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Objective. Proton pump inhibitors (PPIs) are commonly used to treat gastric acidity, and their frequent use may trigger various malfunctioning, such as cardiac, renal, and liver function failure. In the current study, we evaluated the association between the excessive use of the PPIs and the clinical complications of intensive care unit (ICU) septic patients. Methods. A total of 208188 patients were analyzed from 2016 to 2017 through the China Critical Care Sepsis Trial (CCCST) database. The characteristics of the study group and outcome of events from the PPI- and H2 blocker-using groups were reported. To get unbiased results, the data from the target trials were randomly assigned for PPI and H2 blocker groups. Result. The data revealed 43.34 excess deaths (95% confidence intensive (CI) 25.12 to 62.02) per 1000 patients in patients extensively consuming PPI drugs. The sepsis with chronic kidney disease attributed to deaths 21.36; 95% CI (9.34 to 23.23). However, comorbidities, including circulatory diseases (16.34; 95% CI 5.78 to 23.45), nervous system (2.08; 95% CI 1.56 to 6.34), mental disorders (1.87; 95% CI 1.65 to 2.95), genitourinary system (5.23; 95% CI 3.69 to 8.89), and infectious and parasitic disease (4.17; 95% CI 1.44 to 7.49), were also reported. Extensive use of the PPIs and H2 blockers was associated with esophageal adenocarcinoma, Barrett’s esophagus, neoplasms, and GI cancers. Conclusion. We conclude that the excessive use of PPI in sepsis patients triggers chronic kidney disease which has a higher clinical complication rate among others.

Quantitative analysis of acetylcarnitine in additional 58 serum samples.

The identification of serum biomarkers to improve the diagnosis and prognosis of hepatocellular carcinoma has been elusive to date. In this study, we took a mass spectroscopic approach to characterize metabolic features of the liver in hepatocellular carcinoma patients to discover more sensitive and specific biomarkers for diagnosis and progression. Global metabolic profiling of 50 pairs of matched liver tissue samples from hepatocellular carcinoma patients was performed. A series of 62 metabolites were found to be altered significantly in liver tumors; however, levels of acetylcarnitine correlated most strongly with tumor grade and could discriminate between hepatocellular carcinoma tumors and matched normal tissues. Post hoc analysis to evaluate serum diagnosis and progression potential further confirmed the diagnostic capability of serum acetylcarnitine. Finally, an external validation in an independent batch of 58 serum samples (18 hepatocellular carcinoma patients, 20 liver cirrhosis patients, and 20 healthy individuals) verified that serum acetylcarnitine was a meaningful biomarker reflecting hepatocellular carcinoma diagnosis and progression. These findings present a strong new candidate biomarker for hepatocellular carcinoma with potentially significant diagnostic and prognostic capabilities. Cancer Res; 76(10); 2912–20. ©2016 AACR.

Figure legends of supplemental figures 1-5.

Tables S1. Clinical characteristics of subjects in Post-hoc analysis; Tables S2. Clinical characteristics of subjects in validation set; Tables S3. Reproducibility evaluation of LC-MS and GC-MS; Tables S4. 36 metabolites identified by LC-MS; Tables S5. Pearson's correlation analysis in Discovery set; Tables S6. Pearson's correlation analysis in Post-hoc analysis; Tables S7. Acetylcarnitine values in validation set; Figure S1. PCA scores plots of QC samples; Figure S2. Pathological images of HCC tissues; Figure S3. OPLS-DA scores plots of liver tissues; Figure S4. Heat map of 62 identified differential metabolites; Figure S5. Major differential metabolites and pathways in HCC tumors.

