Changhai Hospital

BACKGROUND: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. METHODS: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6) and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. RESULTS: Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e.g., IL-1β, TNF-α, and IL-6) expression, and increased myeloperoxidase activity, neutrophil infiltration, pulmonary edema, and pulmonary endothelial cell apoptosis. Additionally, HSPA12B knockdown worsened survival after CLP surgery. The potential protective mechanisms of HSPA12B may involve the inhibition of ERK phosphorylation and caspase-3 activation in vivo and in vitro. CONCLUSION: HSPA12B protected against sepsis-induced ALI. The potential mechanism may be partly due to the inhibition of ERK phosphorylation and caspase-3 activation. These findings provide a potential therapeutic target for treating sepsis.

AIMS: microRNA (miRNA) is reported to be present in the blood of humans and has been increasingly suggested as a biomarker for diseases. We aim to determine the potential of cardiac-specific miRNAs in circulation to serve as biomarkers for acute myocardial infarction (AMI). METHODS AND RESULTS: By verifying their tissue expression patterns with real-time polymerase chain reaction (PCR) analysis, muscle-enriched miRNAs (miR-1, miR-133a, and miR-499) and cardiac-specific miR-208a were selected as candidates for this study. With miRNA microarray and real-time PCR analyses, miR-1, miR-133a, and miR-499 were present with very low abundance, and miR-208a was absent in the plasma from healthy people. In the AMI rats, the plasma levels of these miRNAs were significantly increased. Especially, miR-208a in plasma was undetected at 0 h, but was significantly increased to a detectable level as early as 1 h after coronary artery occlusion. Further evaluation of the miRNA levels in plasma from AMI patients (n = 33) demonstrated that all four miRNA levels were substantially higher than those from healthy people (n = 30, P < 0.01), patients with non-AMI coronary heart disease (n = 16, P < 0.01), or patients with other cardiovascular diseases (n = 17, P < 0.01). Notably, miR-208a remained undetectable in non-AMI patients, but was easily detected in 90.9% AMI patients and in 100% AMI patients within 4 h of the onset of symptoms. By receiver operating characteristic curve analysis, among the four miRNAs investigated, miR-208a revealed the higher sensitivity and specificity for diagnosing AMI. CONCLUSION: Elevated cardiac-specific miR-208a in plasma may be a novel biomarker for early detection of myocardial injury in humans.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.

Abstract Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 μJ, which is higher than the required endocardial pacing threshold energy (0.377 μJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.

: Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord-derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs. Through high-throughput RNA sequencing and functional analysis, we demonstrated that a group of uMSC-Exos enriched in specific microRNAs (miR-21, -23a, -125b, and -145) played key roles in suppressing myofibroblast formation by inhibiting the transforming growth factor-β2/SMAD2 pathway. Finally, using the strategy we established to block miRNAs inside the exosomes, we showed that these specific exosomal miRNAs were essential for the myofibroblast-suppressing and anti-scarring functions of uMSCs both in vitro and in vivo. Our study revealed a novel role of exosomal miRNAs in uMSC-mediated therapy, suggesting that the clinical application of uMSC-derived exosomes might represent a strategy to prevent scar formation during wound healing. SIGNIFICANCE: Exosomes have been identified as a new type of major paracrine factor released by umbilical cord-derived mesenchymal stem cells (uMSCs). They have been reported to be an important mediator of cell-to-cell communication. However, it is still unclear precisely which molecule or group of molecules carried within MSC-derived exosomes can mediate myofibroblast functions, especially in the process of wound repair. The present study explored the functional roles of uMSC-exosomal microRNAs in the process of myofibroblast formation, which can cause excessive scarring. This is an unreported function of uMSC exosomes. Also, for the first time, the uMSC-exosomal microRNAs were examined by high-throughput sequencing, with a group of specific microRNAs (miR-21, miR-23a, miR-125b, and miR-145) found to play key roles in suppressing myofibroblast formation by inhibiting excess α-smooth muscle actin and collagen deposition associated with activity of the transforming growth factor-β/SMAD2 signaling pathway.

