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Chronic obstructive pulmonary disease (COPD) is a chronic lung disease which feature is progressive airflow obstruction. Singing is a popular and convenient activity that requires people to manage their lung volumes and airflow actively. Despite the well-known benefits of singing to healthy people, the specific effect still remains unclear.To investigate the mental and psychological benefits of singing in patients with stable COPD.We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) on randomized controlled trials (RCTs) including singing exercise as the main intervention in stable COPD. We searched 8 electronic databases, including Web of Science, PubMed, Embase, Cochrane Library, Clinical Trials.gov, and the Physical Therapy Evidence Database (PEDro), CNKI, and Wanfang Database from inception until May 2022. The searching languages was English or Chinese. Data extraction using standardized templates was performed by two independent reviewers. The quality of the studies was assessed using the PEDro scale. Data synthesis was performed with Revman 5.4. The pooled effect sizes are reported by MD and 95% CI.Five RCTs involving 333 patients with stable COPD were included in this meta-analysis. Singing was regarded as the main intervention in the experimental group. Meta-analysis revealed that singing improves quality of life on Short Form 36 physical component summary (SF-36 PCS) (MD = 12.63, 95% CI: 5.52 to 19.73,Based on results of the meta-analysis, singing could be used to improve quality of life (SF-36 PCS) and respiratory muscles (PE

Objective Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a new inhibitor of matrix metalloproteinase (MMP), plays a vital role in tumor invasion. Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of developing lung cancer, however, the role of RECK on COPD has not been studied. This study explored the expression of RECK in COPD patients and its effect on neutrophil function to provide a new scientific basis for the prevention and treatment of COPD. Method Fifty patients with acute exacerbation of COPD and fifty healthy controls were enrolled in the study. RECK was detected in lung tissue, sputum and plasma of subjects as well as in BEAS-2B cells stimulated with cigarette smoke extract (CSE) by immunohistochemistry, ELISA and qRT-PCR. Meanwhile, lung function (FEV1%pred) and inflammatory cytokines (IL-6 and IL-8) were examined, and correlation analysis was performed with RECK expression. The effect of RECK on proliferation, apoptosis, migration and inflammatory cytokines and its potential mechanism were further quantified by neutrophil stimulated with recombinant human RECK protein (rhRECK) combined with CSE using CCK8, flow cytometry, Transwell assay, qRT-PCR, ELISA and Western blot. Results RECK was mainly expressed on airway epithelial cells in normal lung tissue and was significantly diminished in COPD patients. The levels of RECK in sputum and plasma were also significantly decreased in COPD patients. Pearson correlation analysis showed that RECK level in plasma was positively correlated with FEV1%pred (r = 0.458, P P = 0.006, 0.002) in COPD patients. The expression of RECK was decreased in BEAS-2B stimulated with CSE. The migration, inflammation, and MMP-9 expression of neutrophils were promoted by CSE, while inhibited by rhRECK. Conclusions RECK is low expressed in COPD patients and negatively correlated with inflammation. It may inhibit the inflammation and migration of neutrophils by downregulating MMP-9.