Coccidioidomycosis is caused by the dimorphic fungi Coccidioides species which is endemic in the Western hemisphere. Reports on the characteristics of travel-related disseminated coccidioidomycosis in immunocompetent patients are rare, especially in non-endemic regions. The multifaceted symptoms of this condition present a diagnostic challenge to clinicians. This study aimed to review immunocompetent patients diagnosed with disseminated coccidioidomycosis in a tertiary hospital in Eastern China and other non-endemic areas, and to emphasize the importance of combining travel history with clinical manifestations and proper diagnostic examinations. This study retrospectively reviewed a case series of disseminated coccidioidomycosis diagnosed in an academic hospital in Eastern China. We conducted a global literature review of disseminated coccidioidomycosis in immunocompetent patients with travel history. We identified six patients in our case series and reviewed 42 cases in the literature. Travel history included Mexico, Arizona, California, and regions of low endemicity. Extrapulmonary sites of infection, which presented with diverse signs and symptoms, involved the skin and soft tissue, musculoskeletal system, lymph nodes, and central nervous system. Misdiagnoses and diagnostic delays were common. Next-generation sequencing substantially promoted precise diagnosis in our series. The overall prognosis for immunocompetent individuals was positive, mainly benefited from long-term azole therapies. The patients that succumbed had either central nervous system involvement or multiorgan dissemination. Progressive pneumonia with varied symptoms and travel history should alert healthcare professionals in non-endemic areas to consider the possibility of Coccidioides species infection. We recommend detailed history-taking and hypothesis-free detection of pathogens for cases with diagnostic delay.

Background: Peripheral facial paralysis (PFP) is a common neurological disease. Many patients have obtained benefits from the treatment of PFP sequelae by electroacupuncture (EA). However, there is limited evidence for the efficacy between different EA intensities. Hence, this study presents a new approach based on different EA intensities to verify the effectiveness by combining neurological function scales in the sequelae of PFP. Methods: In this placebo-controlled trial, a total of 66 patients with peripheral facial paralysis sequelae will be randomly divided into sensory threshold stimulation, motor threshold stimulation and sham EA groups. All patients undergo two periods in this study, including the treatment period (56 days) and the follow-up period (30 days). House-Brackmann grade and facial disability index scale will be measured as primary outcome before, 4 weeks treatment, after treatment and follow-up. The secondary outcome measures will be facial nerve electromyography (EMG) and blink reflex (BR) detection before and after treatments. Conclusion: This trial will evaluate the effect of different EA intensities for treating sequelae of PFP compared to sham EA. We hope this trial will provide effective treatment parameters for PFP sequelae. Trial registration: ClinicalTrials.gov Identifier: ChiCTR2200062310. Date: August 1, 2022.

DCs regulate humoral immunity against SARS-CoV-2 by regulating CD4 + T cell activation, but the relations between DC phenotypes and functions and anti-RBD antibodies are unclear. We conducted this observational study in Huashan Hospital using a third 6.5U BBIBP-CorV or 25 µg ZF2001 administered at an interval of 4 to 8 months following the previous two doses in healthy adults. anti-RBD response and neutralizing titers against SARS-CoV-2 and VOCs were examined. DC maturation markers and pattern recognition receptors and cytokines produced by DC were measured, and DC function was tested in mixed lymphocyte reaction(MLR). Mean anti-RBD Ab and IgG rose from 22.08 and 9.17 on D0 to 4704.18 and 798.11 on D14(BAU/ml). Meanwhile, the surrogate virus neutralization test(sVNT) elevated from 17.15 on D0 to 2538.83 on D14. The expression of DC maturation markers on D3 and MLR were negatively correlated to sVNT, anti-RBD antibody, and IgG titers on D14(Spearman r=-0.558~-0.326) and D28(Spearman r=-0.615~-0.397), but positively correlated to IgG/Ab ratio(Spearman r = 0.249 ~ 0.509). DC function in activating T cells was also negatively related to anti-RBD antibody titer on D28(r=-0.532~-0.453, p = 0.015 ~ 0.035), and positively correlated with the proportion of anti-RBD IgG in Ab(r = 0.490 ~ 0.561, p = 0.010 ~ 0.032). DC-SIGN level showed a relation to antibody titer and IgG proportion opposite to DC maturation and function and was negatively related to the level of IL-10 produced by DCs. Our research suggested that DCs controlled CD4 + T cells in differentiating into regular T cells, and DC-SIGN might restrain T regular cells by suppressing IL-10 production of DC in anti-SARS-CoV-2 vaccination.

