A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research. In this study, a Bactrian camel was immunized with capsid proteins from different genotypes (1, 3, 4, and avian) of HEV. Then, a phage library (6.3 × 108 individual clones) was constructed using peripheral blood lymphocytes from the immunized camel, and 12 nanobodies against the truncated capsid protein of genotype 3 HEV (g3-p239) were screened. g3-p239-Nb55 can cross-react with different genotypes of HEV and block Kernow-C1/P6 HEV from infecting HepG2/C3A cells. To our knowledge, the epitope recognized by g3-p239-Nb55 was determined to be a novel conformational epitope located on the surface of viral particles and highly conserved among different mammalian HEV isolates. Next, to increase the affinity and half-life of the nanobody, it was displayed on the surface of ferritin, which can self-assemble into a 24-subunit nanocage, namely, fenobody-55. The affinities of fenobody-55 to g3-p239 were ∼20 times greater than those of g3-p239-Nb55. In addition, the half-life of fenobody-55 was nine times greater than that of g3-p239-Nb55. G3-p239-Nb55 and fenobody-55 can block p239 attachment and Kernow-C1/P6 infection of HepG2/C3A cells. Fenobody-55 can completely neutralize HEV infection in rabbits when it is preincubated with nonenveloped HEV particles. Our study reported a case in which a nanobody neutralized HEV infection by preincubation, identified a (to our knowledge) novel and conserved conformational epitope of HEV, and provided new material for researching HEV biology.

A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2.

Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.

Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The 17FCL19 mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1-88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release. IMPORTANCE: Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.

Macro-analysis of climatic factors for COVID-19 pandemic based on Köppen-Geiger climate classification.

This study integrated dynamic models and statistical methods to design a novel macroanalysis approach to judge the climate impacts. First, the incidence difference across Köppen-Geiger climate regions was used to determine the four risk areas. Then, the effective influence of climate factors was proved according to the non-climate factors' non-difference among the risk areas, multi-source non-major component data assisting the proof. It is found that cold steppe arid climates and wet temperate climates are more likely to transmit SARS-CoV-2 among human beings. Although the results verified that the global optimum temperature was around 10 °C, and the average humidity was 71%, there was evident heterogeneity among different climate risk areas. The first-grade and fourth-grade risk regions in the Northern Hemisphere and fourth-grade risk regions in the Southern Hemisphere are more sensitive to temperature. However, the third-grade risk region in the Southern Hemisphere is more sensitive to relative humidity. The Southern Hemisphere's third-grade and fourth-grade risk regions are more sensitive to precipitation.

Microecological health assessment of water environment and sediment based on metagenomics: a case study of Guixi River in Chongqing, China.

River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health.

ARHGAP17 enhances 5-Fluorouracil-induced apoptosis in colon cancer cells by suppressing Rac1.

Colon cancer is a common cause of death in the world, and its main cause of therapy failure is chemoresistance. Apoptosis is de-regulated in colon cancer and is one key mechanism of cancer treatment. We recently reported that reduced expression of ARHGAP17, a Rho GTPase activating protein, correlated with a poor prognosis of colon cancer patients. Here we investigated the role of ARHGAP17 in apoptosis induced by 5-fluorouracil (5-FU) in human colon cancer cells and in mouse xenograft tumor model. We observed a decreased protein level of ARHGAP17 in 5-FU resistant colon cancer cells (HCT116/5-FU and HCT8/5-FU). While ARHGAP17 knockdown attenuated apoptosis upon 5-FU treatment in HCT116 and HCT8, and ARHGAP17 overexpression in HCT116/5-FU and HCT8/5-FU cells increased apoptosis induced by 5-FU. We also found that ARHGAP17 knockdown led to a high level of active Rac1 in HCT116 and HCT8, but ARHGAP17 overexpression reduced active Rac1 in HCT116/5-FU and HCT8/5-FU cells. However, Rac1 inhibitor abolished the effect of ARHGAP17 knockdown, and Rac1 overexpression diminished the effect of ARHGAP17 overexpression on apoptosis induced by 5-FU. Apoptosis was also confirmed by cleaved Caspase-3 and cleaved PARP. Further, we observed that overexpression of ARHGAP17 promoted 5-FU-induced apoptosis and attenuated tumor growth in vivo. Collectively, our data indicate that ARHGAP17 sensitizes chemotherapy-resistant colon cancer cells to apoptosis induced by 5-FU, which is in part through suppressing Rac1.

