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Gene expression and proper downstream cellular functions upon facing environmental shifts depend on the combined and cooperative regulation of genetic networks. Here, we identified cAMP receptor protein (CRP) as a master regulator of (p)ppGpp (guanosine tetra- and penta-phosphate) homeostasis. Via CRP-mediated direct transcriptional regulation of the (p)ppGpp synthetase/hydrolase RelA and SpoT, cAMP-CRP stimulates pervasive accumulation of (p)ppGpp under glucose-limiting conditions. Notably, CRP exerts a nonclassical property as a translational regulator through YfiQ-dependent acetylation of ribosome protein S1 at K247, which further enhances the translation of RelA, SpoT, and CRP itself. From a synthetic biology perspective, this self-activating feedback loop for (p)ppGpp synthesis highlights the function of C RP- m ediated d ual e nhancement (CMDE) in controlling bacterial gene expression, which enables stable activation of genetic circuits. CMDE applied in synthetic circuits leads to a stable increase in p -coumaric acid, cinnamic acid, and pinosylvin production. Our findings showed that CRP-mediated dual circuits for (p)ppGpp regulation enable robust activation that could address bioproduction and other biotechnological needs.IMPORTANCETranscriptional-translational coordination is fundamental for rapid and efficient gene expression in most bacteria. Here, we uncovered the roles of cAMP-CRP in this process. We found that CRP distinctly increases RelA and SpoT transcription and translation, and that acetylation of S1 at K247 accelerates the self-activation of the leading CRP under glucose-limiting conditions. We further found that elevated (p)ppGpp significantly impedes the formation of the cAMP-CRP complex, an active form responsible for transcriptional activation. A model was created in which cAMP-CRP and (p)ppGpp cooperate to dynamically modulate the efficiency of transcriptional-translational coordination responses to stress. More broadly, productive activation in synthetic circuits was achieved through the application of C RP- m ediated d ual e nhancement (CMDE), promising to inspire new approaches for the development of cell-based biotechnologies., Competing Interests: The authors declare no conflict of interest.

This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome's functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4 , a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function., Importance: Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity., Competing Interests: The authors declare no conflict of interest.

Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3',5'-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase D NA i ntegrity s canning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis., Competing Interests: The authors declare no conflict of interest.

Benzene, as a major indoor pollutant, has received widespread attention. In order to better control indoor benzene pollution and protect people's health, the limit value of benzene in the"Standards for indoor air quality (GB/T 18883-2022)'' was reduced from 0.11 mg/m 3 to 0.03 mg/m 3 . This study reviewed and discussed the relevant technical contents of the determination of benzene limit value, including the exposure status of benzene, health effects, and derivation of the limit value. It also proposed prospects for the future direction of formulating indoor air benzene standards.

Objective: To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice. Methods: Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n =5) and a high-fat feeding modeling group ( n =15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n =7) and a UC-MSCs treatment group ( n =7). The UC-MSCs treatment group was given UC-MSCs (1×10 6 /0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro , then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results: In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P <0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P =0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions: UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

In this study, we evaluated a novel functional monomer (4-formylphenyl acrylate [FA]) that can specifically and covalently bind to the dentin collagen matrix as a potential alternative hydrophobic diluent-like monomer for improving the durability of dentin bonding. Experimental adhesives with different FA contents (0%, 10%, 20%, and 30%) were evaluated as partial substituents for the hydrophilic monomer 2-hydroxyethyl methacrylate, with the commercial adhesive One-Step (Bisco, Inc.) employed as the positive control. Their degree of conversion, viscosity, hydrophobicity, mechanical properties, and water absorption/solubility were measured as the comprehensive characterization. In situ zymographic assays were performed to determine the extent to which FA inhibits the endogenous hydrolytic activity of dentin. Finally, the bonding performances of the novel adhesives were evaluated with microtensile strength tests and scanning electron microscopy. The results showed that the incorporation of FA significantly improved the mobility of experimental adhesives attributable to the dilution property of FA. In contrast to the possible compromised rate of polymerization by hydroxyethyl methacrylate, FA exhibited typical characteristics of favorable copolymerization with polymerizable monomers in adhesives and improved the degree of conversion of experimental adhesives. The rigidity and hydrophobic properties of the phenyl framework of the FA molecule conferred superior mechanical properties and hydrolysis resistance to the novel experimental adhesives. An inhibitory effect on gelatinolytic activities within the hybrid layer was also observed in the in situ zymographic assays, even at a low FA concentration (10%). In conjunction with the significantly improved infiltration found via scanning electron microscopy, the experimental adhesives containing FA possessed significantly better-maintained microtensile strength, even after aging. Thus, the incorporation of this novel monomer endowed the experimental adhesives with multiple enhanced functionalities. These remarkable advantages highlight the suitability of the monomer for further applications in clinical practice.

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs . 0.0 (0.0, 1.0); Z =-12.41, P <0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P >0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs . 1.0 (0.5, 2.0); Z =-4.38, P <0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

Objective: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD)., Methods: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING., Results: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane., Conclusions: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes., Methods: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year., Results: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and &lt; 0.01, respectively)., Conclusion: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes., Trial Registration: Not Applicable., (© 2022. The Author(s).)

The dentin collagen matrix that is not completely enveloped by resin adhesive is vulnerable to degradation by intrinsic collagenases during the etch-and-rinse process, which contributes to the deterioration of the bonding interface. Current commercial adhesives have no functional components that can form covalent bonds to the dentin collagen matrix. In this study, a photocurable aldehyde, 4-formylphenyl acrylate (FA), was synthesized and for the first time applied as a primer in adhesive dentistry to covalently bind to collagen. Experimental groups with different concentrations of FA (1%, 3%, 5%, 7%, 9%) were prepared as primers. The cytotoxicity was evaluated by live/dead-cell staining and thiazolyl blue tetrazolium bromide assay. The interaction of FA with collagen was examined by attenuated total reflection Fourier transform infrared spectroscopy, hydroxyproline release under the degradation of type I collagenase, and thermogravimetric analysis. An optimal group was selected based on the degree of conversion of 2 universal adhesives and further divided depending on the treatment time (20 s, 30 s, 1 min, 2 min). The bonding performances were evaluated by microtensile strength before and after aging. Finally, the bonding interface was observed under confocal laser scanning microscopy and scanning electron microscope. The results indicated that FA demonstrated good biocompatibility, dentin modification capability, and infiltration. It not only effectively cross-linked dentin collagen to improve its stability against enzymatic hydrolysis and modify the adhesive interface but also potentially acted as a diluting monomer to induce deep penetration of adhesive resin monomers into the dentin. The bonding strength after aging was improved without jeopardizing the degree of conversion of 2 commercial adhesives. Such prominent advantages of using FA to improve the bonding performance promotes its further application in adhesive dentistry.

