A precise design strategy for a cell-derived extracellular matrix based on CRISPR/Cas9 for regulating neural stem cell function.

The extracellular matrix (ECM) is a natural microenvironment pivotal for stem cell survival, as well as proliferation, differentiation and metastasis, composed of a variety of biological molecular complexes secreted by resident cells in tissues and organs. Heparan sulfate proteoglycan (HSPG) is a type of ECM protein that contains one or more covalently attached heparan sulfate chains. Heparan sulphate chains have high affinity with growth factors, chemokines and morphogens, acting as cytokine-binding domains of great importance in development and normal physiology. Herein, we constructed endogenous HSPG2 overexpression in mouse embryonic fibroblasts based on the CRISPR/Cas9 synergistic activation mediator system and then fabricated a cell-derived HSPG2 functional ECM (ECMHSPG2). The ECMHSPG2 is capable of enriching basic fibroblast growth factor (bFGF), which binds more strongly than the negative control ECM. With a growing bFGF concentration, ECMHSPG2 could better maintain neural stem cell (NSCs) stemness and promote NSC proliferation and differentiation in culture. These findings provide a precise design strategy for producing a specific cell-derived ECM for biomaterials in research and regenerative medicine.

Machine Learning Enables Prediction of Pyrrolysyl-tRNA Synthetase Substrate Specificity.

Knowledge about the substrate scope for a given enzyme is informative for elucidating biochemical pathways and also for expanding applications of the enzyme. However, no general methods are available to accurately predict the substrate specificity of an enzyme. Pyrrolysyl-tRNA synthetase (PylRS) is a powerful tool for incorporating various noncanonical amino acids (NCAAs) into proteins, which enabled us to probe, image, rationally engineer, and evolve protein structure and function. However, the incorporation of a new NCAA typically requires the selection of large libraries of PylRS with randomized mutations at active sites, and this process requires multiple rounds of selection for each new substrate. Therefore, a single aminoacyl-tRNA synthetase with broad substrate promiscuity is ideal to facilitate widespread applications of the genetic NCAA incorporation technique. Herein, machine learning models were developed to predict the substrate specificity of PylRS to accept novel NCAAs that could be incorporated into proteins by three PylRS mutants. The models were built from a training set of 285 unique enzyme-substrate pairs of three PylRS mutants including IFRS, BtaRS, and MFRS against 95 NCAAs. The best BaggingTree (BT) model was then used for virtually screening a NCAAs library containing 1474 phenylalanine, tyrosine, tryptophan, and alanine analogues, and 156 NCAAs were predicted to be accepted by at least one of the three PylRS mutants. Then, 27 NCAAs including 24 positive and 3 negative substrates were experimentally tested for their activities, and 20 of the 24 positive substrates showed weak or strong activity and were accepted by at least one PylRS mutant, among which 11 NCAAs were never reported to be incorporated into proteins before. Three negative substrates did not show any activity. Experimental results suggested that the BT model provides a three-class classification accuracy of 0.69 and a binary classification accuracy of 0.86. This study expanded the substrate scope of three PylRS variants and provided a framework for developing machine learning models to predict substrate specificity of other PylRS variants.

Injectable and Degradable POSS-Polyphosphate-Polysaccharide Hybrid Hydrogel Scaffold for Cartilage Regeneration.

The limited self-repair capacity of articular cartilage has motivated the development of stem cell therapy based on artificial scaffolds that mimic the extracellular matrix (ECM) of cartilage tissue. In view of the specificity of articular cartilage, desirable tissue adhesiveness and stable mechanical properties under cyclic mechanical loads are critical for cartilage scaffolds. Herein, we developed an injectable and degradable organic-inorganic hybrid hydrogel as a cartilage scaffold based on polyhedral oligomeric silsesquioxane (POSS)-cored polyphosphate and polysaccharide. Specifically, acrylated 8-arm star-shaped POSS-poly(ethyl ethylene phosphate) (POSS-8PEEP-AC) was synthesized and cross-linked with thiolated hyaluronic acid (HA-SH) to form a degradable POSS-PEEP/HA hydrogel. Incorporation of POSS in the hydrogel increased the mechanical properties. The POSS-PEEP/HA hydrogel showed enzymatic biodegradability and favorable biocompatibility, supporting the growth and differentiation of human mesenchymal stem cells (hMSCs). The chondrogenic differentiation of encapsulated hMSCs was promoted by loading transforming growth factor-ß3 (TGF-ß3) in the hydrogel. In addition, the injectable POSS-PEEP/HA hydrogel was capable of adhering to rat cartilage tissue and resisting cyclic compression. Furthermore, in vivo results revealed that the transplanted hMSCs encapsulated in the POSS-PEEP/HA hydrogel scaffold significantly improved cartilage regeneration in rats, while the conjugation of TGF-ß3 achieved a better therapeutic effect. The present work demonstrated the potential of the injectable, biodegradable, and mechanically enhanced POSS-PEEP/HA hybrid hydrogel as a scaffold biomaterial for cartilage regeneration.

