[A Meta-analysis of the predictive value of peripheral blood neutrophil to lymphocyte ratio in mortality of patients with acute paraquat poisoning].

Objective: To evaluate the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) in mortality of patients with acute paraquat poisoning. Methods: In March 2022, all literatures about the studies on NLR assessing the mortality of patients with acute paraquat poisoning were searched in the National Library of Medicine PubMed, Embase, Cochrane Library Database, Web of Science, CNKI, Wanfang Medicine Database, Weipu Database, China Biology Medicine disc (SinoMed). The data updated by March 2022, without the limitation of languages. Two researchers extracted literature information independently and conducted literature quality evaluation using QUADAS-2. And the data extracted from the literatures were analyzed with Stata 16 software. Results: A total of 9 studies were included in this Meta-analysis, including 967 patients. And the Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.77 (95%CI: 0.72-0.82, P<0.05), 0.83 (95%CI: 0.74-0.90, P<0.05), 4.63 (95%CI: 2.99-7.15, P<0.05), 0.27 (95%CI: 0.22-0.34, P<0.05) and 17.06 (95%CI: 10.22-28.48, P<0.05), and the area under the curve (AUC) of the summary receiver operator characteristics curve (SROC) was 0.85 (95%CI: 0.81-0.88) . Conclusion: NLR has predictive value in 30-day mortality of patients with acute paraquat poisoning.

Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis.

OBJECTIVE: Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. METHODS: Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by CCK-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. RESULTS: In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1ß-treated NPCs. Mechanistically, QUE suppressed IL-1ß induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. CONCLUSIONS: Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

CT and MRI features of giant cell tumours with prominent aneurysmal bone cysts in the extremities: a comparison with primary aneurysmal bone cysts.

AIM: To test the hypothesis that computed tomography (CT) and magnetic resonance imaging (MRI) could help distinguish between giant cell tumours with prominent aneurysmal bone cysts (GABCs) and primary aneurysmal bone cysts (PABCs) of the extremities. MATERIALS AND METHODS: CT and MRI features of 13 patients with GABCs and 13 patients with PABCs in the extremities were analysed retrospectively. The ages and sex of the patients were also recorded. Independent-samples t-tests were used for continuous variables and Fisher's exact tests were used for categorical variables to compare the differences between the two groups. Diagnostic accuracy, sensitivity, and interobserver agreement were calculated. RESULTS: The average age of patients with GABCs (38.2±15.8 years) was higher than that of patients with PABCs (19.3±12.7 years; p=0.003). The transverse/longitudinal diameter ratio was different between GABCs (0.8±0.3) and PABCs (0.6±0.2; p=0.007). Subchondral bone involvement (92.3% versus 30.8%, p=0.004) and deep lobulation (38.5% versus 0%, p=0.039) were more likely to be noted in patients with GABCs. Surrounding blood vessels were identified in six cases of PABCs (6/13), but not in GABCs (p=0.015). The following characteristics were suggestive of GABCs, older patient age, higher transverse/longitudinal diameter ratio, subchondral bone involvement, and deep lobulation indicated a sensitivity of 84.6%, 76.9%, 75%, and 100%, and a specificity of 84.6%, 69.2%, 90%, and 61.9%, respectively. Conversely, surrounding blood vessels were suggestive of PABCs, with a sensitivity of 46.2% and specificity of 100%. The concordance between the two readers was moderate to nearly perfect. CONCLUSION: Age, subchondral bone involvement, lobulation, transverse/longitudinal diameter ratio, and surrounding blood vessels can be used to distinguish GABCs from PABCs.

Standard diffusion-weighted, intravoxel incoherent motion, and dynamic contrast-enhanced MRI of musculoskeletal tumours: correlations with Ki67 proliferation status.

AIM: To determine whether quantitative parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with the Ki67 proliferation status in musculoskeletal tumours. MATERIALS AND METHODS: Twenty-eight patients with musculoskeletal tumours diagnosed via surgical specimen histological analysis who underwent standard DWI, IVIM, and DCE were reviewed retrospectively. The mean standard DWI (apparent diffusion coefficient [ADC]), IVIM (pure diffusion coefficient [D], pseudo-diffusion coefficient [D∗] and perfusion fraction [ƒ]), and DCE (volume transfer constant [Ktrans], rate constant [Kep], and extravascular extracellular volume fraction [Ve]) parameters were measured and correlated with the Ki67 index. The Ki67 value was categorised as high (>20%) or low (≤20%). RESULTS: The ADC and D values correlated negatively with the Ki67 index (r=-0.711∼-0.699, p<0.001), whereas the Ktrans and Kep values correlated positively with the Ki67 index (r=0.389-0.434, p=0.021, 0.041). The ADC and D values were lower (p<0.001), whereas the Ktrans and Kep values were higher (p=0.011, 0.005) in musculoskeletal tumours with a high Ki67 status than in those in a low status. The ADC and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.953), which is statistically bigger than the AUC of Ktrans and Kep (0.784 and 0.802, respectively). CONCLUSION: ADC, D, Ktrans, and Kep correlate with the Ki67 index. ADC and D are the strongest quantitative parameters for predicting Ki67 status.

