Therapeutic siRNA Loaded to RISC as Single and Double Strands Requires an Appropriate Quantitative Assay for RISC PK Assessment.

In recent years, therapeutic siRNA projects are booming in the biotech and pharmaceutical industries. As these drugs act by silencing the target gene expression, a critical step is the binding of antisense strands of siRNA to RNA-induced silencing complex (RISC) and then degrading their target mRNA. However, data that we recently obtained suggest that double-stranded siRNA can also load to RISC. This brings a new understanding of the mechanism of RISC loading which may have a potential impact on how quantification of RISC loaded siRNA should be performed. By combining RNA immune precipitation and probe-based hybridization LC-fluorescence approach, we have developed a novel assay that can accurately quantify the RISC-bound antisense strand, irrespective of which form (double-stranded or single-stranded) is loaded on RISC. In addition, this novel assay can discriminate between the 5'-phosphorylated antisense (5'p-AS) and the nonphosphorylated forms, therefore specifically quantifying the RISC bound 5'p-AS. In comparison, stem-loop qPCR assay does not provide discrimination and accurate quantification when the oligonucleotide analyte exists as a mixture of double and single-stranded forms. Taking together, RISC loading assay with probe-hybridization LC-fluorescence technique would be a more accurate and specific quantitative approach for RISC-associated pharmacokinetic assessment.

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

Background: The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Methods: Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. Results: A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. Conclusions: The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

Chromium immobilization from wastewater via iron-modified hydrochar: Different iron fabricants and practicality assessment.

The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19 mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.

Assessment of risk factors of lymph node metastasis and prognosis of Siewert II/III adenocarcinoma of esophagogastric junction: A retrospective study.

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

Removal of toilet paper fibers from residential wastewater: a life cycle assessment.

Toilet paper has been reported as one of the major insoluble pollutant components in the influent of wastewater treatment plants. Toilet paper fibers contribute to a large production of sewage sludge, resulting in a high treatment cost and high energy consumption. To find energy-efficient, cost-effective, and environment-friendly technologies for fiber removal and resource recovery from wastewater, a life-cycle assessment (LCA) was performed to analyze the wastewater treatment processes, including a sieving process for removing and recovering suspended solids before the biodegradation units. Based on the LCA results, it was estimated that the sieve screening process saved 8.57% of energy consumption. The construction phase of sieving consumed 1.31% energy cost compared with the operation phase. Environmental impact analysis showed that sieving reduced the impacts of climate change, human toxicity, fossil depletion, and particulate matter formation, which reduced the total normalized environmental impacts by 9.46%. The life-cycle analysis of the removal of toilet paper fibers from wastewater revealed the need to use more efficient methods to enhance the recovery of cellulose fibers.

An Assessment of the Pathological Classification and Postoperative Outcome of Focal Cortical Dysplasia by Simultaneous Hybrid PET/MRI.

OBJECTIVES: The purpose of this research was to investigate whether MRI and Simultaneous Hybrid PET/MRI images were consistent in the histological classification of patients with focal cortical dysplasia. Additionally, this research aimed to evaluate the postoperative outcomes with the MRI and Simultaneous Hybrid PET/MRI images of focal cortical dysplasia. METHODS: A total of 69 cases in this research were evaluated preoperatively for drug-resistant seizures, and then surgical resection procedures of the epileptogenic foci were performed. The postoperative result was histopathologically confirmed as focal cortical dysplasia, and patients then underwent PET and MRI imaging within one month of the seizure. In this study, head MRI was performed using a 3.0 T magnetic resonance scanner (Philips) to obtain 3D T1WI images. The Siemens Biograph 16 scanner was used for a routine scanning of the head to obtain PET images. BrainLAB's iPlan software was used to fuse 3D T1 images with PET images to obtain PET/MRI images. RESULTS: Focal cortical dysplasia was divided into three types according to ILAE: three patients were classified as type I, twenty-five patients as type II, and forty-one patients as type III. Patients age of onset under 18 and age of operation over 18 had a longer duration (p = 0.036, p = 0.021). MRI had a high lesion detection sensitivity of type III focal cortical dysplasia (p = 0.003). Simultaneous Hybrid PET/MRI showed high sensitivity in detecting type II and III focal cortical dysplasia lesions (p = 0.037). The lesions in Simultaneous Hybrid PET/MRI-positive focal cortical dysplasia patients were mostly located in the temporal and multilobar (p = 0.005, 0.040). CONCLUSION: Simultaneous Hybrid PET/MRI has a high accuracy in detecting the classification of focal cortical dysplasia. The results of this study indicate that patients with focal cortical dysplasia with positive Simultaneous Hybrid PET/MRI have better postoperative prognoses.

