[Using geographical detection to analyze responses of vegetation growth to climate change in the Loess Pla-teau, China]. / 基于地理探测的黄土高原植被生长对气候的响应.

In order to explore the responses of different vegetation types to climatic change in the Chinese Loess Plateau (CLP), we analzyed the changes of different vegetation types and their relationships with meteorological factors using trend analysis, Hurst index, and geographical detector model based on normalized difference vegetation index (NDVI). The results showed that NDVI of different vegetation types from 2002 to 2019 was dominated by a growing trend and codirectional moderate persistence. The NDVI of crops in the built-up and adjacent areas decreased significantly. Except for grassland or meadow that was affected by mixed pixels, the spatial variation of NDVI was significant in the growing season (from April to October). The mean NDVI of different vegetation types followed an oder: coniferous forest > broadleaved forest > scrub > meadow > grassland > crop > steppe > desert. The interactions between meteorological factors were synergistic and non-linear enhancement in the CLP. Moreover, the interaction was more prominent under steppe and desert where habitat was fragile. The synergistic effect of precipitation and temperature had a great influence on all vegetation types. Water vapor, relative humidity, sunshine duration, atmospheric pressure, and wind speed had different explanatory powers on NDVI through indirectly affec-ting hydrothermal conditions.

Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system / 中华预防医学杂志

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.

Effect of Extracts from Veronica peregrine on Breast Cancer Cell-induced Osteoclastic Bone Metastasis via Inhibiting Runx2 Activation / 中国实验方剂学杂志

ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina （EVP） on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells， a human breast cancer cell line， into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 （Ck-19） gene in mouse bone marrow was determined by nested polymerase chain reaction（PCR） to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages （BMMs）， we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB （RANK）， Runt-related transcription factor 2 （ Runx2 ）， phosphorylated Runx2 （p-Runx2）， and matrix metalloproteinase-9 （MMP-9） in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases （MMPs）. ResultCompared with that in the blank group， Ck-19 expression was down-regulated in EVP groups （P<0.05）. The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand （sRANKL）， which was inhibited by EVP （P<0.05）. The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group， while EVP groups had lower cathepsin K levels than sRANKL group （P<0.05）. Compared with the blank group， the sRANKL group showed up-regulated RANK expression， Runx2 phosphorylation， and MMP-9 expression （P<0.05）， while the expression levels of RANK， p-Runx2， and MMP-9 were down-regulated when the cells were incubated with EVP （P<0.05）. Furthermore， exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group （P<0.01）， which， however， was reversed in EVP groups （P<0.05）. ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells， which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.

Clinical characteristics of acute kidney injury in cancer patients receiving immune checkpoint inhibitors / 中华肾脏病杂志

Objective:To investigate the incidence, risk factors, and outcomes of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs).Methods:A retrospective analysis was performed on the inpatients who received ICIs therapy in Beijing Shijitan Hospital, Capital Medical University from October 2015 to December 2020. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group, and the patients in the AKI group were further divided into ICIs related AKI (ICIs-AKI) and AKI due to other etiologies. The clinical characteristics of the patients were compared. Multivariate logistic regression was used to analyze the influencing factors of AKI, and sensitivity analysis was used to evaluate the influencing factors of ICIs-AKI.Results:A total of 279 cancer patients over 18 years old were included in this study, in which 175(62.7%) were males. There were 41 patients (14.70%) in AKI group, including 25 patients (8.96%) in ICIs-AKI group and 16 patients (5.73%) in AKI due to other etiologies group. Patients in the AKI group were characterized by higher proportions of hypertension, diuretics use and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, extrarenal immune-related adverse events (irAEs) and a lower plasma albumin level (all P<0.05). The patients in the ICIs-AKI group had higher proportions of new aseptic leukocyturia, blood eosinophil count>500/ml, combined extrarenal irAEs, glucocorticoid use and discontinued ICIs treatment (all P<0.05). Multivariate logistic regression results showed that hypertension ( OR=3.424, 95% CI 1.559-7.522, P=0.002), use of diuretics ( OR=4.620, 95% CI 2.111-10.112, P<0.001), baseline eGFR<60 ml·min -1·(1.73 m 2) -1 ( OR=3.668, 95% CI 1.336-10.070, P=0.012) and extrarenal irAEs ( OR=9.909, 95% CI 4.198-23.391, P<0.001) were associated with AKI in cancer patients receiving ICIs therapy. Sensitivity analysis indicated that the risk factors of ICIs-AKI included use of diuretics and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, similar to the results of the above analysis, extrarenal irAEs ( OR=17.572, 95% CI 6.302-48.995, P<0.001) were also associated with ICIs-AKI independently. Conclusions:AKI is not uncommon in patients treated with ICIs. Concomitant hypertension, baseline eGFR<60 ml·min -1·(1.73 m 2) -1 and use of diuretics are independent risk factors for AKI in such patients. Patients should be alert to the risk of ICIs-AKI when appearing extrarenal irAEs. Distinguishing ICIs-AKI from AKI caused by other causes will present a frequent challenge to clinical practitioners.

