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OBJECTIVE: : To explore the association between napping status and depressive symptoms in urban residents during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: : The survey was embedded in the Wellness Living Laboratory-China (WELL China) cohort study. Health and lifestyle information during the COVID-19 epidemic were obtained via the telephone interview from April 8, 2020 to May 29, 2020. A total of 3075 residents aged 18 to 80 years from Gongshu district of Hangzhou city with complete data were included in the analyses. The World Health Organization-Five Well-being Index (WHO-5) was used to measure depressive symptoms. Multiple logistic regression model was used to assess the association between napping status and depressive symptoms in the participants. RESULTS: : The prevalence of depressive symptoms was 20.6% in the participants during the COVID-19 epidemic. Daytime napping behavior, especially napping time ≤30 min, was associated with a lower risk of prevalent depressive symptoms ( OR=0.61, 95% CI: 0.47–0.79, P

Environmental problems caused by heavy metal pollution in soil have attracted widespread attention worldwide. Identifying and quantifying the heavy metal pollution sources and risks is crucial for subsequent soil management. In this study, an integrated source-risk method for source apportionment and risk assessment based on the PMF model, the geodetector model and the health risk assessment model (HRA) was proposed and applied. Analysis of Hg, As, Pb, Cd, Cu, Ni, Cr, and Zn in 208 topsoils showed that the average contents of eight heavy metals were 1.87-5.86 times greater than corresponding background values, among which Cd and As were relatively high, which were higher than the specified soil risk screening values, high-value areas of heavy metals are mainly concentrated in the central part of the study area. The source apportionment showed that the accumulation of heavy metals was affected by five sources: atmospheric deposition (16.3 %), natural sources (33.1 %), industrial activities dominated by metal mining (15.1 %), industrial activities dominated by metal smelting (12.6 %) and traffic sources (22.9 %). The results of the health risk assessment showed that the carcinogenic risks (adult: 4.74E-05, children: 7.41E-05) of heavy metals in soil to the study population were both acceptable, the non-carcinogenic risk of adult (THI = 0.277) was within the limit, while the non-carcinogenic risk of children (THI = 1.70) was higher than the limit value. Ingestion (89.5 %-95.9 %) contributed the greatest health risk among all exposure routes. Source 3 (arsenic-related industrial activities dominated by metal mining) contributed the most to the HI and CRI of adults and children (all above 50 %), therefore, in the formulation stage of soil management strategy in this area, priority should be given to the control and management of this pollution source. These results can provide more detailed support for environmental protection departments to propose targeted soil pollution control measures.

Surgery is currently a mainstream treatment modality for various solid tumor indications. However, aggressive resection of tumor tissues frequently causes postoperative complications, which severely undermine the well-being of patients. Moreover, the residue tumor cells may substantially increase the risk of local and distant tumor relapse. The recent development in black phosphorus (BP)-based nanomaterials offers a promising opportunity to address these clinical challenges. BP is an emerging nanomaterial with excellent biocompatibility and versatile functionality, which has already demonstrated great potential for a variety of biomedical applications including tumor therapy and tissue engineering. In this review, the recent advances in BP-based nanobiomaterials for the post-surgery treatment of solid tumor have been summarized, while specific emphasis was placed on their capability to continuously inhibit residue tumor growth at the surgery site as well as stimulating various healing mechanisms, aiming to preventing tumor relapse while promoting the healing of surgery-induced traumatic soft/hard tissue injuries. It is anticipated that the nanoengineered BP-based materials may open new avenues to tackle those clinical challenges in surgical treatment of solid tumors.

Bevacizumab (BEV) is an anti-angiogenesis antibody which has shown favorable therapeutic effects on some solid tumors. However, many clinical trials showed that BEV could only improve PFS instead of OS in glioblastoma (GBM) patients. However, some studies indicate that specific molecular subtypes of GBM could still benefit from combination treatment of BEV and Stupp protocol. Through the subgroup analysis of GSE84010 dataset, we found the neural and proneural subgroup can benefit from the administration of BEV in terms of OS, which is statistically significant. The further KEGG pathway enrichment analysis showed cell adhesion molecules (CAMs) pathway was enriched, and the expression of ITGAM has a predictive value for prognosis. These findings can provide some hints for future administration of BEV in newly diagnosed GBM patients.

Mitochondrial abnormalities play critical roles in diabetic tubular injury progression. Dipeptidyl peptidase-4 (DPP4) inhibitors are widely used antihyperglycemic agents that exert renal protective and positive effects against mitochondrial dysfunction in diabetic kidney disease (DKD). However, their underlying mechanism remains unclear. In this study, DPP4 upregulation, mitochondrial fragmentation, and altered mitochondrial dynamics-associated protein expression were observed in the tubules of DBA2/J (D2) diabetic mice with unilateral nephrectomy and in albumin-stimulated tubular cells. The inhibition of DPP4 by sitagliptin (Sita) ameliorated these mitochondrial perturbations both in vivo and in vitro, whereas DPP4 overexpression aggravated mitochondrial fusion-fission disorder and tubular cell injury in albumin-treated HK-2 cells. Downstream of DPP4, the SDF-1α/CXCR4 pathway was significantly suppressed in diabetic tubules. After Sita treatment, this signaling pathway was restored, and the mitochondrial dynamics was improved. Furthermore, a direct interaction between STAT3 and OPA1 was found in the mitochondria of tubular cells, and this effect was weakened by overloading albumin and by CXCR4 siRNA treatment, suggesting a possible link between DPP4-mediated SDF-1α/CXCR4/STAT3 signaling and mitochondrial dysfunction in diabetic tubular cells. The results suggest that a novel mechanism links the DPP4 enzyme to impaired mitochondrial dynamics homeostasis during tubular injury in DKD and highlight that the SDF-1α/CXCR4/STAT3 signaling pathway could become a potential target for managing DKD.