Preliminary results of low-dose computed tomography screening for lung cancer in asymptomatic participants. / 低剂量CTç­›æŸ¥æ— ç—‡çŠ¶ä½“æ£€è€ è‚ºç™Œçš„åˆæ­¥åˆ†æž.

OBJECTIVES: Low dose computed tomography (LDCT) is the best method for early diagnosis of lung cancer. Even though it has been widely used in clinic, the selection of screening objects and the management scheme of pulmonary nodules are still not unified among research institutions. This study aims to evaluate the effect of LDCT in detection effect and follow-up process for pulmonary nodules in asymptomatic participants. METHODS: A total of 1 600 asymptomatic participants (37 to 82 years old), who came from Yantian District People's Hospital, Southern University of Science and Technology, received LDCT. The lung nodules were categorized into positive nodules and semi-positive nodules, and according to the density of positive nodules they were categorized into 4 types: solid nodules (SN), partial solid nodules (pSN), pure ground glass nodules (pGGN), and pleural nodules (PN). The number, detection rate, imaging findings, follow-up change of lung nodules, and the postoperative pathological results of positive nodules were recorded and analyzed. RESULTS: Lung nodules were found in 221 cases by LDCT. The total detection rate of lung nodule was 13.8% (221/1 600), and the detection rate in positive nodules was 4.9% (79/1 600). The detected nodules were mainly single (173 cases), solid (133 cases) and semi-positive nodules (142 cases). Most of nodules (177 cases) had no change in the follow-up process. The enlargement and/or increased density of nodules (5 cases) were lung cancer. Pathological results were obtained in 10 cases, 8 cases were malignant (1 small cell lung cancer and 7 adenocarcinomas), 2 cases were benign (cryptococcal infection and alveolar epithelial dysplasia). The detection rate of lung cancer was 0.5% (8/1 600), and the proportion of early lung cancer was 75% (6/8). CONCLUSIONS: LDCT screening can identify and increase the detection rate in the early lung cancer, which is an effective screening method. It is safe and feasible to take regular follow-up and re-examination for nodules with diameter less than 5 mm. When the size and or density of nodule increases, it indicates the malignant prognosis of the nodule and timely clinical intervention is needed.

Development and Clinical Evaluation of a CRISPR-Based Diagnostic for Rapid Group B Streptococcus Screening.

Vertical transmission of group B Streptococcus (GBS) is among the leading causes of neonatal illness and death. Colonization with GBS usually is screened weeks before delivery during pregnancy, on the basis of which preventive measures, such as antibiotic prophylaxis, were taken. However, the accuracy of such an antenatal screening strategy has been questionable because of the intermittent nature of GBS carriage. We developed a simple-to-use, rapid, CRISPR-based assay for GBS detection. We conducted studies in a prospective cohort of 412 pregnant women and a retrospective validation cohort to evaluate its diagnostic performance. We demonstrated that CRISPR-GBS is highly sensitive and offered shorter turnaround times and lower instrument demands than PCR-based assays. This novel GBS test exhibited an overall improved diagnostic performance over culture and PCR-based assays and represents a novel diagnostic for potential rapid, point-of-care GBS screening.

Modified Judet's quadricepsplasty plus patellar traction for knee stiffness after femoral fracture surgery.