Shuyi Qin,1,2,* Xinjuan Yu,1,2,* Qianli Ma,3,* Li Lin,4 Qinghai Li,1,2 Hong Liu,1,2 Lei Zhang,5 Shuguang Leng,6 Wei Han1,2 1Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Radiology, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 4Department of Pulmonary Medicine, Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China; 5Department of Hospital Infection, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 6Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnShuguang LengDepartment of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USATel +1 505 3489465Email sleng@salud.unm.eduPurpose: To explore a practical marker for quantitatively analyzing the small airway remodeling in COPD by HRCT.Patients and Methods: Twenty-four patients with COPD (GOLD I, n = 7; GOLD II, n = 8; GOLD III+IV, n = 9) and 14 healthy controls (7 normal pulmonary function; 7 small-airway disease (SAD)) were enrolled in the study as five groups, GOLD I, GOLD II, GOLD III+IV, normal and SAD. All subjects underwent HRCT and spirometry. With ISP 9.0, whole emphysema index (EI) and the airway parameters, including wall area (WA), lumen area (LA), airway area (AA) of the 3rd, 5th and 9th generations of bronchi, were measured successively. The ratio of LA/AA and WA/AA in the 3rd, 5th and 9th generations of bronchi were calculated and compared among groups.Results: For the five groups, EI was increased only in GOLD III+IV group (P < 0.05), while the ratio of LA/AA (9-LA/AA) and WA/AA (9-WA/AA) in 9th generation of bronchi have significantly changed since SAD group (P < 0.05). There were significant correlation between FEV1generations of bronchi (r3 = 0.429, r5 = 0.583, r9 = 0.592, respectively, P < 0.05); FEV1% and WA/AA (r3 = – 0.428, r5 = – 0.532, r9 = – 0.570, respectively, P < 0.05); as well as MMEF% and LA/AA (r3 = 0.421, r5 = 0.566, r9 = 0.610, respectively, P < 0.05); MMEF% and WA/AA (r3 = – 0.421, r5 = – 0.529, r9 = – 0.593, respectively, P < 0.05).Conclusion: Small airway remodeling has occurred in the early stage of COPD, while emphysema in the late stage of COPD. The 9-LA/AA and 9-WA/AA are accurate and practical markers for small airway remodeling of COPD.Keywords: COPD, high-resolution CT, emphysema index, pulmonary function test

Objective Diabetes mellitus (DM) is a metabolic illness and it is a result of hyperglycemia ensuing since a deficiency in insulin production, insulin function. Based on WHO statistics, more than 347 million peoples are suffered from the DM globally and it may increase to 694 million in 2030. Vanillic acid (VA) is a phenolic derived compound from dietary vegetations and fruits with the many biological acitivities. This current research was planned to investigate the antidiabetic and anti-inflammatory potential of VA on streptozotocin-challenged DM in rats. Methods Later than an overnight fast, the rats were induced diabetes via one intraperitoneal treatment of STZ (40 mg/kg b.wt) in a newly organized 0.1 M citrate buffer. We analyzed body weight, plasma glucose, liver marker enzymes, insulin, carbohydrate metabolic enzymes, glycosylated hemoglobin, protein profiles, oxidant/antioxidant levels, inflammatory mediators and also evaluate histopathology of pancreatic tissues in normal control and investigational animals. Results Diabetic animals were revealed an increased in HbA1c, blood glucose, food and fluid intake and relative weight of kidney and liver, whereas the reduced level of insulin and body weight. Furthermore, augmented levels of ALT, glucose-6-phosphatase, AST, TBARS, TNF-α, creatinine, LOOH, fructose 1,6-bisphosphatase, ALP, IL-6 and IL-1β whereas, reduced status of antioxidant enzymes were observed in diabetic rats. Histopathological analysis of pancreatic tissues was in support of the biochemical parameters. Conclusions Diabetic rats treated by VA significantly alter all these parameters toward normal levels. These results recommended that the VA is a potential antidiabetic and anti-inflammatory effect for the cure of DM.

Background Postoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients. Methods Four hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry. Results POD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P P P Conclusion The changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations. Trial registration This study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

Objective The aim of this study was to explore the signatures of oral microbiome associated with OSCC using a random forest (RF) model. Patients and methods A total of 24 patients with OSCC were enrolled in the study. The oral microbiome was assessed in cancerous lesions and matched paracancerous tissues from each patient using 16S rRNA gene sequencing. Signatures of mucosal microbiome in OSCC were identified using a RF model. Results Significant differences were found between OSCC lesions and matched paracancerous tissues with respect to the microbial profile and composition. Linear discriminant analysis effect size analyses (LEfSe) identified 15 bacteria genera associated with cancerous lesions. Fusobacterium, Treponema, Streptococcus, Peptostreptococcus, Carnobacterium, Tannerella, Parvimonas and Filifactor were enriched. A classifier based on RF model identified a microbial signature comprising 12 bacteria, which was capable of distinguishing cancerous lesions and paracancerous tissues (AUC = 0.82). The network of the oral microbiome in cancerous lesions appeared to be simplified and fragmented. Functional analyses of oral microbiome showed altered functions in amino acid metabolism and increased capacity of glucose utilization in OSCC. Conclusion The identified microbial signatures may potentially be used as a biomarker for predicting OSCC or for clinical assessment of oral cancer risk.

