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Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009–1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037–2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018–2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

OBJECTIVES The objective of this study was to develop and validate a model, based on the blood biochemical (BBC) indexes, to predict the recurrence of acute pancreatitis patients. METHODS We retrospectively enrolled 923 acute pancreatitis patients (586 in the primary cohort and 337 in the validation cohort) from January 2014 to December 2016. Aiming for an extreme imbalance between recurrent acute pancreatitis (RAP) and non-RAP patients (about 1:4), we designed BBC index selection using least absolute shrinkage and selection operator regression, along with an ensemble-learning strategy to obtain a BBC signature. Multivariable logistic regression was used to build the RAP predictive model. RESULTS The BBC signature, consisting of 35 selected BBC indexes, was significantly higher in patients with RAP (P < 0.001). The area under the curve of the receiver operating characteristic curve of BBC signature model was 0.6534 in the primary cohort and 0.7173 in the validation cohort. The RAP predictive nomogram incorporating the BBC signature, age, hypertension, and diabetes showed better discrimination, with an area under the curve of 0.6538 in the primary cohort and 0.7212 in the validation cohort. CONCLUSIONS Our study developed a RAP predictive nomogram with good performance, which could be conveniently and efficiently used to optimize individualized prediction of RAP.

The triple-negative breast carcinoma (TNBC) is the most aggressive subtype of breast cancer. In TNBC, Aquaporin 1 (AQP1), a water-transporting transmembrane protein, is aberrantly enriched in cytoplasm and causes tumor cell death evasion. However, the carcinogenetic bioactivities of cytoplasmic AQP1 cannot be attributed to the canonical “osmotic engine model”. In the present study, the receptor-interacting protein kinase 1 (RIPK1), a cell death regulator, was identified to negatively mediate AQP1-driven TNBC progression and metastasis. AQP1 overabundance and RIPK1 depletion occurred in TNBC, which were correlated with aggressive oncological features and poor prognosis. AQP1 bound with RIPK1, resulting in the inhibition of RIPK1/RIPK3/MLKL-mediated necroptosis and RIPK1/caspase-8/caspase-3-mediated apoptosis. Genetic inhibition of RIPK1 significantly exacerbated the pro-tumor effect of AQP1, while ectopic expression of RIPK1 notably blunted AQP1 signaling. Mechanistically, AQP1 binds to the D324 site of RIPK1, and facilitates RIPK1 cleavage and inactivation by excessively activating the caspase-8/RIPK1 negative feedback loop. RIPK1D324K overexpression significantly prevented RIPK1 cleavage and weakened the aggressiveness of AQP1-enriched TNBC cells. Overall, our findings clarify the underlying mechanism of cytoplasmic AQP1-driven TNBC progression and metastasis, in which RIPK1 exerts an essential role as a negative mediator and exhibits the potential as a therapeutic target for TNBC.

Aim: To investigate the clinical value of tumor markers in extrapleural tumor metastasis assessment of newly diagnosed lung cancer patients. Materials & methods: This study retrospectively analyzed 306 patients diagnosed with lung cancer accompanied by tumor metastasis. Patients were grouped into extrapleural tumor metastasis and intrapleural tumor metastasis. Seven serum tumor markers were included for analysis. Results: The area under curves of receiver operating characteristic curve based on binning decision tree algorithm were above 0.8 in both training and validation sets. A scorecard with a score below 3 suggested extrapleural tumor metastasis in newly diagnosed lung cancer patients. Conclusion: The serum tumor marker-derived model is a convenient and fast approach for extrapleural cavity metastasis assessment, which may provide positive implications in newly diagnosed lung cancer patients.

The lung lesions of this COVID‐19 patient were slowly absorbed, and the clinical symptoms with shortness of breath were improved slowly in the recovery period.

BACKGROUND AND PURPOSE The aim of this meta-analysis study was to assess the predictive effects of RNF213 p.R4810K on phenotype in moyamoya disease (MMD). METHODS Electronic databases (e.g., Pubmed and EMBASE) were searched, and relevant articles published up to August 2020 were retrieved. Review Manager 5.3 and Stata 12.0 were used for all statistical analyses. Pooled odds ratios, with 95% confidence intervals, and three comparison models were evaluated to analyze the association between RNF213 pR4810K variant and clinical characteristics of MMD patients using a fixed-effects model. RESULTS A total of 2798 patients with MMD were selected and the effects of the heterozygous or homozygous RNF213 p.R4810K variant on 18 clinical features were identified. There were more patients aged