Clinical features of frailty syndrome and its association with all-cause mortality in elderly patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective:To investigate the clinical characteristics and risk factors of frailty syndrome in elderly patients undergoing maintenance hemodialysis (MHD) and the effect of frailty syndrome on all-cause mortality.Methods:This was a prospective cohort study. MHD patients aged≥60 years in 5 hemodialysis centers in Beijing from April to June 2017 were selected as the study subjects. Baseline data were collected and compared, and the patients were then classified into non-frailty, pre-frailty and frailty syndrome groups according to the Fried criteria and followed up until June 2018. The end point event was all-cause death. Multivariate logistic regression was used to analyze the independent risk factors of frailty syndrome. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate among the 3 groups. A multivariate Cox regression model was used to analyze the independent risk factors of all-cause mortality.Results:A total of 204 patients aged (71.65±5.89) years (60-81 years) were enrolled into this study, including 123 males (60.29%), 147 patients (72.06%) in the frailty syndrome group, 41 patients (20.10%) in the pre-frailty group, and 16 patients (7.84%) in the non-frailty group. Patients with frailty syndrome tended to be older, longer dialysis vintage, a higher proportion of diabetes, lower urea clearance index (Kt/V) and lower serum albumin level (all P<0.05). Multivariate Logistic regression showed that factors independently associated with frailty syndrome included age ( OR=1.393, 95% CI 1.241-1.563, P<0.001), history of diabetes ( OR=3.610, 95% CI 1.262-10.327, P=0.017), dialysis vintage ( OR=1.011, 95% CI 1.002-1.020, P=0.019), Kt/V ( OR=0.711, 95% CI 0.516-0.979, P=0.037), serum albumin ( OR=0.754, 95% CI 0.644-0.882, P<0.001) and intact parathyroid hormone (iPTH, OR=1.344, 95% CI 1.024-1.763, P=0.033). Kaplan-Meier survival analysis showed that the cumulative survival rate in frailty syndrome group was significantly lower than those of pre-frailty (Log-rank χ2=7.265, P=0.007) and non-frailty groups (Log-rank χ2=5.238, P=0.022). Multivariate Cox regression analysis indicated that frailty syndrome ( HR=3.832, 95% CI 1.116-13.157, P=0.033), age ( HR=1.074, 95% CI 1.014-1.136, P=0.014), history of diabetes ( HR=2.009, 95% CI 1.067-3.784, P=0.031), cognitive impairment (Montreal cognitive assessment<26, HR=2.627, 95% CI 1.142-6.042, P=0.023), Kt/V ( HR=0.701, 95% CI 0.545-0.902, P=0.006), serum albumin ( HR=0.891, 95% CI 0.806-0.986, P=0.025) and iPTH ( HR=1.226, 95% CI 1.100-1.367, P<0.001) were independently associated with all-cause mortality. Conclusions:The prevalence of frailty syndrome in elderly patients undergoing hemodialysis is high. Ageing, diabetes history, long dialysis vintage, low levels of Kt/V and serum albumin, and elevated iPTH level are independent risk factors for frailty syndrome in such patients. Frailty syndrome is independently associated with an increased risk of all-cause mortality.