Degradation of trichloroethylene by double dielectric barrier discharge (DDBD) plasma technology: Performance, product analysis and acute biotoxicity assessment.

Trichloroethylene is carcinogenic and poorly degraded by microorganisms in the environment. Advanced Oxidation Technology is considered to be an effective treatment technology for TCE degradation. In this study, a double dielectric barrier discharge (DDBD) reactor was established to decompose TCE. The influence of different condition parameters on DDBD treatment of TCE was investigated to determine the appropriate working conditions. The chemical composition and biotoxicity of TCE degradation products were also investigated. Results showed that when SIE was 300 J L-1, the removal efficiency could reach more than 90%. The energy yield could reach 72.99 g kWh-1 at low SIE and gradually decreased with the increase of SIE. The k of the Non-thermal plasma (NTP) treatment of TCE was about 0.01 L J-1. DDBD degradation products were mainly polychlorinated organic compounds and produced more than 373 mg m-3 ozone. Moreover, a plausible TCE degradation mechanism in the DDBD reactors was proposed. Lastly, the ecological safety and biotoxicity were evaluated, indicating that the generation of chlorinated organic products was the main cause of elevated acute biotoxicity.

Assessment of Water Eutrophication at Bao'an Lake in the Middle Reaches of the Yangtze River Based on Multiple Methods.

Based on the monthly monitoring of Bao'an Lake in Hubei Province from 2018 to 2020, the eutrophication level of Bao'an Lake in the middle reaches of the Yangtze River is investigated using the comprehensive trophic level index (TLI), chromophoric dissolved organic matter (CDOM) absorption coefficient, and the phytoplankton water quality biological method. The influencing factors are then identified. The results demonstrate that the overall water quality of Bao'an Lake remained at levels III-V during 2018-2020. Due to different eutrophication assessment methods, the results are different, but all show that Bao'an Lake is in a eutrophication state as a whole. The eutrophication level of Bao'an Lake is observed to vary with time, exhibiting an increasing then decreasing trend between 2018-2020, while levels are high in summer and autumn, and low in winter and spring. Moreover, the eutrophication level of Bao'an Lake presents an obviously varying spatial distribution. Potamogeton crispus is the dominant species of the Bao'an Lake, the water quality is good in spring when Potamogeton crispus vigorously grows, but poor in summer and autumn. The permanganate index (CODMn) and total phosphorous (TP), total nitrogen (TN), and chlorophyll a (Chl-a) contents are identified as the main influencing factors of the eutrophication level of Bao'an Lake, with a significant relationship observed between Chl-a and TP (p < 0.01). The above results provide a solid theoretical basis for the ecological restoration of Bao'an Lake.

Attitude Disparity and Worrying Scenarios in Genetic Discrimination-Based on Questionnaires from China.

Objectives: As genetic testing is increasingly used in non-medical fields, the judgment of people's potential conditions based on predictive genetic information inevitably causes genetic discrimination (henceforth GD). This article aimed to systematically investigate the disparity in attitudes and worrying scenarios concerning GD in China. Methods: A questionnaire survey of 555 respondents was conducted. Statistical tests were used to examine disparity in attitudes between gender, age, and education. A descriptive analysis was also conducted to explore other worrying scenarios. Results: It shows that (1) men are more tolerant of GD compared to women, and (2) participants aged between 18 and 30 years old possess the highest objection to GD. However, (3) no indication can attest to the relationship between educational level and perspective on GD. In addition, (4) the acceptance of gene testing in the three most common scenarios is ranked in descending order as follows: partner choice, insurance services, and recruitment. Moreover, (5) worrying scenarios relating to GD include: education, social occasions, medical services, fertility, shopping, and so on. Conclusions: Based on the results, suggestions proposed include developing a blacklist mechanism in the field of genetic data application and strengthening the security regulations for the commercial use of genetic data.