Metabolism regulation centred on insulin resistance is increasingly important in nonalcoholic fatty liver disease (NAFLD). This review focuses on the interactions between the host cellular and gut microbial metabolism during the development of NAFLD. The cellular metabolism of essential nutrients, such as glucose, lipids and amino acids, is reconstructed with inflammation, immune mechanisms and oxidative stress, and these alterations modify the intestinal, hepatic and systemic environments, and regulate the composition and activity of gut microbes. Microbial metabolites, such as short-chain fatty acids, secondary bile acids, protein fermentation products, choline and ethanol and bacterial toxicants, such as lipopolysaccharides, peptidoglycans and bacterial DNA, play vital roles in NAFLD. The microbe-metabolite relationship is crucial for the modulation of intestinal microbial composition and metabolic activity. The intestinal microbiota and their metabolites participate in epithelial cell metabolism via a series of cell receptors and signalling pathways and remodel the metabolism of various cells in the liver via the gut-liver axis. Microbial metabolic manipulation is a promising strategy for NAFLD prevention, but larger-sampled clinical trials are required for future application., (© 2021 The Society for Applied Microbiology.)

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group ( P all<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P <0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth( OR =1.239,95% CI 1.036-1.442, P =0.023), aortic angulation( OR =1.128, 95% CI 1.044-1.312, P =0.038)and LVOT tract coverage index ( OR =1.123, 95% CI 1.003-1.315, P =0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve ( AUC )=0.697, 95% CI 0.554-0.851, P =0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

The article "LncRNA DLEU1 accelerates the malignant progression of clear cell renal cell carcinoma via regulating miRNA-194-5p, by G.-Z. He, S.-Y. Yu, Q.-P. Zhou, M.-L. Chen, Y.-W. Zhang, Y. Zheng, Z.-B. Zhang, Z.-Y. Han, J. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10691-10698-DOI: 10.26355/eurrev&#95;201912&#95;19768-PMID 31858537" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19768.

Objective: To investigate the clinical value of carbon nanoparticles zonal tracer technique in lymph node retrieval of gastric cancer (GC). Methods: A retrospective cohort study was carried out. Clinicopathological data of GC patients who underwent radical D2 resection with carbon nanoparticles tracer in The First Affiliated Hospital of Hainan Medical University and Hainan Cancer Hospital from December 2015 and February 2019 were collected. Those with postoperative pathology of T1-2, Borrmann IV type GC, distant metastasis, preoperative neoadjuvant chemotherapy and incomplete data were excluded. A total of 181 patients were enrolled in this study, including 113 cases from the First Affiliated Hospital of Hainan Medical University and 68 cases from Hainan Cancer Hospital. Patients were categorized into two groups based on the methods of carbon nanoparticles tracer: zonal tracer group and traditional tracer group. In the traditional tracer group, 0.1-0.3 ml of carbon nanoparticle was injected subserously at the upper, lower, left and right 4 injection points 0.5 cm away from the edge of the tumor in the normal serous membrane. In the zonal tracer group, on the basis of the traditional tracer group, 0.1-0.3 ml of carbon nanoparticle was injected subserously at the first branch of the suprapyloric right gastric artery into the stomach, the first branch of the subpyloric right gastroepiploic artery into the stomach, the first branch of the minor curvature left gastric artery into the stomach and the first branch of the greater curvature left gastroepiploic artery into the stomach, respectively. The display of lymphatic vessels in each location and lymph nodes in each group by the tracing method was observed. The number of black-stained lymph nodes, the black staining rate of lymph nodes, the total number of detected lymph nodes, the total number of positive lymph nodes, and the metastatic rate of lymph node were compared between the two groups. Results: Eighty-nine patients were assigned to zonal tracer group, and 92 patients to traditional tracer group. There were no significant differences in baseline information between the two groups (all P >0.05). The median number of black-stained lymph nodes (median: 25.0 vs. 13.5, Z =-7.158, P <0.001) and the black staining rate of lymph nodes [(70.8±12.0)% vs. (47.1±15.7)%, t =11.399, P <0.001) in the zonal tracer group were significantly higher than those in the traditional tracer group. The total detected number of lymph nodes (37.5±11.5 vs. 29.6±11.8, t =4.581, P <0.001) and the total number of negative lymph nodes (31.3±12.5 vs. 24.9±11.1, t =3.621, P <0.001) were significantly higher in the zonal tracer group than those in the traditional tracer group. There were no significant differences in the total number of positive lymph nodes (median: 4.0 vs. 3.0, Z =-1.485, P =0.137), lymph node metastatic rate [78.7% (70/89) vs. 72.8% (67/92), χ(2)=0.834, P =0.361] and metastatic degree [median: 11% vs. 10%, Z =-0.483, P =0.629] between the two groups. Conclusion: The carbon nanoparticles zonal tracer method can increase the black-staining rate of lymph nodes and the detected number of lymph nodes, thus improving the accuracy of gastric cancer staging.