BACKGROUND: To investigate the clinical effect of modified Judet quadricepsplasty (MJ) combined with patella traction designed by ourselves in the treatment of knee joint rigidity after a femoral fracture. METHODS: We retrospectively reviewed the clinical data of 21 patients with stiff knee joint after a femoral fracture treated by modified Judet quadricepsplasty combined with patella traction designed by the author from May 2014 to January 2017. The age at revision surgery was 20-57 (36 ± 12) years. The time between fracture fixation to quadricepsplasty was five to 23 (15 ± 5) months, and the follow-up was 11-32 (18 ± 6) months. Pre-operative, intra-operative, post-operative and final follow-up range of motion (ROM), the total traction time, and complications were assessed. The knee joint function was evaluated according to Judet's classification scheme. RESULTS: Knee ROM was 5-60 (36 ± 13) ° pre-operatively, and 30-80 (53 ± 13) ° after MJ (an increase of 0-30 (17 ± 10)) (p < 0.05). The duration of patellar traction was ten to 14 (11 ± 2) days. Knee ROM after traction device removal was 90-100 (92 ± 3) °, an increase of 10-65 (39-14) ° compared with the ROM after arthrolysis (p < 0.05). The follow-up duration was 11-32 (18 ± 6) months. Knee ROM at final follow-up was 80-130 (104 ± 12) °, an increase of 40-100 (68 ± 16) 8° compared with pre-operatively (p < 0.05), and of - 10-40 (12 ± 13) ° compared with the ROM after traction removal (p < 0.05). Knee function was excellent in 14 cases (67%), good in 6 (28%), and fair in one (5%). CONCLUSIONS: The MJ plus patellar traction lengthens the contracted quadriceps femoris, thus restoring knee function within a short period of time.

TRIM52 promotes colorectal cancer cell proliferation through the STAT3 signaling.

BACKGROUND: The tripartite motif (TRIM) family proteins are implicated in the pathogenesis of various human malignancies. The up-regulation and oncogenic roles of TRIM52 have been reported in hepatocellular carcinoma. In the current study, we aimed to examine its expression and possible function in colorectal cancer (CRC). METHOD: Immunohistochemical staining or immunoblotting analysis was carried out to detect protein expression. Cell proliferation and apoptosis was evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry assay, respectively. RESULTS: TRIM52 expression was increased in 67.5% of CRC tissues (54/80) compared to matched normal colonic mucosa. TRIM52 expression was closely related with tumor size (p = 0.0376), tumor stage (p = 0.0227) and overall survival (p = 0.0177). Short hairpin RNAs (shRNAs) targeting TRIM52 had the potential anti-proliferative effects on CRC cell lines, SW480 and LoVo, by inducing cell apoptosis. In addition, an in vivo xenograft experiment confirmed the in vitro results. In addition, TRIM52 shRNAs decreased the phosphorylation of STAT3, but increased the protein expression of SHP2, a negative regulator of STAT3 phosphorylation. TRIM52 formed a complex with SHP2 and promoted the ubiquitination of SHP2. Furthermore, inhibition of the STAT3 signaling by AG490 in RKO cells significantly abolished the effects of TRIM52 overexpression on cell proliferation, apoptosis and STAT3 activation. CONCLUSIONS: TRIM52 might exert oncogenic role in CRC via regulating the STAT3 signaling pathway.

Nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents.

A new nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents was developed, which afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalen-1-ols and 1,2-alkyl amide derivatives in moderate to excellent yields (up to 99% yield) under mild conditions. In this work, we successfully avoided obtaining hydride addition byproducts arising from ß-hydride elimination on an ethyl nickel species. Furthermore, a plausible mechanism for the ring-opening reaction was also proposed.

The Stroke Stigma Scale: a reliable and valid stigma measure in patients with stroke.

OBJECTIVE: The objective of the study is to analyse the psychometric properties of the Stroke Stigma Scale, a novel scale to assess perceived stigma of patients with stroke. DESIGN: This is a psychometric study. SETTING: Neurology or rehabilitation units in three hospitals in China. SUBJECTS: A total of 288 patients with stroke. INTERVENTIONS: None. MEASURES: The content validity of the Stroke Stigma Scale was assessed through expert consultation. Criterion validity was evaluated based on the scale's relationships with the Stigma Scale for Chronic Illness and the Self-rating Depression Scale. Construct validity was assessed using exploratory factor analysis, and internal consistency was tested with Cronbach's α. RESULTS: The final version Stroke Stigma Scale consists of 16 items. It showed strong positive correlations with both the Stigma Scale for Chronic Illness (ρ = 0.89, P < 0.001) and the Self-rating Depression Scale (ρ = 0.82, P < 0.001). The exploratory factor analysis revealed four components of the Stroke Stigma Scale: internalized stigma, physical impairment, discrimination experience, and social isolation, which were strongly associated with our perceived stroke stigma model. Cronbach's α for the total scale was 0.92, and that of each subscale was 0.77-0.86. The test-retest reliability with intra-class correlation coefficients of the total scale was 0.92 (P < 0.001), and intra-class correlation coefficients of each subscale were 0.74-0.89 (P < 0.001). CONCLUSIONS: The Stroke Stigma Scale is a reliable and valid measure of perceived stigma in patients with stroke, which may be useful in stigma prevention and stroke rehabilitation.