A retrospective study on complete blood count (CBC) with differential results of patients who presented to the fever clinic of Tongji Hospital with symptoms of COVID-19-like illness between February 1, 2020 and February 20, 2020 was performed through case reviewing Inclusion criteria were fever with a body temperature above 37 3 degreesC, accompanied or not accompanied by cough, chest tightness, muscle ache, shortness of breath and diarrhea Patients with hematopathy, cancer and sepsis were excluded The SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing of throat swab was performed in the laboratory of Tongji Hospital These patients with COVID-19-like symptoms were divided into two groups Patients diagnosed with COVID-19 according to the WHO interim guidance and confirmed by RT-PCR testing were included in the SARS-CoV-2-positive patient group (SPPG) Patients with two or more consecutive negative RT-PCR test results were included in the SARS-CoV-2-negative patient group (SNPG) Patients with co-infection of SARS-CoV-2 and other respiratory viruses including influenza A/B, respiratory syncytial virus and adenovirus were also excluded in SPPG Sysmex XN-9000 hematology analyzer was used to obtain the CBC with differential results for patients in each group CBC with differential results at the request of clinicians at the initial evaluations was recorded along with age and gender for each patient Decreased WBC*LYM was observed in SARS-CoV-2-infected patients compared with SARS-CoV-2-negative patients with suspected symptoms in this study WBC*LYM can be used as a supplementary parameter to help clinicians in their first contact with suspected patients awaiting SARS-CoV-2 RT-PCR results

An in-depth understanding of the ecological and health risks posed by heavy metals originating from various pollution sources is critical for foresighted soil-quality management. Based on 220 grid samples (2 × 2 km) analyzed for eight heavy metals (Cd, Hg, As, Pb, Cr, Ni, Cu, and Zn) in the Chenshui (CS) watershed of Hunan Province, China, we applied an integrated approach for identifying and apportioning pollution sources of soil heavy metals and exploring their source-specific pollution risks. This approach consists of three sequential steps: (1) source identification by combining the positive matrix factorization model with geostatistical analysis; (2) quantification of ecological, carcinogenic, and non-carcinogenic risks in a source-specific manner; (3) prioritization of sources in a holistic manner, considering both ecological risks and human health risks. Cd (68.0%) and Hg (13.3%) dominated the ecological risk in terms of ecological risk index; As dominated the non-carcinogenic health risk in terms of total hazard index (THI; adults: 84.8%, children: 84.7%) and the carcinogenic health risk in terms of total carcinogenic risk index (TCRI; adults: 69.0%, children: 68.8%). Among three exposure routes, oral ingestion (89.4-95.2%) was the predominant route for both adults and children. Compared with adults (THI = 0.41, TCRI = 7.01E-05), children (THI = 2.81, TCRI = 1.22E-04) had greater non-carcinogenic and carcinogenic risks. Four sources (F1-4) were identified for the CS watershed: atmospheric deposition related to coal-burning and traffic emissions (F1, 18.0%), natural sources from parent materials (F2, 34.3%), non-ferrous mining and smelting industry (F3, 37.9%), and historical arsenic-related activity (F4, 9.8%). The F3 source contributed the largest (45.2%) to the ecological risks, and the F4 source was the predominant contributor to non-carcinogenic (52.4%) and carcinogenic (64.6%) risks. The results highlight the importance of considering legacy As pollution from abandoned industries when developing risk reduction strategies in this region. The proposed methodology for source and risk identification and apportionment formulates the multidimensional concerns of pollution and the various associated risks into a tangible decision-making process to support soil pollution control.

Ferroptosis is a nonapoptotic iron-dependent cell death pathway with a significant clinical potential, but its translation is impeded by lack of tumor-specific ferroptosis regulators and aberrant tumor iron metabolism. Herein, we report a combinational strategy based on clinically tested constituents to selectively induce ferroptosis in metabolically reprogrammed tumor cells through cooperative GPX4-inhibition and ferritinophagy-enabled Fe2+ reinforcement. Azido groups were first introduced on tumor cells using biocompatible long-circulating self-assemblies based on polyethylene glycol-disulfide-N-azidoacetyl-d-mannosamine via metabolic glycoengineering. The azido-expressing tumor cells could specifically react with dibenzocyclooctyne-modified disulfide-bridged nanoassemblies via bioorthogonal click reactions, where the nanoassemblies were loaded with ferroptosis inducer RSL3 and ferritinophagy initiator dihydroartemisinin (DHA) and could release them in a bioresponsive manner. DHA-initiated ferritinophagy could degrade intracellular ferritin to liberate stored iron species and cooperate with the RSL3-mediated GPX4-inhibition for enhanced ferroptosis therapy. This tumor-specific ferroptosis induction strategy provides a generally applicable therapy with enhanced translatability, especially for tumors lacking targetable endogenous receptors. National Research Foundation (NRF) This study is financially supported by the National Natural Science Foundation of China (32122048, 11832008, 92059107, and 51825302), the Chongqing Graduate Scientific Research and Innovation Program (cYB20047 and cYS20043), the Fundamental Research Funds for the Central Universities (2021CDJLXB001, 2021CDJZYJH-002, and 2020CDJYGZL009), the Chongqing Outstanding Young Talent Supporting Program (cstc2021ycjh-bgzxm0124), the Returning Overseas Scholar Innovation Program (CX2018062, CX2021098, and CX2020045), the Natural Science Foundation of Chongqing Municipal Government (cstc2020jcyj-msxmX0834 and cstc2021jcyj-jqX0022), and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03) and Competitive Research Programme (CRP26-2021-0058).

Bioenergy (ATP) is essentially required for supporting the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). However, factors such as high ROS levels and decreased glucose metabolism severely limit the bioenergy production in osteoporotic MSCs. We have prepared CaCO

Heavy metals in soil are a great threat to ecosystems and human health. The rapid development of industrialization has created a serious risk of heavy metal pollution in soil. The study took the industrial-intensive Dahetan subbasin as the typical area. The factors and interactions that affected the distribution of soil heavy metals (Cd, Hg, As, Pb and Cr) in the typical area were explored based on the Geodetector model. The analysis results were extended to predict high-risk areas of heavy metal pollution in the soil in the Xiangjiang River basin. The results showed that Cd, As and Pb were significantly affected by local industrial and mining activities, and Hg and Cr were primarily affected by natural factors, such as pH and soil type. Compared to a single factor, the interaction between factors had a greater impact on the concentration of heavy metals. The high-risk areas of soil heavy metal pollution in the Xiangjiang River basin were primarily concentrated in the upper reaches and middle reaches.Significant overlapping of high-risk areas of multiple heavy metals occurred in the west, middle and south of the basin. The spatial visualization of the high-risk areas was realized, and the influence of several factors was integrated via layer superposition. This study proposes a new idea to predict the high-risk areas of soil pollution in large-scale areas to provide a reference for the regional prevention and control of soil pollution.