Septic-associated encephalopathy (SAE) is a critical manifestation of sepsis that leads to long-term cognitive impairment. Interleukin (IL)-17A has been shown to mediate neuronal apoptosis in central nervous system diseases, while oxidative stress has been found to have a detrimental effect in SAE. However, the relationship between IL-17A and oxidative stress in SAE remains unclear. This study aimed to investigate the effects of secukinumab on alleviating cognitive impairment in a rat model of sepsis, as well as examine its underlying molecular mechanism of action.A total of 282 male 8-week-old Sprague-Dawley rats were randomly subjected to cecal ligation and puncture (CLP) or sham treatment followed by volume resuscitation immediately after surgery. Secukinumab was administered intranasally 1 h post-CLP. Rats were given the p-ERK activator ceramide C6 intracerebroventricularly (i.c.v) 24 h before CLP surgery. Recombinant rIL-17A was administered i.c.v. at 0 h in naive rats, followed by intraperitoneal injection of the AKT inhibitor GDC0068 1 h post-rIL-17A injection. Clinical scores, body weight, and survival rate were assessed. In addition, immunofluorescence staining, neurobehavioral tests, Nissl staining, and western blotting were performed. Cognitive function was assessed 15-20 days post-CLP using the Morris water maze test.IL-17A and IL-17RA protein expression levels in the rat hippocampus increased and peaked 24 h post-CLP. Furthermore, IL-17RA was found to be expressed in neurons. The survival rate after CLP was 50%. Following CLP, an increased clinical score and significant decrease in body weight were observed. However, treatment with secukinumab led to a decrease in the clinical score of rats 24 h post-CLP. CLP resulted in spatial and memory impairment and anxiety-like behaviors in rats, while secukinumab treatment significantly alleviated cognitive impairment compared to the CLP group (p 0.05). In addition, oxidative stress and neuronal apoptosis were found to be increased in the CLP group, while secukinumab significantly reduced oxidative stress and neuronal apoptosis in the hippocampus following CLP. Furthermore, secukinumab treatment led to a significant decrease in the protein expression levels of p-AKT, p-ERK1/2, Romo1, and Bax, together with increased Bcl-2 protein expression. Finally, treatment with ceramide C6 and GDC0068 abolished the neuroprotective effects of secukinumab post-CLP.Our results demonstrated that secukinumab attenuated oxidative stress and neuronal apoptosis and partially ameliorated cognitive impairment via the IL-17RA/AKT/ERK1/2 pathway in a rat model of sepsis. Thus, secukinumab may be a potential therapeutic strategy for septic patients.

Aims The coronavirus disease 2019 (COVID‐19) has spread rapidly around the globe, causing significant morbidity and mortality. This study aims to describe electrocardiographic (ECG) characteristics of COVID‐19 patients and to identify ECG parameters that are associated with cardiac involvement. Methods and results The study included patients who were hospitalized with COVID‐19 diagnosis and had cardiac biomarker assessments and simultaneous 12‐lead surface ECGs. Sixty‐three hospitalized patients (median 53 [inter‐quartile range, 43–65] years, 76.2% male) were enrolled, including patients with (n = 23) and without (n = 40) cardiac injury. Patients with cardiac injury were older, had more pre‐existing co‐morbidities, and had higher mortality than those without cardiac injury. They also had prolonged QTc intervals and more T wave changes. Logistic regression model identified that the number of abnormal T waves (odds ratio (OR), 2.36 [95% confidence interval (CI), 1.38–4.04], P = 0.002) and QTc interval (OR, 1.31 [95% CI, 1.03–1.66], P = 0.027) were independent indicators for cardiac injury. The combination model of these two parameters along with age could well discriminate cardiac injury (area the under curve 0.881, P

The current global epidemiology of COVID-19 is now characterized by the emergence and rapid spread of the SARS-CoV-2 Omicron variant on a global scale1,2. Despite the variant’s prompt predominance, there remain knowledge gaps in its origin and evolution history3–6. Here, we show that Omicron lineage SARS-CoV-2 is characterized by the feature of chimera. It was generated by genomic recombination of two early PANGO lineages of SARS-CoV-2. In the recombination event, strains with medium or high circulating intensity like SARS-CoV-2/human/USA/COR-21-434196/2021 belonging to PANGO lineage BA.1 provided the fundamental genome and served as the major parents, while the rare lineage strains like SARS-CoV-2/human/IRN/Ir-3/2019 belonging to B.35, as the minor parents, hybridized their genomic fractions into the major genomes at position 21593-23118nt. This recombination event results in 22 amino acid residue substitutions for the variant of Omicron, including 16 in the pivotal RBD of the spike protein. These substitutions have led to some subtle variations in the spatial structure and the affinity to hACE2 receptor of the spike protein7,8, thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics9–12. The global spread and explosive growth of the SARS-CoV-2 in human population increase opportunities for future recombination13–15.