Characteristics of hypertension in the last 16 years in high prevalence region of China and the attribute ratios for cardiovascular mortality.

BACKGROUND: Tianjin is one of the cities with the highest prevalence of hypertension in China and one of the first regions to develop community management of hypertension. Our aim was to analyze the characteristics of hypertension in the last 16 years, and estimate the population attributable fraction for cardiovascular mortality in Tianjin, China. METHODS: We compared the epidemiological characteristics of hypertension between 2002 and 2018 by analyzing data from the National Nutrition and Chronic Disease Risk Factor Survey. Subsequently, we obtained the cause-specific mortality in the same year from the Tianjin All Cause of Death Registration System (CDRS), and the population attributable fraction was used to estimate the annual cardiovascular disease (CVD) deaths caused by hypertension. RESULTS: In 2002 and 2018, the crude prevalence, awareness, treatment rate in diagnosed, control rate in treated, and overall control rate of hypertension were 36.6% and 39.8%, 36.0% and 51.9%, 76.0% and 90.1%, 17.4% and 38.3%, 4.8% and 17.9%, respectively (P < 0.05). The mean SBP for males between the ages of 25 and 50 was significantly higher in 2018 than in 2002. The number of CVD deaths attributed to hypertension was 13.8 thousand in 2002 (account for 59.1% of total CVD deaths), and increased to 21.7 thousand in 2018 (account for 58.8% of total CVD deaths). The population attributable fraction have increased in the age groups of 25-44 and 75 and above, and decreased in the age group of 45-74 from 2002 to 2018. CONCLUSIONS: Compare to 2002, the proportion of CVD deaths attributed to hypertension remains high, particularly among younger and older people, despite a very significant increase in treatment and control rates for hypertension in 2018.

High sodium diet intake and cardiovascular diseases: An attributable death study in Tianjin, China.

There is clear evidence that high sodium intake is associated with many health issues including hypertension and cardiovascular diseases (CVDs). Several national and worldwide studies have estimated deaths from CVDs attributable to high sodium. But how to evaluate the impact of high sodium intake on diseases using regional routine monitoring and investigation data is necessary and important. Our study aimed to quantitatively evaluate the high sodium intake attributed to CVDs deaths based on the routine monitoring data from China National Nutrition and Health Survey (CNNHS) in Tianjin, China. The population attributable fractions (PAF) were calculated by comparing the observed systolic blood pressure (SBP) distribution with the theoretical minimum or counterfactual distribution by sex and age groups. The results showed that CVDs deaths due to elevated SBP were 22728 (95% uncertainty intervals: 22679-23050), accounting for 62.8% of total CVDs deaths. According to sodium intake recommended by World Health Organization (WHO), PAF of CVDs deaths attributable to high sodium diet in our study was 14.6% of total CVDs deaths, accounting for 5228 (95% UI: 5005-5998) cases. The dietary sodium intake of residents is nearly three times than sodium intake recommended by WHO. If sodium intake was reduced to reference level, the potential avoidable CVD deaths attributable to the SBP-raising effect were more than 5200 among adults 25 aged and over in Tianjin. This evaluation method can be extended to other cities.

