Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

[Constructing an early-warning model for mortality risk in heat stroke patients based on Fisher discriminant analysis].

Objective: To establish an early warning model to assess the mortality risk of patients with heat stroke disease. Methods: The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model. Results: The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%. Conclusion: The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

The impact of acute-phase reaction on mortality and re-fracture after zoledronic acid in hospitalized elderly osteoporotic fracture patients.

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.

[The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in dialysis patients].

Objective: To investigate the consistency of skeletal muscle mass by CT at 1st lumbar vertebrae (L1) and 3rd lumbar vertebrae (L3) levels and the correlation of skeletal muscle density (SMD) at L1 level with prognosis in dialysis patients. Methods: A total of 1 020 patients who underwent initial dialysis and had CT examination data in four centers (Zhongda Hospital Affiliated to Southeast University, the Third Affiliated Hospital of Soochow University, Taizhou People's Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Yangzhou University) from January 2014 to December 2019 were retrospectively collected. The skeletal muscle index (SMI) and SMD at L1 and L3 CT images were measured and calculated in patients with both L1 and L3 level CT images. The consistency of SMI and SMD at L1 and L3 levels was analyzed, and the cut-off value of SMI and SMD at L1 level for predicting all-cause mortality and their correlation with the prognosis of dialysis patients were studied. Cox regression model was used to analyze the risk factors for all-cause death and cardiac death. Results: A total of 383 patients had both L1 and L3 level images, including 233 males and 150 females. The average SMD value of 16 samples (4.2%) exceeded the 95% consistency limit range (-8.71 to 7.75 HU), and the average SMI value of 15 samples (3.9%) exceeded the 95% consistency limit range (-20.45 to 9.53 HU). The optimal cut-off value of SMD at L1 level for predicting all-cause mortality was 36.46 HU and the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.658 (95%CI: 0.596-0.721, P<0.001), with the sensitivity and specificity of 83.8% and 57.5%, respectively. SMI at L1 level was not significantly associated with all-cause mortality (P=0.299). Multivariate Cox regression analysis showed that low SMD at L1 level was associated with all-cause mortality (HR=2.861, 95%CI: 1.576-5.193, P=0.001) and cardiac death (HR=3.771, 95%CI:1.462-9.724, P=0.006). Conclusions: SMD at L1 levelis consistent with SMD at L3 level and can be used to evaluate muscle mass. Low SMD is a risk factor for mortality in dialysis patients.

[Early results of modified Bikini approach periacetabular osteotomy for the treatment of developmental hip dysplasia under 50 years of age].

Objective: To investigate the efficacy and safety of modified Bikini approach periacetabular osteotomy in the treatment of developmental hip dysplasia under 50 years of age. Methods: The clinical data of 39 patients with developmental hip dysplasia who underwent periacetabular osteotomy in the Department of Orthopedics, Guizhou Provincial People's Hospital from June 2016 to June 2021 were retrospectively analyzed.Among them, 20 patients (21 hips) underwent the improved Bikini approach (study group) and 19 patients (20 hips) underwent the improved Smith-Petersen approach (control group).In the study group, there were 3 males and 17 females, aged(M(IQR))27.5 (14.3) years (range:11 to 44 years).In the control group, there were 2 males and 17 females, aged 27.5 (19.3) years (range:17 to 47 years).Both groups were sutured in the same manner by the same physician.Incision length, operation time, intraoperative blood loss and complications were recorded.X-ray images, anterior central marginal angle (ACE), lateral central marginal Angle (LCE) and acetabulum tilt angle (Tonnis AI) were measured before and after the operation.The coverage rate of acetabulum to femoral head (AHI) was measured and calculated, and the healing time was observed.Harris Hip score, International Hip score (IHOT)-12 and visual analogue scale (VAS) were recorded before and after surgery.Vancouver Scar Scale (VSS) score and patient and observer scar assessment scale (POSAS) score were recorded 12 months after surgery.The independent sample t test,Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All patients successfully completed the operation.There was no significant difference in operation time and intraoperative blood loss between the two groups (all P>0.05).The incision length of the study group was smaller than that of the control group, and the difference was statistically significant (10.5(5.0)cm vs.15.0(3.0),W=309.000,P=0.007).Patients were followed up for (19.1±11.1) months (range:12 to 60 months).Femoral nerve stretching injury occurred in 2 cases and sciatic branch fracture occurred in 1 case in the study group, all of which recovered to normal at 3 months follow-up, while no corresponding injury occurred in the control group.Lateral femoral cutaneous nerve injury occurred in 3 cases in the study group and 2 cases in the control group.Delayed wound healing occurred in 1 case in each of the two groups, and both healed after re-operation debridement and suture.Pubic branch nonunion occurred in 4 patients in the study group and 5 patients in the control group.There were no serious complications such as sciatic nerve and femoral blood vessel injury between the 2 groups, and there was no statistical significance in the incidence of complications between the 2 groups (52.4%(11/21)vs.40.0%(8/20),χ2=0.631,P=0.427).The clinical healing time of the patient was (4.5±1.3) months after surgery (range:3.0 to 8.0 months).There were no significant differences in ACE, LCE, Tonnis AI and AHI between the 2 groups (all P>0.05).At the last follow-up, there were no significant differences in VAS,Harris hip score and IHOT-12 score between the two groups (all P>0.05).The incision scars in the study group were smaller than those in the control group, and the differences in VSS and POSAS were statistically significant (all P<0.05). Conclusion: Compared with the improved Smith-Petersen approach, the improved Bikini approach has the same early clinical efficacy in the treatment of patients with developmental hip dysplasia under the age of 50, and has the advantages of smaller postoperative incision scars, more hidden and beautiful incision, and no serious complications, which is worthy of further study and promotion.