Background Liver abscess is a common emergency in the emergency department. However, cerebral venous sinus thrombosis (CVST) is a rare and serious cerebrovascular disease. Cases of CVST in patients with Klebsiella pneumoniae primary liver abscess (KLA) have not been described in the literature. We report a case of CVST in patients with KLA. Case presentation A 54-year-old male patient came to our department with a fever for 2 days and altered mental status for 1 day. Abdominal computed tomography (CT) and liver magnetic resonance imaging (MRI) revealed multiple liver abscesses. The blood culture was identified as Klebsiella pneumoniae sepsis. Head contrast-enhanced MRI and magnetic resonance venography (MRV) imaging showed multiple thrombus formation in the right transverse sinus and sigmoid sinus. The patient's infection and thrombosis were controlled within one week of multidisciplinary comprehensive treatment such as antibiotic and antithrombotic therapy, and a good clinical recovery during the 1-month follow-up. Conclusion CVST after liver abscess is rare, clinicians should be aware of this complication and vigilant for the possibility of bacterial meningitis. The underlying mechanisms need to be further studied.

Background: Multiple organ dysfunction is a complex and lethal clinical feature with heterogeneous causes and is usually characterized by tissue injury of multiple organs. Tenascin-C (TNC) is a matricellular protein that is rarely expressed in most of the adult tissues, but re-induced following injury. This study aimed to evaluate serum TNC in predicting mortality in critically ill patients with multiple organ dysfunction.Methods: Adult critically ill patients with at least two organs dysfunction and an increase of Sequential Organ Failure Assess (SOFA) score ≥ 2 points within 7 days were prospectively enrolled into two independent cohorts. The emergency (derivation) cohort was a consecutive series and the patients were from Emergency Department. The inpatient (validation) cohort was a convenience series and the patients were from medical wards. Their serum samples at the first 24 h after enrollment were collected and subjected to TNC measurement using ELISA. The association between serum TNC level and 28-day all-cause mortality was investigated, and then the predictive value of serum TNC was analyzed.Results: A total of 110 patients with a median age of 64 years (53, 73) were enrolled in the emergency cohort. Compared to the survivors, serum TNC in the non-survivors was significantly higher (467.7 vs. 197.5 ng/ml, p < 0.001). Multivariate logistic regression analysis revealed that the association between serum TNC and 28-day mortality was independent of sepsis or critical illness scores such as SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II), and Simplified Acute Physiology Score (SAPS II), respectively (p < 0.001 for each). The area under receiver operating characteristic curve of serum TNC for predicting mortality was 0.803 (0.717–0.888) (p < 0.001), similar with SOFA 0.808 (0.725–0.891), APACHE II 0.762 (0.667–0.857), and SAPS II 0.779 (0.685–0.872). The optimal cut-off value of serum TNC was 298.2 ng/ml. Kaplan–Meier analysis showed that the survival of patients with serum TNC ≥ 300 ng/ml was significantly worse than that of patients with serum TNC < 300 ng/ml. This result was validated in the inpatient cohort. The sensitivity and specificity of serum TNC ≥ 300 ng/ml for predicting mortality were 74.3 and 74.7% in the emergency cohort, and 63.0 and 70.1% in the inpatient cohort, respectively.Conclusion: Serum TNC was associated with mortality in critically ill patients with multiple organ dysfunction, and would be used as a prognostic tool for predicting mortality in this population.