Mutability-Landscape-Guided Engineering of l-Threonine Aldolase Revealing the Prelog Rule in Mediating Diastereoselectivity of C-C Bond Formation.

l-threonine aldolase (LTA) catalyzes C-C bond synthesis with moderate diastereoselectivity. In this study, with LTA from Cellulosilyticum sp (CpLTA) as an object, a mutability landscape was first constructed by performing saturation mutagenesis at substrate access tunnel amino acids. The combinatorial active-site saturation test/iterative saturation mutation (CAST/ISM) strategy was then used to tune diastereoselectivity. As a result, the diastereoselectivity of mutant H305L/Y8H/V143R was improved from 37.2 %syn to 99.4 %syn . Furthermore, the diastereoselectivity of mutant H305Y/Y8I/W307E was inverted to 97.2 %anti . Based on insight provided by molecular dynamics simulations and coevolution analysis, the Prelog rule was employed to illustrate the diastereoselectivity regulation mechanism of LTA, holding that the asymmetric formation of the C-C bond was caused by electrons attacking the carbonyl carbon atom of the substrate aldehyde from the re or si face. The study would be useful to expand LTA applications and guide engineering of other C-C bond-forming enzymes.

Biomedical polymer scaffolds mimicking bone marrow niches to advance in vitro expansion of hematopoietic stem cells.

Hematopoietic stem cell (HSC) transplantation provides an effective platform for the treatment of hematological disorders. However, the donor shortage of HSCs and immune responses severely restrict the clinical applications of HSCs. Compared to allogeneic transplantation, autogenous transplantation poses less risk to the immune system, but the problem associated with insufficient HSCs remains a substantial challenge. A significant strategy for obtaining sufficient HSCs is to promote the expansion of HSCs. In vivo, a bone marrow microenvironment supports the survival and hematopoiesis of HSCs. Therefore, it is crucial to establish a platform that mimics the features of a bone marrow microenvironment for the in vitro expansion of HSCs. Three-dimensional (3D) scaffolds have emerged as the most powerful tools to mimic cellular microenvironments for the growth and proliferation of stem cells. Biomedical polymers have been widely utilized as cell scaffolds due to their advantageous features including favorable biocompatibility, biodegradability, as well as adjustable physical and chemical properties. This review focuses on recent advances in the study of biomedical polymer scaffolds that mimic bone marrow microenvironments for the in vitro expansion of HSCs. Bone marrow transplantation and microenvironments are first introduced. Then, biomedical polymer scaffolds for the expansion of HSCs and future prospects are summarized and discussed.

Attributable fraction of tobacco smoking on selected cancer deaths in the past decade using mortality case-control study in Tianjin, China.

INTRODUCTION: This study aims to estimate the impact of smoking-attributable mortality of selected cancers, in the period 2010-2019 in Tianjin, China. METHODS: A case-control study was conducted to assess the smoking-attributed major causes of cancer deaths. Unmatched multiple logistic regression was used to calculate mortality risk ratios. RESULTS: Smoking-attributable cancer deaths were 23709 (28.87%) among adult males and 8648 (13.37%) among adult females in the period 2010-2019 in Tianjin, China. Lung cancer remains the largest cause of smoking-attributable deaths; among men, the death rates were 49.06% of lung cancers, 27.55% of mouth, pharynx, larynx, or esophagus cancers, 13.56% of kidney and other urinary cancers, and 10.11% of liver cancers; among women the corresponding death rates were 31.56% of lung cancers and 10.59% of the mouth, pharynx, larynx, or esophagus cancer, 10.56% of bladder cancers. Smoking-attributed cancer deaths in men increased from 1817 in 2010 to 2695 in 2019; for women, the number remained stable at just over 800 per year during the past decade. CONCLUSIONS: At least one in three cancer deaths in men and one in six in women would be potentially preventable through appropriate control of tobacco smoking in Tianjin, China. Effective control programs against tobacco smoking should be further implemented.

Seed priming with protein hydrolysate promotes seed germination via reserve mobilization, osmolyte accumulation and antioxidant systems under PEG-induced drought stress.