Tumor Suppressive Role of ARHGAP17 in Colon Cancer Through Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: A few Rho GTPase activating proteins (RhoGAPs) have been identified as tumor suppressors in a variety of human cancers. ARHGAP17, a member of RhoGAPs, has been reported to be involved in the maintenance of tight junction and epithelial barrier. The present study aimed to explore its expression in colon cancer and the possible function in colonic carcinogenesis. METHODS: The mRNA and protein expression was assessed by realtime PCR and immunoblotting, respectively. Cell Counting Kit-8 (CCK-8) and Transwell assays were performed to evaluate cell proliferation and invasion, respectively. RESULTS: We found that ARHGAP17 expression was obviously lower in colon cancer specimens than in normal colonic mucosa. ARHGAP17 expression was associated with tumor stage, size and differentiation. In vitro analysis demonstrated that ARHGAP17 overexpression inhibited cell growth and invasion of HCT-8 and HCT-116 cells. In addition, an in vivo experimental metastasis model showed that ARHGAP17 overexpression restricted cancer metastasis to the lung. Mechanically, we found that Wnt signaling contributed to the functions of ARHGAP17 in colon cancer cells. Gene set enrichment analysis (GSEA) in The Cancer Genome Atlas dataset showed that the Wnt signaling pathway was negatively associated with ARHGAP17 expression. The mRNA expression of ß-catenin (an important signaling transducer of canonical Wnt signaling) gene (CTNNB1) was negatively correlated with ARHGAP17 expression. Immunoblot analysis of downstream effectors of ß-catenin (c-Myc/p27 and MMP7) in ARHGAP17 overexpressing colon cancer cells and metastatic tumors within the lung also validated the GSEA result. ARHGAP17 overexpression increased the phosphorylation of glycogen synthetase kinase 3ß, and decreased ß-catenin nuclear localization and transcriptional activity. Furthermore, inhibition of Wnt signaling by Wnt Inhibitor Factor-1 (WIF-1) in HIEC cells with ARHGAP17 knockdown significantly attenuated the promotion effects of ARHGAP17 knockdown on cell proliferation, invasion and the activation of ß-catenin. CONCLUSION: these results suggest that ARHGAP17 might serve as a tumor suppressor in colon cancer progression and metastasis through Wnt/ß-catenin signaling pathway.

Water-Promoted Ir-Catalyzed Ring-Opening of Oxa(aza)benzonorbornadienes with Fluoroalkylamines.

A highly effective water-promoted iridium-catalyzed ring-opening reaction of oxa(aza)benzonorbornadienes with fluoroalkylamines was developed for the synthesis of fluorinated trans-1,2-amino alcohol or diamine derivatives. Tetrabutylammonium iodide (TBAI) was necessary as an additive for excellent yields in the presence of [Ir(COD)Cl]2 catalyst. Fluorinated trans-1,2-amino alcohol or diamine derivatives could be obtained in good to excellent yields (up to 98%) under mild conditions within a shorter period. Another interesting finding was that the addition of water could greatly enhance the ring-opening reaction. In addition, a plausible mechanism for the ring-opening reaction was proposed.

FSHR and LHR Expression and Signaling as Well as Maturation and Apoptosis of Cumulus-Oocyte Complexes Following Treatment with FSH Receptor Binding Inhibitor in Sheep.