Objective To investigate the safety and efficacy of wide local excision combined with aminolevulinic acid (ALA) photodynamic therapy (PDT) for the treatment of scrotal Paget's disease in patients of advanced age. Methods Data were collected for 16 patients (mean age, 68.44 years) with scrotal Paget's disease treated with wide local excision combined with ALA PDT and followed up from June 2014 to February 2018. Pathological examination after wide local excision confirmed Paget's disease. The patients underwent three courses of ALA PDT postoperatively and were followed up to determine the curative effect and complications in the short and middle term. Results The disease duration ranged from 4 to 76 months (mean, 36 months). Ten patients underwent simple excision, six underwent skin flap transfer, and two required reoperations due to skin flap necrosis and infection. The patients were followed up for 3 to 42 months after ALA PDT, during which time two patients developed metastasis (recurrence rate, 12.50%). No other serious complications occurred during follow-up except for lower limb movement disorder in one patient (6.25%). Conclusions Wide local excision combined with ALA PDT shows good clinical efficacy and a low complication rate in patients of advanced age with scrotal Paget's disease.

Background: Acute kidney injury (AKI) is a complex clinical disorder with sudden decay in renal function. Ischemia-reperfusion injury (IRI) has been regarded as the main etiology for the occurrence of AKI. MicroRNAs have been consistently shown to be involved AKI. Objectives: We aimed to investigate the role of miR-155 in AKI and its underlying mechanism. Methods: Ischemia-reperfusion (I/R)-induced AKI rat model and hypoxia-reoxygeneration (H/R)-induced NRK-52E cell model were established. The concentrations of serum creatinine and blood urea nitrogen were measured to evaluate renal function. Hematoxylin and eosin staining and TUNEL assay were performed to assess the severity of kidney injury. Additionally, quantitative real-time-PCR and western blot analysis were subjected to determine the expression of miR-155, TCF4, and apoptosis-related proteins, respectively. Moreover, cell proliferation and apoptosis were evaluated by Cell Counting Kit-8, bromodeoxyuridine, and flow cytometry analyses, respectively. Luciferase reporter assay was used to validate the direct targeting of TCF4 with miR-155. The protein levels of TCF4 and its downstream proteins in cells were measured by western blot. Results: The expression level of miR-155 was upregulated in both I/R-induced AKI rat model and H/R-treated NRK-52E cells. Moreover, overexpression of miR-155 promoted H/R-induced NRK-52E cells apoptosis and suppressed cell proliferation, while inhibition of miR-155 expression exerted opposite effects. Additionally, TCF4 was identified as a target of miR-155, of which expression was downregulated both in vivo and in vitro. Furthermore, the activity of Wnt/β-catenin signaling pathway was promoted following overexpression of TCF4 in NRK-52E cells, and this effect was attenuated by the increasing miR-155 expression. Conclusion: We demonstrated that miR-155 exacerbated AKI involving the targeting and regulation of TCF4/Wnt/β-catenin signaling pathway, indicating a novel regulatory network and elucidating a potential target for IRI-induced AKI treatment.

Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46–65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.

Background Dysregulation of both mitochondrial biogenesis and mitophagy is critical to sustain oncogenic signaling pathways. However, the mechanism of mitophagy in promoting hepatocellular carcinoma (HCC) progression remains poorly understood. In this study, we investigated the clinical significance and biological involvement of mitochondrial inner membrane protein STOML2 in HCC. Methods STOML2 was identified by gene expression profiles of HCC tissues and was measured in tissue microarray and cell lines. Gain/loss-of-function experiment was applied to study the biological function of STOML2 in HCC. Flow cytometry, Western blotting, laser confocal microscopy, transmission electron microscopy, and co-immunoprecipitation were used to detect and analyze mitophagy. ChIP and luciferase reporter assay were conducted to evaluate the relationship between STOML2 and HIF-1α. The sensitivity to lenvatinib was assessed in HCC both in vitro and in vivo. Results Increased expression of STOML2 was found in HCC compared with paired peritumoral tissues. It was more significant in HCC with metastasis and correlated with worse overall survival and higher probability of recurrence after hepatectomy. Upregulation of STOML2 accelerated HCC cells colony formation, migration and invasion. Mechanically, TCGA dataset-based analysis showed enrichment of autophagy-related pathways in STOML2 highly-expressed HCC. Next, STOML2 was demonstrated to interact and stabilize PINK1 under cellular stress, amplify PINK1-Parkin-mediated mitophagy and then promote HCC growth and metastasis. Most interestingly, HIF-1α was upregulated and transcriptionally increased STOML2 expression in HCC cells under the treatment of lenvatinib. Furthermore, higher sensitivity to lenvatinib was found in HCC cells when STOML2 was downregulated. Combination therapy with lenvatinib and mitophagy inhibitor hydroxychloroquine obtained best efficacy. Conclusions Our findings suggested that STOML2 could amplify mitophagy through interacting and stabilizing PINK1, which promote HCC metastasis and modulate the response of HCC to lenvatinib. Combinations of pharmacologic inhibitors that concurrently block both angiogenesis and mitophagy may serve as an effective treatment for HCC.