Research progress of famesyltransferase and its inhibitors in cancer therapy / 中国药理学通报

Famesyltransferase, a membrane-associated protein, catalyzes the addition of the 15-carbon fragment of famesyl diphosphate to the cysteine SH group of the CAAX motif containing protein substrates to regulate the function of target proteins through famesylation. As one of the most important target proteins of FTase, oncogenic forms of Ras mutants have been reportedly involved in more than 30% human cancers, and are known to play critical roles in cancer development and progression. Despite decades of research, Ras inhibitors are so elusive that no therapeutic agents directly targeting Ras mutants have been clinically approved, the primary reason for which is the lack of druggable pockets on the surface of Ras. Therefore, FTase, the main regulator of Ras protein, has gradually become a research hotspot, and many FTase inhibitors have been developed, synthesized and used for the treatment of malignant tumors. In the present review, we briefly describe the regulation of Ras functions by FTase and the role of FTase in cancers, and mainly explore the research progress of FTase inhibitors as a promising strategy for cancer therapy.

Dihydromyricin inhibited hepatic lipid deposition induced by high-fat diet in obese mice by activating SIRT1-AMPK pathway / 中国药理学通报

Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg

A prospective cohort study on the association of cognitive impairment and all-cause mortality in the middle and elderly adult patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective:To investigate the association between cognitive impairment and all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis (HD).Methods:A prospective cohort study was conducted. Patients from 11 HD centers in Beijing between April and June 2017 were enrolled. Baseline data were collected, and a series of neuropsychological batteries covered 5 domains of cognitive function were applied for the assessment of cognitive function. The patients were then classified as normal and cognitive impairment groups according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V) and followed-up until June 2018. The clinical characteristics of the two groups of patients were compared. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the independent influencing factors of all-cause mortality, to determine the relationship between cognitive impairment and different cognitive domain impairments and all-cause death.Results:A total of 613 patients were enrolled, of which 496(80.91%) patients had cognitive impairment. Compared with the normal cognitive function group, the patients in the cognitive impairment group tended to be older, longer dialysis vintage, a higher proportion of diabetes, hypertension, and stroke, increased serum iPTH level, and lower education level and urea clearance index (Kt/V) (all P<0.05). After (49.53±8.42) weeks of follow-up, Kaplan-Meier survival analysis showed that the cumulative survival rate of cognitive impairment group was significantly lower than that of cognitive normal group (Log-rank χ2=8.610, P=0.003). Multivariate Cox regression analysis showed that history of diabetes ( HR=2.742, 95% CI 1.598-4.723, P<0.001), coronary heart disease ( HR=1.906, 95% CI 1.169-3.108, P=0.010), dialysis vintage (every increase of 1 month, HR=1.007, 95% CI 1.003-1.011, P=0.001), serum level of albumin (every increase of 1 g/L, HR=0.859, 95% CI 0.809-0.912, P<0.001), cognitive impairment ( HR=2.719, 95% CI 1.088-6.194, P=0.032) were independently associated with all-cause mortality. Multivariate Cox regression analysis on different cognitive domains also indicated that memory impairment ( HR=2.571, 95% CI 1.442-4.584, P<0.001), executive function impairment ( HR=3.311, 95% CI 1.843-5.949, P=0.001) and three, four, five domains combined impairment ( HR=5.746, 95% CI 1.880-17.565, P=0.002; HR=12.420, 95% CI 3.690-41.802, P<0.001; HR=13.478, 95% CI 3.381-53.728, P<0.001) were independently related to all-cause mortality. Conclusions:Cognitive impairment is an independent risk factor of all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis, and the risk is significantly increased in patients with the impairment of the domains of memory, executive function, or in the combination of three to five cognitive domains.