Objective: To study the clinical application effect of modified nasopharyngeal swab sampling for 2019 novel coronavirus nucleic acid detection. Methods: This study covered the period from January 14 to March 1, 2020.The supine position method and the protective face screen were used to collect nasopharyngeal swabs from February 24 onwards, before which, the nasopharyngeal swabs were collected by sitting position method. All the patients who were diagnosed with suspected/confirmed 2019 novel coronavirus infection were admitted from February 19 with the nasopharyngeal swabs collected outside the hospital before admission. (1) Thirty-four swabbing operators meeting the inclusion criteria of the study were recruited in this retrospective cohort study. They were grouped according to the collection method of nasopharyngeal swabs. Sixteen operators of Wuhan Taikang Tongji Hospital who applied the supine position method and the protective face screen were included in supine position method+ protective face screen group (15 males and 1 female, aged 34-49 years); 18 operators (12 from the First Affiliated Hospital of Army Medical University (the Third Military Medical University), 1 from Wuhan Jiangxia Mobile Cabin Hospital, 5 from the East District of People's Hospital of Wuhan University) who applied the traditional sitting position method were included in sitting position method group (2 males and 16 females, aged 25-49 years). In supine position method+ protective face screen group, when collecting sample, the patient lay flat and wore a special protective face screen for nasopharyngeal swab sampling, with neck slightly extending and face turning to the opposite side of the operator about 10°. The self-designed questionnaire was used to investigate the cooperation, the incidence of nausea, coughing, sneezing, and struggling of patients evaluated by the operators, the operation time for a single swab sample, the fear of operation and the perceived exposure risk of operators in the two groups. (2) Sixty-five patients (22 males and 43 females, aged 25-91 years) admitted to Wuhan Taikang Tongji Hospital who successively received the sitting position method and supine position method+ protective face screen for nasopharyngeal swabs sampling and with complete nucleic acid detection results were included. The positive rates of nucleic acid detection by the two sampling methods of nasopharyngeal swabs of the patients were statistically analyzed. (3) Forty-one patients who could express their feelings accurately were selected out of those 65 patients (12 males and 29 females, aged 27-83 years). The comfort of patients in the process of sampling by the two methods was investigated. (4) Thirty-four patients (10 males and 24 females, aged 25-83 years) with two or more consecutive negative results of nucleic acid detection of nasopharyngeal swabs by sitting position method were selected from the above 65 patients. The positive rate of nucleic acid detection of nasopharyngeal swab of patients by supine position method+ protective face screen, i. e. negative to positive rate was statistically analyzed. Data were statistically analyzed with t test, Wilcoxon signed rank test, and chi-square test. Results: (1) Compared with those of sitting position method group, the cooperation score of patients evaluated by the operators in supine position method+ protective face screen group was significantly higher ( Z =-4.928, P <0.01), the incidence of nausea, choking cough, sneezing, and struggling of patients evaluated by the operators, and the fear of operation score and the perceived exposure risk score of operators in supine position method+ protective face screen group were significantly lower ( Z =-5.071, -5.046, -4.095, -4.397, -4.174, -5.049, P <0.01), and the operation time for a single swab sample in supine position method+ protective face screen group was significantly longer ( t =223.17, P <0.01). (2) The positive rate of nucleic acid detection of nasopharyngeal swabs by supine position method+ protective face screen was 60.00% (39/65), which was obviously higher than 41.54% (27/65) by sitting position method ( χ (2)=4.432, P <0.05). (3) The comfort score of the 41 patients during nasopharyngeal swabs sampling by supine position method+ protective face screen was significantly higher than that by sitting position method ( Z =-5.319, P <0.01). (4) Of the 34 patients with two or more consecutive negative results of nucleic acid detection of nasopharyngeal swabs by sitting position method, the rate of negative to positive of nucleic acid detection was 26.47% (9/34) after sampling by supine position method+ protective face screen. Conclusions: Compared with the traditional sitting position method, detection of 2019 novel coronavirus nucleic acids of nasopharyngeal swabs collected by supine method combined with protective face screen is worth promoting, because of its better comfort of patients, low exposure risk for operators, in addition to reducing in the false negative result to some extent, which may help reduce false recurrence of discharged patients.

Objective: To explore the short-term effects of ambient PM 2.5 on the outpatient visits of allergic conjunctivitis among children in Shenzhen. Methods: It was a ecological study. Data on daily visits including date of visit, sex and age from children with allergic conjunctivitis were collected from Shenzhen Eye Hospital and Shenzhen Children's Hospital in 2018. Related data on air pollution (PM 2.5 , PM 10 , SO 2 , NO 2 , CO and O 3 ) and meteorology (atmospheric pressure, temperature and relative humidity) were also collected. Pearson correlation analysis was used for normal distribution data and Spearman rank correlation analysis was used for non-normal distribution data. Generalized additive model was used to estimate the impact of PM 2.5 pollution on allergic conjunctivitis outpatients and the lagging effects. Results: In 2018, there were 16 133 allergic conjunctivitis outpatients in the two hospitals. The maximum age was 18 years and the minimum age was 2 months. Males accounted for 49.3%. The daily average concentration of PM 2.5 was 22 (15, 31) μg/m 3 . Changes of the concentration of PM 2.5 had a positive correlation with the amount of allergic conjunctivitis visits, and the Spearman correlation coefficient was 0.150 ( P =0.004). The single pollutant model showed that the strongest effect appeared at 3 days ( RR =1.111， 95% CI :1.071-1.152). A 10 μg/m 3 increase of PM 2.5 would result in an excessive number of allergic conjunctivitis outpatients as much as 11.112% (95% CI ：7.011%-15.212%). In the multiple air pollutants models, after the introduction of NO 2 , O 3 and CO, the concentration of PM 2.5 showed an enhanced effect on the number of hospital visits due to allergic conjunctivitis on the same day, and the difference was statistically significant ( P <0.05). Conclusion: Changes of the concentration of PM 2.5 h ad a positive correlation with daily outpatient visits of allergic conjunctivitis among children in Shenzhen. (Chin J Ophthalmol, 2020, 56: 608-614) .

Coronavirus disease 2019 (COVID-19) can cause great damage to the elderly patients and lead to high mortality. The clinical presentations and auxiliary examinations of the elderly patients with COVID-19 are atypical, due to the physiological ageing deterioration and basal pathological state. The treatment strategy for the elderly patients has its own characteristics and treatment protocol should be considered accordingly. To improve the diagnosis, treatment, and prevention of COVID-19 in the elderly, the Expert Committee of Geriatric Respiratory and Critical Care Medicine, China Society of Geriatrics established the "Expert consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly" . We focused on the clinical characteristics and key points for better treatment and prevention of COVID-19 in the elderly. (1) For diagnosis, atypical clinical presentation of COVID-19 in the elderly should be emphasized, which may be complicated by underlying disease. (2) For treatment, strategy of multiple disciplinary team (mainly the respiratory and critical care medicine) should be adopted and multiple systemic functions should be considered. (3) For prevention, health care model about integrated management of acute and chronic diseases, in and out of hospital should be applied.

Objective: To investigate the electrophysiological features of patients with subacute combined degeneration (SCD). Methods: The electrophysiological data of 85 hospitalized patients in Department of Neurology, First Medical Centre, Chinese PLA General Hospital from January 2014 to September 2018 were retrospectively analyzed. Results: Abnormality rate of motor nerve conduction (27.4%(93/339)) was lower than that of sensory nerve conduction (45.9%(107/233)) ( P< 0.001). Abnormality of sensory nerve action potential amplitude was more frequent than conduction velocity abnormality (22.7%(53/233) vs 4.7%(11/233), P= 0.001). Abnormality rate of needle electromyogram (EMG) was higher in lower limbs than upper limbs (31.9%(59/185) vs 5.7%(5/87), P< 0.001). Spontaneous potentials were unrelated to disease duration or severity. Abnormal somatosensory evoked potential (SEP) results appeared more frequent in lower limbs (80.8%(118/146)) than upper limbs (61.1%(77/126)) ( P< 0.001). SEP abnormalities (71.7%(195/272)) were more common than nerve conduction abnormalities (35.0%(200/572)). Abnormal findings presented in 15/16 of visual evoked potential (VEP) studies. Neurological severity score were correlated with electrophysiological findings. Conclusions: Posterior funiculus is more likely to be affected than peripheral nerves in SCD patients. The sensory nerves rather than motor nerves, lower limbs rather than upper limbs, axons of sensory nerves rather than myelin, are more severely affected. Electrophysiological tests can provide evidence in early diagnosis, lesions location, and disease severity evaluation for SCD.