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.

Background and Aims: Accumulated studies have evaluated the effects of glucokinase regulatory protein (GCKR) gene polymorphisms on the risk of nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD), but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained unclear. The aim of this study was to investigate the association between GCKR gene polymorphisms (rs780094 and rs1260326) and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population. Methods: GCKR rs780094 and rs1260326 gene polymorphisms were genotyped by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with (n = 82) or without (n = 142) CAD, and in healthy controls (n = 152). Serum lipid profiles’ levels were determined using biochemical methods. Statistical analyses were conducted using SPSS 22.0 statistical software. Results: As the results showed, significant differences in the serum lipid profiles existed between each group. No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group. The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value, and serum fasting plasma glucose and TG levels in the overall subjects, respectively. In addition, the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD + CAD patients. Conclusions: GCKR rs780094 and rs1260326 polymorphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population. GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.

BACKGROUND: Myocardial injury induced by refeeding syndrome (RFS) is one of the important causes of deterioration in critically ill patients. Sirtuin-3 (SIRT3) has been shown to regulate mitochondrial autophagy in myocardial ischemia/reperfusion injury; however, the role of mitochondrial autophagy on RFS-related myocardial injury in patients in critical condition has not been reported on. METHODS: Thirty Sprague-Dawley (SD) rats were divided into 3 groups (n=10 each group): the control group; the standard calorie refeeding (SCR) group; and the low calorie refeeding (LCR) group. The rats were weighed every third or four days from day 1 to day 14. On day 14, all rats were anesthetized and received an echocardiography test. Blood and bronchoalveolar lavage fluid (BALF) were collected and tested for arterial oxygen pressure (PaO(2)), phosphorus (P), and calcium (Ca), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin 1 (cTnI), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6. The histopathological change of hearts and lungs were evaluated, and lung injury score was calculated. Mitochondrial autophagy related proteins (including Beclin1, LC3, mitofusin-2, Mfn2, PINK1, Parkin, and SIRT3) were analyzed using a Western blot. To evaluate the effect of SIRT3, 20 rats were divided into 2 groups (n=10 each group): The adeno-associated virus 9 (AAV9-Nc) group; and the AAV9-SIRT3 overexpression (AAV9-SIRT3) group. The protocols for rats were the same as the SCR group since day 22 after injection of AAV9. The protein expressions of PINK1, Parkin, and SIRT3 were compared between the AAV9-Nc group and AAV9-SIRT3 group. RESULTS: SCR caused significant decline in cardiac contractility and increased inflammatory cell infiltration in myocardial tissue. Meanwhile, Beclin1, LC3, PINK1, Parkin, and SIRT3 levels decreased, while Mfn2 showed no significant change. Furthermore, significant positive correlations were also found between SIRT3 and P, PINK1, and Parkin, and significant negative correlations were found between SIRT3 and CK-MB, LDH, and cTnI. Overexpression of SIRT3 activated the PINK1/Parkin mediated mitochondrial autophagy. CONCLUSIONS: SIRT3 has an essential role in RFS-related myocardial injury during LPS induced chronic sepsis in rats, probably via regulating mitochondrial autophagy.

BACKGROUND Effective identification of patients with suspected COVID-19 is vital for the management. This study aimed to establish a simple clinical prediction model for COVID-19 in primary care. MATERIAL AND METHODS We consecutively enrolled 60 confirmed cases and 152 suspected cases with COVID-19 into the study. The training cohort consisted of 30 confirmed and 78 suspected cases, whereas the validation cohort consisted of 30 confirmed and 74 suspected cases. Four clinical variables - epidemiological history (E), body temperature (T), leukocytes count (L), and chest computed tomography (C) - were collected to construct a preliminary prediction model (model A). By integerizing coefficients of model A, a clinical prediction model (model B) was constructed. Finally, the scores of each variable in model B were summed up to build the ETLC score. RESULTS The preliminary prediction model A was Logit (YA)=2.657X₁+1.153X₂+2.125X₃+2.828X₄-10.771, while the model B was Logit (YB)=2.5X₁+1X₂+2X₃+3X₄-10. No significant difference was found between the area under the curve (AUC) of model A (0.920, 95% CI: 0.875-0.953) and model B (0.919, 95% CI: 0.874-0.952) (Z=0.035, P=0.972). When ETLC score was more than or equal to 9.5, the sensitivity and specificity for COVID-19 was 76.7% (46/60) and 90.1% (137/152), respectively, and the positive and negative predictive values were 75.4% (46/61) and 90.7% (137/151), respectively. CONCLUSIONS The ETLC score is helpful for efficiently identifying patients with suspected COVID-19.