[Occupational exposure level and requirements for radiation protection of nuclear medical staff].

With the rapid development of nuclear medicine, the number of nuclear medical staff has increased a lot in the past few years in China. Close-range operations, such as preparation and injections of radiopharmaceuticals, are usually carried out in nuclear medicine department. And the use of unsealed radionuclides may also create internal exposure risk. So, occupational exposure of nuclear medical staff is a main issue of occupational health management in China. In this paper, the occupational exposure level and requirements for radiation protection of nuclear medical staff are introduced to provide references for the related work that radiological health technical institutions carry out.

Experimental Evidence of Intrinsic Current Generation by Turbulence in Stationary Tokamak Plasmas.

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

[Association analysis between genetic variants of matrix metalloproteinase enzyme 2 gene and the blood pressure of children and adolescents].

Objective: To explore the association between genetic variants of matrix metalloproteinase enzyme 2 (MMP2) gene and the blood pressure of children and adolescents. Methods: This cross-sectional study was performed in 2016 and included 4 155 children and adolescents in the urban area of Guangzhou. Physical examinations (including body height, weight, and blood pressure), questionnaires (including general characteristics, physical exercise, parental educational level, household income, etc.), and blood sampling were performed. Multivariable linear regression models were used to investigate the associations of MMP2 genetic variations (rs243865, rs7201) and the genetic risk score (GRS) level with standardized blood pressure. Mediating effect of standardized body mass index (BMI) was further assessed by process analysis in the association between GRS level and blood pressure, and potential additive interaction between physical activity and GRS level was analyzed using the product term in the regression model. Results: A total of 4 155 primary and secondary schoolchildren were finally included in the analysis, consisting of 1 401 (33.7%) second grade pupils of primary school, 1 422 (34.2%) first grade pupils of middle school, and 1 332 (32.1%) first-grade students of senior high school. After adjusting for age, sex, parental educational level, and family income, as compared to the rs243865 TT genotype, the CC/CT genotype increased diastolic blood pressure (DBP) by 0.461 standard deviations (SD) (ß for dominant model=0.461, 95%CI 0.199-0.723). When compared to the rs7201 CC genotype, the AA/AC genotype showed 0.147 SD higher systolic blood pressure (SBP) (ß for recessive model=0.147, 95%CI 0.014-0.279) and 0.171 SD increased DBP (ß for recessive model=0.171, 95%CI 0.039-0.304). For each increment of GRS level, SBP and DBP increased by 0.151 SD (ß for dominant model=0.151, 95%CI 0.029-0.272) and 0.242 SD (ß=0.242, 95%CI 0.120-0.363), respectively. The mediating effect of BMI accounted for 28.3% and 12.6% of the total effect of GRS on SBP and DBP, respectively. After controlling BMI, the direct effect of GRS on DBP remained statistically significant (P<0.001). The insufficient moderate-to-vigorous physical activity (<0.5 h/d) showed a significant interaction with GRS on SBP under additive scale (ß for interaction=0.518, 95%CI 0.088-0.949, P=0.018). Conclusions: rs243865 and rs7201 variants in MMP2 gene are associated with the elevated blood pressure of children and adolescents. Obesity may yield a mediation role in the associations, while insufficient physical activity may have a positively additive interaction with MMP2 genetic variants.

Efficacy of annual zoledronic acid in initial percutaneous kyphoplasty patients with osteoporotic vertebral compression fractures: a 3-year follow-up study.