Importance: Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective: To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants: This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures: Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results: The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%]; P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years; P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years; P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance: In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

-methyladenosine; MEFs, mouse embryo fibroblasts; Mer, mutated estrogen receptor domains; METTL3, methyltransferase like 3; METTL14, methyltransferase like 14; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin kinase complex 1; NMVCs, neonatal mouse ventricular cardiomyocytes; PCNA, proliferating cell nuclear antigen; PE, phosphatidylethanolamine; PI, propidium iodide; PTMs, post-translational modifications; PVDF, polyvinylidenedifluoride; RIP, RNA-immunoprecipitation; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TUBA: tublin alpha; WTAP, WT1 associated protein; YTHDF, YTH N6-methyladenosine RNA binding protein.

Objective Since December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed. Design Five datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion. Results Cell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon. Conclusion This study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.

As one of the most common chemical materials, titanium dioxide (TiO2) has been prepared and widely used for many years. Among all the applications, the biomedical applications of TiO2 have motivated strong interest and intensive experimental and theoretical studies, owing to its unique photocatalytic properties, excellent biocompatibility, high chemical stability, and low toxicity. Advances in nanoscale science suggest that some of the current problems of life science could be resolved or greatly improved through applying TiO2. This paper presents a critical review of recent advances in the biomedical applications of TiO2, which includes the photodynamic therapy for cancer treatment, drug delivery systems, cell imaging, biosensors for biological assay, and genetic engineering. The characterizations and applications of TiO2 nanoparticles, as well as nanocomposites and nanosystems of TiO2, which have been prepared by different modifications to improve the function of TiO2, are also offered in this review. Additionally, some perspectives on the challenges and new directions for future research in this emerging frontier are discussed.

Abstract Bone related diseases have caused serious threats to human health owing to their complexity and specificity. Fortunately, owing to the unique 3D network structure with high aqueous content and functional properties, emerging hydrogels are regarded as one of the most promising candidates for bone tissue engineering, such as repairing cartilage injury, skull defect, and arthritis. Herein, various design strategies and synthesis methods (e.g., 3D‐printing technology and nanoparticle composite strategy) are introduced to prepare implanted hydrogel scaffolds with tunable mechanical strength, favorable biocompatibility, and excellent bioactivity for applying in bone regeneration. Injectable hydrogels based on biocompatible materials (e.g., collagen, hyaluronic acid, chitosan, polyethylene glycol, etc.) possess many advantages in minimally invasive surgery, including adjustable physicochemical properties, filling irregular shapes of defect sites, and on‐demand release drugs or growth factors in response to different stimuli (e.g., pH, temperature, redox, enzyme, light, magnetic, etc.). In addition, drug delivery systems based on micro/nanogels are discussed, and its numerous promising designs used in the application of bone diseases (e.g., rheumatoid arthritis, osteoarthritis, cartilage defect) are also briefed in this review. Particularly, several key factors of hydrogel scaffolds (e.g., mechanical property, pore size, and release behavior of active factors) that can induce bone tissue regeneration are also summarized in this review. It is anticipated that advanced approaches and innovative ideas of bioactive hydrogels will be exploited in the clinical field and increase the life quality of patients with the bone injury.

Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy.