Persistently activated IL‐6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) in non–small‐cell lung cancer (NSCLC) treatment. miR‐206 has been verified to be dysregulated and plays as a negative regulator in lung cancer. However, whether miR‐206 may overcome IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer remains elusive. In this study, we investigated the role of miR‐206 in IL6‐induced gefitinib‐resistant EGFR‐mutated lung cancer cell lines. We showed that forced miR‐206 expression restored gefitinib sensitivity in IL6‐induced gefitinib‐resistant EGFR‐mutant lung cancer cells by inhibiting IL6/JAK1/STAT3 pathway. Specifically, mechanistic investigations revealed that miR‐206 blocked IL‐6/STAT3 signalling via directly targeting the 3'‐UTR of intracellular IL‐6 messenger RNA. Moreover, IL‐6 induced miR‐206 down‐regulation by reducing the cropping process of primary miR‐206 (pri‐miR‐206) into the Drosha/DGCR8 complex. Taken together, our findings reveal a direct role of miR‐206 in regulating IL‐6/STAT3 pathway and contrarily activated IL‐6/STAT3 signalling mediates the miR‐206 maturation process in gefitinib‐resistant EGFR‐mutant lung cancer cells.

Lung cancer is a common malignant tumor in clinic and easy to have bone metastases. Vascular endothelial growth factor (VEGF) is an angiogenic factor. Matrix metalloproteinases (MMPs) is associated with invasion and metastases. This study was to detect VEGF, microvessel density (MVD), MMP-2 and MMP-9 (MMP-2/9) levels in the serum and tissues of lung cancer patients with bone metastases to analyze the relaitonship between these changes and lung cancer with bone metastases. 60 patients with metastatic tumor of lung cancer were selected as experimental group, primary malignant tumor of bone and benign osteoma were regarded as control group, the contents of VEGF, MMP-2/9 in blood and tissues were analyzed by ELISA and IHC, respectively. VEGF, MVD, MMP-2/9 levels in serum and tissues of lung cancer bone metastasis group were significantly higher than that of primary bone tumor group and benign bone tumor group and their changes were significantly associated with pathological types of lung cancer, numbers and sizes of primary foci, numbers of bone metastases, other organ metastases and whether or not receiving radiotherapy and chemotherapy (P < 0.05). In conclusion, the level of VEGF, MVD, MMP-2/9 is significantly elevated in lung cancer patients with bone metastases, suggesting that these molecules might be involved in the pathogenesis of lung cancer with bone metastases.

Kai Liu,1,* Xinjuan Yu,2,* Xuefen Cui,2 Yi Su,2 Lixin Sun,3 Jiulong Yang,4 Wei Han2 1Department of Rehabilitation, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesia, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 4Hospital Office, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnJiulong YangHospital Office, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, 266071, People’s Republic of ChinaTel +86 532 88905509Email qdyxkp@163.comBackground: The proprioceptive neuromuscular facilitation (PNF) stretching could improve the contractile capacity of respiratory muscles, but the effect on pulmonary function, when it is combined with aerobic training, remains unknown.Objective: To evaluate the effect of PNF combined with aerobic training on respiratory symptoms, pulmonary function and neck/shoulder mobility in patients with COPD.Design: Randomized controlled trial.Participants: Fifty-five COPD patients were randomly divided into PNF group (n=28) and control group (n=27).Intervention: On the basis of conventional treatment, the control group performed 30 min aerobic training on a treadmill, while the PNF group added 10-minute PNF stretching 3 times every training day. Both groups did their training in 5 days per week for 6 weeks.Measures: Measures were taken before and after 6 weeks of training. COPD Assessment Test (CAT), dyspnea Visual Analog Scale (VAS), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), inspiratory capacity (IC), inspiratory reserve volume (IRV), 6-minute walk test (6MWT), the range of motion (ROM) of head protraction, shoulder flexion, and the non-dominant pectoralis minor muscle (PmM) length were measured.Results: All the indicators of both groups were significantly improved after 6 weeks of intervention except for FVC, FEV1 and PmM length. Compared to the control group, the PNF group showed significant improvement in the CAT score, dyspnea VAS score, IC, IRV, 6MWT, as well as head protraction ROM and shoulder flexion ROM. Furthermore, IC was positively correlated with the head protraction ROM and PmM length (r=0.415, 0.579, P=0.028, 0.001); IRV was positively correlated with the shoulder flexion ROM (r=0.405, P=0.032) in the PNF group.Conclusion: PNF stretching combined with aerobic training reduces dyspnea and improves some pulmonary function measures, which is associated with neck/shoulder mobility, in COPD patients.Keywords: chronic obstructive pulmonary disease, proprioceptive neuromuscular facilitation stretching, aerobic training, pulmonary function

Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC (n = 30), advanced gastric cancer (AC) (n = 30), and chronic gastritis (CG) (n = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of Helicobacter pylori and the cagA and vacA virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of MUC1 rs4072037 was associated with an increased abundance of Ochrobactrum. The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, H. pylori infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.

The incidence of gastric hyperplastic polyps (HPs) has been on the rise in recent years. The contribution of Helicobacter pylori infection to this trend has remained to be elucidated. The present study aimed to explore the association between HPs and H. pylori in China, an area with a high infection rate of H. pylori. In order to study trends of HPs and H. pylori infection over the past decades, cases encountered from 2009 to 2018 were assessed and a total of 109,150 consecutive patients who underwent esophagogastroduodenoscopy at Qingdao Municipal Hospital (Qingdao, China) were enrolled. The incidence of HPs and the prevalence of H. pylori were determined and their correlation was explored. Gastric HPs were detected in 1,497 patients (1.6%) who received gastric biopsies. The incidence of HPs exhibited a rising trend, with a ~4-fold increase in the annual detection rate from 2009 to 2018. The prevalence of H. pylori infection was inversely associated with the prevalence of HPs (adjusted odds ratio, 0.66). The prevalence of H. pylori in the examined cohort decreased with time (r=-0.76, P=0.011). The decreasing trend of H. pylori infection was negatively correlated with the rising trend of HPs (r=-0.64, P=0.048), further indicating an inverse association between them. The difference in the prevalence of HPs between H. pylori-negative and -positive patients increased with age (r=0.80, P=0.018). The age-associated increase was slower in H. pylori-infected patients. The decline in H. pylori infection with time appeared to not be associated with the birth cohort effect, suggesting the decline was not caused by exposure to environmental factors during an early period of life. The present results indicated that the incidence of gastric HPs increased with the decline in H. pylori infection, demonstrating an inverse association between the occurrence of HPs and the infection.

Dendritic fibromyxolipoma (DFML) is a rare variant of spindle cell lipoma. It is characterized by extensive myxoid change and the presence of stellate cells with dendritic processes. The present study reports three cases of DFML that arose from the limbs and thoracic cavity. Pathologically, the tumor was composed of mature adipocytes admixing with patch spindle cells in a myxoid stroma. The cell atypia was not apparent and mitotic figures were rare. Immunohistochemistry revealed that the spindle cells were strongly positive for CD34. The three patients demonstrated no significant issues during a two-year's follow-up without evidence of recurrence and metastasis. The current study additionally reviewed all reported DFML cases in the PubMed database and Chinese journals.

Contribution of host genetic backgrounds in the development of gastric microbiota has not been clearly defined. This study was aimed to characterize the biodiversity, structure and composition of gastric microbiota among twins. A total of four pairs of twins and eight unrelated individuals were enrolled in the study. Antral biopsies were obtained during endoscopy. The bacterial 16S rRNA gene was amplified and pyrosequenced. Sequences were analyzed for the composition, structure, and α and β diversities of gastric microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria were the most predominant phyla of gastric microbiota. Each individual, twins as well as unrelated individuals, harbored a microbiota of distinct composition. There was no evidence of additional similarity in the richness and evenness of gastric microbiota among co-twins as compared to unrelated individuals. Calculations of θYC and PCoA demonstrated that the structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. In contrast, the structure of microbiota was altered enormously by Helicobacter pylori infection. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. This property of gastric microbiota could facilitate the studies discerning the role of microbiota from genetic grounds in the pathogenesis.