BACKGROUND/AIMS: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI) influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM) and apoptosis of cumulus-oocyte complexes (COCs) of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. METHODS: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL) and FSH (10IU/mL). The harvested COCs were observed under an inverted microscope and maturation rates of COCs were determined. Real time RT-PCR and Western blotting were utilized to detect mRNA and protein levels of FSHR and LHR. The concentrations of FSH, LH and caspase-3 were determined using especial ELISA kits for sheep, respectively. RESULTS: Maturation rates of COCs decreased gradually as FRBI concentrations increased from 0 to 40µg/mL, reaching a bottom value of 23.76% of the FRBI-4 group. The maximal apoptosis rate was detected in the FRBI-4 group. IP3 contents of FRBI-3 and FRBI-4 groups were reduced as compared to control group (CG) and FSH groups (P<0.05). Levels of FSHR protein of FRBI-3 and FRBI-4 groups as well as LHR protein of FRBI-4 group were significantly less than that of CG and FSH group. FSH contents of four FRBI treatment groups were gradually decreased along with the supplementation doses of FRBI. Caspase-3 contents of FRBI groups were reduced with a maximum reduction of the FRBI-2 group. CONCLUSION: Our results revealed supplement of FRBI into IVM media could dose-dependently decrease the maturation rate and increase apoptosis rate of sheep COCs. A lower dose of FRBI treatment slightly promoted IP3 production, but a higher dose of FRBI reduced IP3 production. FRBI suppressed the mRNA and protein expression levels of FSHR and LHR in sheep COCs. Our study will help to therapy effectively ovarian diseases, improve ovarian and follicular functions, and further to promote fertility of humans and animals.

Validation of the Chinese version of the FOUR score in the assessment of neurosurgical patients with different level of consciousness.

BACKGROUND: The Glasgow Coma Scale (GCS) is currently the most widely used scoring system for comatose patients. A decade ago, the Full Outline of Unresponsiveness (FOUR) score was devised to better capture four functional aspects of consciousness (eye, motor responses, brainstem reflexes, and respiration). This study aimed to validate the Chinese version of the FOUR score in patients with different levels of consciousness. METHODS: The study had two phases: (1) translation of the FOUR score, and (2) assessment of its reliability and validity. The Chinese version of the FOUR score was developed according to a standardized protocol. One hundred-twenty consecutive patients with acute brain damage, admitted to Nanfang Hospital (Southern Medical University, Guangdong, China) from November 2014 to February 2015, were enrolled. The inter-rater agreement for the FOUR score and GCS was evaluated using intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were established to determine the scales' abilities to predict outcome. RESULTS: The rater agreement was excellent both for FOUR (ICC = 0.970; p < 0.001) and GCS (ICC = 0.958; p < 0.001). The FOUR score yielded an excellent test-retest reliability (ICC = 0.930; p < 0.001). Spearman's correlation coefficients between GCS and the FOUR score were high: r = 0.932, first rating; r = 0.887, second rating (all p < 0.001). Areas under the curve (AUC) for mortality were 0.834 (95 % CI, 0.740-0.928) and 0.815 (95 % CI, 0.723-0.908) for the FOUR score and GCS, respectively. CONCLUSIONS: The Chinese version of the FOUR score is a reliable scale for evaluating the level of consciousness in patients with acute brain injury.

Interaction of body mass index and hemoglobin concentration on blood pressure among pregnant women in Guangxi, China.