Biomacromolecule therapeutic systems are intrinsically susceptible to degradation and denaturation. Nanoformulations are promising delivery vehicles for therapeutic biomacromolecules (antibodies, genes and so on). However, their applications in these areas still face many challenges including in vivo stability, premature leakage and accurate tumor recognition. In this study, a generally applicable new strategy for tumor-targeted delivery of biomacromolecules was developed through the hierarchical integration of degradable large-pore dendritic mesoporous silica nanoparticles (dMSNs) and cyclodextrin-modified polyamidoamine (PAMAM-CD) dendrimers. The orifice rim of the dMSNs was modified with ROS-responsive nitrophenyl-benzyl-carbonate (NBC) groups while disulfide-bonded azido ligands were subsequently grafted onto the inner channel walls via heterogeneous functionalization. The PAMAM-CD was then interred into the dendritic pores via click reactions and supramolecularly loaded with archetypal hydrophobic small-molecule anticancer model drug (SN-38) and therapeutic model gene (Bcl-2 siRNA), after which dMSNs were eventually coated with a 4T1 cancer cell membrane (CCM). Experimental evidence demonstrated that the synthesized nanocarriers could efficiently deliver therapeutic cargos to target cancer cells and release them in the tumor cytosol in a cascade-responsive manner. This biomimetic nanoplatform presents a novel strategy to efficiently deliver biomolecular therapeutics in a tumor-targeted manner.

A tumor redox-activatable micellar nanoplatform based on the naturally occurring biomacromolecule hyaluronic acid (HA) was developed for complementary photodynamic/chemotherapy against CD44-positive tumors. Here HA was first conjugated with l-carnitine (Lc)-modified zinc phthalocyanine (ZnPc) via disulfide linkage and then co-assembled with tirapazamine (TPZ) to afford the physiologically stable micellar nanostructure. The mitochondria-targeted photodynamic activity of ZnPc-Lc could efficiently activate the mitochondrial apoptosis cascade and deplete the oxygen in the tumor intracellular environment to amplify the hypoxia-dependent cytotoxic effect of TPZ.

Background To predict the risk and severity of acute respiratory distress syndrome (ARDS) following severe acute pancreatitis (SAP) by artificial neural networks (ANNs) model. Methods ANNs model was constructed by clinical data of 217 SAP patients. The model was first trained on 152 randomly chosen patients, validated and tested on the 33 patients and 32 patients respectively. Statistical analysis was used to assess the value of it. Results The training, validation, and test set were not significantly different for 13 variables. After training, ANNs retained excellent pattern recognition ability. When ANNs model was applied to the test set, it revealed a sensitivity of 87.5%, and an accuracy of 84.43%. Significant differences were found between ANNs model and logistic regression model. When ANNs model is used to identify ARDS, the area under ROC was 0.859 + 0.048. Meanwhile, pancreatic necrosis rate, lactic dehydrogenase and oxyhemoglobin saturation were the most important independent variables. Compared with the Berlin definition, the ANN model shows a good accuracy of 73.1% for total severity of ARDS. Conclusion ANNs model is a valuable tool in dealing with risk prediction of ARDS following SAP. In addition, it can extract informative risk factors of ARDS via the ANNs model.

Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage (DAD) of the lungs and microthrombus formation, resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extra-pulmonary organs are directly caused by the virus needs further investigation.

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical success against hematologic malignancies. However, the transition of CAR-T cell therapies for solid tumors is limited by heterogenous antigen expression, immunosuppressive microenvironment (TME), immune adaptation of tumor cells and impeded CAR-T-cell infiltration/transportation. Recent studies increasingly reveal that tumor physical microenvironment could affect various aspects of tumor biology and impose profound impacts on the antitumor efficacy of CAR-T therapy. In this review, we discuss the critical roles of four physical cues in solid tumors for regulating the immune responses of CAR-T cells, which include solid stress, interstitial fluid pressure, stiffness and microarchitecture. We highlight new strategies exploiting these features to enhance the therapeutic potency of CAR-T cells in solid tumors by correlating with the state-of-the-art technologies in this field. A perspective on the future directions for developing new CAR-T therapies for solid tumor treatment is also provided.

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall β-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies.

To predict the mortality of acute respiratory distress syndrome (ARDS) by using a radial basis function (RBF) artificial neural network (ANN) model. This study included 217 patients who were admitted between June 2013 and November 2019. The RBF ANN model and logistic regression (LR) model were based on twelve factors related to ARDS. Statistical indexes were used to determine the value of the prediction in the two models. The sensitivity, specificity and accuracy of the RBF ANN model to predict mortality were 83.6%, 88.5% and 82.5%, respectively. Significant differences were found between the RBF ANN and LR models (P

Surgery is the mainstream treatment for melanoma, but its clinical implementation suffers from some major drawbacks including residual infiltrating melanoma cells at resection margins and severe tissue injury. In this study, a nanocomposite scaffold is developed for in-situ therapy after melanoma surgery as well as wound healing, which is fabricated by embedding photothermal-capable black phosphorus nanosheets (BPNSs) into bioresorbable Gelatin-PCL (GP) nanofibrous scaffold. GP scaffold is a clinically-tested biomaterial with temperature sensitivity and tissue-healing effect, while the BPNSs are loaded with the anticancer antibiotic of doxorubicin (DOX) and conjugated with NH2-PEG-FA for tumor-targeted delivery. The GP scaffold could undergo a sol-gel transition upon NIR irritation and release the BPNSs in situ. During this process, most of the BP-based nanoformulations were selectively internalized by the melanoma cells for the cooperative photothermal therapy and heat-triggerable DOX therapy, while some of the loaded DOX was released into the wound tissue to create a tumor-suppressive microenvironment. Moreover, BPNSs could be gradually degraded to phosphates/phosphonates and thus enhance tissue repair by activating the ERK1/2 and PI3K/Akt pathway. Meanwhile, the detached DOX molecules would also enter the wound tissues for continuous melanoma inhibition. Considering the anti-melanoma and wound healing effect of this composite scaffold, it may offer a facile strategy for the wound treatment after melanoma surgery.

To search for hematological parameters changes in human rotavirus (HRV) infectious acute gastroenteritis in children and find useful parameters for the differential diagnosis in low re-source environments.In this study, children less than 5 years old were divided into three groups which were rotavirus-positive acute gastroenteritis (RPAG) (101), rotavirus-negative acute gastroenteritis (RNAG) (121), and control (97) groups. First visit complete blood count (CBC) results, lymphocyte to monocyte ratio (LMR), and neutrophil to lymphocyte ratio (NLR) were recorded for each child. CBC examinations were performed using the Sysmex XS-800i hematology analyzer, while fecal HRV antigen identifications were performed by immunochromatography in fresh stool specimens. The differences in parameters among different groups were tested with SPSS 15.0. Diagnostic values were evaluated using the receive operating characteristic curve for selected parameters.Compared to controls, the LYM, LYM%, MPV, and LMR in RPAG were significantly lower, but the MON, MON%, NEU, NEU%, and NLR were significantly higher. Compared to RNAG, RPAG had significantly lower LYM, LYM%, and LMR and significantly higher NEU% and NLR. Among all parameters, the area under the curve (AUC) of LMR was largest when controls were used as a reference (sensitivity: 76.24, specificity: 95.88, accuracy: 85.86). However, LYM had the largest AUC when RNAG was used as a reference.Decreased LYM and MPV and increased NEU and MON were observed in RPAG. Low LMR and high NLR may indicate HRV infection in children with acute gastroenteritis and, therefore, can be useful markers for the diagnosis and differential diagnosis of HRV infection in low resource environments, thereby preventing overuse of antibiotics and antiviral.