A cross-sectional study on the characteristics of cognitive impairment in middle-aged and elderly patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective:To investigate the clinical features and associated influencing factors of cognitive impairment in middle-aged and elderly Chinese adult patients undergoing maintenance hemodialysis (HD).Methods:A cross-sectional study was conducted among HD patients from 11 centers in Beijing city from April 2017 to June 2017. A neuropsychological battery covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied in cognitive function assessment. Patients were classified as normal cognitive function group and cognitive impairment group according to the fifth version of the diagnostic and statistical manual of mental disorders criteria (DSM-V). Multivariate binary logistic regression was used to analyze the independent influencing factors of cognitive impairment. Results:A total of 613 HD patients were included in the study, and the prevalence of cognitive impairment was 80.91% (496/613). Attention impairment (81.05%) and memory impairment (63.51%) were the most common impaired domains, and 79.23% was concomitant impairment across two or more cognitive domains among those with cognitive impairment. Compared with the patients in the normal cognitive function group, the patients in the cognitive impairment group had senior age, longer dialysis vintage, higher proportion of diabetes, hypertension, and stroke, higher level of serum intact parathyroid hormone (iPTH), lower education level, and lower urea clearance index (Kt/V) (all P<0.05). Factors were independently associated with cognitive impairment including increasing age ( OR=1.110, 95% CI 1.072-1.150, P<0.001), education time>12 years (with education time<6 years as reference, OR=0.323, 95% CI 0.115-0.909, P=0.032), history of diabetes ( OR=2.151, 95% CI 1.272-3.636, P=0.004), history of stroke ( OR=2.546, 95% CI 1.244-5.210, P=0.011), increased dialysis vintage ( OR=1.016, 95% CI 1.010-1.022, P<0.001), reduced Kt/V( OR=0.008, 95% CI 0.002-0.035, P<0.001), and increased iPTH level ( OR=1.002, 95% CI 1.002-1.003, P=0.012). Conclusions:The prevalence of cognitive impairment in middle-aged and elderly adult Chinese patients undergoing HD is high. Memory and attention are the most commonly impaired domains. Increasing age, low education level, history of diabetes and stroke, increased dialysis vintage, reduced Kt/V and increased serum iPTH are the independent influencing factors associated with cognitive impairment.

Danshen Injection Inhibits SKOV3 Cell Proliferation in Vitro by Interfering with Their Interaction with Platelets / 中国实验方剂学杂志