KEY MESSAGE: Seed priming with pig blood protein hydrolysate improves tomato seed germination and seedling growth via regulation of reserve mobilization, osmotic adjustment, and antioxidant mechanism under drought conditions. Protein hydrolysates obtained from agro-industrial byproducts are widely recognized because of their positive roles in regulating plant responses to environmental stresses. However, little is known regarding the roles of animal protein hydrolysates in mediating seed drought tolerance and its underlying mechanisms. This study investigated the potential effects of seed priming on tomato seed germination and seedling growth under PEG-induced drought stress using protein hydrolysates derived from pig blood (PP). PP priming effectively alleviated the drought-induced reduction in seed germination traits, resulting in improved tomato seedling growth. PP priming enhanced the gene expressions and activities of amylase and sucrose synthase and soluble sugar, soluble protein, and free amino acid levels, thereby promoting reserve mobilization in seeds. PP priming also reduced osmotic toxicity through increased accumulations of proline, soluble protein, and soluble sugar. Drought stress substantially enhanced reactive oxygen species production and the subsequent increases in malondialdehyde levels and Evans blue solution uptake, which were substantially alleviated after PP priming via the improved activities of enzymatic and non-enzymatic antioxidants. Moreover, the increased DPPH free radical scavenging capacity and ferric reducing antioxidant power indicated that PP-treated tomato seedings had high antioxidant activities under drought stress. Therefore, PP priming is a novel, promising, and practicable method for improving tomato seed germination and seedling growth under drought stress.

High-efficiency brain-targeted intranasal delivery of BDNF mediated by engineered exosomes to promote remyelination.

The regeneration of myelin sheaths is the ultimate goal of the treatment of demyelination disease, including multiple sclerosis (MS). However, current drugs for MS mainly target the immune system and can only slow down the disease development and do not promote the differentiation of oligodendrocyte precursor cells (OPCs) abundant in the myelin injury region into mature oligodendrocytes to form a new myelin sheath. Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of OPC proliferation and differentiation into mature oligodendrocytes. Exosomes, a kind of nanoscale membrane vesicle secreted by cells, can be used as potential therapeutic drug delivery vectors for central nervous system diseases. Here, brain-targeted modification and BDNF intracellular-loaded exosomes were produced through engineering HEK293T cells, which can promote the differentiation of OPCs into mature oligodendrocytes in vitro. The intranasal administration of the brain-targeted engineered exosome-mediated BDNF was a highly effective delivery route to the brain and had a significant therapeutic effect on remyelination and motor coordination ability improvement in demyelination model mice. The combination of intranasal administration with brain-targeted and BDNF-loaded designed exosomes provides a strategy for efficient drug delivery and treatment of central nervous system diseases.

Three-dimensional CT angiography facilitates uniportal thoracoscopic anatomic lung resection for pulmonary sequestration: a retrospective cohort study.

BACKGROUND: Pulmonary sequestration (PS) is a rare lesion with independent blood supply from an anomalous systemic artery. A timely resection is considered as the best treatment for PS. Three-dimensional computed tomography angiography (3D-CTA) has been widely utilized for precise thoracic surgery. This study aimed to investigate the role of preoperative 3D-CTA and resection simulation in uniportal video-assisted thoracoscopic surgery (VATS) anatomical lung surgery for PS. METHODS: The data of 20 consecutive PS patents undergoing anatomic lung resection between April 2011 and May 2021 in a single centre were retrospectively reviewed. These patients were divided into the 3D-CTA group (10 patients) and the control group (10 patients) according to the initial surgical planning with or without 3D-CTA. The perioperative parameters regarding safety and fluency such as the incidence of conversion to open thoracotomy, operation time, blood loss, complications and chest tube duration were analyzed. RESULTS: This cohort included 12 female and 8 male patients, with a mean age of 45 years old (range 24-60 years). Nine cases demonstrated recurrent febrile, cough, or hemoptysis; whereas the other 11 patients were asymptomatic on admission. Eighteen (90.0%) intralobar and 2 extralobar PS were confirmed, whereas 18 (90.0%) lesions were located in the left thorax. The feeding vessels originated from the thoracic aorta in 16 patients (80.0%), the abdominal aorta in 3 (15.0%), and the inferior phrenic artery in 1 patient (5.0%). There was no major bleeding or 30 days mortality. The initial surgical planning included 9 uniportal and 1 two-port VATS in the 3D-CTA group, as compared with 10 two-port VATS in the control group. Thirteen lobectomies, 5 segmentectomies and 2 mass excisions were performed. However, no conversion was needed in the 3D-CTA group; whereas 6 (60.0%) conversions (4 to multiple-port and 2 to thoracotomy) occurred in the control group, indicating a significant difference (P = 0.003). In addition, the operation time in the 3D-CTA group was significantly shorter than those in the control group [(108.5 ± 24.9) min vs. (154.5 ± 39.4) min, P = 0.006]. The other surgery-related outcomes were similar between the two groups. CONCLUSION: Preoperative 3D-CTA facilitates the safe and fluent performance of uniportal VATS anatomical lung resection for PS with shortened operation time and lessened surgical conversions.