Due to rapid urbanization, industrialization, agricultural development, and mining activities, soil heavy metal pollution has become a severe issue in China. To explore the regional heavy metal ecological risk of lake sediment and surrounding topsoil, we analyzed 237 lakes, with 1797 lake sediment sampling points and 1164 surrounding topsoil sampling points. Lower mean concentrations were detected for most heavy metals in soils than sediment (except for Hg). Cd and Hg in sediments and soils showed a more significant variation, with the coefficient of variation exceeding 110%. Linear regressions and Pearson's correlation analyses demonstrated that sediments and soils exhibited significant positive correlations. The principal heavy metals exceeding the Agricultural Soil Control Standard (ASCS) in sediments and soils were As and Cd, respectively. The Yunnan-Guizhou Plateau Lake Region (YGPLR) was the most seriously affected, exceeding the ASCS for Cd. The lakes with the most severe pollution were located in YGPLR impacted by the high background concentration of heavy metals in soil and mineral development activities. The Eastern Plain Lake Region, the Southeast Lake Region, and the Northeast Plain and Mountain Lake Region showed a clear anthropogenic impact. Lakes in the Inner Mongolia-Xinjiang Lake Region and the Tibetan Plateau Lake Region were estimated to have relatively low ecological risks due to their sparse population and slight environmental disturbance. The impact of geochemical factors on the ecological risk of heavy metals in lake sediments is more substantial than that of human activities at the regional scale.

Low-grade inflammatory indicators are widely used in the diagnosis and prognosis of different diseases, particularly, in cancers. The establishing of reference intervals (RIs) are necessary to provide baselines for the interpretation and application of the indicators in clinical. A retrospective review was organized to include ostensibly healthy subjects aged18 years old to establish RIs based on gender and age for systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-platelet ratio (MPV/PLT), MPV and red blood cell distribution width - standard deviation (RDW-SD). Another 5012 healthy persons were included to validate the RIs. The differences among gender, age, and Body Mass Index (BMI) groups were compared to assess their influences on each indicator. A total of 26,242 males and 11,934 females were included. All indicators differed between males and females except NLR. Compared with males, the values of SII, PLR, MPV and RDW-SD were higher while MPV/PLT lower in females. The values of SII, NLR and PLR increased with age in females between 18 and 50 years old, declined in 51-60 years old group, then increased with age again. Values of MPV/PLT and RDW-SD increased with age. The values of SII increased with BMI while PLR, MPV, and MPV/PLT decreased. We effectively established RIs for the indicators. They will help with predicting disease progression in various clinical practices. Gender, age, and BMI were suggested to be taken into consideration when these parameters were applied in clinical.

Background In the context of the COVID‐19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in‐hospital death in patients with severe COVID‐19. Methods All ≥18‐year‐old patients with confirmed severe COVID‐19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in‐hospital death. Results A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow‐up period. The median age of non‐survivors was significantly older than survivors (69 [64‐76.5] years vs 64 [56‐71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non‐survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 × 109/L (OR, 58.35; 95%CI: 2.16‐1571.69; P = .016), hypersensitivity C‐reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29‐171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45‐4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36‐91.62; P = .024) were risk factors for in‐hospital death. Conclusion The risk factors of neutrophil count, hypersensitivity C‐reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID‐19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID‐19., Neutrophil count, hypersensitivity C‐reactive protein, creatine kinase, and blood urea nitrogen were risk factors for in‐hospital death in patients with severe COVID‐19. Virus direct attack and cytokine storm play a major role in fatal outcomes.

Background: Despite the high mortality of cardiovascular disease (CVD) in diabetic patients with renal injury, few studies have compared cardiovascular characteristics and outcomes between patients with diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). Methods: A total of 326 type 2 diabetes mellitus patients with renal biopsy were assigned to DN and NDRD groups. Echocardiography and Doppler ultrasound were performed to evaluate left ventricular hypertrophy (LVH) and peripheral atherosclerosis disease (PAD). Renal and cardiovascular survival rates were compared between the DN and NDRD groups by Kaplan-Meier analysis. Risk factors for renal and cardiovascular events in DN patients were identified by a Cox proportional hazards model. Results: In total, 179 patients entered the DN group (54.9%) and 147 made up the NDRD group (45.1%). The presence of diabetic retinopathy, family history of diabetes, and dependence on insulin therapy were associated with the presence of DN. DN patients had more CVD with more severe LVH and PAD. Poorer renal (log-rank χ2 = 26.534, p < 0.001) and cardiovascular (log-rank χ2 = 16.257, p < 0.001) prognoses were seen in the DN group. DR (HR 1.539, 95% CI 1.332–1.842), eGFR (HR 0.943, 95% CI 0.919–0.961), and 24-h proteinuria (HR 1.211, 95% CI 1.132–1.387) were identified as risk factors for renal endpoints. Age (HR 1.672, 95% CI 1.487–1.821), HbA1C (HR 1.398, 95% CI 1.197–1.876), and 24-h proteinuria (HR 1.453, 95% CI 1.289–1.672) were associated with cardiovascular endpoints. Conclusion: Patients with DN had more severe CVD along with poorer renal and cardiovascular prognoses than those with NDRD.

The chemotherapeutic efficacy of paclitaxel against hypoxic tumors is usually unsatisfactory, which is partially due to the so-called hypoxia-induced drug resistance. The mechanism of hypoxia-induced resistance is primarily associated with hypoxia-inducible factor 1α (HIF-1α), which is an oxygen-sensitive transcriptional activator coordinating the cellular response to hypoxia. Apigenin is a natural occurring HIF-1α inhibitor that can suppress the expression of HIF-1α through multiple pathways and reverse the hypoxia-induced resistance found in cancer cells. Here we report that the use of apigenin can suppress the HIF-1α expression in hypoxic tumors through the simultaneous inhibition of the AKT/p-AKT pathway and HSP90, which is beneficial for enhancing the anticancer activity of the co-administered paclitaxel. The potential synergistic effect of apigenin and paclitaxel was further validated on HepG2 cell line and tumor-bearing mouse models.