[Spontaneous focal lamina cribrosa defect in glaucoma and its relationship with nonprogressive glaucomatous neuropathy].

Objective: To investigate the relationship between the spontaneous focal lamina cribrosa (LC) defect and the progression of visual field defect (VFD) in primary open-angle glaucoma (POAG). Methods: Case-control study. The patients who were diagnosed as POAG with at least 5 visual field results had been collected from June 2018 to January 2019 at Beijing Tongren Hospital Affiliated to Capital Medical University. Serial imaging by swept source optical coherence tomography B-Scan of the optic discs were acquired at the end of the follow-up and LC defects status were reviewed. Intraocular pressure, mean defects of visual field, central corneal thickness and axis length were recorded in the follow-up duration. Eyes were classified as having either progressive or nonprogressive VFD, and associating factors were evaluated by χ(2) or Fisher's test, mixed-effect model analysis and multivariate Logistical regression analysis. Results: A total of 32 subjects (64 eyes) were enrolled in the study with mean age of (47±14) years, the group consisted of 17 males and 15 females. Fourty-five eyes showed nonprogressive VFD. LC defects were more common in eyes without (28/45) rather than with progressive VFD (5/19) (χ(2)=6.896, P=0.009). Eyes with nonprogressive VFD showed longer axis length[(26.82±1.34) mm vs. (25.79±1.44) mm; t=6.589, P=0.013] and wider LC defects diameter[211 (165-326) µm vs. 114 (106-156) µm; Z=4.797, P=0.042]. Multivariate Logistic regression analysis revealed that the presence of LC defect was significantly associated with nonprogressive VFD (odds ratio=0.217, P=0.012). There were 7 subjects with asymmetry VFD and the incedence of LC defects without progression (7/7) is higher than fellow eye with progression (1/7, P=0.002). There was only one patient with progressive VFD showed one LC defect with an smaller diameter (169 µm) than that in the contralateral eyes with stable VFD (269 µm). Conclusions: LC defects are more common in eyes with nonprogressive VFD. Spontaneous LC defects are associated with nonprogressive glaucomatous defects and could be a protective factor for POAG. (Chin J Ophthalmol, 2019, 55:338-346).

Effects of methotrexate on the quality of oocyte maturation in vitro.

Methotrexate (MTX), an antifolate drug, is widely used for clinical treatment of malignancies and ectopic pregnancy. Many studies have documented that MTX has strong side-effects on rapidly dividing somatic cells. However, its side-effects on female reproductive cells have not been widely reported. Combined with in vitro culture, two-photon fluorescence imaging and three-dimensional reconstruction, this study analyzed the effects of MTX on oocyte maturation time, chromosome arrangement, karyotype, spindle morphology, and the localization of microtubule organizing centers (MTOCs). Compared with a control group (84%), the rate of germinal vesical breakdown in the MTX group dropped to 73% (P < 0.05). The rate of the first polar body extrusion in the MTX group (53%) was also below the control group (63%; P < 0.05). The rate of abnormal chromosomal arrangement in the MTX group was 60%, but 24% in the control group (P < 0.05). The matured oocyte karyotypes showed 20 univalents in both control and MTX groups, while point-shaped DAPI signals were detected in the MTX group. The rate of abnormal spindle in the MTX group was 49%, but 17% in the control group (P < 0.05). MTOCs in oocytes with normal spindles concentrated at the poles, while MTOCs in oocytes with abnormal spindles were scattered around the poles or in the ooplasm. MTX changes the structures of chromosomes and spindles, potentially by interfering with DNA methylation. The above results indicate a basis for understanding negative effects of MTX on oocyte maturation quality, and provide information for the clinical application of MTX in female patients.

[Relationship between myocardial microRNA-30a expression and myocardial fibrosis in rats post myocardial infarction].