Specific anti-glioma targeted-delivery strategy of engineered small extracellular vesicles dual-functionalised by Angiopep-2 and TAT peptides.

Glioma is one of the primary malignant brain tumours in adults, with a poor prognosis. Pharmacological reagents targeting glioma are limited to achieve the desired therapeutic effect due to the presence of blood-brain barrier (BBB). Effectively crossing the BBB and specifically targeting to the brain tumour are the major challenge for the glioma treatments. Here, we demonstrate that the well-defined small extracellular vesicles (sEVs) with dual-targeting drug delivery and cell-penetrating functions, modified by Angiopep-2 and trans-activator of transcription peptides, enable efficient and specific chemotherapy for glioma. The high efficiency of engineered sEVs in targeting BBB and glioma was assessed in both monolayer culture cells and BBB model in vitro, respectively. The observed high targeting efficiency was re-validated in subcutaneous tumour and orthotopic glioma mice models. After loading the doxorubicin into dual-modified functional sEVs, this specific dual-targeting delivery system could cross the BBB, reach the glioma, and penetrate the tumour. Such a mode of drug delivery significantly improved more than 2-fold survival time of glioma mice with very few side effects. In conclusion, utilization of the dual-modified sEVs represents a unique and efficient strategy for drug delivery, holding great promise for the treatments of central nervous system diseases.

Substrate access path-guided engineering of L-threonine aldolase for improving diastereoselectivity.

The L-threonine aldolase from Leishmania major was engineered to improve its diastereoselectivity by a CAST/ISM strategy, providing insights into the relationship between the physico-chemical properties of the substrate access path and diastereoselectivity. The steric hindrance, hydrophobic interaction and π-π interaction cooperated to improve the diastereoselectivity of the enzyme, with a diastereomeric excess (de) value reaching 96.3%syn from 26.8%syn.

Spatial-temporal characteristics and regional differences of the freight transport industry's carbon emission efficiency in China.

The freight transport industry is an important field in which to achieve the goal of carbon emission reduction within the transportation industry. Analyzing the spatial-temporal characteristics and regional differences in the freight transport industry's carbon emissions efficiency (CEE) is an essential prerequisite for developing a reasonable regional carbon abatement policy. However, few studies have conducted an in-depth analysis of the freight transport industry's CEE from the perspective of geographic space. This study combines the super-efficiency slack-based measure (SBM) model and the window analysis model to measure the freight transport industry's CEE in 31 Chinese provinces from 2008 to 2019. We then introduced a spatial autocorrelation analysis and the Theil index to analyze the spatial-temporal evolution characteristics and regional differences in the freight transport industry's CEE in China. The results show that (1) the overall level of the freight transport industry's CEE is low, with an average of 0.534, which showed a weak downward trend during the study period. This indicates that the freight industry's CEE has not improved, and there is a massive requirement for energy conservation and emission reduction. (2) From 2008 to 2019, CEE gradually shows a spatial distribution pattern of being "low in the west and high in the east," with a significant, positive spatial correlation (all passed the significance level test at P < 0.01). This indicates that the spatial diffusion and inhibition of the freight transport industry's CEE in adjacent areas cannot be ignored. (3) The overall differences in the freight transport industry's CEE show a fluctuating upward trend from 2008 to 2019. The inter-regional differences of the three regions (east, central, and west) are the main contributors of the total differences. Therefore, narrowing inter-regional gaps in CEE is one of the main ways to improve the freight transport industry's CEE.