Objective:To investigate the inhibitory effects of Danshen injection against ovarian cancer cell proliferation induced by the interaction between platelets and cancer cells. Method:The induction of platelets on SKOV3 growth <italic>in vitro</italic> and the inhibitory effect of Danshen injection at 12，24，and 48 g·L^-1 were observed by 3-（4，5-Dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） and cell colony formation assays. The content of transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） in the platelet-tumor cell interaction system and platelet supernatant and the effect of Danshen injection on TGF-<italic>β</italic>₁secretion were detected by enzyme-linked immunosorbent assay （ELISA）. The influences of tumor cell culture supernatant on platelet aggregation and secretion and the inhibitory effect of Danshen injection were determined by microplate assay and ELISA. The effects of Danshen injection on platelet nuclear factor kappa B （NF-<italic>κ</italic>B） signaling pathway were assayed by Western Blot. Result:Compared with the blank group， the platelet induction group exhibited significantly elevated absorbance at <italic>A</italic>₅₇₀（<italic>P</italic><0.01）， while the absorbance at <italic>A</italic>₅₇₀ in the platelet + Danshen injection group was significantly lower than that in the platelet induction group （<italic>P</italic><0.01）. The comparison with the Danshen injection group revealed that the cell proliferation inhibitory rate in the platelet + Danshen injection group at the same dose was more significant （<italic>P</italic><0.01）. The number of colonies in the platelet induction group was obviously increased in contrast to that in the blank group（<italic>P</italic><0.05）， while the number of colonies in the platelet + Danshen injection group was significantly lower than that in the platelet induction group（<italic>P</italic><0.05，<italic>P</italic><0.01）. As demonstrated by comparison with the blank group， TGF-<italic>β</italic>₁content in the supernatant of the platelet induction group rose remarkably（<italic>P</italic><0.01）， whereas that in the platelet + Danshen injection group declined（<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the platelet + Danshen injection group displayed more obvious inhibition（<italic>P</italic><0.01）. Compared with the blank group， Danshen injection significantly reduced the TGF-<italic>β</italic>₁content in platelet supernatant（<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant change in the content of TGF-<italic>β</italic>₁in SKOV3 supernatant treated with Danshen injection. The platelet aggregation， thromboxane A₂（TXB₂）， and serotonin （5-HT） secretion in the SKOV3 cell supernatant induction group were significantly increased as compared with those in the blank group （<italic>P</italic><0.01）， while such indexes in the cell supernatant induction + Danshen injection group were obviously decreased （<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the cell supernatant induction + Danshen injection group displayed more obvious inhibition at the same dose（<italic>P</italic><0.01）. Compared with the blank group， the platelet induction group exhibited obviously up-regulated phosphorylated TGF-<italic>β</italic>-activated kinase-1 （TAK-1） and NF-<italic>κ</italic>B， but down-regulated phosphorylated inhibitory protein of NF-<italic>κ</italic>B （I<italic>κ</italic>B）（<italic>P</italic><0.01）， which however were significantly reversed in the platelet + Danshen injection group<bold>（</bold><italic>P</italic><0.01）. Conclusion:Danshen injection affect the proliferation of SKOV3 cells by inhibiting their interaction with platelets， which may be related to the inhibited secretion of TGF-<italic>β</italic>₁.

Clinical investigation of the risk factors of aortic arch calcification and its association with long term prognosis among the patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective:To explore the related risk factors of aortic arch calcification (AoAC) and the relationship between AoAC and long-term outcome in maintenance hemodialysis patients.Methods:The patients who underwent hemodialysis in the Blood Purification Center of Beijing Shijitan Hospital Affiliated to Capital Medical University from March to June 2015 were recruited. Calcification of the aortic arch was estimated with plain chest radiology. The patients were divided into AoAC group and no-AoAC group. Multivariate binary logistic regression was used to analyze the influencing factors of AoAC. Kaplan-Meier analysis and Cox regression model were used to examine the association between AoAC and adverse prognostic events (all-cause death and cardiovascular events).Results:There were 157 hemodialysis patients included in this study, with age of (62.63±15.05) years (30-90 years old) and 85 males (54.14%). The median follow-up time was 54(20, 54) months. There were 99 cases (63.06%) in AoAC group and 58 cases (36.94%) in no-AoAC group. The age, proportion of diabetes history, serum corrected calcium and triglyceride levels in AoAC group were higher than those in no-AoAC group (all P<0.05), while the proportion of using active vitamin D, serum albumin and intact parathyroid hormone level were lower than those in no-AoAC group (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.109, 95% CI 1.067-1.152, P<0.001), diabetes ( OR=4.110, 95% CI 1.551-10.890, P=0.004), longer dialysis duration ( OR=1.026, 95% CI 1.010-1.043, P=0.001), higher systolic pressure ( OR=1.039, 95% CI 1.012-1.067, P=0.005) and higher triglycerides levels ( OR=1.932, 95% CI 1.148-3.125, P=0.013) were the independent risk factors of AoAC, and higher hemoglobin was a protective factor ( OR=0.967, 95% CI 0.938-0.998, P=0.035) of AoAC. Sixty-three cases (63.64%) died, and 78 cases (78.79%) had cardiovascular events in AoAC group. Fourteen cases (24.14%) died, and 12 cases (20.69%) had cardiovascular events in no-AoAC group. Kaplan-Meier analysis showed higher incidence rate of all-cause death (Log-rank χ2=22.499, P<0.001) and cardiovascular events (Log-rank χ2=50.797, P<0.001) in patients with AoAC. Multivariate Cox regression analysis showed AoAC was the independent risk factor of all-cause death ( HR=2.003, 95% CI 1.039-3.859, P=0.038) and cardiovascular events ( HR=5.642, 95% CI 3.003-10.600, P<0.001). Conclusions:Older age, diabetes mellitus, longer dialysis duration, hypertension, higher triglyceride levels and lower hemoglobin are significantly associated with AoAC. AoAC is the independent risk factor of all-cause death and cardiovascular events in maintenance hemodialysis patients.