Lower-Limb Motor Assessment With Corticomuscular Coherence of Multiple Muscles During Ankle Dorsiflexion After Stroke.

Motor impairment after stroke is generally caused by damage to the neural networks that control movement. Corticomuscular coherence (CMC) is a valid method to analyze the functional connectivity of the corticospinal pathway between the cerebral cortex and muscles. However, current studies on CMC in stroke patients only focused on the upper limbs. The functional connectivity between the brain and lower limbs in stroke patients has not been well studied. Therefore, twelve stroke patients and fifteen healthy controls were recruited and their electroencephalogram (EEG) and electromyogram (EMG) of Tibialis Anterior (TA), Lateral Gastrocnemius (LG) and Medial Gastrocnemius (MG) during unilateral static ankle dorsiflexion were recorded. We found the mean beta and gamma CMC values of Cz electrode of stroke patients were significantly lower than those of healthy controls (p < 0.05). The brain topography showed significant coherence in the center of the cerebral cortex in healthy controls, while there was no significant coherence in stroke patients. For clinical assessment, there was a significant positive correlation between CMC and lower limb Fugl-Meyer Assessment (FMA) for Cz-TA in beta band (r = 0.6296, p = 0.0282), Cz-LG in beta band (r = 0.6816, p = 0.0147), and Cz-MG in gamma band (r = 0.6194, p = 0.0317). A multiple linear regression model was established between CMC and lower limb FMA ( R2 = 0.6600 , p = 0.0280). Therefore, CMC between the cerebral cortex and lower limb muscles may be used as a new rehabilitation assessment biomarker in stroke.

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.

Introduction: Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. Methods: The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. Results & discussion: CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.

Kazakh "free women" grit-Chinese Kazakh women's clothing image in the context of multicultural integration of silk road.

In recent years, Chinese clothing cultural heritage and knowledge genealogy along the Silk Road have become the research headline attracting public attention. In particular, Kazakh clothing in Northwestern China has become the focus of today's traditional national culture. Kazakh, located at the intersection of the Silk Road, has an important position. The traditional clothing made by various social factors reflects the style and identity integration throughout history in cultures along the Silk Road, taking women's clothing as an example. Kazakh women are good at crafts, which is reflected in their strong grit. They gradually changed their role and traditional values, which has guided their social role. At the same time, it also reflects the awakening of Kazakh women's feminist consciousness to a large extent, and complies with Confucianism, along with the mainstream value of "advanced gender culture" of the world's outstanding civilization achievements. This paper summarizes the form, color, and patterns of Kazakh women's clothing by analyzing the garment, headdress, and footwear in Xinjiang Uygur Autonomous Region Museum, Aksai Kazakh National Museum, and Capital Museum of China. Through the analysis, this paper further probes into the multicultural integration between Kazakh and the regions along the Silk Road and interprets the idea represented by the forms, colors, and patterns in the clothing to promote the inheritance and development of traditional and regional cultures together with ethnic features along the Silk Road.

A Comparative Assessment Study of Known Small-molecule GPVI Modulators.

The GPVI platelet receptor was recently validated as a safe antiplatelet target for the treatment of thrombosis using several peptidic modulators. In contrast, few weakly potent small-molecule GPVI antagonists have been reported. Those that have been published often lack evidence for target engagement, and their biological efficacy cannot be compared because of the natural donor variability associated with the assays implemented. Herein, we present the first side-by-side assessment of the reported GPVI small-molecule modulators. We have characterized their functional activities on platelet activation and aggregation using flow cytometry as well as light transmission and electrical impedance aggregometry. We also utilized microscale thermophoresis (MST) and saturation transfer difference (STD) NMR to validate GPVI binding and have used this along with molecular modeling to suggest potential binding interactions. We conclude that of the compounds examined, losartan and compound 5 are currently the most viable GPVI modulators.