Introduction Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT) in leukemia. Numerous investigations have demonstrated that minimal residual disease (MRD) before or after alloHSCT is prognostic of relapse risk. These MRD data were collected at specific checkpoints and could not dynamically predict the relapse risk after alloHSCT, which needs serial monitoring. Methods In the present study, we retrospectively analyzed MRD measured with multi-parameter flow cytometry in 207 acute myeloid leukemia (AML) patients (acute promyelocytic leukemia excluded), and 124 acute B lymphoblastic leukemia (ALL) patients. A three-step method based on joint model was used to build a relapse risk prediction model. Results The 3-year overall survival and relapse-free survival rates of the entire cohort were 67.1% ± 2.8% and 61.6% ± 2.8%, respectively. The model included disease status before alloHSCT, acute and chronic graft-versus-host disease, and serial MRD data. The time-dependent receiver operating characteristics was used to evaluate the ability of the model. It fitted well with actual incidence of relapse. The serial MRD data collected after alloHSCT had better discrimination capabilities for recurrence prediction with the area under the curve from 0.67 to 0.91 (AML: 0.66-0.89; ALL: 0.70-0.96). Conclusion The joint model was able to dynamically predict relapse-free probability after alloHSCT, which would be a useful tool to provide important information to guide decision-making in the clinic and facilitate the individualized therapy.

Objective The aim of this study is to predict the risk of severe acute pancreatitis (SAP) associated with acute lung injury (ALI) by artificial neural networks (ANNs) model. Methods The ANNs and logistic regression model were constructed using clinical and laboratory data of 217 SAP patients. The models were first trained on 152 randomly chosen patients, validated and tested on the 33 patients and 32 patients respectively. Statistical indices were used to evaluate the value of the forecast in two models. Results The training set, validation set and test set were not significantly different for any of the 13 variables. After training, the back propagation network retained excellent pattern recognition ability. When the ANNs model was applied to the test set, it revealed a sensitivity of 87.5%, specificity of 83.3%. The accuracy was 84.43%. Significant differences could be found between ANNs model and logistic regression model in these parameter. When ANNs model was used to identify ALI, the area under receiver operating characteristic curve was 0.859 ± 0.048, which demonstrated the better overall properties than logistic regression modeling (AUC = 0.701 + 0.041) (95% CI: 0.664–0.857). Meanwhile, pancreatic necrosis rate, lactic dehydrogenase and oxyhemoglobin saturation were the important factors among all thirteen independent variable for ALI. Conclusion The ANNs model was a valuable tool in dealing with the clinical risk prediction problem of ALI following to SAP. In addition, our approach can extract informative risk factors of ALI via the ANNs model.

Background As effective quality management tools, quality indicators (QIs) are widely used in laboratory medicine. This study aimed to analyze the results of QIs, identify errors and provide quality specifications (QSs) based on the state-of-the-art. Methods Clinical laboratories all over China participated in the QIs survey organized by the National Health Commission of People’ Republic of China from 2015 to 2017. Most of these QIs were selected from a common model of QIs (MQI) established by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All participants were asked to submit general information and original QIs data through a medical quality control data collection system. The results of QIs were reported in percentages and sigma, except turnaround time (TAT) which was measured in minutes. The 25th, 50th and 75th percentiles were, respectively, calculated as three levels of QSs, which were defined starting from the model proposed during the 1st Strategic Conference of the EFLM on “Defining analytical performance 15 years after the Stockholm Conference on Quality Specification in Laboratory Medicine”. Results A total of 76 clinical laboratories from 25 provinces in China continuously participated in this survey and submitted complete data for all QIs from 2015 to 2017. In general, the performance of all reported QIs have improved or at least kept stable over time. Defect percentages of blood culture contamination were the largest in the pre-analytical phase. Intra-laboratory TAT was always larger than pre-examination TAT. Percentage of tests covered by inter-laboratory comparison was relatively low than others in the intra-analytical phase. The performances of critical values notification and timely critical values notification were the best with 6.0σ. The median sigma level of incorrect laboratory reports varied from 5.5σ to 5.7σ. Conclusions QSs of QIs provide useful guidance for laboratories to improve testing quality. Laboratories should take continuous quality improvement measures in all phases of total testing process to ensure safe and effective tests.

Ferroptosis is an emerging antitumor option and has demonstrated unique advantages against many tumor indications. However, its efficacy is potentially hindered by the endogenous lipid peroxide-scavenging mechanisms and the reliance on acidic pH. Herein, we have developed a nanointegrated strategy based on clinically-safe components to synergistically remodel glutathione and lactate metabolism in tumor cells for enhanced ferroptosis therapy. We first conjugated ferrocene on PEGylated polyamidoamine dendrimers via ROS-cleavable thioketal linkage, which would further self-assemble with the glutathione (GSH)-depleting agent diethyl maleate (DEM) and monocarboxylate transporter 4-inhibiting siRNA (siMCT4) to afford biostable nanoassemblies (siMCT4-PAMAM-PEG-TK-Fc@DEM). The nanoassemblies could be activated by the elevated ROS levels in tumor intracellular environment and readily release the incorporated therapeutic contents, afterwards DEM could directly conjugate to GSH to disrupt the glutathione peroxidase 4 (GPX4)-mediated antioxidant defense while siMCT4 could block the MCT4-mediated efflux of lactic acid and acidify the intracellular milieu, both of which could improve the ferrocene-catalyzed lipid peroxidation and induce pronounced ferroptotic damage. The siMCT4-PAMAM-PEG-TK-Fc@DEM nanoplatform demonstrated high ferroptosis-based antitumor potency and good biocompatibility in vitro and in vivo, which may offer new avenues for the development of more advanced antitumor therapeutics with improved translatability. This article is protected by copyright. All rights reserved.

Metformin is a clinically-approved anti-diabetic drug with emerging antitumor potential, but its antitumor activity is highly susceptible to local glucose abundance. Herein, we construct a nanotherapeutic platform based on biocompatible constituents to sensitize tumor cells for metformin therapy via cooperative glucose starvation. The nanoplatform was synthesized through the spontaneous biomineralization of glucose oxidase (GOx) and metformin in amorphous calcium phosphate nanosubstrate, which was further modified with polyethylene glycol and cRGD ligands. This biomineralized nanosystem could efficiently deliver the therapeutic payloads to tumor cells in a targeted and bioresponsive manner. Here GOx could catalyze the oxidation of glucose into gluconic acid and H2O2, thus depleting the glucose in tumor intracellular compartment while accelerating the release of the entrapped therapeutic payloads. The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56δ and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3β-MCL-1 axis with negligible side effects. This study may offer new avenues for targeted tumor therapy in the clinical context.