Additional file 2: Supplementary Tables.

To investigate the safety and efficacy of single percutaneous tract combined with flexible nephroscopy in the Management of 2-4 cm renal calculi.We retrospectively analysed the treatment data of patients with 2-4 cm renal calculi from June 2010 to June 2017. The data included 217 cases of percutaneous nephrolithotomy (PNL), 441 cases of retrograde intrarenal surgery (RIRS) and 217 cases of single-access percutaneous nephrolithotomy combined with flexible nephroscopy (PNCFN). The collected data were analyzed.A total of 875 cases were studied, with an average age of 42.35 ± 10.29 years. Group PNCFN showed the highest stone-free rates (SFRs)(73.7 vs 66.7 vs 80.2, P = .00), best patient satisfaction (89.84 vs 87.23 vs 92.29, P = .00). The length of stay was shorter in the RIRS group relative to the other two groups (5.22 vs 5.65 vs 3.72, P = .00). Haemoglobin decrease (10 g/L) was higher in group PNL than that in group RIRS and group PNCFN (P = .012). Hospitalization fees (RMB) were Increased in group PNCFN compared with that in group PNL and group RIRS (34563.45 vs 21334.69 vs 33343.16, P = .000). Treatment protocols of PNL decreased from 17.51% to 9.22%, those for RIRS from 5.22% to 17.69%, peaking at 2012, PNCFN from 8.29% to 15.67% showed a rapid growth trend.The percutaneous nephrolithotomy combined with flexible nephroscopy treatment on renal calculi of 2-4 cm was associated with higher stone-free rates and better patient satisfaction than RIRS and PNL.

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

Additional file 1. Search strategy.

Introduction Even though transurethral resection of the prostate (TURP) is the standard surgical treatment for benign prostatic hyperplasia (BPH), there is a high rate of postoperative retrograde ejaculation. Aim To evaluate the effectiveness of TURP with preservation of the bladder neck in comparison with that of standard TURP. Material and methods This is a retrospective study. 137 men with BPH were divided into two groups: TURP with preservation of the bladder neck and standard TURP were performed respectively in group A and group B. The patients were evaluated preoperatively and at 3, 6 and 12 months after surgery by International Prostate Symptom Score (IPSS), health-related quality of life (HRQL) score, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR) and the rate of complications including retrograde ejaculation. Results There was no statistically significant difference between groups in terms of the operative duration, catheterization period, hemoglobin decrease, and hospital stay. At the 3-month follow-up, the rates of incontinence and retrograde ejaculation in group A were lower than those in group B. At the 6- and 12-month follow-ups, the difference in the frequency of retrograde ejaculation remained constantly stable whereas the incontinence rates were similar in both groups. The IPSS, HRQL score, Qmax, PVR and the rate of complications including hematuria, clot retention, urinary tract infection, urethral stricture, and bladder neck contracture evaluated at 3, 6 and 12 months also displayed a very similar response in the two groups. Conclusions Comparable with standard TURP, TURP with preservation of the bladder neck appears to provide a satisfactory clinical outcome in decreasing early postoperative incontinence and lowering the rate of retrograde ejaculation.

