameter uncertainties zero in a finite time. On the basis of Lyapunov stability theory, appropriate adaptive laws are derived to deal with the unknown parameters of the systems. And the convergence of the parameter errors is guaranteed in a finite time. The proposed method can be applied to a variety of chaos systems. Numerical simulations are given to demonstrate the efficiency of the proposed control scheme.

Single crystals of the title compound, dipotassium aluminium tin(IV) tris[phosphate(V)], K2AlSn(PO4)3, were synthesized by a high temperature reaction in a platinum crucible. In the structure, the AlIII and SnIV atoms occupy the same site on a threefold rotation axis with occupational disorder in a 1:1 ratio. In the three-dimensional structure, Al/SnO6 octahedra and PO4 tetrahedra are interconnected via their vertices, yielding a [Al/SnP3O12]n framework. The K atoms (site symmetry 3) reside in the large cavities delimited by the [Al/SnP3O12]n framework, and are surrounded by 12 O atoms.

In the title coordination polymer, [HgBr2(C14H10N4S2)]n, the HgII atom is four-coordinated in a distorted tetrahedral geometry by the two N atoms of the pyridyl groups of different 3,6-bis(2-pyridylsulfanyl)pyridazine ligands and two Br atoms. The bridging function of the cis ligands leads to a helical chain structure along [100].

In the title compound, 2C18H16N2O2·H2O, the dihedral angles between the quinoline rings and the benzene rings in the two independent acetamide molecules are 80.09 (5) and 61.23 (5)°. The crystal packing is stablized by O—H...N and N—H...O hydrogen bonds between the acetamide and water molecules.