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic threatening global public health. In the current paper, we describe our successful treatment of three COVID-19 pneumonia patients cases including severe cases and cases with mortality risk factors. One 32-year-old male COVID-19 patient was diagnosed with severe COVID-19 pneumonia and moderate ARDS. The second COVID-19 pneumonia patient had a history of diabetes and chronic bronchitis. The third case of COVID-19 pneumonia was an 82-year old female patient. All three cases had severe COVID pneumonia and therefore were aggressively managed with a multidisciplinary and personalized therapeutic approach that included nutritional support, antiviral pharmacotherapy, active control of comorbidities, prevention of complication development and psychological intervention. Our experience highlights the importance of the use of a multidisciplinary therapeutic approach that tailors to the specific condition of the patient in achieving a favorable clinical outcome.

ObjectivePrecise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.MethodsA case–control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.ResultsAn obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1–79.6; p = 1.6 × 10−141). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 × 10−7).ConclusionsStrong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system with poor prognosis. Although the field of immunotherapy in glioma is developing rapidly, glioblastoma is still prone to recurrence under strong immune intervention. The major challenges in the process of immunotherapy are evaluating the curative effect, accurately distinguishing between treatment-related reactions and tumor recurrence, and providing guidance for clinical decision-making. Since the conventional magnetic resonance imaging (MRI) is usually difficult to distinguish between pseudoprogression and the true tumor progression, many studies have used various advanced imaging techniques to evaluate treatment-related responses. Meanwhile, criteria for efficacy evaluation of immunotherapy are constantly updated and improved. A standard imaging scheme to evaluate immunotherapeutic response will benefit patients finally. This review mainly summarizes the application status and future trend of several advanced imaging techniques in evaluating the efficacy of GBM immunotherapy.

ObjectivesFor colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer.MethodsWe searched the PubMed and Ovid MEDLINE databases up to May 1, 2021 and screened studies for eligibility. Thirteen studies published from 2015 to 2021 with 5062 patients were included finally. We extracted and calculated hazard ratios (HRs) and odds ratios (ORs) of overall survival (OS) and objective response rates (ORRs) and their 95% confidence intervals (95% CIs). Pooled HR and OR were evaluated to compare OS and ORR between TMB-high and TMB-low groups in colorectal cancer patients. Meanwhile, we assessed heterogeneity with the I2 statistic and p-values and performed publication bias assessments, sensitivity analyses, and subgroup analyses to search the cause of heterogeneity.ResultsThe TMB-high patient group had a longer OS than the TMB-low patient group (HR = 0.68, 95% CI: 0.51, 0.92, p = 0.013) among colorectal cancer patients receiving ICIs. In addition, the TMB-high patient group was superior in terms of ORR (OR = 19.25, 95% CI: 10.06, 36.82, p < 0.001) compared to the TMB-low patient group.ConclusionsIn conclusion, this meta-analysis revealed that TMB can be used as a potential predictive biomarker of colorectal cancer patients receiving ICI therapy. Nevertheless, this finding is not stable enough. Therefore, many more randomized controlled trials are needed to prove that TMB is reliable enough to be used clinically to predict the efficacy of immunotherapy in colorectal cancer. And the most relevant biomarker remains to be determined when TMB high overlaps with other biomarkers like MSI and TILs.

Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

Background: Ischemic stroke (IS) is a significant disease which threatens human health condition. Genome-wide association studies (GWAS) have demonstrated that two intergenic single- nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 G>A on chromosome 12p13 are associated with IS susceptibility. However, later studies came to contradictory outcomes. Thus, we carried out a meta-analysis to identify the association between nerve injury-induced protein 2 (NINJ2) gene polymorphisms (rs11833579 and rs12425791) and the risk of IS. Methods: PubMed, Embase, Web of Science, CBM, Wanfang, VIP, and CNKI databases were searched until March 2019. Data was analyzed by RevMan 5.3 and STATA 12.0 software. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the association. Results: Eighteen qualified articles were selected in total. For rs12425791 and rs11833579, a total of 14055 cases with 13148 controls and 10635 cases with 10462 controls, respectively, were identified for the present study. Our meta-analysis found that rs12425791 was associated with IS for three genetic models (allele model: OR=1.04, 95% CI: 1.00-1.08, P=0.04; dominant model: OR=1.06, 95% CI: 1.01-1.12, P=0.01 and heterozygous model: OR=1.07, 95% CI: 1.01-1.12, P=0.02). Whereas rs11833579 polymorphism was not associated with IS among different genetic models. Conclusion: NINJ2 gene rs12425791 confers a susceptible factor for IS, while there is no association between NINJ2 gene rs11833579 and IS. Larger sample size studies should be performed to find the association between NINJ2 gene and IS.