Effects of sleep quality on cognitive function in elderly patients undergoing hemodialysis / 中华老年医学杂志

Objective:To investigate the effects of sleep quality on cognitive function in elderly patients undergoing hemodialysis.Methods:In this cross-sectional study, the cognitive function in hemodialysis patients was evaluated by Montreal Cognitive Assessment(MoCA)and the sleep quality was accessed by Pittsburgh sleep quality index(PSQI). The related indexes of cognitive function were compared and the relationship between cognitive function and sleep quality was analyzed by using multiple binary Logistic regression method.Results:A total of 121 elderly hemodialysis patients aged 67.4±7.2 years with cognitive impairment of 76 cases(62.8%)were included in the study.Numbers(%)of cases with very good, good, general and poor sleep quality were 33(27.3%), 39(32.2%), 14(11.6%)and 35(28.9%), respectively.The proportion of patients with pretty good sleep quality was lower in cognitive impairment group than in normal cognitive group(13/76 or 17.1% vs.20/45 or 44.4%, P<0.001). The proportion of patients with poor sleep quality was higher in cognitive impairment group than in normal cognitive group(29/76 or 38.2% vs.6/45 or 13.3%, P<0.05). Multiple binary Logistic regression analysis showed that age( OR: 1.128, 95% CI: 1.083-1.175, P<0.001), a education level( OR: 0.353, 95% CI: 0.151-0.556, P<0.05), hypertension( OR: 2.508, 95% CI: 1.189-5.291, P<0.05), diabetes( OR: 1.913, 95% CI: 1.045-3.502, P<0.05), stroke( OR: 4.044, 95% CI: 1.439-11.365, P<0.05), dialysis age( OR: 1.016, 95% CI: 1.010-1.023, P<0.001), KT/V( OR: 0.025, 95% CI: 0.005-0.122, P<0.001)and parathormon(iPTH)( OR: 1.002, 95% CI: 1.000-1.003, P<0.05)were associated with cognitive impairment.After adjusting for above factors, sleep quality was also correlated with cognitive impairment( OR: 1.180, 95% CI: 1.108-1.258, P<0.001), showing that the risk of cognitive impairment increased by 1.18 times with every one point increase in PSQI scores. Conclusions:Cognitive impairment is associated with age, education level, hypertension, diabetes, stroke, dialysis age, KT/V and iPTH in elderly hemodialysis patient, and sleep quality is also an independent risk factor for cognitive impairment.

Clinical Analysis of BRAFV600E Mutation and Its Correlation With Sonographic Image Characteristics in Papillary Thyroid Carcinoma in Chinese Coastal Areas.