Objective To systematically determine the diagnostic value of contrast-enhanced ultrasound (CEUS) in the assessment of acute pancreatitis. Methods Relevant studies were identified by searching the database up to December 2016. Patient clinical characteristics and diagnostic sensitivity and specificity were extracted. The summary receiver operating characteristic (ROC) curve was used to examine the accuracy of CEUS. A meta-analysis was performed to evaluate the clinical utility in the diagnosis and evaluation of acute pancreatitis. Results From 27 citations, seven were included in the meta-analysis, with a total of 421 cases. We detected the heterogeneity of the studies and evidence of publication bias. The methodological quality was moderate. The pooled weighted sensitivity with a corresponding 95% confidence interval (CI) was 0.92 (95% CI: 0.88, 0.95), the specificity was 0.84 (95% CI: 0.78, 0.90), the positive likelihood ratio was 5.38 (95% CI: 3.21, 9.00), the negative likelihood ratio was 0.13 (95% CI: 0.05, 0.36), and the diagnostic odds ratio was 49.37 (95% CI: 14.69, 165.94). The area under the ROC curve was 0.9273 (95% CI: 0.8916, 0.9790). Conclusions CEUS is a reliable, non-invasive imaging modality with no radiation exposure and a high sensitivity and specificity for the assessment of severity of acute pancreatitis. Nonetheless, it should be applied cautiously, and large-scale, well-designed trials are necessary to assess its clinical value.

The World Health Organization Study Group on Tobacco Product Regulation (WHO TobReg) proposed mandated ceilings on 9 prioritized mainstream cigarette smoke constituents determined from the market-specific median of nicotine-normalized yield distributions. Considering the requirements for assessing and reporting of compliance with ceilings, it is of great importance to estimate the measurement uncertainty. To have a better understanding of influence of measurement uncertainty on the WHO recommended regulation for cigarette smoke constituents, in the present study, the measurement uncertainties were evaluated systematically based on series of collaborative studies reported by three different authorities over the years from 2012 to 2016, according to the approaches guided in ISO/TS 21748. Furthermore, the compliance assessment of 20 representative cigarette samples with proposed ceilings was conducted by taking measurement uncertainty into account. This work demonstrated that measurement uncertainty had great influence on the implementation of the regulated mandated lowering of toxic smoke constituents, both on the setting of ceilings and the compliance assessment as well.

The accurate prediction of portosplenomesenteric vein thrombosis (PVT) in patients with acute pancreatitis(AP) is very important but may also be difficult because of our insufficient understanding of the characteristics of AP-induced PVT. The purpose of this study is to design a decision tree model that provides critical factors associated with PVT using an approach that makes use of classification and regression tree (CART) algorithm.The analysis included 353 patients with AP who were admitted between January 2011 and December 2015. CART model and logistic regression model were each applied to the same 50% of the sample to develop the predictive training models, and these models were tested on the remaining 50%. Statistical indexes were used to evaluate the value of the prediction in the 2 models.The predicted sensitivity, specificity, positive predictive value, negative predictive value, and accuracy by CART for PVT were 78.0%, 87.2%, 64.0%, 93.2%, and 85.2%, respectively. Significant differences could be found between the CART model and the logistic regression model in these parameters. There were significant differences between the CART and logistic regression models in these parameters (P.05). When the CART model was used to identify PVT, the area under receiver operating characteristic curve was 0.803, which demonstrated better overall properties than the logistic regression model (area under the curve=0.696) (95% confidence interval, 0.603-0.812).The CART model based on serum amylase, d-dimer, Acute Physiology and Chronic Health Evaluation II, and prothrombin time is more likely to predict the occurrence of PVT induced by AP.

Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cancer cells exhibit enhanced resistance to the ferroptotic damage induced by common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) and Erastin and that the monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Additionally, blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. In vitro and in vivo evidence confirms that lactate regulates the ferroptosis of HCC cells and highlights its translational potential as a therapeutic target for ferroptosis-based tumor treatment. Published version

Background To explore the characteristics and regularity of complete blood count (CBC) changes among influenza A–positive child patients and to discover parameters that can help with the diagnosis and differential diagnosis. Methods One hundred and ninety‐one influenza A–positive children, two hundred and nineteen influenza A–negative children with influenza‐like symptoms, and two hundred and forty‐seven healthy children were included in this study. They were divided into three groups: influenza A–positive patient group, influenza A–negative patient group, and control group. Reverse transcriptase polymerase chain reaction testing and Sysmex XS‐800i hematology analyzer were used to obtain influenza A and CBC results, respectively. CBC along with parameters including lymphocyte‐to‐monocyte ratio (LMR), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), mean platelet volume/platelet ratio (MPV/PLT), and lymphocyte*platelet (LYM*PLT) was calculated and recorded for each child. The differences in these parameters among different groups were tested with SPSS 15.0. The diagnostic values were also evaluated. Results The LYM and PLT of child patients with influenza A were significantly lower than those of both influenza A–negative patients with influenza‐like symptoms and healthy controls. Among all the parameters, LYM*PLT has the largest area under the curve and the highest diagnostic value, followed by MPV/PLT. Compared with using LMR or MPV/PLT, the diagnostic value of using LYM alone was, on the contrary, higher. Conclusions Low LYM*PLT and high MPV/PLT may indicate influenza A infection in children with influenza‐like symptoms, which can be a useful indicator for diagnosis and differentiation of influenza A infection.

BACKGROUND: Acute graft versus host disease (aGvHD) is a major factor that limits the successful outcomes of allogeneic hematopoietic cell transplantation (alloHSCT). Currently, there are few validated biomarkers that can help predict the risk of aGvHD in clinical settings. METHODS: We performed an integrated metabolomics and transcriptomics study and identified biomarkers that distinguish alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in 2 separate cohorts. RESULTS: Pathway analysis of 38 significantly altered metabolites and 1,148 differentially expressed genes uncovered a distinctly altered glycerophospholipid (GPL) metabolism network. Subsequently, we developed an aGvHD risk score (GRS) based on 5 metabolite markers from GPL metabolism to predict the risk of aGvHD. GRS showed a positive predictive value of 92.2% and 89.6% in the training and validation cohorts, respectively. In addition, high GRS was correlated with poor overall survival. Gene expressions of GPL-related lipases were significantly altered in aGvHD samples, leading to dysregulated GPLs. CONCLUSION: Using integrative “Omic” analysis, we unraveled a comprehensive view of the molecular perturbations underlying the pathogenesis of aGvHD. Our work represents an initial investigation of a unique metabolic and transcriptomic network that may help identify aGvHD at an early stage and facilitate preemptive therapy. FUNDING: National Natural Science Foundation of China (NSFC; 81530047, 81870143, 81470321, 81770160, 81270567, 81270638, 81573396, 81703674) provided funding for material, processing, metabolomics, and transcriptomics studies. This work was also supported by Shanghai Sailing Program from Science and Technology Commission Shanghai Municipality (17YF1424700), the Scholarship from Shanghai Municipal Health and Family Planning Commission (2017BR012), and the Special Clinical Research in Health Industry in Shanghai (20184Y0054). The projects supporting young scholars are 17YF1424700 (to YL), 2017BR012 (to XH), and 20184Y0054 (to QC).