With the development of multifunctional imaging, gadolinium (Gd)-bearing inorganic nanoparticles (NPs), which were doped with trivalent lanthanide (Ln3+), have been applied in magnetic resonance imaging (MRI) and optical imaging owing to their high payload of Gd3+ ions and specific optical characteristics. In this study, we chose GdVO4 codoped with Eu3+ and Bi3+ as the host material to generate a highly efficient contrast agent (CA) for MRI and long-term luminescence imaging. The new CA emits strong and stable luminescence because of its strong characteristic emissions, resulting from the energy-transfer process from the vanadate groups (VO4 3-) to the Eu3+ and Bi3+ dopants. Additionally, these NPs provided conspicuous T 1 and T 2 relaxation time-shortening characteristics, which result in MRI enhancement. GdVO4:Eu3+,Bi3+ NPs were tested on liver tumor-bearing nude mice, and showed improved liver tumor contrast in T 2-weighted MR images (T 2WI). The dual-modal imaging probe exhibited no cytotoxicity or organ toxicity, reflecting its excellent biocompatibility. Thus, GdVO4:Eu3+,Bi3+ has the potential to be used for bioassays in vitro and liver tumor targeting in vivo. The results reveal the great promise of using the designed GdVO4:Eu3+,Bi3+ NPs as luminescent and MRI dual-mode bioprobes for clinical bioimaging applications.

ObjectiveImmediate early response 5 (IER5) plays a core role in cell cycle and response to irradiation. However, its role in glioma remains unclear. We aimed to evaluate its prognostic significance in glioma based on The Cancer Genome Atlas data resource.MethodsThe Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were employed to explore the relationship between IER5 expression and clinicopathological features. Kaplan–Meier and Cox regression analyses were implemented to investigate the relationship of IER5 with prognosis. A nomogram to estimate the impact of IER5 on prognosis was created based on the Cox multivariate data. We performed gene set enrichment analysis (GSEA) to determine the key signaling cascades associated with IER5. Immunohistochemistry was performed to examine IER5 expression in a tissue microarray (TMA) of glioma samples.ResultsImmediate early response 5 gene expression was elevated in glioma patients. The level of IER5 was significantly correlated with WHO grade [OR = 6.71 (4.34–10.68) for G4 vs. G2 and G3], IDH (isocitrate dehydrogenase enzyme) status [OR = 13.35 (8.92–20.46) for wild-type (WT) vs. mutated (Mut)], epidermal growth factor receptor status [OR = 8.42 (4.32–18.43) for Mut vs. WT], age [OR = 0.27 (0.18–0.41) for ≤ 60 years vs. >60 years], and histological type [OR = 7.13 (4.63–11.31] for glioblastoma vs. astrocytoma, oligoastrocytoma, and oligodendroglioma). Univariate analyses revealed that high IER5 expression was linked to short overall survival (OS) [hazard ratio (HR): 3.747; 95% confidence interval (CI): 2.847–4.933; and P < 0.001]. High IER5 expression was linked to poor OS in multivariate analyses (HR: 2.474; 95% CI: 1.552–3.943; and P < 0.001). TMA results showed that high IER5 protein levels were related to short OS (HR: 1.84; 95% CI: 1.10–3.07; and P = 0.021) and poor disease-specific survival (HR: 1.82; 95% CI: 1.09–3.04; and P = 0.023). GSEA showed that many tumor related pathways were enriched differentially in the IER5-high expression group. The C-index and calibration plots of the nomogram showed an effective estimation performance in glioma patients.ConclusionHerein, we established that IER5 plays a critical role in glioma progression and prognosis, which might be an important biomarker for the prognosis of glioma patients.

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis.Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram.Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model.Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.

Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application., Precision Clinical Medicine, 4 (2)

This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment.A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes.For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P0.05). The factors were not consistent in the different groups of age at onset.In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.