Objective: To analyze the relationship of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) with diabetes mellitus in community residents aged ≥15 years in Pudong new district of Shanghai, and provide evidence for the prevention and treatment of diabetes mellitus. Methods: Using multi-stage stratified cluster sampling method, a total of 7 194 community residents aged ≥15 years were surveyed by using questionnaire, physical examination and laboratory tests in 2016. The relationship of BMI, waist circumference and waist-hip ratio with diabetes mellitus was analyzed by χ (2) test, single factor linear correlation and logistic regression analyses. Results: In 2016, the crude prevalence rate of diabetes mellitus in Pudong was 27.37 % , which was 12.75 % after standardization. The prevalence rate of diabetes mellitus was slightly higher in men than in women and was increased with age. The levels of FPG, 2 h plasma glucose and HbA1c were positively correlated with BMI, WC and WHR. After adjusting the confounding factors, multiple logistic regression analysis showed that obesity ( OR =1.351, P <0.01), excessive waist circumference ( OR =1.255, P <0.01) and high WHR ( OR =1.291, P <0.01) were risk factors for diabetes mellitus. Conclusions: The increase of obesity, WC and WHR will increase the risk for diabetes mellitus. It is important to maintain healthy weight, especially the control of WC and WHR, reduce the accumulation of abdominal fat to reduce the risk for diabetes mellitus.

Objective: The aim of this study was to illustrate the role of long non-coding RNA (lncRNA) DLEU1 in regulating the malignant progression of clear cell renal cell carcinoma (ccRCC) by targeting microRNA-194-5p (miRNA-194-5p)., Patients and Methods: DLEU1 expression level in ccRCC tissues and para-cancerous tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between DLEU1 expression and pathological indexes of ccRCC patients was assessed. After the silence of DLUE1, the proliferative and migratory abilities of ACHN and 786-O cells were evaluated. Furthermore, Dual-Luciferase reporter gene assay and rescue experiments were conducted to identify the role of DLEU1/miRNA-194-5p in regulating the ccRCC progression in vitro., Results: DLEU1 expression was markedly up-regulated in ccRCC tissues when compared with para-cancerous tissues. The rates of lymphatic metastasis and distant metastasis in ccRCC patients with a high level of DLEU1 were significantly higher, whereas the prognosis was significantly worse. Transfection of si-DLEU1 remarkably attenuated proliferative and migratory abilities of ACHN and 786-O cells. MiRNA-194-5p was identified as the target gene of DLEU1. In addition, the knockdown of miRNA-194-5p could reverse the regulatory effect of DLEU1 on the proliferative and metastatic abilities of ccRCC., Conclusions: DLEU1 is closely related to lymphatic metastasis, distant metastasis, and poor prognosis of ccRCC. It aggravates the progression of ccRCC by targeting miRNA-194-5p.

Purpose: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures., Methods: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year., Results: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs., Conclusion: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.

Objective: The current study aimed to examine the role and mechanism of a conserved long noncoding RNA termed NORAD (noncoding RNA activated by DNA damage, also named LINC00657) in gastric cancer (GC) progression., Patients and Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine the expression level of relevant genes in GC cell lines. Cell proliferation was examined by cell counting kit-8 (CCK-8) assays. Cell migration and invasion were detected by transwell migration and invasion assays. Protein levels of the indicated genes were detected by Western blotting. Cell apoptosis was examined by flow cytometry., Results: Results showed that NORAD knockdown decreased cell proliferation, migration and invasion but increased cell apoptosis. NORAD knockdown affected the expression of genes related to apoptosis and Epithelial-Mesenchymal Transition (EMT). In addition, NORAD's depletion resulted in reduced Ras Homolog Family Member A (RhoA) and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) expression. Furthermore, NORAD's expression was positively correlated with RhoA and ROCK1 expressions in GC based on The Cancer Genome Atlas (TCGA) database., Conclusions: Our results demonstrate the oncogenic role of NORAD in gastric cancer progression.

Objective: To evaluate the efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism(PE). Methods: PE was diagnosed by CT pulmonary angiography(CTPA). After risk stratification, a total of 79 PE patients (age (58.9±14.9) years old)were treated with catheter-directed interventional therapy via pulmonary vessels. The changes of pulmonary hemodynamics were compared before and after treatment. The risk of complications and side effects were observed. Results: The pulmonary artery pressure was changed followed by interventional therapy. The interventional therapy significantly decreased mean pulmonary arterial pressure (mPAP) from (35.3±11.2)mmHg (1 mmHg=0.133 kPa) to (30.0±10.6)mmHg ( t= 8.803, P< 0.05) and the echocardiographic derived right ventricular dimension to left ventricular dimension (RV/LV) ratio from 0.93±0.16 to 0.83±0.15 ( t= 6.868, P< 0.05). The arterial partial pressure of oxygen was increased from (69.0±8.6)mmHg to (75.1±9.9)mmHg ( t= 8.561, P< 0.05) . The oxygen saturation was also increased from (93.9±2.9)% to (95.1±1.9)% at 24 h after the treatment ( t= 2.621, P< 0.05) . Patients were further grouped as high-risk group ( n= 28) and intermediate risk group ( n= 51). mPAP and RV/LV ratio were significantly reduced in the two subgroups (all P< 0.05) and the range of reduction was more significant in the high-risk group. Five patients experienced minor bleeding complication, 3 patients suffered worsened dispone post procedure and were treated with mechanical ventilation, 1 patient died, and 1 patient developed recurrent PE. Conclusion: The catheter-directed interventional therapy improves pulmonary hemodynamics and reduces load of right ventricle both in high-risk or intermediate risk PE patients, this therapy strategy is safe and effective for patients with PE.

Objective: To evaluate the intervention effects of response to heatwave in communities of four cities, China. Methods: Baseline survey on heatwave and climate change related knowledge, attitude and practice (KAP) was conducted in the pilot communities in Harbin, Nanjing, Shenzhen and Chongqing, using face-to-face questionnaire interview in November, 2011 to November, 2013. Finally, 1 604 residents were interviewed. Intervention measures were implemented in summers of 2013 and 2014, including delivering early warning information of heatwave health risk and launching health education and promotion. The second survey was conducted in same communities using the same questionnaire and sampling method as baseline survey in November, 2014, and 1 640 residents were interviewed. The Chi-square test was used to compare the demographic characteristics and KAP of community residents between before and after intervention, and the factors that affected the intervention effect were selected by logistic multiple stepwise regression model. Results: The age of the residents interviewed before and after intervention was (46.4 ± 15.5) years and (45.0 ± 15.9) years, respectively. Overall, the residents' awareness rates of heatwave before and after intervention were 70.5% (1 131/1 604) and 82.9% (1 359/1 640) (χ 2 =69.40, P< 0.001). The rate of residents who had wished to receive early warning information increased 6.3% (χ 2 =41.11, P< 0.001), which reached 94.6% (1 551/1 604) after intervention from 88.3% (1 416/1 604) in baseline survey. Both heatwave health risk early warning and health education had big impacts to residents. There were 92.7% (1 105 residents) among the 1 192 residents who had received the early warning information arrange work and rest time according to the early warning information and 93.0% (1 231 residents) among the 1 323 residents who knew about health education activities being conducted in community thought that the community health education activities had made active role in protecting health from heatwaves. After a series of intervention, male had a effect on attitude about hot wave than female in Nanjing and Chongqing, OR (95 %CI ) were 1.48(1.02-2.16) and 1.45 (1.18-2.05) , respectively; compared with subjects below primary school education, people with college degree or above had higer KAP in all cities ( ORs range from 1.18 to 2.05), P< 0.05; regular physical exercise ( ORs range from 1.39 to 2.70) also had profound impacts on KAP in all cities ( P< 0.05). Conclusion: s Early warning and health education were effective measures to enhance residents' response capacity to climate change.