Inflammation plays an important role in the pathogenesis of diabetes complications. This study aims to assess the association between circulating inflammatory biomarkers TNF receptors (TNFRs) and the risk of renal disease progression, cardiovascular disease (CVD) events, and mortality in patients with diabetes.PubMed and Embase databases were comprehensively searched up to March 2019. Data were extracted independently by two reviewers. A random effects model was performed for the pooled analyses.Five studies in 3316 subjects assessed TNFRs with renal disease in patients with type 1 diabetes and showed both TNFR-1 and TNFR-2 were consistently associated with the renal outcomes. Fourteen studies in 7696 subjects evaluated TNFRs in patients with type 2 diabetes. The pooled risk ratio per doubling increase in TNFR-1 and TNFR-2 for renal disease progression was more than two (2.64 [1.98, 3.52] and 2.23 [1.69, 2.94]). The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness. Moreover, higher TNFR-1 and TNFR-2 was also significantly associated with CVD events and mortality in patients with type 2 diabetes.Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression, CVD events, and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future.

Approximately 4000 diseases are associated with malfunctioning genes in a particular cell type. Gene-based therapy provides a platform to modify the disease-causing genes expression at the cellular level to treat pathological conditions. However, gene delivery is challenging as these therapeutic genes need to overcome several physiological and intracellular barriers in order, to reach the target cells. Over the years, efforts have been dedicated to develop efficient gene delivery vectors to overcome these systemic barriers. Chitosan, a versatile polysaccharide, is an attractive non-viral vector material for gene delivery mainly due to its cationic nature, biodegradability and biocompatibility. The present review discusses the design factors that are critical for efficient gene delivery/transfection and highlights the recent progress of gene therapy using chitosan-based carriers. Published version

Several animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD. In an inducible tubular cell–specific RTN1A-knockdown mouse model subjected to folic acid nephropathy (FAN) or aristolochic acid nephropathy, reduction of RTN1A expression during the initial stage of AKI attenuated ER stress and kidney cell injury in early stages and renal fibrosis development in later stages. Treatment of wild-type mice with tauroursodeoxycholic acid, an inhibitor of ER stress, after the induction of kidney injury with FA facilitated renoprotection similar to that observed in RTN1A-knockdown mice. Conversely, in transgenic mice with inducible tubular cell–specific overexpression of RTN1A subjected to FAN, induction of RTN1A overexpression aggravated ER stress and renal injury at the early stage and renal fibrosis at the late stage of FAN. Together, our human and mouse data suggest that the RTN1A-mediated ER stress response may be an important determinant in the severity of AKI and maladaptive repair that may promote progression to CKD.

To evaluate the safety and feasibility of radical surgery for giant desmoid in abdominal wall accompanied with the repair of giant myofascial defect using synthetic prosthesis.We analyzed the clinical and follow-up data of 31 patients with giant desmoid in abdominal wall undergoing radical resection and immediate abdominal wall reconstruction with synthetic prosthesis from January 2007 to January 2017 retrospectively. Patients were recruited at the Diagnostic and Therapeutic Center of Hernia and Abdominal Wall Diseases, the First Affiliated Hospital of Chinese PLA General Hospital and the Department of General Surgery, Chinese PLA General Hospital. Operative conditions, morbidity of complication, short- and long-term outcomes were summarized. All the patients underwent radical resection and infiltrated organs or tissues were simultaneously treated. Synthetic prosthesis was used to perform primary-intention reconstruction of giant myofascial defect in anterior or lateral abdominal wall. Bridging repair procedure for incisional hernia was used to perform double border fixation between prosthesis border and myofascial defect border. Placement and fixation of prosthesis followed the idea of "conformal repair", then prosthesis was finally repaired as arch in accordance with original abdominal wall.Of 31 patients, 28 cases were female with mean age of 35.2 (16-58) years and 3 were male with mean age of 42.6 (20-79) years. Six initial cases (19.4%) were diagnosed by preoperative biopsy, and 25 recurrent cases (60.6%) were diagnosed by medical history. The mean minimal diameter of tumors was 18.2 (14-25) cm, and the mean maximal diameter was 45.3 (32-53) cm. All 31 patients underwent radical resection and immediate abdominal wall reconstruction using synthetic prosthesis in bridging fashion successfully, and rapid pathological examination showed that all resection margins were negative. The average operative time was 335 (245-610) min, and the average intra-operative blood loss was 1260 (500-3500) ml. The size of abdominal wall defect after removal of desmoid ranged from 21 cm × 23 cm to 35 cm × 60 cm. The defects in 29 patients were repaired with compound synthetic prosthesis and the defects in 2 patients were repaired with compound prosthesis and polypropylene mesh. Four patients(12.9%) developed postoperative infection, in whom 3 patients had prosthesis infection during 1 month postoperatively, then 1 case recovered with conservative therapy, the other 2 cases were healed after the removal of infected prosthesis at 2 weeks and 3 months postoperatively, respectively; 1 patient had infection of artificial vessel prosthesis and received a second operation to remove the infected artificial vessel. The other 27 patients recovered smoothly and got primary intention wound healing. These 31 patients were followed up for a median of 60.5 (10-121) months with complete data. No marginal recurrence, incisional hernia, and abdominal wall bulge happened. One patient undergoing removal of all anterior and lateral abdominal wall had difficult defecation and urination during the first month after operation, and recovered through practising chest breathing. Ten patients developed fresh desmoids in other body positions postoperatively within 1-3 years, in whom 3 patients died of intestinal obstruction due to rapid neoplasm development and 7 patients survived with tumor receiving conservative therapy. All the 28 survival patients could restore normal life and workand have appropriate sports.Radical resection and immediate reconstruction of giant myofascial defect using synthetic prosthesis for patients with giant desmoid in abdominal wall is safe and effective.