Background Lupus enteritis (LE), a main cause of acute abdominal pain in systemic lupus erythematosus (SLE) patients, is a serious and potentially fatal complication. This study aimed to identify clinical serological indicators to establish a nomogram to assess LE in SLE patients with gastrointestinal manifestations. Methods The clinical and laboratory data of SLE patients with gastrointestinal manifestations that were hospitalized in the West China Hospital from January 2010 to January 2020 were retrospectively analyzed. The least absolute shrinkage and selection operator logistic regression model was used to select potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated using a receiver operating characteristic curve, a calibration curve, and decision curve analysis (DCA). Findings We included a total of 8,505 SLE patients, of which 251 had experienced gastrointestinal manifestations. The patients were randomly divided into training (n = 176) and validation (n = 75) groups. The LRA (LE Risk Assessment) model consisted of 11 significantly associated variables, which included complement 4, antineutrophil cytoplasmic antibody, albumin, anion gap, age, d -dimer, platelet, serum chlorine, anti-Sjogren's-syndrome-related antigen A, anti-ribosomal P protein, and anti-ribonucleoprotein. In the training and validation cohorts, the areas under the curve were 0.919 (95% confidence interval [CI]: 0.876–0.962) and 0.870 (95% CI: 0.775–0.964), respectively. The nomogram demonstrated excellent performance in the calibration curve and DCA. Interpretation The LRA model exhibits good predictive ability in assessing LE risk in SLE patients with gastrointestinal manifestations. Funding This work was supported by the National Key Research and Development Program of China (Project no. 2016YFC0906201) and by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Project No. ZYGD18015).

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus’ pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5’ gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

Background The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. Methods Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. Results Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046). Conclusions The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.

Introduction Worldwide, the incidence and mortality of lung cancer are at the highest levels, and the most lesions are located in the lung periphery. Despite extensive screening and diagnosis, the pathologic types of peripheral pulmonary lesions (PPLs) are difficult to diagnose by noninvasive examination. This study aimed to identify a novel index—time difference of arrival (TDOA)—to discriminate between benign inflammation and malignant PPLs. Methods Using contrast-enhanced ultrasound (CEUS), we retrospectively analyzed 96 patients with PPLs who had undergone biopsy to confirm the pathologic types. All data were collected from Dazhou Central Hospital between December 2012 and July 2019. The parameters of CEUS were analyzed by two assistant chief physicians of ultrasound diagnosis. Area under the receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the diagnostic ability of different indices. Results We found that the TDOA significantly distinguished benign inflammation from malignant lesions. The TDOA was markedly increased in patients with malignant lesions than benign inflammation lesions (P < 0.001). Compared with conventional time-intensity curve (TIC) indices, TDOA showed high diagnostic accuracy (area under the curve = 0.894). Moreover, conventional diagnostic indices did not affect the diagnostic performance of TDOA by adjusting the receiver operating characteristic curve. Conclusion TDOA is feasible for the diagnosis of benign inflammation and malignant PPLs.

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy.

Background: The aim of this study is to evaluate the clinical efficacy of vitamin D (VitD) supplementation in terms of response to treatment and improvement of disease activity in rheumatoid arthritis (RA).Methods: This study analyzed 1180 RA patients' records treated at Mianyang Central Hospital from February 2015 to July 2019. The patients were allocated into VitD group and control group based on their medical regimens. The outcome measures were primary efficacy, defined as treatment response-based EULAR response criteria in RA, and secondary efficacy, defined as improvement in disease activity indicators. Safety was evaluated according to the incidence of all-cause infections.Results: At month 6, the primary efficacy revealed that there were 22.8% good responders and 19.0% moderate responders in the VitD group, and 22.3% good responders and 22.3% moderate responders in the control group; there were no differences between the two groups (p = 0.754). The similar primary efficacy outcomes were observed at months 3, 12, and >12. The secondary efficacy indicated that there were no differences in most indexes between the two groups at months 1, 3, 6, 12, and >12. The subgroups (based on baseline DAS28 (CRP), glucocorticoids use and disease duration) analysis results suggested that VitD group didn't have the advantage for treating RA. The incidence of infections was similar in the two groups.Conclusion: VitD supplementation did not provide additional benefit for anti-rheumatic treatment. These data supported the need for prospective, randomized, controlled trials to evaluate the role of VitD supplementation in treating RA.