Host immunogenetic setting is involved in the regulation of human papillomavirus (HPV) infection and development of condyloma acuminatum (CA). We investigated the correlation of two common single nucleotide polymorphisms (SNPs) (−607C/A and −137G/C) of IL-18 with the susceptibility of CA in a large Chinese cohort. Out of 408 CA patients analyzed, 300 had HPV infection transmitted through sexual contact (SC) and 108 through non-sexual contact (NSC). In addition, 360 healthy volunteers were enrolled as controls. SNPs at positions −607C/A and −137G/C in IL-18 promoter were analyzed. Comparing CA patients to healthy controls, no dominant relevance was found between the IL-18 promoter −607 C/A or −137G/C polymorphisms and the CA disease either identified genotypically (p > 0.05) or by allelically (p > 0.05). However, the IL-18 promoter −137G/C polymorphism genotype and allele frequencies in the NSC CA group, but not between in the SC group, were significantly higher than in the controls. There was no dominant relevance between IL-18-607C/A polymorphism genotype and allele frequencies among SC, NSC CA patients, and controls. Our study demonstrates that polymorphism −137G/C in IL-18 promoter is significantly correlated with risk of CA in NSC patients. Keywords: Condyloma acuminatum, Human papillomavirus, Cytokine, Single nucleotide polymorphism, IL-18

Background: Gastric microbiome has been well characterized gastric cancer. Alterations associated with gastric cancer have been identified. However, little is known regarding the dysbiotic features in early gastric cancer. Methods: Gastric microbiome was assessed in early gastric cancer (n=30), advanced gastric cancer (n=30) and chronic gastritis (n=60). Random forest machine learning algorithm was used to identify signatures capable of predicting early gastric cancer. In addition, influence of Helicobacter pylori virulence and cancer-associated single nucleotide polymorphisms in PRKAA1, PTGER4, PSCA, MUC1 and UNC5CL on gastric microbiome was determined. Findings: There were significant differences in the microbial profile and composition between early and advanced gastric cancer, suggesting alterations associated with cancer progression. Compared with chronic gastritis, 32 bacteria genera were found to be enriched or depleted in early gastric cancer. Production of urease and synthesis of bacteria flagellum were decreased, while glycolysis of fructose and hydrolysis of glycosides were enhanced. The correlation network became simplified and fragmented. A microbial signature enclosing 24 bacteria was identified, which could distinguish early gastric cancer from chronic gastritis with an AUC value of 0.97. H. pylori had impacts on gastric microbiome. The minor allele of MUC1 SNP rs4072037 was associated with increased abundance of Ochrobactrum. Interpretation: Gastric microbiome showed distinct features in early gastric cancer. The identified microbial signature could be used as biomarkers for predicting early gastric cancer. Funding: National natural Science Foundation of China (31870777, 81602144). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: This study was approved by the Research Ethnics Committee of Qingdao Municipal Hospital, China. Informed written consent was obtained from all participants.

BACKGROUND Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) affecting more than 2.5 million people worldwide. However, the exact etiology of MS remains unknown, recent research indicated that High-mobility group box 1(HMGB1) might contribute to MS pathogenesis. By evaluating HMGB1 levels of peripheral blood mononuclear cells (PBMC), serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients and the controls, to reveal the relationship of HMGB1 levels and MS patients. METHODS The PubMed, EMBASE, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFangData were searched for relevant studies. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated as effect size, random-effects model was used when I2 > 50%. Subgroup analysis was conducted by subtype of MS, categories of controls, country and mean age. RESULTS A total of 7 studies with 364 patients of MS and 222 controls were included. The results of this study showed that HMGB1 protein levels of PBMC and CSF in patients with MS were significantly higher than those of controls (SMD = 4.36, 95% CI = 3.69-5.02, and SMD = 0.85, 95% CI = 0.42-1.28, respectively), but we found no significant difference in HMGB1 mRNA level of PBMC and serum HMGB1 protein level between MS patients and controls. In the subgroup analysis, RRMS patients had a higher HMGB1 level in serum (p