This study investigated the efficacy of annual zoledronic acid (ZOL) administration against previously treated recompression vertebral fractures (RVF) and new vertebral fractures (NVF) in initial percutaneous kyphoplasty (PKP) patients with osteoporotic vertebral compression fractures (OVCF) over a 3-year follow-up period. INTRODUCTION: Although PKP achieves a satisfactory outcome, previously treated RVF and NVF can limit its effectiveness. The annual infusion of ZOL over 3 years can improve fracture protection, particularly in the vertebrae. We hypothesized that ZOL can reduce the incidence of RVFs and/or NVFs, and improve the clinical outcomes of PKP. METHODS: This was a placebo-controlled, double-blind prospective trial of 154 PKP patients (mean age: 70 years) with OVCFs. Patients were randomly assigned to receive a single infusion of ZOL (5 mg) or placebo (78 ZOL vs. 76 placebo) at 1 week, 12 months, and 24 months after surgery. Patients were followed-up for 36 months. RESULTS: ZOL treatment lowered the risk of RVF by ~ 65% over the 36-month period when compared to placebo controls (6.41% in ZOL vs. 18.42% in placebo groups; relative risk, 0.35; 95% CI, 0.13 to 0.92). ZOL also reduced the risk of NVF by ~ 73% (3.85% in ZOL vs. 14.47% in placebo groups; relative risk, 0.27; 95% CI, 0.08 to 0.92). ZOL also significantly reduced the vertebral height lost rate (HLR) at 12, 24, and 36 months. ZOL also improved the visual analog scale (VAS), Oswestry disability index (ODI) scores, and bone mineral density (BMD). CONCLUSION: Annual ZOL administration significantly lowers the risk of RVFs and NVFs, improving the clinical outcome of initial PKP in patients with OVCFs over a 3-year follow-up period. TRIAL REGISTRATION: ChiCTR2000029307.

Postpartum bilateral sacral stress fracture without osteoporosis-a case report and literature review.

PURPOSE: Sacral stress fractures are rare complications which can arise during pregnancy or in the early postpartum period. We report a case and discuss the findings of a confirmed postpartum sacral stress fracture in a 39-year-old multiparous woman and review previous case reports in the literature of sacral stress fracture related to pregnancy. METHODS: A review of the literature was conducted to examine the main characteristics of sacral stress fractures related to pregnancy. The Ovid/Medline, Embase and Google Scholar databases were searched with the inclusion criteria: human studies, English language, intrapartum, postpartum (within 6 months of parturition), sacrum and stress fracture. Our exclusion criteria included pubic fractures, vertebral fractures and non-English articles. The search terms included "stress fracture", "postpartum", "pregnancy", "atraumatic" and the wildcard "sacr*". Thirty-four cases were found and summarised in Table 2. RESULTS: A total of 65% of patients had onset of symptoms postpartum. Most patients did not have risk factors for sacral stress fractures including macrosomia, excessive pregnancy weight gain, heparin exposure, rapid vaginal delivery or predisposition to accelerated osteoporosis. Lumbar radiculopathy can be a feature of sacral stress fracture and it is more common (17.6%) than reported in the literature (2%). MRI is the preferred imaging modality for its safety profile in pregnancy and high sensitivity. A total of 70% reported normal bone mineral density (BMD). The mainstay treatment for sacral stress fractures includes relative bed rest, analgesia and modified weight-bearing exercises. Most patients have favourable outcome with complete symptom resolution. CONCLUSION: Sacral stress fractures in the absence of osteoporosis are rare complications of pregnancy that can present with lumbar radiculopathy. Conservative management often produces good clinical outcomes.

Formation of Stable Schwarz Crystals in Polycrystalline Copper at the Grain Size Limit.

A prototype Schwarz crystal (SC) structure of dividing-space minimal grain boundaries (GBs) constrained by coherent twin boundaries (CTBs) was recently discovered in extremely fine-grained polycrystalline Cu. In this Letter, constraining effects of 3D CTB network on the formation and thermostability of SC are addressed via atomistic simulations. GB migration and evolution of CTB network trigger formation of SC diamond. CTB constraints are critical to generate GBs of zero mean curvature underlying vanishing capillary pressure, and to counterbalance the elastic driving forces of lattice. GB motion can be suppressed at temperatures close to the melting point with GB aperture down to 3 nm.

Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation.

Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.

[Establishment of a nomogram model for predicting hematoma expansion in intracerebral hemorrhage and its multidimensional evaluation].