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease, mainly caused by polycystic kidney disease 1/2 (PKD1/2) gene mutation. The main manifestation is the formation of multiple progressive enlarged cysts in both kidneys, which can be accompanied by decreased glomerular filtration rate, hypertension, liver cyst and cerebral aneurysm. About 45% of patients will progress to end-stage renal failure before the age of 60. ADPKD gene sequencing can be chosen for suspicious patients with atypical clinical features, no positive family history, and inconspicuous imaging findings. In the ADPKD positive families, imaging examination is the main means of diagnosing ADPKD. Height-adjusted total kidney volume (htTKV) and kidney growth rate are commonly used to monitor ADPKD disease progression and prognosis. There is no effective treatment for ADPKD to stop its progress. Drugs such as tolvaptan and bosutinib can delay the renal disfunction and they have been applied to clinical therapy in Europe and America.常染色体显性多囊肾病(autosomal dominant polycystic kidney disease，ADPKD)是一种常见的遗传性疾病，主要由多囊肾病(polycystic kidney disease，PKD)1/PKD2基因突变引起，以双肾多发、进行性增大的囊肿为主要表现，可同时伴有肾小球滤过功能减退、高血压、肝囊肿及脑动脉瘤，约45%的患者在60岁之前进展为终末期肾衰竭。ADPKD基因测序可用于临床特征不典型、没有阳性家族史、影像学表现不明显的患者。在ADPKD阳性的家系中，影像学检查是诊断ADPKD的主要手段。按身高调整后的肾总体积(height-adjusted total kidney volume，htTKV)和肾增长率是目前常用的监测ADPKD进展和判断预后的指标。ADPKD暂无终止其疾病进展的有效治疗措施。ADPKD治疗药物托伐普坦和伯舒替尼能延缓htTKV的增加，已在欧美等地区应用于临床。.

BACKGROUND In developed countries, prostate cancer (PCa) is a frequently diagnosed cancer with the second highest fatality rate. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) stably expressed in cells and involved in a series of carcinomas. However, few research studies have reported on the role of circRNAs in PCa. MATERIAL AND METHODS We used qRT-PCR to detect the expression of circMYLK (circRNA ID: hsa_circ_0141940) and miR-29a in PCa tissues and cell lines. MTT, colony formation, and TUNEL assays were performed to analysis the cell viability of PCa cells. Transwell and wound scratch assays were performed to investigate the cell invasion and migration of PCa cells. RESULTS In the present study, we confirmed that circMYLK expression level was significantly higher in PCa samples and PCa cells than in normal tissues and normal prostatic cells. The upregulated circRNA-MYLK promoted PCa cells proliferation, invasion, and migration; however, si-circRNA-MYLK significantly accelerated the PCa cell apoptosis. We also observed that the aforementioned function of circRNA-MYLK on PCa cells was affected through targeting miR-29a. CONCLUSIONS We confirmed circRNA-MYLK was an oncogene in PCa and revealed a novel mechanism underlying circRNA-MYLK in PC progression.

Background Meningitis is a serious complication occurring after neurosurgical operations, which can result in severe morbidity and high mortality. This retrospective cohort study aimed to determine the risk factors of postoperative meningitis in a large clinical center of neurosurgery in China. Methods Patients who underwent a neurosurgical procedure between January 2014 and December 2015 were selected, and 1016 cases were included our final analysis. On the basis of propensity scores, 84 patients with postoperative meningitis were successfully matched to 84 patients without postoperative meningitis. Results After propensity score matching, age, hospitalization duration, intraoperative use of corticoids, intraoperative use of antibiotics, external ventricular drainage, lumbar drainage, enteral nutrition, duration of surgery, major craniotomy, and transsphenoidal surgery were associated with postoperative meningitis. Furthermore, preoperative use of corticoids, intraoperative use of corticoids, intraoperative use of antibiotics, external ventricular drainage, lumbar drainage, and major craniotomy were independent predictors of postoperative meningitis in propensity score-matched cohort. A prediction model including these 6 independent predictors was established. Finally, receiver operating characteristic curve and discriminant analysis confirmed that this model has strong predictive power for evaluating postoperative meningitis. Conclusions The prediction model built in our study can be an excellent tool for predicting meningitis after neurosurgical procedures.

Background/Aims: Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme in the transport of long-chain fatty acids for β-oxidation. Increasing evidence has indicated that CPT1A plays an important role in carcinogenesis. However, the expression and prognostic value of CPT1A in hepatocellular carcinoma (HCC) have not been extensively studied. Methods: Here, we collected 66 post-operative liver cancer tissue samples. Gene profile expression was tested by RT-PCR. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox’s Proportional Hazard Model was used for confirming the selected markers’ predictive efficiency for HCC patients’ survival. A simple risk scoring system was created based on Cox’s regression modeling and bootstrap internal validation. Results: Cox multivariate regression analysis demonstrated that CPT1A, tumor size, intrahepatic metastasis, TNM stage and histological grade were independent risk factors for the prognosis of HCC patients after surgery. Our genetic and clinical data-based (GC) risk scoring system revealed that HCC patients whose total score≥3 are more likely to relapse and die than patients whose total score < 3. Finally, the good discriminatory power of our risk scoring model was validated by bootstrap internal validation. Conclusions: The genetic and clinical data-based risk scoring model can be a promising predictive tool for liver cancer patients’ prognosis after operation.