A considerable number of studies have been conducted to study the microbial profiles in inflammatory conditions. A common phenomenon in inflammatory bowel disease (IBD) is the reduction of the diversity of microbiota, which demonstrates that microbial diversity negatively correlates with disease severity in IBD. Increased microbial diversity is known to occur in disease remission. Species diversity plays an important role in maintaining the stability of the intestinal ecosystem as well as normal ecological function. A reduction in microbial diversity corresponds to a decrease in the stability of the ecosystem and can impair ecological function. Fecal microbiota transplantation (FMT), probiotics, and prebiotics, which aim to modulate the microbiota and restore its normal diversity, have been shown to be clinically efficacious. In this study, we hypothesized that a reduction in microbial diversity could play a role in the development of IBD.

Objective Microbiota is potentially linked to the development of cancer. However, the features of microbiota in gastric cancer remain unclear. The aim of this study was to characterize the gastric microbiota in cancer. Methods A total of 315 patients, including 212 patients with chronic gastritis and 103 patients with gastric cancer, were enrolled in the study. The bacterial load of gastric mucosa was determined using quantitative PCR. To analyze the biodiversity, structure, and composition of microbiota, amplicons of the 16S rRNA gene from 12 patients were pyrosequenced. The sequences were processed and subsequently analyzed. Results The amount of bacteria in gastric mucosa was estimated to be 6.9×108 per gram tissue on average. It was higher in Helicobacter pylori-infected patients (7.80±0.71) compared with those uninfected (7.59±0.57, P=0.005). An increased bacterial load up to 7.85±0.70 was detected in gastric cancer compared with chronic gastritis (P=0.001). The unweighted principal coordinate analysis showed that the structure of microbiota in gastric cancer was more diversified. Five genera of bacteria with potential cancer-promoting activities were enriched in gastric cancer. The weighted principal coordinate analysis showed that the presence of Helicobacter pylori markedly altered the structure of microbiota, but had little influence on the relative proportions of the other members in the microbiota. Conclusion Findings from this study indicated an altered microbiota in gastric cancer with increased quantity of bacteria, diversified microbial communities, and enrichment of bacteria with potential cancer-promoting activities. These alterations could contribute toward the gastric carcinogenesis.

Background Recently, Beclin-1 expression in hepatocellular carcinoma (HCC) and non-tumor liver tissue have been investigated by several studies. However, the results are controversial. The aim of this study was to clarify the role of Beclin-1 in the occurrence of HCC by comparing the difference of Beclin-1 expression between HCC and non-tumor liver tissue. Methods An electronic retrieve for relevant studies was performed in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wan Fang and Chinese VIP databases updated to December 31, 2017. Newcastle-Ottawa-Scale (NOS) was used to assess the quality of the eligible studies. Sensitivity, subgroup, and publication bias analyses were also carried out in this meta-analysis. Statistical analysis was performed by Review Manager 5.3 and STATA 12.0. Results Six high-quality studies with 357 HCC patients were eligible. There was no significant difference of Beclin-1 expression between HCC and non-tumor liver tissue (OR = 2.48, 95%CI = 0.64-9.58, P = 0.19). However, sensitivity analysis showed that Beclin-1 was lower in HCC than in non-tumor liver tissue after omitting Kang et al.'s study (OR = 4.14, 95% CI = 1.75-9.81, P = 0.001), and heterogeneity was not evident (P = 0.14, I² = 43%). Subgroup analysis suggested that heterogeneity may stem from ethnicity. The funnel plot and Egger's test (P = 0.900) demonstrated that no significant publication bias was present in this meta-analysis. Conclusion This meta-analysis indicated that there was no significant difference of Beclin-1 expression between HCC and non-tumor liver tissue.Read Complete Article at ijSciences: V72018031625 AND DOI: http://dx.doi.org/10.18483/ijSci.1625