Background and Purpose— A growing body of evidence indicates genetic components play critical roles in moyamoya disease (MMD). Firm conclusions from studies of this disease have been stymied by small sample sizes and a lack of replicative results. This meta-analysis was conducted to determine whether these genetic polymorphisms are associated with MMD. Methods— PubMed, Google Scholar, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify potentially relevant studies published until January 2020. The Review Manager 5.2 and Stata 15.0 software programs were used to perform the statistical analysis. Heterogeneity was assessed using the Cochran Q test and quantified using the I 2 test. Results— Four thousand seven hundred eleven MMD cases and 8704 controls in 24 studies were included, evaluating 7 polymorphisms in 6 genes. The fixed-effect odds ratios (95% CI) in allelic model of MMP-2 rs243865 were 0.60 (0.41–0.88) ( P =0.008). In the country-based subgroup analysis, the fixed-effect odds ratios (95% CI) of RNF213 rs112735431 in allelic model were China, 39.74 (26.63–59.31), Japan, 74.65 (42.79–130.24) and Korea, 50.04 (28.83–86.88; all P RNF213 rs148731719 variant, 2.17 (1.36–3.48; P =0.001), 2.20 (1.35–3.61; P =0.002), the TIMP-2 rs8179090 variant, 0.33 (0.25–0.43; P P =0.440) and the MMP-3 rs3025058 variant, 0.61 (0.47–0.79; P =0.0002), 0.55 (0.41–0.75; P =0.0001), respectively. Conclusions— RNF213 rs112735431 and rs148731719 were positively, and TIMP-2 rs8179090, MMP-2 rs243865, and MMP-3 rs3025058 were inversely associated with MMD using multiple pathophysiologic pathways. Studies in larger population should be conducted to clarify whether and how these variants are associated with MMD.

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03–1.83) and homozygous model (OR=1.54, 95% CI=1.15–2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18–2.42; homozygous: OR=1.99, 95% CI=1.38–2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02–1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.

Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery., Breast cancer: nanoparticles highlight problematic lymph nodes Fluorescent nanoparticles designed by researchers in China will help surgeons detect key sites where breast cancer spreads around the body. Tumours undergoing metastasis start by targeting sentinel lymph nodes, which are difficult to distinguish from normal or inflamed lymph nodes. Zhihong Zhang at Huazhong University of Science and Technology, Wuhan and co-workers, designed nanoparticles just 40 nm in size coated in hyaluronic acid, which binds to proteins overexpressed by breast cancer cells. The nanoparticles also include fluorescent dye molecules that are easily detected by photoacoustic microscopy. Six hours after injecting the nanoparticles into mice, the researchers observed strong photoacoustic signals at the centres of sentinel lymph nodes, while other lymph nodes showed signals only at their edges. This ability to distinguish important metastatic sites will guide surgeons in removing problematic tissue during breast cancer surgery.

COVID-19 has become a global pandemic, but with very little is known about it. In this single-centered, retrospective study, we collected all 37 confirmed cases of COVID-19 diagnosed in Dazhou, Sichuan, China from January 23 to February 25, 2020，and analyzed the demographic, clinical, and laboratory data. All of the cases were either imported from Wuhan and transmitted in family clusters. The average age of the patients was 45.76 ± 13.1 years. The average duration of pharyngeal swabs was 20.65 ± 6.7 days. Four (10.8%) patients were asymptomatic, 33 (89.1%) patients had increased lactic acid, 17 (45.9%) patients had increased fibrinogen C (Fib-C), and 5 (13.5%) patients had increased D-Dimers. 29 (87.9%) cases were positive for new coronavirus-specific antibodies, 4 (10.8%) cases were positive for viral nucleic acid in stool samples, 1 (2.7%) patient had positive culture of Klebsiella pneumonia. Therefore, we can predict that Lopinavir/ritonavir and abidol may not be effective in treating COVID-19.Elevated lactic acid, Fib-C, and D-dimer in patients may be predictors of disease progression. The new coronavirus-specific IgM and IgG antibodies can help to diagnose the disease. We need to pay attention to the risks posed by fecal nucleic acid positive patients.Authors Chun Liu, FanXin Zeng, and PingXi Wang contributed equally to this work.

The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5’ mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR-and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.