Effect of Helicobacter pylori-Associated Chronic Gastritis on Autonomous Activity and Sleep Quality in Mice.

Many reports have shown that patients with Hp-associated chronic gastritis exhibit anxiety and poor sleep quality. However, less is known about the effects and specific manifestations of Hp-associated chronic gastritis on autonomous activity and sleep quality in animals. Here, we investigated the effect of Helicobacter pylori (Hp)-associated chronic gastritis on autonomous activity and sleep quality in mice. To do this, a Hp-associated chronic gastritis mouse model was first established, then analyzed for autonomous activity, relative to controls, for 15 min using an autonomous activity tester. Next, sleep quality of mice was detected by sodium pentobarbital-induced sleep experiment and results compared between groups. The results showed that male mice in the model group exhibited higher activity counts but lower forelimb lift counts, relative to those in the control group, although there were no significant differences (all p > .05). Conversely, female mice in the model group recorded lower activity counts, albeit at no significant difference (p > .05), and significantly lower counts of forelimb lift (p < .05), relative to those in the control group. Notably, male mice in the model group had longer sleep latency and shorter sleep duration than those in the control group, albeit at no significant differences (all p > .05). On the other hand, female mice in the model group recorded significantly longer sleep latency as well as shorter sleep duration compared to those in the control group (all p < .01). We conclude that Hp-associated chronic gastritis exerts certain effects on autonomous activity and sleep quality of mice in a gender-dependent manner. Notably, female mice with Hp-associated chronic gastritis had lower activity and forelimb lift counts, as well as prolonged sleep latency, and shortened sleep duration. These effects were all statistically significant except for activity counts.

Bonding Character, Electron Delocalization, and Aromaticity of Cyclo[18]Carbon (C18 ) Precursors, C18 -(CO)n (n=6, 4, and 2): Focusing on the Effect of Carbonyl (-CO) Groups.

The bonding character, electron delocalization, and aromaticity of the cyclo[18]carbon (C18 ) precursors, C18 -(CO)n (n=6, 4, and 2), have been studied by combining quantum chemical calculations and various electronic wavefunction analyses with different physical bases. It was found that C18 -(CO)n (n=6, 4, and 2) molecules exhibit alternating long and short C-C bonds, and have out-of-plane and in-plane dual π systems (πout and πin ) perpendicular to each other, which are consistent with the relevant characteristics of C18 . However, the presence of carbonyl (-CO) groups significantly reduced the global electron conjugation of C18 -(CO)n (n=6, 4, and 2) compared to C18 . Specifically, the -CO group largely breaks the extensive delocalization of πin system, and the πout system is also affected by it but to a much lesser extent; as a consequence, C18 -(CO)n (n=6, 4, and 2) with larger n shows weaker overall aromaticity. Mostly because of the decreased but still apparent πout electron delocalization in the C18 -(CO)n (n=6, 4, and 2), a notable diatropic induced ring current under the action of external magnetic field is observed, demonstrating the clear aromatic characteristic in the molecules. The correlation between C18 -(CO)n (n=6, 4, and 2) and C18 in terms of the gradual elimination of -CO from the precursors showed that the direct elimination of two CO molecules in C18 -(CO)n (n=6, 4, and 2) has a synergistic mechanism, but it is kinetically infeasible under normal conditions due to the high energy barrier.

Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis.

Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.

Urban-rural disparity in cancer mortality and changing trend in Tianjin, China, during 1999 and 2016.

OBJECTIVE: Compare the urban-rural disparity in cancer mortality and changing trend during the past 18 years in Tianjin, China. METHODS: Cancer death data were obtained from Tianjin All Cause of Death Registration System (CDRS), which covers the whole population of Tianjin. We calculated and compared the constituent ratio of cancer deaths, age-standardized mortality rate(ASR)and changing trends between urban and rural areas. RESULTS: From 1999 to 2016, a total of 245,744 cancer deaths were reported, accounting 21.7% of all deaths in Tianjin. The ASR of total cancer mortality was higher in urban areas than in rural areas. A total of 33,739 persons were avoided dying of cancers in rural area compared to the urban death level from 1999 to 2016, which was 40.1% compare to the current level of rural areas. But the gap between urban and rural areas became narrowed gradually. The urban-rural ratios (urban/rural) of total cancer mortality changed from 1.76 (125.7/71.5)[95%CI,1.67,1.84] in 1999 to 1.11 (99.6/90.0)[95%CI,1.06,1.15] in 2016. The ASR of lung, liver and esophagus cancer became higher in rural areas than in urban areas in 2016. CONCLUSION: Cancer transition was obviously occurred in Tianjin and showed different speeds and big gap between urban and rural areas. Much more attention was needed to pay in rural areas which still have increasing trends in most cancers mortality recently.