OBJECTIVE: To explore the potential role and mechanism of microRNA(miR)-30a in myocardial fibrosis after myocardial infarction (MI). METHODS: Rats were randomly divided into 1 week MI group (n=11), 2 weeks MI group (n=13) and 4 weeks MI group (n=15) by applying random number table after left anterior descending coronary artery ligation. Rats in Sham group were examined at respective time points (n=16). Heart function was monitored by echocardiography. Myocardial collagen volume fraction (CVF) was determined on Masson stained sections. Myocardial expression of collagen Ⅰ and Ⅲ was determined by immunohistochemistry. The myocardial mRNA level of miR-30a, TGF-ß1 and CTGF were detected by real time-quantitative PCR analysis. The myocardial protein levels of TGF-ß1 and CTGF were measured by Western blot analysis. RESULTS: The LVEDD ((8.37±0.58) mm) and LVESD ((6.12±0.82) mm) in 4 weeks MI group were significantly higher than those in Sham group ((6.08±0.57) mm, (4.17±0.60) mm), all P<0.01. The FS ((27.0±3.9) %) and LVEF ((51.0±6.3) %) in 4 weeks MI group were significantly lower than those in Sham group ((47.0±2.1) %, (82.0±2.3)%), all P<0.01. The level of myocardial CVF in 1 week MI group, 2 weeks MI group and 4 weeks MI group were significantly higher than in Sham group (all P<0.01) in a time-dependent manner. The level of myocardial collagen Ⅰ and Ⅲ was increased gradually from 1 week to 4 weeks post MI compared with Sham group (all P<0.01). The collagen Ⅰ/Ⅲ ratio was similar between 1 week MI group and Sham group (P=0.58), however, which was significantly higher in 2 weeks MI group and 4 weeks MI group compared with Sham group (all P<0.01), and the ratio was significantly higher in 4 weeks MI group than 2 weeks MI group (P<0.01). The level of miR-30a was significantly and gradually reduced in all MI groups compared with Sham group (all P<0.01). The mRNA and protein levels of TGF-ß1 and CTGF were significantly and gradually increased after MI compared with Sham group (all P<0.001). CONCLUSIONS: Our results indicate that overexpression of miR-30a after MI might be a potential strategy for suppressing myocardial fibrosis by modulating the mRNA and protein levels of TGF-ß1 and CTGF.

Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs.

OBJECTIVE: The main objective of this study was to investigate, in a population of normal postmenopausal women, the association between menopause and severity of lumbar disc degeneration from the first lumbar to the first sacral vertebra on magnetic resonance imaging. METHODS: Between January 2010 and May 2013, 846 normal women and 4230 intervertebral discs were retrospectively analyzed. Age, height, weight and years since menopause (YSM) were recorded. Disc degeneration was evaluated using the modified Pfirrmann grading system. RESULTS: Compared to premenopausal and perimenopausal women, postmenopausal women had more severe disc degeneration after removal of age, height and weight effects (p < 0.0001). Postmenopausal women were divided into six subgroups for every 5 YSM. When YSM was below 15 years, there was a significant difference between every two groups, i.e. groups 1-5 YSM, 6-10 YSM and 11-15 YSM (p < 0.01). A positive trend was observed between YSM and severity of disc degeneration, respectively, i.e. L1/L2 (r = 0.235), L2/L3 (r = 0.161), L3/L4 (r = 0.173), L4/L5 (r = 0.146), L5/S1 (r = 0.137) and all lumbar discs (r = 0.259) (p < 0.05 or 0.01). However, when YSM was above 15, there was no difference, i.e. groups 16-20 YSM, 21-25 YSM and 26-30 YSM (p > 0.05), and the significance correlation also disappeared (p > 0.05). CONCLUSION: Menopause is associated with disc degeneration in the lumbar spine. The association almost entirely occurred in the first 15 years since menopause, suggesting estrogen decrease may be a risk factor for lumbar disc degeneration.

Insulin promotes T cell recovery in a murine model of autoimmune myocarditis.