This study analyzed the characteristics of BRAFV600E mutation in papillary thyroid carcinoma (PTC) in Chinese coastal areas. We intended to identify noninvasive methods to determine BRAFV600E status in thyroid nodules prior to surgery. BRAFV600E mutation and the sonographic characteristics of thyroid nodules were investigated in 670 PTC patients in our hospital. We aimed to determine the relationship between BRAFV600E mutation and the clinicopathological and sonographic imaging characteristics of PTC. The mutation rate of the BRAFV600E was 78.2%. BRAFV600E mutation was significantly associated with central node (univariate analyses, P = .005; multivariate analyses, P < .001, odds ratio [OR] = 10.255) and lateral node metastases (univariate analyses, P = .001; multivariate analyses, P < .001, OR = 22). It was less frequent in PTC coexisting with Hashimoto's thyroiditis (univariate analyses, P = .016; multivariate analyses, P < .001, OR = .034). Nodules without blood flow had a significantly higher mutation rate of BRAFV600E in PTC patients (univariate analyses, P = .026). BRAFV600E mutation was significantly associated with high suspicion in the Thyroid Imaging Reporting and Data System 5 (univariate analyses, P = .004; multivariate analyses, P = .014, OR = 6.456). Our results strongly suggest that BRAFV600E mutation plays a potential role in lymph node metastasis (central node metastasis, OR = 10.225; lateral node metastasis, OR = 22). Some sonographic imaging features might be helpful in estimating the status of BRAFV600E preoperatively.

Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer is the most common endocrine system malignancy. Scientists have done considerable research into the molecular mechanisms involved, but many mechanisms remain undiscovered. MATERIAL AND METHODS We performed a comprehensive analysis of the whole-transcriptome resequencing derived from thyroid tissues and paired papillary thyroid cancer (PTC) and showed that lysophosphatidic acid receptor 5 (LPAR5) is strongly overexpressed in thyroid carcinoma. Then, we used TPC-1 and KTC-1 to explore the effect of LPAR5 knockdown on colony formation, migration, proliferation, invasion, and apoptosis of PTC cell line cells. AKT activator was used for the recovery test. Finally, we designed proteomic experiments to explore the role of LPAR5 in the AKT pathway and the EMT process. RESULTS Cell function experiments showed that LPAR5 knockdown can significantly induce apoptosis of KTC-1 and TPC-1 cells. Furthermore, LPAR5 can promote PTC metastasis and tumorigenesis by activating the PI3K/AKT pathway and decreasing its cancer-promoting effect when using AKT agonist. We also found that LPAR5 can regulate the expression of EMT-related proteins, which affect invasion and migration. CONCLUSIONS In summary, downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.

NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT.

Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial-mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.

[Spatial and temporal changes of farmland soil acidification and their influencing factors in different regions of Guangdong Province, Chin]. / å¹¿ä¸œçœä¸åŒåŒºåŸŸå†œç”°åœŸå£¤é ¸åŒ–æ—¶ç©ºå˜åŒ–åŠå ¶å½±å“å› ç´ .

Based on the three datasets from 1980s, 2010 and 2015 in Guangdong Province, we analyzed the spatial and temporal variations of soil pH in farmlands in different regions of Guangdong Province and analyzed the driving factors for such variations. The results showed that the spatial distribution of soil pH in Guangdong Province changed significantly in different periods. During 1980s to 2010, soil pH showed an acidification trend with a decline of 0.3, and increased by 0.09 from 2010 to 2015, with more uneven trend and more obvious acid base differentiation. From the perspective of each region, there was generally a trend of acidification from the 1980s to 2010. From 2010 to 2015, the average pH value of farmland soil in the Pearl River Delta increased by 0.27, while that on the east wing and west wing decreased by 0.05 and 0.15 respectively, showing a unapparent change of soil pH in the mountainous area. Our results showed that soil acidification in diffe-rent areas of Guangdong Province was affected by natural factors such as soil itself and precipitation. In addition, anthropogenic factors such as acid rain, unreasonable fertilization and the planting structure of high-yielding crops were also the main causes of soil acidification. Industrialization, urbanization, mining development, and the spread of soil testing formula fertilization increased soil pH in local areas. Our results could provide theoretical guidance for controlling and alleviating soil acidification and improving the quality of cultivated land in different areas.

Enhanced antiproliferative activity of antibody-functionalized polymeric nanoparticles for targeted delivery of anti-miR-21 to HER2 positive gastric cancer.