Background This study aimed to explore the possibility of serum tumor markers (TMs) combinations in assessing tumor metastasis in patients with lung cancer. Methods We performed a retrospective analysis of 541 patients diagnosed with lung cancer between January 2016 and December 2017 at the Pneumology Department of Dazhou Central Hospital. Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA153, CA199, CA724, cytokeratin 19 fragment (CYFRA), and neuron‐specific enolase (NSE) levels were quantified in each patient at the time of lung cancer diagnosis. Metastasis was confirmed by computed tomography, and/or positron emission tomography, and/or surgery or other necessary methods. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the performance of the model. Results Of the 541 patients eligible for final analysis, 253 were detected with metastasis and 288 were detected without metastasis. Compared with those in nonmetastatic patients, the serum CEA, CA125, CA199, CA153, CYFRA, and NSE levels were notably higher in metastatic patients (P, The study developed a predictive model integrated with age, gender, and seven serum tumor markers (based on cut‐off value), which was efficient and reliable for assessing tumor metastasis before traditional standard methods are applied in highly suspected lung cancer patients. The predictive model combined with the decision tree model could provide some positive suggestions in the clinic.

SUMMARYAn increasing number of cases of novel coronavirus pneumonia (NCP) infected with 2019-nCoV have been identified in Wuhan and other cities in China, since December 2019. We analyzed data on the 17 confirmed cases in Dazhou to provide the epidemiologic characteristics of NCP outside Wuhan. Among them, 12 patients were still quarantined in the hospital, 5 patients were discharged NCP patients according to the national standards. Compared with non-discharged NCP patients, the discharged NCP patients had younger ages. Moreover, discharged NCP patients had higher heart rate, lymphocytes levels and monocytes levels than non-discharged NCP patients on admission to the hospital. Notably, all of 17 patients had abnormal increased C-reactive protein levels, and 16 patients had abnormal computed tomography images. This study provided some information that younger age, higher lymphocytes levels and monocytes levels at the diagnoses of 2019-nCoV may contributed to faster recovery and better therapeutic outcome.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by destructive polyarthritis and systemic complications. It increases cardiovascular morbidity and mortality. However, the mechanism underlying RA-related cardiac damage remains largely unknown. Here, we found and characterized a non-human primate (NHP) model with spontaneous RA similar to the human conditions. Compared with the control group, the cardiac function in RA monkeys showed progressively deterioration; histologically, we found significantly increased inflammatory cell infiltration, cell death, and fibrosis in RA monkey heart tissue. Mechanistically, the upregulated receptor-interacting protein kinase 1 (RIPK1) in RA monkey heart tissue bound to voltage-dependent anion-selective channel 1 (VDAC1), increased VDAC1 oligomerization, and subsequently induced cardiac cell death and functional impairment. These findings identified that RIPK1-VDAC1 pathway is a promising target to treat cardiac impairment in RA. This unique model of RA will provide a valuable tool for mechanistic and translational studies.

The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer. Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876–85. ©2018 AACR.

Breast cancer (BC) is one of the leading causes of death among women worldwide. The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein–protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation. Eight hub genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2, HSP90AA1, FGF2, PIK3R1 and RAC2. Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin. In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.

To validate, update, and extend the role of RNF213 p.R4810K (GA) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups.A total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated.In China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P0.017) in the GA than in the GG group: female, age at onset18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10The incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.

Methylenetetrahydrofolate reductase gene (MTHFR), transcobalaminII (TCN2) and ring finger protein 213 (RNF213) are related to homocysteine (Hcy) level and are of great significance for hypertension. We aimed to evaluate the associations of MTHFR (rs1801133, rs1801131, rs9651118), TCN2 (rs117353193) and RNF213 (rs9916351) with hypertension and blood pressure (BP). A total of 953 patients with hypertension and 1103 controls were enrolled. Genotyping was performed by Taqman. Logistic regression analysis indicated that A allele of TCN2 rs117353193 under the dominant model had a significantly protective effect (P=0.045) after adjustment, which showed that AA+GA genotype has a lower risk than GG. Additionally, the average diastolic BP (DBP) (P=0.044) and mean arterial pressure (MAP) (P=0.035) levels were significantly different between genotypes of RNF213 rs9916351. Further pairwise comparison showed that the average systolic BP (SBP) level of the TT genotype carriers were significantly higher than in CC (P=0.024), and the average DBP and MAP levels of the TT genotype carriers were higher than in CT (P=0.044, P=0.012, respectively) and CC (P=0.048, P=0.010, respectively). In the recessive model, the average SBP (P=0.043), DBP (P=0.018) and MAP (P=0.017) levels with the TT genotype carriers were significantly higher than in CT+CC. Multiple linear regression analysis suggested that RNF213 rs9916351 in the recessive model had significant effects on SBP (P=0.025), DBP (P=0.017) and MAP (P=0.010) as a risk factor. However, no associations were observed between MTHFR and hypertension. TCN2 rs117353193 might serve as a protective factor in hypertension, and RNF213 rs9916351 might be a risk factor that is linked to increase BP level in Northeast Chinese population.