Glucose-insulin-potassium (GIK) is a useful adjunct to myocarditis. Besides its essential action in energy metabolism, insulin also exerts an anti-inflammatory effect. This study investigated the effect of insulin on myocardial inflammation in experimental autoimmune myocarditis (EAM) in mice and its potential role in T cell regulation. Mice were divided randomly into a normal control group, a saline-treated EAM group and an insulin-treated EAM group. The histopathological changes of myocardium, α-myosin heavy chain (MyHCα)(614-629) antigen-specific autoantibody titre, the serum level of cardiac troponin I (cTnI), mitogen-activated protein kinase (MAPK) family members' activity and content were measured. Furthermore, the phenotype of T lymphocyte subsets in splenocytes was analysed to evaluate the immune status of mice. Insulin reduced serum cTnI of EAM mice on days 14 and 21 (P < 0·05) after immunization, with no changes in blood glucose and autoantibody production. Western blot revealed that extracellular signal-regulated protein kinase (ERK1/2) may be a determining factor in this process. Total ERK1/2 and phospho-ERK1/2 (p-ERK1/2) were both up-regulated in insulin-treated mice after immunization. We also found that insulin treatment promoted T cell recovery without changing the naive-to-memory T-cell ratio; in particular, CD3(+) T cells in insulin-treated mice proliferated more vigorously than in control mice (P < 0·05). We report here for the first time that insulin alleviates myocarditis in the EAM model. These data show that insulin has a direct effect on T cell proliferation in EAM. It is possible that GIK or insulin may assist T cell recovery towards normal in myocarditis, especially for diabetic or hyperglycaemic patients.

[Curcumol reverses temozolomide resistance in glioma cells by regulating the UTX/MGMT axis].

OBJECTIVE: To explore the mechanism through which curcumol reverses primary drug resistance in glioma cells. METHODS: The inhibitory effect of 10, 20, and 40 µg/mL curcumol were observed in human glioma cell lines A172 and U251. UTX-overexpressing glioma cells constructed by lentiviral transfection were treated with curcumol (40 µg/mL), temozolomide (TMZ; 10 µg/mL), or both, and the changes in cell viability, clone formation capacity and apoptosis were assessed using MTT assay, cell clone formation experiment, and flow cytometry; UTX activity in the cells was determined using a UTX detection kit, and the enrichment of UTX and H3K27me3 in the MGMT promoter region was detected with ChiP-qPCR. The protein expressions in glioma cells were detected using Western blotting and immunohistochemistry. In a nude mouse model bearing glioma xenografts, the effects of curcumol (20 mg/kg), TMZ (20 mg/kg) and their combination on tumor growth and expressions of UTX, H3K27me3 and MGMT were evaluated. RESULTS: Curcumol significantly inhibited the proliferation (P<0.05) and promoted apoptosis of cultured glioma cells (P<0.01). Curcumol, but not TMZ, produced significant inhibitory effect on tumor growth in the tumor-bearing mice (P<0.01). Curcumol significantly inhibited UTX activity and increased the expression level of H3K27me3 protein in the glioma cells. UTX overexpression obviously decreased H3K27me3 protein expression and reversed the effects of curcumol on glioma cell proliferation and apoptosis (P<0.01). Curcumol reduced the enrichment of UTX and H3K27me3 in the MGMT promoter region (P<0.05) and decreased MGMT protein expression, which was reversed by UTX overexpression. In both the in vivo and in vitro experiments, curcumol combined with TMZ significantly increased H3K27me3 protein expression in the glioma cells, reduced the expression of its downstream target gene MGMT, and enhanced TMZ sensitivity of the glioma cells. CONCLUSION: Curcumol can enhance glioma cell sensitivity to TMZ by regulating the UTX/MGMT axis.

Insulin Resistance-Varying Associations of Adiposity Indices with Cerebral Perfusion in Older Adults: A Population-Based Study.

OBJECTIVES: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance. DESIGN: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study. SETTING AND PARTICIPANTS: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans. METHODS: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis. RESULTS: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted ß-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05). CONCLUSION: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.

Four-dimensional visualization and quantitative analysis of meiotic spindle movements in live mouse oocytes.

This paper made a different attempt of real-time observation of the meiotic spindle movements in living mouse oocyte using a convenient method. This method was based on an experimental phenomenon discovered in our work. In living mouse oocytes, a high concentration of calcium ions (Ca(2+)) was observed throughout the region occupied by the initial meiotic spindle. After Ca(2+) labelling with Fura-2, a weakly fluorescent area (WFA) appeared on each side of the chromosomes. The activities of the WFAs changed during spindle development. By real-time tracking of WFAs, we were able to indirectly observe the meiotic spindle movements. Occasionally, it was observed that the first meiotic spindle rotated from an orientation parallel to the cortex to become perpendicular, instead of migrating from the oocyte centre to the cortex along its axis. Moreover, we analysed this uncommon rotation of the first meiotic spindle and found that the whole rotation process can be divided into two phases: the early slow-speed rotation and the subsequent rapid-speed rotation. We further characterized this rotation with respect to rotational speed and acceleration at all the stages of development. By using a two-photon laser-scanning microscope in combination with Fura-2 dye that is nondamaging to oocytes, we provide a convenient method for indirect visualization and quantitative analysis of spindle movements by real-time tracking of WFAs. This method is easy to operate and master, and economical with time and effort.