BACKGROUND: Body mass index (BMI) and hemoglobin (Hb) are positively associated with hypertensive disorders among pregnant women. The aim of this study was to estimate a potential interaction between high BMI and high Hb concentrations on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in pregnancy. METHODS: We recruited 4497 single-birth women aged 18-43 years who received routine antenatal care at three hospitals of Guigang, Guangxi, China, from December 2007 to January 2011. Of 4497 participants, 3472 women were in the first trimester, with following up, 2986 women and 2261 women were left in the second and third trimester, respectively. Clinical data were derived from medical records of each woman. We used multivariable linear regression, by trimesters of pregnancy, to evaluate the associations of high BMI and high Hb concentrations with SBP and DBP according to cross-sectional design. RESULTS: In multivariable analyses, BMI was positively associated with SBP throughout all trimesters, but the corresponding association for Hb concentrations only in the first trimester, whereas both BMI and Hb concentrations were positively associated with DBP in the first and third trimesters. After full adjustment for confounding, the average differences in SBP and DBP comparing women with high BMI and high Hb to those with non-high BMI and non-high Hb were 2.9 mmHg (95% CI: 0.8 to 5.0 mmHg) and 3.9 mmHg (95% CI: 1.5 to 6.3 mmHg) in the first trimester, 2.6 mmHg (95% CI: 0.4 to 4.8 mmHg) and 1.5 mmHg (95% CI: -1.3 to 4.3 mmHg) in the second trimester, and 4.8 mmHg (95% CI: 2.3 to 7.4 mmHg) and 5.7 mmHg (95% CI: 3.2 to 8.3 mmHg) in the third trimester, respectively. With respect to the interaction, significant combined effects between high BMI and high Hb were confirmed on SBP (P = 0.02) and DBP (P = 0.004) in the third trimester, and the amount of interaction on SBP and DBP were 2.0 mmHg (95% CI: 0.1 to 3.9 mmHg) and 2.3 mmHg (95% CI: 0.4 to 4.3 mmHg), respectively. CONCLUSION: Our findings suggest that high BMI and high Hb concentrations may have a synergistic effect on blood pressure in late stage of pregnancy.

Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation.

BACKGROUND: Non-Hodgkin's lymphoma incidence rates vary between European and Asian populations. The reasons remain unclear. This two-sample two-step Mendelian randomisation (MR) study aimed to investigate the causal relationship between anthropometric indicators (AIs) and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and the possible mediating role of basal metabolic rate (BMR) in Europe. METHODS: We used the following AIs as exposures: body mass index (BMI), whole-body fat mass (WBFM), whole-body fat-free mass (WBFFM), waist circumference(WC), hip circumference(HC), standing height (SH), and weight(Wt). DLBCL and FL represented the outcomes, and BMR was a mediator. A two-sample MR analysis was performed to examine the association between AIs and DLBCL and FL onset. We performed reverse-MR analysis to determine whether DLBCL and FL interfered with the AIs. A two-step MR analysis was performed to determine whether BMR mediated the causality. FINDINGS: WBFFM and SH had causal relationships with FL. A causal association between AIs and DLBCL was not observed. Reverse-MR analysis indicated the causal relationships were not bidirectional. Two-step MR suggested BMR may mediate the causal effect of WBFFM and SH on FL. CONCLUSIONS: We observed a causal relationship between WBFFM and SH and the onset of FL in Europeans, Which may explain the high incidence of follicular lymphoma in Europeans.

[Changes and influence factors of soil matrix infiltration in Chinese fir plantations with different stand ages in northern Guangxi]. / æ¡‚åŒ—åœ°åŒºä¸åŒæž—é¾„æ‰æœ¨äººå·¥æž—åœŸå£¤åŸºè´¨å ¥æ¸—å˜åŒ–åŠå½±å“å› ç´ .

Soil matrix infiltration is an important pathway for plantations to obtain water, which affects ecological benefits and water conservation function of plantations. The changes of soil matrix infiltration and its influencing factors in different growth stages of Chinese fir plantations remain unclear. We measured soil matrix infiltration process using a tension infiltrometer in Chinese fir plantations (5, 8, 11, and 15 years old) of Beijiang River Forest Farm in Rongshui, Guangxi, and analyzed soil basic physicochemical properties to identify the dominant factors influencing soil matrix infiltration. The results showed that initial infiltration rate, stable infiltration rate, and cumulative infiltration increased with stand ages. The ranges of different stand ages were 141-180 mm·h-1, 109-150 mm·h-1, and 188-251 mm, respectively. The initial infiltration rate, stable infiltration rate, and cumulative infiltration were significantly positively correlated with soil capillary porosity, soil organic matter, soil water stable macroaggregate, sand content, and clay content, while negatively correlated with soil bulk density and silt content. Early thinning had a positive effect on soil matrix infiltration, but thinning measures after 11 years did not enhance soil matrix infiltration further. Philip model was optimal for describing soil matrix infiltration process in this region. In conclusion, soil matrix infiltration capacity of Chinese fir plantations gradually increased from young to middle-aged stands, but matrix infiltration capacity tended to stabilize after 11 years old. Silt content and water stable macroaggregate were the dominant factors influencing matrix infiltration.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.