Actualizing a High-Energy Bipolar-Stacked Solid-State Battery with Low-Cost Mechanically Robust Nylon Mesh-Reinforced Composite Polymer Electrolyte Membranes.

To meet the rapidly growing and diversified demand for energy storage, advanced rechargeable batteries with high-performance materials and efficient battery configuration are widely being exploited and developed. Bipolar-stacked electrode coupling with solid-state electrolytes enables achieving batteries with high output voltage, high energy density, and simple components. Here, a polymer electrolyte membrane is designed with polyethylene oxide containing bis(trifluoromethanesulfonyl)-imide as the electrolyte, succinonitrile as the plasticizer, and nylon mesh as a reinforcement for the bipolar-stacked battery. The as-prepared nylon mesh-reinforced polymer electrolyte membrane shows advantageous features, that is, excellent ionic conductivity (3.38 × 10-4 S cm-1) at room temperature, low interface impedance, and good tolerance against the expansion caused by the plating/stripping of the Li anode and the electrode upon cycling. When used as a polymer electrolyte membrane in the bipolar-stacked battery, the LiFePO4(LFP)-Li4Ti5O12(LTO) cell with three cells connected in series delivers a higher discharge voltage (5.4 V) and a volumetric energy density (0.328 mW h cm-3), nearly 3 times as much as that of the LFP-LTO battery. In addition, LiFePO4-Li pouch cells using the polymer electrolyte membrane can sustain the abuse tests including bending, cutting, and nail penetration well. These results pave a new avenue to develop high-performance polymer electrolyte membranes and allow for the design of high-voltage and volumetric energy density bipolar-stacked batteries.

Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis.

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

Emissions, measurement, and control of odor in livestock farms: A review.

Odor emissions from intensive livestock farms have attracted increased attention due to their adverse impacts on the environment and human health. Nevertheless, a systematic summary regarding the characteristics, sampling detection, and control technology for odor emissions from livestock farms is currently lacking. This paper compares the development of odor standards in different countries and summarizes the odor emission characteristics of livestock farms. Ammonia, the most common odor substance, can reach as high as 4100 ppm in the compost area. Sampling methods for point and area source odor emissions are introduced in this paper, and odor analysis methods are compared. Olfactometers, odorometers, and the triangle odor bag method are usually used to measure odor concentration. Odor control technologies are divided into three categories: physical (activated carbon adsorption, masking, and dilution diffusion), chemical (plant extract spraying, wet scrubbing, combustion, non-thermal plasma, and photocatalytic oxidation), and biological (biofiltration, biotrickling, and bioscrubbing). Each technology is elucidated, and the performance in the removal of different pollutants is summarized. The application scopes, costs, operational stability, and secondary pollution of the technologies are compared. The generation of secondary pollution and long-term operation stability are issues that should be considered in future technological development. Lastly, a case analysis for engineering application is conducted.

A risk factor-based predictive model for new-onset hypertension during pregnancy in Chinese Han women.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is one of the leading causes of maternal and neonatal mortality, increasing the long-term incidence of cardiovascular diseases. Preeclampsia and gestational hypertension are the major components of HDP. The aim of our study is to establish a prediction model for pregnant women with new-onset hypertension during pregnancy (increased blood pressure after gestational age > 20 weeks), thus to guide the clinical prediction and treatment of de novo hypertension. METHODS: A total of 117 pregnant women with de novo hypertension who were admitted to our hospital's obstetrics department were selected as the case group and 199 healthy pregnant women were selected as the control group from January 2017 to June 2018. Maternal clinical parameters such as age, family history and the biomarkers such as homocysteine, cystatin C, uric acid, total bile acid and glomerular filtration rate were collected at a mean gestational age in 16 to 20 weeks. The prediction model was established by logistic regression. RESULTS: Eleven indicators have statistically significant difference between two groups (P < 0.05). These 11 factors were substituted into the logistic regression equation and 7 independent predictors were obtained. The equation expressed including 7 factors. The calculated area under the curve was 0.884(95% confidence interval: 0.848-0.921), the sensitivity and specificity were 88.0 and 75.0%. A scoring system was established to classify pregnant women with scores ≤15.5 as low-risk pregnancy group and those with scores > 15.5 as high-risk pregnancy group. CONCLUSIONS: Our regression equation provides a feasible and reliable means of predicting de novo hypertension after pregnancy. Risk stratification of new-onset hypertension was performed to early treatment interventions in high-risk populations.