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Circulating follicular helper T (cTfh) cells are a novel subset of cluster of differentiation (CD)4+ helper T cells. Interleukin (IL)-21 and C-X-C motif chemokine ligand (CXCL)13 are the principal effectors and chemotactic regulatory factors of Tfh. However, the roles of IL-21 and CXCL13 in gastric cancer have not yet been completely elucidated. The aim of the present study was to investigate the distribution of cTfh cells, and the expression of IL-21 and CXCL13 in patients with gastric cancer was evaluated in order to ascertain the significance and potential mechanisms of these effectors in gastric cancer. A total of 50 patients with gastric cancer were enrolled as the study subjects, with 30 healthy individuals selected as controls. The percentage of cTfh cells (cTfh%) in the peripheral blood was calculated using flow cytometry. They are identified in the present study as CD4+ chemokine C-X-C receptor (CXCR)5+ inducible T cell co-stimulator (ICOS)+ cells. The serum levels of IL-21 and CXCL13 were determined by ELISA. The cTfh% in the peripheral blood and the concentration of IL-21 and CXCL13 in the serum were significantly higher in patients with gastric cancer compared with the control group. cTfh% was significantly higher in patients with lymph node metastasis, Tumor-Node-Metastasis (TNM) stage III-IV and low differentiation. The concentrations of IL-21 and CXCL13 in patients with lymph node metastasis and/or TNM III-IV were significantly higher than in those without lymph node metastasis or with TNM I-II. There was a positive correlation between cTfh%/CXCL13 and IL-21/CXCL13, while there was no correlation between cTfh%/IL-21. cTfh cells and associated factors (IL-21/CXCL13) may be involved in the development and progression of gastric cancer. There may be mutual regulation among cTfh cells, IL-21 and CXCL13.

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.

Exclusive enteral nutrition (EEN) has been proven to be effective and safe in treating pediatric Crohn’s disease (CD). EEN induces pediatric CD remission possibly through three pathways: (1) direct anti-inflammatory effects, (2) improved epithelial barrier function, and (3) modulation of the gut microbiota. Recent studies have demonstrated that modulation of the gut microbiota plays a major role in EEN-induced remission. Variations of microbial components, which directly influence the diversity and metabolic functions of the gut microbiota, are closely associated with the immunological conditions of the gut and the susceptibility to diseases. The reduction of proinflammatory microbial components and harmful microbial metabolites after EEN treatment greatly decreases the inflammatory injuries of the gut.

Objective To investigate the association between the genotypes, sequence variations and phylogenetic origins of strains of Helicobacter pylori with gastric cancer in Chinese patients. Methods Strains of H. pylori were isolated from patients with chronic gastritis and gastric cancer. Genotypes of the cagA and vacA genes were determined using polymerase chain reaction. Sequence analysis was used to detect variations in the 3′ and 5′ regions of cagA, and to detect known polymorphisms in cagE. A phylogenetic tree was constructed based on the analysis of seven housekeeping genes. Results A total of 67 strains of H. pylori were analysed. Nearly all strains of H. pylori carried cagA (65/67; 97.0%), an East Asia type of the cagA 3′ region (63/65; 96.9%) and the vacA intermediate (i)1 genotype (65/67; 97.0%). None of the H. pylori strains examined had sequence variations in the 5′ region of cagA or cagE. Phylogenetic analyses, however, revealed that strains of H. pylori from gastric cancer tended to cluster together. Conclusions Virulent strains of H. pylori were highly prevalent, but virulent genotypes of H. pylori associated with gastric cancer were not detected in this geographical region.

Inflammation may play a role in postoperative cognitive dysfunction. 5′ Adenosine monophosphate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-α are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5′ adenosine monophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1–7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis factor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

There are a large number of bacteria inhabiting the human body, which provide benefits for the health. Alterations of microbiota participate in the pathogenesis of diseases. The gastric microbiota consists of bacteria from seven to eleven phyla, predominantly Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. Intrusion by Helicobacter pylori (H. pylori) does not remarkably interrupt the composition and structure of the gastric microbiota. Absence of bacterial commensal from the stomach delays the onset of H. pylori-induced gastric cancer, while presence of artificial microbiota accelerates the carcinogenesis. Altered gastric microbiota may increase the production of N-nitroso compounds, promoting the development of gastric cancer. Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.