OBJECTIVES: To investigate the potential risk factors for endoscopic retrograde cholangiopancreatography (ERCP) complications and to identify whether the risk factors are different for pancreatitis and asymptomatic hyperamylasemia. METHODS: Consecutive ERCP procedures were studied at 14 centers in China from May 2006 to April 2007. The complications after the patients' first-only procedures were evaluated. Multivariate analysis based on the first-only procedures was used to identify the risk factors. RESULTS: A total of 3,178 procedures were performed on 2,691 patients. Overall, complications developed in 213 (7.92%) patients, pancreatitis in 116 (4.31%), and asymptomatic hyperamylasemia in 396 (14.72%). In the multivariate analysis, female gender (adjusted odds ratios (ORs): 1.52, 95% confidence interval (CI): 1.14-2.02, P=0.004), periampullary diverticulum (OR: 2.02, 95% CI: 1.49-2.73, P<0.001), cannulation time >10 min (OR: 1.51, 95% CI: 1.08-2.10, P=0.016), > or =1 pancreatic deep wire pass (OR: 1.80, 95% CI: 1.33-2.42, P<0.001), and needle-knife precut (OR: 2.70, 95% CI: 1.42-5.14, P=0.002) were risk factors for overall complications. Female gender (OR: 1.84, 95% CI: 1.25-2.70, P=0.002), age < or =60 year (OR: 1.59, 95% CI: 1.06-2.39, P=0.025), cannulation time>10 min (OR: 1.76, 95% CI: 1.13-2.74, P=0.012), > or =1 pancreatic deep wire pass (OR: 2.77, 95% CI: 1.79-4.30, P<0.001), and needle-knife precut (OR: 4.34, 95% CI: 1.92-9.79, P<0.001) were risk factors for pancreatitis. Cannulation time>10 min (OR: 1.96, 95% CI: 1.52-2.54, P<0.001), > or =1 pancreatic deep wire pass (OR: 2.24, 95% CI: 1.74-2.89, P<0.001), needle-knife precut (OR: 2.34, 95% CI: 1.32-4.14, P=0.004), and major papilla pancreatic sphincterotomy (OR: 1.71, 95% CI: 1.23-2.37, P=0.001) were risk factors for asymptomatic hyperamylasemia. CONCLUSIONS: Patient-related factors are as important as procedure-related factors in determining high-risk predictors for post-ERCP overall complications and pancreatitis. However, the risk factors for asymptomatic hyperamylasemia may be mostly procedure related.

In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and meta-analysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs = 2.01, 95% CI: 1.61-2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q = 136.68, p < 0.001, I(2) = 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR = 1.56; 95% CI: 1.30-1.87), with no significant evidence of heterogeneity among studies (Q = 1.16, p = 0.56, I(2) =0%). There were no significant publication bias (p = 0.79 for Egger's regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.

Local recurrence is a common cause of treatment failure for patients with solid tumors. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and, thereby improve prognosis. Here, we report in vivo assembly of the second near-infrared window (NIR-II) emitting downconversion nanoparticles (DCNPs) modified with DNA and targeting peptides to improve the image-guided surgery for metastatic ovarian cancer. The NIR-II imaging quality with DCNPs is superior to that of clinically approved ICG with good photostability and deep tissue penetration (8 mm). Stable tumor retention period experienced 6 h by in vivo assembly of nanoprobes can be used for precise tumor resection. Superior tumor-to-normal tissue ratio is successfully achieved to facilitate the abdominal ovarian metastases surgical delineation. Metastases with ≤1 mm can be completely excised under NIR-II bioimaging guidance. This novel technology provides a general new basis for the future design of nanomaterials for medical applications.

Harvesting biomechanical energy in vivo is an important route in obtaining sustainable electric energy for powering implantable medical devices. Here, we demonstrate an innovative implantable triboelectric nanogenerator (iTENG) for in vivo biomechanical energy harvesting. Driven by the heartbeat of adult swine, the output voltage and the corresponding current were improved by factors of 3.5 and 25, respectively, compared with the reported in vivo output performance of biomechanical energy conversion devices. In addition, the in vivo evaluation of the iTENG was demonstrated for over 72 h of implantation, during which the iTENG generated electricity continuously in the active animal. Due to its excellent in vivo performance, a self-powered wireless transmission system was fabricated for real-time wireless cardiac monitoring. Given its outstanding in vivo output and stability, iTENG can be applied not only to power implantable medical devices but also possibly to fabricate a self-powered, wireless healthcare monitoring system.