Objective: To establish a nomogram model for hematoma expansion (HE) prediction after intracerebral hemorrhage (ICH) and evaluate its performance in a multidimensionally way. Methods: A total of 348 ICH patients who were firstly diagnosed and hospitalized in the Second Affiliated Hospital of Soochow University from January 2017 to December 2019 were collected retrospectively. There were 236 males and 112 females, and their age ranged from 18 to 94 (62.0±14.6) years. All patients were divided into HE group (n=121) or non-HE group (n=227) according to the presence or absence of HE. The clinical and imaging features were compared between the two groups. Multivariate logistic regression analysis was performed for determining the independent predicting factors for HE prediction and a Nomogram model was established by using these factors. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effectiveness, accuracy and clinical practicability of the model, respectively. Bootstrap method was used for internal validation. Results: There were significant differences in onset time, swirl sign, history of anticoagulants administrations, systolic blood pressure when admission, Glasgow coma scale (GCS) scores and RBC distribution width between the two groups[(1.77(1.0, 2.5) h vs 2(1, 3) h, 72 cases (59.5%) vs 94 cases (41.4%), 17 cases (14.0%) vs 15 cases (6.6%), (170.69±29.19) mmHg(1 mmHg=0.133 kPa) vs (163.84±26.07) mmHg, 11(8, 14) scores vs 14(10, 15) scores, 44.3% (41.2%, 46.8%) vs 42.4% (40.1%, 45.3%);respectively, all P<0.05]. Multivariate logistic regression analysis demonstrated that onset time (OR=0.809, 95%CI: 0.682-1.961, P=0.015), swirl sign (OR=0.562, 95%CI:0.349-0.905, P=0.018), history of anticoagulants administrations (OR=0.394, 95%CI: 0.180-1.861, P=0.020), and GCS (OR=0.881, 95%CI: 0.815-1.952, P=0.001) were the predicting factors for HE. The area under the curve (AUC) of the Nomogram model was 0.735(95%CI: 0.687-0.805), which demonstrated that the model has an ideal prediction effectiveness. The calibration curve showed that the prediction probability of HE of the model fits well with the actual probability, and with high calibration. DCA showed relatively wide range of optional threshold probability of the model (ranging from 14% to 72%), the clinical practicability of this model was high. The internal validation results showed a C-index of 0.703, indicated a good discrimination power. Conclusion: The established Nomogram model can predict the HE of ICH with good prediction effectiveness, discrimination power and with good clinical practicability, which can be capable of providing an intuitive and visual guidance tool for timely identifying ICH patients who may have HE.

Adipokinetic hormone enhances CarE-mediated chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens.

Adipokinetic hormone (AKH), the principal stress-responsive neurohormone in insects, has been implicated in insect responses to insecticides. However, the functionality of AKH and its mode of signalling in insecticide resistance are unknown. Herein, we demonstrated that the enhanced activity of carboxylesterases (CarEs) is involved in the chlorpyrifos resistance in Nilaparvata lugens [brown planthopper (BPH)]. Chlorpyrifos exposure significantly induced the expression of AKH and its receptor AKHR in the susceptible BPH (Sus), and these two AKH signalling genes were over-expressed in the chlorpyrifos-resistant strain (Res) compared to Sus. RNA interference (RNAi) against AKH or AKHR decreased the CarE activity and suppressed the BPH's resistance to chlorpyrifos in Res. Conversely, AKH peptide injection elevated the CarE activity and enhanced the BPH's survival against chlorpyrifos in Sus. Furthermore, five CarE genes were identified to be positively affected by the AKH pathway using RNAi and AKH injection. Among these CarE genes, CarE and Esterase E4-1 were found to be over-expressed in Res compared to Sus, and knockdown of either gene decreased the BPH's resistance to chlorpyrifos. In conclusion, AKH plays a role in enhancing chlorpyrifos resistance in the BPH through positive influence on the expression of CarE genes and CarE enzyme activity.

Hypoxia-responsive miR-346 promotes proliferation, migration, and invasion of renal cell carcinoma cells via targeting NDRG2.

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. In this study, we investigated the role of miR-346 in RCC cells under hypoxia. OS-RC-2 and 786-O cells were cultured in 1% O2 or normal oxygen. Cell proliferation, migration, and invasion abilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, transwell migration, and invasion assays, respectively. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-346 and N-myc downstream-regulated gene 2 (NDRG2). Then bioinformatics analysis, dual-luciferase reporter assay, and RNA immunoprecipitation were carried out to determine the relationship between miR-346 and NDRG2. The protein expression of NDRG2 was detected by western blot assay. Hypoxia promoted cell proliferation, migration, and invasion in OS-RC-2 and 786-O cells. Meanwhile, we found that miR-346 was upregulated in RCC cells under hypoxia as relative to normoxia. miR-346 deletion could decrease the viability, migration, and invasion abilities of RCC cells under hypoxia. Besides, our data demonstrated that NDRG2 was a target gene of miR-346. The expression of NDRG2 in OS-RC-2 and 786-O cells was lower under hypoxia than under normal oxygen conditions. Moreover, NDRG2 overexpression could inhibit cell proliferation, migration, and invasion in RCC cells under hypoxia. And NDRG2 silencing reversed the inhibitory effects of the miR-346 inhibitor on the viability, migration, and invasion abilities of RCC cells in hypoxia conditions. miR-346 promoted the viability, migration, and invasion of RCC cells under hypoxia by targeting NDRG2.