Background: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures., Methods: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342)., Results: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change., Conclusions: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

Objective: To assess the association between the concentration of the air pollutant PM 2.5 and daily outpatient visits for respiratory disease. Methods: All records of daily outpatient visits to three hospitals in Shenzhen from January 1 to December 31, 2013 were collected. Daily air pollution monitoring and meteorology data from the same period were also collected in Shenzhen. The data were analyzed using a semiparametric generalized additive model with Poisson distribution of time series analysis controlling for long-term and seasonal trends, flu, DOW, public holidays, and meteorological factors. The excess risk( ER )of respiratory disease and its 95% CI value were calculated, along with the incremental increase of 10 μg/m 3 in PM 2.5 concentration. Results: Number of outpatient visits for respiratory diseases totaled 1 428 672(daily range: 1 790-5 228). The annual average PM 2.5 concentration was 40.2 μg/m 3 (daily range: 7.2-137.1 μg/m 3 ). The lag1 factor had the most significant impact on the lag effect. We estimated that a 10 μ g/m 3 increase in day-before PM 2.5 concentration was associated with a 1.809%(95% CI : 1.709%-1.909%) ER of visits for respiratory disease. After controlling for other pollutants(NO 2 , CO, and O 3 ), the effect remained stable. When NO 2 , CO, and O 3 were introduced separately, for every 10 μg/m 3 rise in PM 2.5 concentration, the excess risk of daily outpatient visits for respiratory disease was 1.814%(95% CI : 1.706%-1.923%), 2.780%(95% CI : 2.668%-2.892%), and 1.513%(95% CI : 1.403%-1.624%), respectively. With simultaneous control of NO 2 and O 3 , NO 2 and CO, and CO and O 3 , for every 10 μg/m 3 rise in PM 2.5 concentration, the excess risk of respiratory disease was 1.369%(95% CI : 1.242%-1.497%), 2.709%(95% CI : 2.590%-2.828%), and 2.577%(95% CI : 2.452%-2.702%), respectively. With simultaneous control of NO 2 , CO, and O 3 , for every 10 μg/m 3 rise in PM 2.5 concentration, the excess risk of respiratory disease was 2.370%(95% CI : 2.231%-2.509%). Conclusions: PM 2.5 can increase the risk of outpatient visits for respiratory disease in Shenzhen.

Depression is a common neuropsychiatric disorder which has been associated with a wide range of structural and functional changes within specific brain regions. Ginsenoside Rg1 has been shown to exert a number of neuroprotective effects as demonstrated in various in vivo and in vitro studies. However, little information is available regarding the site and mechanisms of ginsenoside Rg1 in promoting antidepressant effects. The present study aimed to investigate the neuroprotective and ameliorating effects of ginsenoside Rg1 on depression-like behavior as induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS was effective in producing depression-like behaviors in rats as indicated by decreased responses in sucrose preference and forced swim tests which were associated with ultrastructural changes in neurons within the amygdala. Moreover, levels of PKA and CREB phosphorylation and the expression of brain-derived neurotrophic factor (BDNF) were decreased in the amygdala of CUMS rats. Remarkably, chronic ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) treatment significantly ameliorated these behavioral and biochemical alterations associated with CUMS-induced depression. Taken together, the results of the present study demonstrate that ginsenoside Rg1 exhibits antidepressant-like effects against CUMS-induced depression. This amelioration of depression-like behaviors by ginsenoside Rg1 appears to be mediated, at least in part, by a CREB-regulated increase of BDNF expression in the amygdala of rats. Therefore, these findings reveal the therapeutic potential of ginsenoside Rg1 for use in clinical trials in the treatment of depression., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

We sought to determine the predictors of primary episodes of mild diastolic dysfunction (DD) in a cohort of women aged >45 years, who had >2 echocardiography from 2009 to 2012. Patients were excluded if they had prior diagnosis of coronary artery disease, heart failure, valvular heart disease or echocardiographic evidence of DD. Mild DD was defined as: left ventricular ejection fraction>50%, E/A ratio<0.75, and E/e'⩽8. Out of the total 758 subjects (age 64.15±7.24 years), 109 (14.3%) had developed mild DD, during a mean followup period of 3 years. Independent predictors of mild DD included: age (P<0.001), history of hypertension (P=0.022), body mass index (BMI) (P<0.001), total triglycerides (TG) (P=0.016), inter ventricular septal thickness (P=0.015) and brachial-ankle pulse wave velocity (baPWV) ⩾16 m s(-1) (P<0.001). E/A ratio was inversely associated with age (r=-0.337, P<0.001), baPWV (r=-0.359, P<0.001), BMI (r=-0.290, P<0.001) and TG (r=-0.255, P<0.001). The Area Under roc Curve for a linear combination of age, BMI, baPWV and TG was 0.738 (95% confidence interval: 0.683-0.804, P<0.001), which was superior to any of the variables taken alone. In summary, many middle-aged or elderly women may develop mild DD within a relatively short period of 3 years. Several subclinical abnormalities and cardiovascular parameters were determined to contribute to the onset of DD.

Objective: In this study, we investigated the molecule mechanisms of podocyte injury and proteinuria and the protective effects of losartan., Methods: This study set up three groups: a control group; an Ang II group (Ang II 10(-6) mol/l, Sigma); and a losartan group (losartan 10(-6) mol/l, Sigma). We used RT-PCR assay to detect TRPC6 mRNA expression, and Western blot to detect TRPC6 protein expression., Results: TRPC6 overexpression was the basic change of podocyte injury and proteinuria occurrence. Losartan can treat podocyte injury and proteinuria induced by Ang II via downregulation of TRPC6 in podocytes., Conclusion: These findings maybe provide an ideal drug target for the diagnosis and treatment of acquired glomerular diseases., (© The Author(s) 2015.)