Clinical characteristics and prognosis in patients with urosepsis from intensive care unit in Shanghai, China: a retrospective bi-centre study.

BACKGROUND: The purpose of this study was to retrospectively analyze clinical characteristics and prognostic risk factors of urosepsis patients admitted to two intensive care units in Shanghai, China. METHODS: Clinical data from patients diagnosed with urosepsis were retrospectively retrieved and analyzed from ICU in two regional medical centers from January 2015 to December 2019. RESULTS: Two hundred two patients were included in the subsequent analysis eventually, with an average age of 72.02 ± 9.66 years, 79.21% of the patients were female and the mortality rate of 15.84%.The proportion of patients with chronic underlying diseases such as diabetes and hypertension was relatively high (56.44, 49.50%, respectively), and the incidence of shock was also high (41.58%) correspondingly. The most common pathogen isolated was Escherichia coli (79.20%), of which the extended-spectrumß-lactamases (ESBLs)(+) accounted for 42.57%. In multivariate analysis, the strongest predictors for death were mechanical ventilation (OR 7.260, 95% CI 2.200-23.963; P = 0.001),chronic kidney disease (CKD) (OR 5.140, 95% CI 1.596-16.550; P = 0.006), APACHE II score (OR 1.321, 95% CI 1.184-1.473; P < 0.001) and lactate (OR 1.258, 95% CI 1.037-1.527; P = 0.020). Both APACHE II score and lactate had the ideal predictive value, with the area under the ROC curve (AUC) of 0.858 and 0.805 respectively. CONCLUSION: The patients with urosepsis were characterized by a higher proportion of female, older age, more percentage of comorbidities in this region, and patients with ESBLs (+) Escherichia coli infection were more prone to shock. Mechanical ventilation, comorbidity with CKD, APACHE II score and lactate were independent risk factors for death in urosepsis patient, but lactate level and APACHE II score had better predictive value for prognosis.

External validation and comparison of two versions of simplified sequential organ failure assessment scores to predict prognosis of septic patients.

BACKGROUND: Evidence shows that simplified SOFA scoring system has better clinical practice. OBJECTIVE: This study aimed to validate and compare the scores acquired with simplified organ dysfunction criteria optimized for electronic health records (eSOFA), and simplified and accurate sequential organ failure assessment (sa-SOFA) for their accuracies in predicting the prognosis of septic patients. METHODS: This retrospective observational study was conducted at three major academic hospitals. Clinical data from 574 patients diagnosed with sepsis following the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)were retrospectively retrieved and analysed. Scores from the quick sequential organ failure assessment (qSOFA) and sequential organ failure assessment (SOFA) were used as reference scores. The area under the receiver operating characteristic curve (AUROC) was used to assess the performance of eSOFA and sa-SOFA scores in predicting in-hospital mortality. RESULTS: AUROC analysis demonstrated the predictability of the four scoring systems for sepsis surveillance, listed in descending order as: sa-SOFA, 0.790 (95% confidence interval [CI]: 0.754-0.822); SOFA, 0.774 (95% CI: 0.738-0.808); eSOFA, 0.729 (95% CI: 0.691-0.765); and qSOFA, 0.618 (95% CI: 0.577-0.658). Moreover, sa-SOFA and SOFA scores (Z = 1.950, P = .051) did not significantly differ from each other in discriminatory power, but the sa-SOFA score had a higher power than eSOFA score (P values < .001). CONCLUSION: sa-SOFA appeared to have performed better than eSOFA score for predicting in-hospital mortality in patients' sepsis. Further large prospective studies are needed to externally validate.