Diabetes has been a disease of public health concern for a number of decades. It was in the 1930s when scientists made an interesting discovery that the disease is actually divided into two types as some patients were insensitive to insulin treatment then. Type 2 Diabetes which happens to be the non-insulin dependent one is the most common form of the disease and is caused by the interaction between genetic and non-genetic factors. Despite conflicting results, numerous studies have identified genetic and non-genetic factors associated with this common type of diabetes. This review has summarized literature on some genes and non-genetic factors which have been identified to be associated with Type 2 diabetes. It has sourced literature from PubMed, Web of Science and Medline without any limitation to regions, publication types, or languages. The paper has started with the introduction, the play of non-genetic factors, the impact of genes in general, and ended with the interaction between some genes and environmental factors.

Pancreatic cancer (PC) is a seriously malignant tumor with a low 5-year survival rate. The relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and PC has been reported by several studies. However, the results were controversial. Thus, we conducted a meta-analysis to summarize available data on MTHFR gene and PC. We searched PubMed, Embase, Web of Science, Wanfang, CNKI databases prior to July 2019. Data were analyzed by RevMan 5.3 and STATA 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the association. Subgroup analysis, sensitivity analysis and assessment of publication bias were performed in this study. Ten articles with 17 reports (10 for C677T, 7 for A1298C) were eligible for inclusion in the meta-analysis (1864 cases and 3165 controls for C677T, and 1488 cases and 1946 controls for A1298C). Our meta-analysis detected that C677T was associated with PC for three genetic models (allele model: OR = 1.24, 95% CI: 1.00–1.53, P = 0.047; recessive model: OR = 1.39, 95% CI: 1.04–1.86, P = 0.027; homozygous model: OR = 1.60, 95% CI: 1.04–2.45, P = 0.034). In the stratified analyses according to ethnicity, source of controls and genotyping method, significant association was observed in genotyping method subgroup. For the A1298C polymorphism, no significant association was observed either in overall analysis or in subgroup analysis under all genetic models. MTHFR gene C677T rather than A1298C polymorphism may be associated with PC. Larger sample size studies should be performed to find the association between MTHFR gene and PC.

To investigate the clinical manifestations, pathological features, treatment, and prognosis of a special type of podocytopathy in patients with lupus nephritis (LN). The clinical data, including clinical manifestations, pathological features, immunological markers, treatment, and prognosis of one patient with lupus podocytopathy (LP), were retrospectively analyzed. Relevant literature was also reviewed. The patient was clinically diagnosed with a rare type of LP-based on medical history, clinical manifestations, laboratory tests, renal biopsy results, and relevant literature. After treatment with steroids combined immunosuppressive agents, the clinical symptoms were improved, and the nephropathy was completely reversed. The disease condition was stable during follow-up. LP is a specific pathological change in the spectrum of LN, with nephrotic syndrome (NS) as its primary clinical manifestation. Patients may also have severe lupus-associated injuries affecting multiple systems. Immunosuppressive agents combined with steroids can improve clinical symptoms.

Demand for rapid quantitation of polyions such as heparin and protamine are ever growing. Previous paper-based and polymeric optical and electrochemical sensing devices required more than several hours for signal stabilization. Therefore, signals were acquired with fixed sample exposure time modes, which was time-consuming and technically demanding. We present here for the first time the optical detection of protamine and heparin in equilibrium mode with emulsified nanospheres. The method significantly shortens the response time from hours to typically less than 10 s and offers tunable, sensitive, and colorimetric detection within the clinically relevant range (10 to 100 mg/L) for heparin. The improved characteristics are attributable to the small size of the nanospheres (ca. 50 nm in diameter) as well as the reversible recognition at the nanoscale liquid-liquid interface. Detection of the anticoagulant heparin was also successfully demonstrated in human blood serum background.

Hyperinsulinemia is the earliest symptom of insulin resistance (IR), but a causal relationship between the two remains to be established. Here we show that a protein kinase D2 (PRKD2) nonsense mutation (K410X) in two rhesus monkeys with extreme hyperinsulinemia along with IR and metabolic defects by using extreme phenotype sampling and deep sequencing analyses. This mutation reduces PRKD2 at both the mRNA and the protein levels. Taking advantage of a PRKD2-KO mouse model, we demonstrate that PRKD2 deletion triggers hyperinsulinemia which precedes to IR and metabolic disorders in the PRKD2 ablation mice. PRKD2 deficiency promotes β-cell insulin secretion by increasing the expression and activity of L-type Ca2+ channels and subsequently augmenting high glucose- and membrane depolarization-induced Ca2+ influx. Altogether, these results indicate that down-regulation of PRKD2 is involved in the pathogenesis of hyperinsulinemia which, in turn, results in IR and metabolic disorders., Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.