This study aims to research the effect of dihydroartemisinin on the proliferation, metastasis and apoptosis in human osteosarcoma cells 143B and the underlying mechanism. This study designed five groups for experiment and control, using dimethylsulfoxide (DMSO), and docosahexaenoic acid (DHA) at concentrations of 15, 25, 35 μmol.L-1 respectively. Experiments including methyl thiazolyl tetrazolium (MTT) assay, clone formation assay, Hoechst 33258 staining assay, luciferase reporter plasmid assay, Western blot and scratch test were carried out. In addition, SPSS 18.0 software from IBM was used for statistical analysis and all the data obtained from the experiments were expressed as mean ± SD, and variance was used to compare the difference between the groups. DHA is proved to be able to inhibit the proliferation and metastasis of osteosarcoma cells, as well as leaving a positive effect on apoptosis in the cytomorphosis. It achieves regulation over the human osteosarcoma cells by keeping the expression of related protein under control.

Objective: To build a quantitative assessment system for normative cancer pain management., Patients and Methods: Two groups of 60 patients with malignant lower bowel obstruction were formed: the study group (n=30) patients receiving routine small intestinal decompression and enteral nutrition, and the control group (n=30) patients receiving nasogastric decompression and parenteral nutrition. The weight, protein indicators and occurrence of complications in the two groups were compared during the treatment., Results: The weight gain, increase of albumin and prealbumin, and complication rate were (1.9667 ± 1.38298) kg, (2.9133 ± 1.38258) g/L, (18.5333 ± 10.92840) mg/L and 26.67% in the study group compared with (0.6667±0.87428) kg, (1.5500 ± 0.72099) g/L, (12.9333 ± 8.47688) mg/L and 86.67% in the control group. There were statistically significant differences (t = -4,352,-4.789, -2.218; χ2 = 21.9910; p < 0.05 or p < 0.01) between the two groups., Conclusions: The application of small bowel decompression tubes can improve the nutritional status, physical fitness, reduce complications in patients with malignant lower intestinal obstruction.

Background: The aim of this study was to evaluate whether genetic variations in the transforming growth factor-β (TGF-β) pathway influenced clinical outcome of advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations treated with gefitinib., Patients and Methods: Two hundred six patients with advanced lung adenocarcinomas were enrolled in this study. EGFR mutation in these tumors was detected. Among them, 106 patients with EGFR mutation and 37 of 100 patients with wild type were treated with gefitinib. Genotype of 33 single-nucleotide polymorphisms (SNPs) from 13 genes involved in the TGF-β signaling pathway was determined, and their association with survival time was analyzed. Univariate and multivariate analyses were carried out to assess the role of biological/clinical parameters in progression-free survival (PFS) and overall survival (OS) using Pearson's χ(2) test, log-rank test, and Cox proportional hazards model., Results: Among SNPs analyzed, multivariate analysis showed the cytidylate and thymidine (CT) genotype of SMAD3: rs11632964 was associated with a longer OS and PFS when the entire cohort of 143 patients were included; the association was significant in the patients with EGFR mutant tumors (30.8 versus 17.5 months; log-rank P = 0.020; and 20.8 versus 9.4 months; log-rank P = 0.001), when compared with patients with wild-type EGFR tumors. In patients with mutant EGFR, the CT genotype of SMAD3: rs11071938 and the cytidylate and cytidylate genotype of SMAD3: rs6494633 were also found to be associated with better PFS. Dual luciferase reporter assays showed gefitinib-resistant PC9/G cells transfected with SMAD3: rs11632964T allelic reporter construct showed significantly lower luciferase activities compared with cells expression C allelic reporter construct. There was significantly decreased expression of SMAD3 and pi-SMAD3 in the PC-9/G cells compared with PC-9., Conclusions: Among the candidate genes involved in the TGF-β pathway, the polymorphisms of SMAD3 appear to be highly predictive of outcome of patients with lung adenocarcinoma after gefitinib treatment, especially in those with EGFR mutations., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The phosphorylation of nephrin plays an important role in maintaining the normal structure and function in podocytes. Dexamethasone (Dex) is usually used to treat glomerular diseases with proteinuria. In this study, we observated the effect of Dex and angiotensin II (AngII) on the change of nephrin phosphorylation in cultured podocytes. In vitro, cultured podocytes were exposed to AngII (10(-6) mol/L) pretreated with or without Dex (100 nM) for different time periods. Nck or Fyn were silenced by small interfering RNA (siRNA), nephrin and its phosphorylation expression were analyzed by Western blotting. In vitro, the phosphorylation of nephrin was significantly reduced after AngII stimulation (P < 0.05). Dex significantly resisted podocyte injury inducted by AngII via increasing the phosphorylation of nephrin (P < 0.05), siRNA silencing Nck can partially inhibited nephrin phosphorylation, siRNA silencing Fyn can completely inhibited nephrin phosphorylation. Phosphorylation of nephrin is important for the survival status of podocytes. Glucocorticoid treatment for human glomerulonephritis may exert its function by regulating Nck and Fyn complex to promote phosphorylation of nephrin. These results elucidate a novel mechanism of glucocorticoid treatment for glomerulonephritis.

Annexin A3 participates in various biological processes, including tumorigenesis, drug resistance, and metastasis. The aim of this study was to investigate the expression of Annexin A3 in gastric cancer and its relationship with cell differentiation, migration, and invasion of gastric cancer cells. Annexin A3 expression in gastric cancer tissues was detected by quantitative real-time PCR and Western blotting. The proliferation of gastric cancer cells was measured by the MTT assay. Cell migration and invasion were determined via wound healing and transwell assays, respectively. Knock down of endogenous Annexin A3 in gastric cancer BGC823 cells was performed using siRNA technology. The expression of Annexin A3 was significantly upregulated in gastric cancer tissues, and negatively correlated with the differentiation degree. Silencing of endogenous Annexin A3 suppressed the proliferation, migration, and invasion of BGC823 cells. Additionally, the expression of p21, p27, TIMP-1, and TIMP-2 was upregulated, and the expression of PCNA, cyclin D1, MMP-1, and MMP-2 decreased in cells treated with Annexin A3-siRNA. Annexin A3 was upregulated in gastric cancer cells. Deletion of endogenous Annexin A3 significantly inhibited gastric cancer cell proliferation, migration, and invasion.

The aim of this study was to characterize updated HIV subtypes in Yunnan to determine their origins and distribution within the population. RT-PCR of both the gag and env genes were sequenced from Yunnan province inhabitants newly diagnosed with HIV-1. Sequence data from 290 samples were used for statistical analysis of subtype distribution and phylogenetic tree construction. Distribution data were adjusted to account for different geographical distributions of HIV-1 subtypes in the population. Phylogenetic analysis revealed six HIV-1 subtypes in Yunnan, including eight types of unique recombination forms (URFs). The most prevalent subtypes in this province, CRF07&#95;BC (18·9%), CRF08&#95;BC (39·1%), CRF01&#95;AE (22·4%), and URFs (subtype C, 5·9% and subtype B, 4·5%), were all recombinants. We found significant differences in the distribution of these HIV-1 subtypes not only geographically, but also between various ethnic groups and with respect to transmission routes. Our findings indicate a complex population of HIV-1 subtypes, URFs, and recombinant subtypes in Yunnan province. This diversity could make the prevention and control of HIV infection in Yunnan more difficult due to the possibility of virus recombination or infection by multiple subtypes.