Assessment of two different HER2 scoring systems and clinical relevance for colorectal cancer.

Although the positivity of human epidermal growth factor receptor 2 (HER2) is low in colorectal cancer (CRC), anti-HER2 is becoming a new target therapy in metastatic colorectal cancer (mCRC). However, assessment of the HER2 scoring system was still not established in CRC. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma (GEA criteria) and the HERACLES diagnostic criteria (HERACLES criteria) in a large cohort of Chinese CRC patients. The HER2 positivity was 2.9% (43/1490) and 2.6% (39/1490) in CRCs based on the GEA criteria and the HERACLES criteria, and 3.7% (9/243) in mCRC according to both criteria. HER2 status was associated with primary tumor location (P = 0.037), regional lymph node metastasis (P = 0.035), and TNM stage (P = 0.022) in CRCs based on the HERACLES criteria. No such association was found based on the GEA criteria. Furthermore, HER2 positive only presented in patients with RAS gene wild type (P = 0.001). Significant difference was only observed between the HER2-positive and HER2-negative groups in terms of disease-free survival for stage II-III CRCs (P = 0.048) according to the HERACLES criteria, but not based on the GEA criteria. Our findings suggest that the frequency of HER2 overexpression or amplification was low in Chinese CRC patients, and provide a rationale for further evaluation of HER2 in CRC based on the HERACLES criteria and the HER2 diagnostic criteria for gastroesophageal adenocarcinoma.

First genetic assessment of brackish water polychaete Tylorrhynchus heterochaetus: mitochondrial COI sequences reveal strong genetic differentiation and population expansion in samples collected from southeast China and north Vietnam.

Tylorrhynchus heterochaetus is a widespread benthic polychaete worm found in coastal brackish waters of the west Pacific. It has high ecological and economic value as a biomarker of water quality and as a high-quality feed in aquaculture and fisheries and is considered a delicacy in some areas of Asia. However, it has experienced a marked reduction in recent years due to overexploitation as well as changes in the environment and climate. Here, to comprehensively understand its genetic background and thus provide insights for better conservation and utilization of this species, we assessed the genetic variability and demographic history of T. heterochaetus individuals sampled from eight locations along the coasts of southeast China and north Vietnam based on mitochondrial cytochrome c oxidase I ( COI) sequences. We observed high haplotype diversity ( Hd), with an average of 0.926, but relatively low nucleotide diversity ( π), with a mean of 0.032 across all samples. A total of 94 polymorphic sites and 85 haplotypes were identified among 320 individuals. The pairwise genetic distances among haplotypes ranged from 0.001 to 0.067, with the high intraspecific divergence possibly reflecting geographic isolation and gene pool fragmentation. Significant genetic structures were revealed among the studied locations; specifically, the eight locations could be treated as six genetically different populations based on pairwise Φ ST results (0.026-0.951, P<0.01). A significant pattern of isolation-by-distance was detected between the genetic and geographic distances ( r=0.873, P=0.001). Three geographic lineages were defined based on phylogenetic tree and network analyses of COI haplotypes. AMOVA results indicated that genetic variations mainly occurred among the three lineages (89.96%). Tests of neutrality and mismatch distribution suggested that T. heterochaetus underwent recent population expansion. These results provide the first report on the genetic status of T. heterochaetus and will be valuable for the management of genetic resources and better understanding of the ecology and evolution in this species.