Da Vinci robotic surgical system has brought giant evolution to minimally invasive surgery, and also improved the development of hernia surgery. Recently, Da Vinci robotic surgical system has been successfully applied to the repair of incisional hernia, inguinal hernia, and esophageal hiatal hernia. In the area of incisional herniorrhaphy, endowrist with 7 degrees of freedom, high definition and naked eye 3D imaging system can make Da Vinci robotic surgical system easy to complete the subtle suture in the anterior abdominal wall from the abdominal cavity. As a result, transabdominal preperitoneal repair(TAPP), intraperitoneal onlay mesh(IPOM) or the posterior components separation techniques (pCST) can be easily accomplished. In the repair of esophageal hiatus hernia, the high definition field and flexible machine wrist of the Da Vinci robotic surgical system also make the identification of nerve and artery more accurate, and the local suture more easy, and the prosthetic placement and fixation more reliable. However, in the field of inguinal hernia repair, the traditional 2D laparoscopic technology is able to provide patients with sufficient minimally invasive advantages, and Da Vinci robotic surgical system does not have obvious advantage because of its expensive cost. Previous small-sample and retrospective studies showed that Da Vinci robotic hernia repair was safe and effective, and had more fineness and dexterity than conventional laparoscopic hernia repair. However, large-sample prospective randomized control trials are still absent for short- and long-term evaluation of Da Vinci robotic hernia repair. With the accumulation of robotic hernia repair cases, the increase of surgical experience, and the development of clinical trials, Da Vinci robotic surgical system will play more important role in hernia repair.

To improve the management level of patients' information of schistosomiasis control stations in Nanchang City, the B/S three-layer architecture and ASP+SQL technology were applied to formulate the WEB-based management system of chronic schistosomiasis patients' information, so as to achieve the information sharing of chronic schistosomiasis among schistosomiasis control stations.

The aim of this study was to use Six Sigma(SM) (Motorola Trademark Holdings, Libertyville, IL) techniques to analyze the quality of point-of-care (POC) glucose testing measurements quantitatively and to provide suggestions for improvement.In total, 151 laboratories in China were included in this investigation in 2014. Bias and coefficient of variation were collected from an external quality assessment and an internal quality control program, respectively, for POC glucose testing organized by the National Center for Clinical Laboratories. The σ values and the Quality Goal Index were used to evaluate the performance of POC glucose meters.There were 27, 30, 57, and 37 participants in the groups using Optium Xceed™ (Abbott Diabetes Care, Alameda, CA), Accu-Chek(®) Performa (Roche, Basel, Switzerland), One Touch Ultra(®) (Abbott), and "other" meters, respectively. The median of the absolute value of percentage difference varied among different lots and different groups. Among all the groups, the Abbott One Touch Ultra group had the smallest median of absolute value of percentage difference except for lot 201411, whereas the "other" group had the largest median in all five lots. More than 85% of participate laboratories satisfied the total allowable error (TEa) requirement in International Organization for Standardization standard 15197:2013, and 85.43% (129/151) of laboratories obtained intralaboratory coefficient of variations less than 1/3TEa. However, Six Sigma techniques suggested that 41.72% (63/151) to 65.56% (99/151) of the laboratories needed to improve their POC glucose testing performance, in either precision, trueness, or both.Laboratories should pay more attention on the practice of POC glucose testing and take actions to improve their performance. Only in this way can POC glucose testing really function well in clinical practice.

Summary Introduction/objective: fast-tract surgery (FTS) has been rapidly embraced by surgeons as a mechanism for improving patient care and driving down complications and costs. The aim of this study was to determine if any improvement in outcomes occurred after FTS protocol for selective double portazygous disconnection with preserving vagus (SDPDPV) compared with non-FTS postoperative care. Methods: patients eligible for SDPDPV in the period January 2012-April 2014 were randomly selected for the FTS group or non-FTS group. A designed protocol was used in the FTS group with emphasis on an interdisciplinary approach. The non-FTS group was treated using previously established standard procedures. The number of postoperative complications, time of functional recovery and duration of hospital stay were recorded. Results: patients in the FTS group (n=59) and non-FTS group (n=57) did not differ in terms of preoperative data and operative details (p>0.05). The FTS procedure led to significantly better control and faster restoration of gastrointestinal functions, food tolerance, rehabilitation and hospital discharge (p0,05). O procedimento FTS levou à melhora significativa do controle e à restauração mais rápida das funções gastrointestinais, tolerância alimentar, reabilitação e alta hospitalar (p

This is a review of nanotherapeutic systems, specifically those that exhibit controlled release of the encapsulated bioactive compound. The survey includes the delivery of a range of bioactive compounds, from lipophilic small molecules to hydrophilic proteins and siRNA molecules. The research into enabling sustained delivery of these compounds from nanocarriers has been prolific, but clinical success has been harder to achieve. This is partly because achieving true sustained duration of action over several days is difficult when the carrier dimensions become less than about 400 nm, due to the much shorter diffusion path length compared to micron-sized carrier systems. Other options must be sought to control the efflux of incorporated bioactives, particularly when these bioactives have moderate to high hydrophilicity. A few of these options are discussed critically in this review. We also answer the question: is controlled release needed for nanotherapies? We present the case for controlled release in specific conditions, with two examples from our own work: one for treatment of glaucoma, and the second for inhibition of fibrosis following surgery. The former is sustaining the release of a small-molecule lipophilic drug, while the latter focusses on sustained siRNA delivery.

Background/Aims: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. Methods: 159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellitus patients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. Results: We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. Conclusions: CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.

SUMMARY OBJECTIVES To evaluate the epidemiological characteristics of acute pancreatitis (AP) and explore potential relationships between these factors and severity. METHODOLOGY Data-sets of 5,659 patients with AP from health statistics and the Information Center of Jiangsu province, between 2014 and 2016, were analyzed. A self-organizing map (SOM) neural network was used for data clustering. RESULTS Biliary acute pancreatitis (BAP) (86.7%) was the most frequent etiological factor. A total of 804 (14.2%) patients had severe acute pancreatitis (SAP). The mean age of patients was 53.7 + 17.3 (range 12~94y). Most of the AP patients were married (75.4%); 6% of mild /moderately severe AP (MAP/MASP) patients were unmarried, which was less than SAP patients (P=0.016). AP patients with blood type AB in the general population (8.8%) was significantly lower than that of AP cases (13.9%) (P=0.019) and SAP cases(18.7%) (P=0.007). The number of AP patients in southern Jiangsu was much higher than that in northern Jiangsu province, especially in Nanjing (1229, 21.7%). The proportion of acute alcoholic pancreatitis (AAP) in the north of Jiangsu (Xuzhou 18.4%) was much higher than that in southern Jiangsu (Suzhou 2.6%). The whole sample was divided into five classes by SOM neural network. If BAP patients were male, old, divorced, and blood type AB or B, they were more likely to develop SAP. Middle-age, unmarried or divorced male patients with blood type B/AB who suffered from HAP or AAP were also more likely to develop SAP. CONCLUSIONS The number of unmarried patients with MAP/MASP was smaller than that of SAP. Blood types AB and B were more frequent in AP, especially in SAP. The differences between southern Jiangsu and northern Jiangsu, in number of AP patients and the proportion of AAP, were significant. In class I and class IV, the ratio of SAP was much higher than in other classes and the whole sample.