Podocyte impairment is a key pathogenic even in the initiation and development of glomerular diseases associated with proteinuria. The type 2 diabetic patients is characterized by progressive increases in albuminuria which are associated with the development of characteristic histopathological features. Losartan had a benefit in decreasing albuminuria in type 2 diabetic patients,suggesting that losartan may have another effect other than blockade of the traditional renin-angiotensin system (RAS). However, the mechanism has remained undetermined. Glucose transporter 1 (GLUT1) is the predominant basal glucose transporter. In the kidney, GLUT1 was overexpressed predominantly in glomerular mesangial cells and in small vessels, rather than in podocytes. The increased glomerular GLUT1 mimicked diabetes-induced glomerular GLUT1 expression. In this study, we hypothesized that increased GLUT1 expression induced by angiotensinII (AngII) contributes to the progression of podocytes injury, losartan can block the effect of AngII and protect podocytes via stabilizing the expression of GLUT1, our results strongly suggest that losartan has a direct and protective effect on podocytes. This represents a novel mechanism by which losartan may protect podocyte from apoptotic death and improve podocyte function via stabilizing the expression of GLUT1. This finding underlines the crucial role of GLUT1 in the pathogenesis of podocyte injury and proteinuria.

Using two-dimensional gel electrophoresis (2-DE), we examined proteomic changes in the caudal part of the spinal trigeminal nucleus induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus (ES-SSS) in conscious rats. After image analysis of 2-DE gels, nine protein spots of interest were excised from the gels and identified by liquid chromatography-tandem mass spectrometry. Among the nine, succinate semialdehyde dehydrogenase (SSADH) was found to be down-regulated after ES-SSS. This result was validated with Real-time polymerase chain reaction and Western blot analyses. Because SSADH degrades GABA, decreased expression of it increases the local concentration of GABA in the caudal part of the spinal trigeminal nucleus after ES-SSS; this has not been reported before and may participate in the modulation of trigeminovascular headache., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

In this prospective, open-labeled study, 240 cancer patients were assigned to either a high-dose glucocorticoids (HDG) group that received chemotherapy containing HDG, or a control group that received chemotherapy without glucocorticoids. The Pittsburgh Sleep Quality Index (PSQI) was chosen to assess insomnia. The results of the study showed that dimensions of sleep latency, sleep duration, and sleep efficiency had the three largest differences in values and numbers of patients, with a score increase in the HDG group compared to the control group (p < 0.001). After chemotherapy in the HDG group, the PSQI score significantly increased in patients with stage II cancer (both p < 0.05), and patients diagnosed with lymphoma (p < 0.01), whereas the complete response and partial response rates (p < 0.05) had the smallest elevations. The average score of each dimension did not significantly decrease after hypnotics (p > 0.05). Our study suggests that the major clinical manifestations of insomnia in cancer patients receiving chemotherapy containing HDG include difficulty falling asleep, short sleep duration, and low sleep efficiency. however, we cannot definitively state that hypnotics can improve poor sleep quality.

Annual H3N2 subtype influenza outbreaks in Guangdong, China are a severe public health issue and require ongoing monitoring of emerging viral variants. The variation and evolution of haemagglutinin (HA) and neuraminidase (NA) genes of influenza isolates from Guangdong during 2007-2011 and others from GenBank were analysed using Lasergene 7.1 and MEGA 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (HI). Susceptibility to antiviral drugs was correlated with genetic mutations. Phylogenetic analysis and alignment of HA and NA genes were performed on 18 Guangdong isolates and 26 global reference strains. The non-synonymous (dN) evolutionary rate of HA1 was 3.13 times that of HA2. Compared with the A/Perth/16/2009 vaccine HA gene, homologies of Guangdong isolates were between 98.8-99.7% and 98.0-98·4% in 2009 and 2010, respectively. Amino-acid substitutions were found in five epitopes of HA1 from Guangdong isolates between 2007 and 2011, especially in epitopes B (N160K) and D (K174R/N). The K189E/N/Q and T228A mutations in the receptor-binding site (RBS) occurred in the 2010 strains, which affected the antigenicity of HA1. The antigenicity of the epidemic H3N2 isolates in 2010 was somewhat different from that of A/Perth/16/2009. The Guangdong H3N2 isolates were determined to be oseltamivir-resistant with IC50 of 0.396 ± 0.085 nmol/l (n=17) and zanamivir-resistant with IC50 of 0.477 ± 0.149 nmol/l (n=18). Variations were present in epitopes B and D, two sites in the RBS and two glycosylation sites in the Guangdong H3N2 HA1 gene. The majority of the Guangdong H3N2 isolates were sensitive to oseltamivir and zanamivir. Compared to the World Health Organization 2012 vaccine strains, Guangdong H3N2 strains varied genetically and antigenically to some degree.

Apoptosis, which is usually a response to the microenvironment, requires inactivation of prosurvival molecules. Apoptosis contributes to loss of podocytes in the course of renal injury, an event closely associated with the development of proteinuria. Dexamethasone (DEX) is the standard of care for most forms of nephrotic syndrome. However, the precise mechanisms of DEX action on podocytes are unknown. This study examined the hypothesis that cultured podocytes exposed to puromycin aminonucleoside (PAN) showed a reduced rate of apoptosis upon DEX exposure. Apoptotic podocytes seemed to be related to increased Bad mRNA and protein expressions. DEX reduced apoptosis by decreasing Bad mRNA and protein expressions, thereby protecting podocytes. These findings provided insights into the beneficial effects of DEX directly on podocytes. The present study illustrated the signal transduction mechanism of podocyte apoptosis induced by PAN., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives., Methods: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded., Results: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients)., Conclusion: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Objective: To identify the risk factors for catheter migration and demonstrate possible mechanisms of this migration., Design: Retrospective study., Setting: Chang Gung Memorial Hospital, a tertiary medical centre in Taiwan., Patients: Patients who underwent implantation of intravenous ports via the superior vena cava (SVC)., Interventions: Procedures involving catheter placement and re-intervention for catheter migration., Main Outcome Measures: The anatomic location of the catheter tip was confirmed by plain chest X-rays (postero-anterior view). From these plain radiographs, the distance (in cm) between the carina and catheter tip and the angle (in degrees) between the locking nut and catheter were measured., Methods: A total of 1542 procedures related to intravenous port implantation were retrospectively reviewed but only procedures involving implantation via the SVC were included in the analysis. The study group was composed of 31 interventions because of catheter migration, while the control group consisted of 1475 implantation and re-intervention procedures except those involving catheter migrations., Results: Shallow catheter-tip location (p < 0.0001) and the presence of lung cancer (p = 0.006) were risk factors for catheter migration., Conclusions: Shallow catheter-tip location and the presence of lung cancer are risk factors for catheter migration. Strategies that ensure low catheter-tip location and avoid increased thoracic pressure may be useful preventive measures., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Functional dyspepsia (FD) is a common disease without an established optimal treatment., Aim: To determine (i) the effect of acupuncture in relieving FD symptoms and improving life quality; (ii) the effect difference between acupoint and non-acupoint; and (iii) the effect difference among different acupoints., Methods: A total of 712 eligible patients were included and randomly assigned to six groups (Group A: specific acupoints of the stomach meridian; Group B: non-specific acupoints of the stomach meridian; Group C: specific acupoints of alarm and transport points; Group D: specific acupoints of the gallbladder meridian; Group E: sham acupuncture of non-acupoints; and Group F: itopride). A treatment period of 4 weeks (continuous five sessions per week), and a follow-up period of 12 weeks were arranged. The outcomes were the (i) patients' response, (ii) symptoms improvement measured using the Symptom Index of Dyspepsia and (iii) quality-of-life improvement based on Nepean Dyspepsia Index., Results: All groups had an improvement in dyspepsia symptoms and the QoL at the end of treatment, and the improvement was sustained for 4 weeks and 12 weeks. The overall response rate was significantly higher in acupuncture group A (70.69%), and lower in sham acupuncture group (34.75%), compared with itopride and other acupuncture groups. Similarly, the difference in symptoms and QoL improvement was significant between group A and the other acupuncture groups., Conclusions: Acupuncture is effective in the treatment of functional dyspepsia, and is superior to non-acupoint puncture. The benefit of acupuncture relies on acupoint specificity., (© 2012 Blackwell Publishing Ltd.)