Size Dependence of Grain Boundary Migration in Metals under Mechanical Loading.

The greatly increased grain boundary (GB) mobility in nanograined metals under mechanical loading is distinguished from that in their coarse-grained counterparts. The feature leads to softening of nanograined materials and deviation of strength from the classical Hall-Petch relationship. In this Letter, grain size dependences of GB migration in nanograined Ag, Cu, and Ni under tension were investigated quantitatively in a wide size range. As grain size decreases from submicron, GB migration intensifies and then diminishes below a critical grain size. The GB migration peaks at about 80, 75, and 38 nm in Ag, Cu, and Ni, respectively. The suppression of GB migration below a critical size can be attributed to GB relaxation during sample processing or by postthermal annealing. With relaxed GBs the governing deformation mechanism of nanograins shifts from GB migration to formation of through-grain twins or stacking faults. GB relaxation, analogous to GB segregation, offers a novel approach to stabilizing nanograined materials under mechanical loading.

Phase I-II clinical trial design: a state-of-the-art paradigm for dose finding.

Background: Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk-benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious. Patients and methods: We review the phase I-II paradigm and the EffTox design, which utilizes both efficacy and toxicity to choose optimal doses for successive patient cohorts and find the optimal P2RD. We conduct a computer simulation study to compare the performance of the EffTox design with the traditional 3 + 3 design and the continuous reassessment method. Results: By accounting for the risk-benefit trade-off, the EffTox phase I-II design overcomes the limitations of conventional toxicity-based phase I designs. Numerical simulations show that the EffTox design has higher probabilities of identifying the optimal dose and treats more patients at the optimal dose. Conclusions: Phase I-II designs, such as the EffTox design, provide a coherent and efficient approach to finding the optimal P2RD by explicitly accounting for risk-benefit trade-offs underlying medical decisions.

[Esophageal motility and reflux characteristics in gastroesophageal reflux disease patients with or without extra-esophageal symptoms].

Objective: To investigate esophageal motility and reflux characteristics in gastroesophageal reflux disease (GERD) with and without extra-esophageal symptoms by high-resolution manometry and 24 h esophageal multichannel intraluminal impedance combined pH (MII-pH) monitoring. Methods: From February 2016 to June 2017, GERD patients with and without extra-esophageal symptoms were enrolled in this prospective controlled study. Esophageal HRM and 24 h MII-pH monitoring were performed. The differences in esophageal motility and reflux parameters were further analyzed between 30 GERD patients with extra-esophageal symptoms and 30 simple GERD patients. Results: The GERD symptom scores didn't show statistical difference between two groups. The GERD symptom scores didn't show statistical difference between two groups. The relaxation pressure of lower esophageal sphincter(LES), the integrated relaxation pressure, and the recovery time of upper esophageal sphincter(UES) of GERD patients with extra-esophageal symptoms were all lower than those of patients without extra-esophageal symptoms [(15±7) vs (21±11)mmHg, (8±3) vs (10±5)mmHg, (388±168) vs (492±170)ms, 1 mmHg=0.133 kPa], and the differences were statistically significant(all P<0.05). The main classification of esophageal motility type of GERD patients with extra-esophageal symptoms was mild esophageal motility disorders (27%, 8/30), and the occurrence of ineffective esophageal motivation was 20% (6/30), which were similar with simple GERD patients. The proximal reflux percentages of weak acid reflux and nonacid reflux, abnormal nonacid reflux in GERD patients with extra-esophageal symptoms were significantly higher than those in simple GERD patients [84.6% (73.2%, 100.0%) vs 75.0% (60.0%, 87.65%), P=0.048; 90.0% (45.8%, 100.0%) vs 0(0, 100.0%), P=0.017; 46.7% vs 3.3%, P=0.03]. Conclusions: The pathogenesis of GERD with extra-esophageal symptoms may be different from typical GERD. Increase of proximal esophageal reflux and abnormal nonacid reflux may all participate in the mechanisms of GERD with extra-esophageal symptoms.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions.

The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional 'window of opportunity' endpoints should be included.