Aims To investigate the progression of obesity-related type 2 diabetes mellitus (T2DM) in rhesus monkeys, especially dynamic changes in insulin and glucagon. Materials and methods We followed a cohort of 52 rhesus monkeys for 7 years throughout the progression of obesity-related T2DM. Intravenous glucose tolerance tests were performed every 6 months to evaluate dynamic changes in glucose, insulin and glucagon levels. Results Obesity in rhesus monkeys increased the overall mortality and T2DM morbidity. During the progression of T2DM, glucagon remained consistently elevated, while insulin initially increased in compensation but then dropped to below normal levels when the monkeys developed overt T2DM. After a glucose challenge, both the first and second phases of insulin secretion increased during the early stage of T2DM; in later stages the first phase was delayed and the second phase was diminished. Conclusion Our findings showed that, beside the decreased insulin level, hyperglucagonaemia also plays an important role in the development of T2DM.

Background Carcinoembryonic antigen (CEA) as a diagnostic or prognostic marker has been widely studied in patients with lung cancer. However, the relationship between serum CEA and tumor metastasis in lung cancer remains controversial. This study aimed to investigate the ability of serum CEA to assess tumor metastasis in lung cancer patients. Methods We performed a retrospective analysis of 238 patients diagnosed with lung cancer from January to December 2016 at pneumology department of Dazhou Central Hospital (Dazhou, China). Serum CEA levels were quantified in each patient at the time of diagnosis of lung cancer. Metastasis was confirmed by computed tomography (CT), and/or positron emission tomography (PET) and/or surgery or other necessary detecting methods. Results Of the 213 patients eligible for final analysis, 128 were diagnosed with metastasis and 85 were diagnosed without metastasis. Compared to non-metastatic patients, the serum CEA was markedly higher in patients with metastasis (p Conclusion Our study suggested the serum CEA as a valuable marker for tumor metastases assessment in newly diagnosed lung cancer patients, which could have some implications in clinical application.

Background Nonalcoholic fatty liver disease (NAFLD) is a significant contributor to global hepatic disorders. ADIPOQ gene single‐nucleotide polymorphisms have been associated with NAFLD susceptibility, but with inconsistent results across the studies. This study aimed to investigate the association between ADIPOQ polymorphisms (+276G>T, rs1501299 and −11377C>G, rs266729) and the risk of NAFLD. Methods PubMed, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify the relevant published literature. Statistical analyses were calculated with STATA 11.0 software and RevMan 5.2. Summary odds ratios (OR) and 95% confidence intervals (CIs) were generated to assess the strength of the associations. Results Eleven relevant articles with a total of 3,644 participants (1,847 cases/1,797 controls) were included. Our meta‐analysis results revealed that ADIPOQ gene +276G>T polymorphism was not associated with NAFLD under various genetic models (allele model: OR = 0.99, 95% CI [0.69, 1.41]; dominant model: OR = 1.06, 95% CI [0.71, 1.58]; recessive model: OR = 0.83, 95% CI [0.42, 1.65]; homozygous model: OR = 0.86, 95% CI [0.38, 1.95]; heterozygous model: OR = 1.10, 95% CI [0.80, 1.53]; respectively). Moreover, no statistical significant association was found between +276G>T and NAFLD risk in the subgroups. ADIPOQ gene −11377C>G polymorphism significantly increased the risk of NAFLD (allele model: OR = 1.49, 95% CI [1.28, 1.75]; dominant model: OR = 1.64, 95% CI [1.35, 1.99]; recessive model: OR = 1.77, 95% CI [1.16, 2.70]; homozygous model: OR = 2.13, 95% CI [1.38, 3.28]; heterozygous model: OR = 1.58, 95% CI [1.29, 1.93]; respectively). Conclusion ADIPOQ gene −11377C>G may be a risk factor for NAFLD, while there was no association between ADIPOQ gene +276G>T polymorphism and the risk of NAFLD. Further studies are needed to detect the relationship between these ADIPOQ polymorphisms and NAFLD.