Myrmecia incisa Reisigl H4301 is a green coccoid freshwater microalga that is rich in arachidonic acid (20:4n-6, ArA) especially grown under a nitrogen starvation stress. A fatty acid elongase gene, MiFAE, was cloned based on a selected expressed sequence tag (EST) from a M. incisa cDNA library. To examine the function, the MiFAE gene was heterologously expressed in Saccharomyces cerevisiae. The fatty acid profile of the transgenic yeast was analyzed by gas chromatography-mass spectrometry (GC-MS), and the results illustrated that the enzyme encoded by MiFAE was able to elongate γ-linolenic acid (18:3n-6, GLA) and stearidonic acid (18:4n-3, SDA) to di-homo-γ-linolenic acid (20:3n-6, DGLA) and eicosatetraenoic acid (20:4n-3, ETA), respectively, suggesting that the cloned MiFAE gene seemed to encode a Δ6 fatty acid elongase. Expression of a MiFAE-GFP fusion encoded by a pYES2 vector showed that this Δ6 fatty acid elongase localized to the endoplasmic reticulum (ER) of yeast for fatty acid elongation. Quantitative real-time PCR results showed that the relative transcription level of MiFAE in M. incisa grown under a nitrogen starvation stress was increased, but it rapidly declined under conditions of nitrogen replenishment. GC-MS analysis revealed that the contents of DGLA, a direct product catalyzed by Δ6 fatty acid elongase, and ArA, the terminal product of fatty acid biosynthesis in this microalga, increased and decreased accompanying the shift from nitrogen starvation to replenishment, although there was a 40h lag time for ArA increment. The correlation between the up-regulated and down-regulated transcription of MiFAE and ArA content in response to a nitrogen starvation/replenishment shift showed that nitrogen could regulate the transcription of the MiFAE gene and that this gene is critical and responsible for the biosynthesis and accumulation of ArA in the cytoplasm of M. incisa., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Relapsing polychondritis (RP) is a rare autoimmune disease that affects cartilage throughout the body, causing episodic and progressive inflammation. Although rare, RP has diverse acute and subacute nervous system complications, which may sometimes precede systemic manifestations. Here, we report four patients with RP who presented with meningoencephalitis or meningitis without infectious aetiology. In addition, we review the literature for this disease with regard to clinical manifestations and treatment options., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Many hospitals would benefit from a reduction in the length of inpatient hospital stays; in this regard, nursing approaches require complementation to ensure optimized nursing care. Such action is particularly important in general hospitals in Korea, where the ratio of patients to nurses is more than 10:1., Objectives: This study aimed to determine the effectiveness of a unit-coordinator system in complementing primary nursing in general hospitals as a means of reducing inappropriate hospital stays., Methods: The unit-coordinator system was implemented in seven wards in a hospital in Seoul for 8 weeks. The existing primary nursing system was maintained, and newly placed unit-coordinators organized the activities within each ward. The numbers of early admissions and early discharges were determined by assessing the electronic administrative records of the hospital. Further, the number of patients who had undergone check-ups and chemotherapy on the day of admission was confirmed from the daily reports of each ward. The effect of the unit-coordinator system on nurse satisfaction was assessed through direct interviews., Findings: Early-discharge and early-admission numbers increased significantly after implementation of the unit-coordinator system. Early admission allowed check-ups and treatments to be performed on the day of admission. Thus, this system reduced the length of hospital stay by 1 day, and the total reduction of inappropriate hospital stays over the 8-week study period was 66 days. Further, the unit-coordinator system also increased nurse satisfaction., Conclusion: The unit-coordinator system is an effective method of complementing primary nursing and reducing inappropriate hospital stays., (© 2010 The Authors. International Nursing Review © 2010 International Council of Nurses.)

The lateral nucleus of the amygdala (LA) is a critical structure involved in fear conditioning. We recently showed that regulated exocytosis and endocytosis of postsynaptic A-amino-3-hydroxy-5-methylisoxazole-4-propionate subtype of glutamate receptors (AMPARs) are involved in the expression of N-methyl-D-aspartate subtype glutamate receptors (NMDARs) dependent long-term potentiation (LTP) and long-term depression (LTD) in coronal slices of the LA. However, the molecular mechanisms of this effect remain unclear. In the present study, we investigated the role of distinct NMDAR subtypes in the endocytosis of AMPARs during LTD expression at the synapses of the thalamic inputs to the LA neurons. Here we show that the NMDARs antagonist DL-2-amino-5-phosphonovalerate (D-APV) blocked the induction of LTD and thus prevented endocytosis of surface AMPARs, indicating that NMDAR activation enhanced the internalization of AMPARs in LTD expression. Furthermore, the selective blocking of GluN2B-containing NMDARs completely abolished the NMDAR-induced AMPAR endocytosis, whereas preferential inhibition of GluN2A-containing NMDARs did not block the NMDAR-induced AMPAR endocytosis during LTD expression. These results suggest that there exist a preferred NMDAR subtype for AMPAR internalization and activation of GluN2B-containing NMDARs represent the predominate pathway triggered during the early stages of this NMDAR-induced endocytosis of AMPARs during LTD in the thalamic inputs to the LA of juvenile rats., (Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)