MiR-21 is an oncogenic miR frequently elevated in gastric cancer. Overexpression of miR-21 decreases the sensitivity of gastric cancer cells to trastuzumab, which is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2. However, optimization of miRNA or its anti-miRNA oligonucleotides (AMOs) for delivery is a challenge. Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including AMOs. This study is a continuation of our earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target gastric cancer cells with HER2 receptor over-expression using anti-miRNA-21 antisense oligonucleotides (AMO-21). The antibody conjugates (HER-PEG-PCL NPs) act against target cells via antibody-dependent mechanisms and also based on encapsutalated AMO-21. X-ray photoelectron spectroscopy validated the presence of trastuzumab on NP surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a stable antibody expression. The cell line specificity, cellular uptake, AMO-21 delivery, and cytotoxicity of the HER-PEG-PCL NPs were investigated. We found that the antibody conjugates significantly enhanced the cellular uptake of NPs. The HER-PEG-PCL NPs effectively suppressed the target miRNA expression in gastric cancer cells, which further up-regulated phosphatase and tensin homolog (PTEN). As a result, the sensitivity of HER2-expressing gastric cancer cells to trastuzumab was enhanced. The approach enhances the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity of immune effector cells. The antitumor effects of AMO-21-HER-PEG-PCL NPs were compared with trastuzumab in xenograft gastric cancer mice. The results provide insight into the biological and clinical potential of targeted AMO-21 delivery using modified trastuzumab for gastric cancer treatment.

Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma.

AIM: To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS: A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS: Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

[Prediction of Distribution of Soil Cd Concentrations in Guangdong Province, China].

Heavy metals are one of the principal soil pollution sources. Contaminated soils affect the quality of agricultural products, and then threaten human health. Prediction of the contaminants distribution in the soil is the foundation of pollution evaluation and risk control. A total of 1000 soil profiles were collected to investigate the spatial variation of soil cadmium (Cd) concentration in Guangdong province. These datasets were divided into two groups, about 900 samples for model training and the other 100 for model validation. Six frequently used GIS spatial interpolation methods including Spline, Natural Neighbor, Ordinary Kriging, Inverse Distance Weighted, Local Polynomial Interpolation and Radial Basis Function, and Cubist which is a type of rule-based model were compared to determine their suitability parameters for estimating soil Cd concentration. Nine different resolutions including 2000, 1500, 1000, 800, 500, 300, 200, 150, and 90 m were selected to calculate, evaluate and compare their accuracy. The results showed that, 1 Quantitative assessment of the continuous surfaces showed that there was a large difference in the accuracy of the seven methods. Cubist was superior to GIS-based spatial interpolation methods at all resolutions. Cubist was the best tool for mapping the spatial distribution of Cd in soils with thirty-seven specific predictors relevant to the source and behavior of Cd (parent material, land use, soil type, soil properties, population density, gross domestic product per capita, and the lengths and classes of the roads surrounding the sampling sites, climatic factors, etc.) at 300 m×300 m resolution. The second was Spline, its accuracy was optimal at the 1500 m×1500 m resolution. 2 Results of Cubist suggested that the soil Cd spatial distribution was primarily dependent on the properties of soil regional parent materials. And soil samples with higher Cd concentration mainly located in Carboniferous and Quaternary areas. 3 Spatially, Cd concentrations were higher in the Pearl River Delta region and north of Guangdong Province. Many hotspots existed throughout the Pearl River Delta region due to transportation and pollution of the river. The major anthropogenic inputs of heavy metals to soils and the environment were metalliferous mining and smelting in the north of Guangdong Province. The soil Cd geometric mean concentration of 0.147 mg·kg-1 was lower than that of China, however it varied from zero to 6.056 mg·kg-1. The areas with soil Cd concentrations greater than 1.0 and 3.0 mg·kg-1 were 160 km2 and 2140 km2 respectively, accounting for 0.09% and 1.18% of the total area of Guangdong Province.