We compared hepatic and serum lipid changes in hepatocellular carcinoma (HCC) patients to have a better understanding of the molecular pathogenesis of this disease and discovery novel lipid biomarkers. Hepatic and serum lipid profiling was conducted in paired liver and serum samples from 50 HCC patients and 24 healthy controls. A total of 20 hepatic and 40 serum lipid signatures were identified, yet there was hardly any significant correlation between them. The results indicated that triglycerides and phosphatidylcholines contributed significantly to altered hepatic lipids, whereas triglycerides and phosphatidylethanolamine-based plasmalogens (PEp) contributed most to altered serum lipids. In serum, PEp (36:4) and (40:6) showed a fair capability to discriminate HCC patients from healthy controls, and were significantly associated with HCC tumor grades (p < 0.05), and thus were identified as potential diagnostic and prognostic biomarkers of HCC. These findings were confirmed by a validation study conducted in an independent cohort consisting of 18 HCC, 20 cirrhosis patients, and 20 healthy controls. This study suggests that hepatic and serum lipid signatures of HCC have to be considered as mostly independent, and the results imply potential roles of PEp species, particularly PEp (36:4) and (40:6), as serum biomarkers for HCC diagnosis and progression.

Background/Aims: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomark ers for differentiating S0-S2 (early fibrosis) from S3-S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. Methods: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative poly merase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0-S2 from S3-S4. Re sults: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis pro gressed from S0-S2 to S3-S4 (p

Type I IFNs play crucial roles in antiviral immune responses. By inducing cellular resistance to viral infection and apoptosis of virus-infected cells, they impair virus replication and eliminate the invading pathogens. However, in CHB patients, generation of type I IFN was significantly impaired and the underlying mechanisms have not been fully understood. MicroRNA-548 family has been implicated in regulating antiviral response upon various infections. Here we explored the potential role of miR-548j in modulating type I IFN production in CHB. We found that miR-548j expression increased in MoDCs from CHB patients than that from healthy volunteers and transient transfection of miR-548j mimic led to a marked decrease of IFN-α/β production in MoDCs from healthy volunteers while blockade of miR-548j by anti-miR-548j significantly restored IFN-α/β secretion in MoDCs from CHB patients. In addition, Zinc finger and BTB domain containing 11 (ZBTB11) was predicted and finally confirmed to be a target of miR-548j. Forced expression of ZBTB11 also restored IFN-α/β secretion in MoDCs from CHB patients. These results indicate the involvement of miR-548j in aberrant production of type I IFN in CHB patients, and provide a potential target for developing anti-HBV therapies.

The identification of serum biomarkers to improve the diagnosis and prognosis of hepatocellular carcinoma has been elusive to date. In this study, we took a mass spectroscopic approach to characterize metabolic features of the liver in hepatocellular carcinoma patients to discover more sensitive and specific biomarkers for diagnosis and progression. Global metabolic profiling of 50 pairs of matched liver tissue samples from hepatocellular carcinoma patients was performed. A series of 62 metabolites were found to be altered significantly in liver tumors; however, levels of acetylcarnitine correlated most strongly with tumor grade and could discriminate between hepatocellular carcinoma tumors and matched normal tissues. Post hoc analysis to evaluate serum diagnosis and progression potential further confirmed the diagnostic capability of serum acetylcarnitine. Finally, an external validation in an independent batch of 58 serum samples (18 hepatocellular carcinoma patients, 20 liver cirrhosis patients, and 20 healthy individuals) verified that serum acetylcarnitine was a meaningful biomarker reflecting hepatocellular carcinoma diagnosis and progression. These findings present a strong new candidate biomarker for hepatocellular carcinoma with potentially significant diagnostic and prognostic capabilities. Cancer Res; 76(10); 2912–20. ©2016 AACR.

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real-time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non-cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.