Prolonged exclusive breastfeeding, autumn birth and increased gestational age are associated with lower risk of fever in children with hand, foot, and mouth disease.

Epidemics of hand, foot, and mouth disease (HFMD) have been emerging and reemerging in recent years. This study aims to investigate whether breastfeeding and other factors may affect the profile of fever and disease course in children with HFMD. Three hundred seventy-two preschool children with HFMD were included. The demographics, environmental factors, and delivery- and feeding-associated factors in the children were obtained and their effects on the profile of fever and disease course were analyzed. Of the 372 children, 139 (37.37%) had fever during the disease course. Gender, breastfeeding pattern, birth season and gestational age were significantly different between the children with and without fever (p = 0.034, p < 0.0001, p = 0.035 and p = 0.013, respectively). After multivariate-adjusted analysis, prolonged exclusive breastfeeding (p = 0.001, OR 0.401, 95% CI 0.229-0.704), autumn birth (p = 0.007, OR 0.409, 95% CI 0.214-0.784) and higher gestational age (p = 0.029, OR 0.089, 95% CI 0.010-0.781) were protective factors for the incidence of fever.

Effects of Cu underlayer on the growth and magnetic properties of FePt thin films on MgO (001) substrate.

During ordering process of face centered tegragonal (fct) L1(0) phase of the FePt alloy, there exist three growth variants of axes (001) from original disordered fcc structured phase. When FePt film was directly deposited on the MgO (001) substrate, the variant perpendicular to the film plane grew, resulting in a low out-of-plane coercivity of 1.3 kOe. By using Cu underlayer, two variants lying in the film plane got same chance to grow, which caused an in-plane perpendicular alignment of the tetragonal axes of FePt L1(0) phases. The crystallographic relationship between Cu and FePt layers is Cu (100)<100>//fct FePt (100)<100>. A high in-plane coercivity of 4.6 kOe was obtained due to the high density of micro-defects (mcro-twins, anti-phase boundaries, etc.) in the film plane. This work demonstrated a way of selecting the growth variants of ordering process to adjust the magnetic properties of the ordered FePt thin films.

[Smith-Kingsmore syndrome caused by MTOR gene variation: 2 cases and literature review].

Objective: To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. Methods: The clinical data of 2 children carrying MTOR gene variant, diagnosed at Xi'an Children's Hospital from April 2018 to April 2021, were retrospectively summarized."MTOR"and"Smith-Kingsmore syndrome"were used as key words to search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and OMIM up to August 2021. The characteristics of MTOR gene variation and the clinical phenotype of children with Smith-Kingsmore syndrome were summarized. Results: Two children were both females, aged 1.5 years and 2 years respectively, the onset age were both in infancy. They both had developmental delay, megalencephaly and abnormal face. Both whole exome sequencing revealed a de novo heterozygous missense variant in MTOR gene. One case carried c.5395G>A (p.Glu1799Lys) and the other case carried c.7234G>C (p.Asp2412His). There was no literature of MTOR gene variation in Chinese. So far, a total of 45 cases were reported worldwide with detailed clinical information. Eleven variations in MTOR gene were involved, which were all heterozygous missense mutations. Among them, p.Glu1799Lys was the most common sites (28 cases,62%). Another case carried c.7234G>C (p.Asp2412His) was not reported before. Summarizing the 47 cases (including these 2 cases), 46 cases had developmental delay or intellectual disability, 9 cases had developmental regression,42 cases had megalencephaly, 30 cases had facial malformation,16 cases had hypotonia, 17 cases had autism spectrum disorders, 3 cases had hyperactivity, 3 cases had obsessive compulsive disorder, 13 cases had eye diseases, 11 cases had cutaneous vascular malformation, and 9 cases had hypoglycemia. Conclusions: The main clinical features of Smith-Kingsmore syndrome include megalencephaly, developmental delay or intellectual disability, and facial malformation, which can be combined with epilepsy, autism spectrum disorder, hypotonia, hypoglycemia and so on. The variation of MTOR gene is the cause of Smith-Kingsmore syndrome.

[Effects of climate changes on the distribution of Rhipicephalus microplus in China].

OBJECTIVE: To identify the environmental factors affecting the geographical distribution of Rhipicephalus microplus in China, and to examine the impact of climate changes on the distribution of R. microplus in China. METHODS: The national and international publications pertaining to the geographical distribution of R. microplus in China were retrieved, and the geographical location was extracted. The suitable habitats of R. microplus and the dominant environmental factors affecting the distribution of suitable habitats of R. microplus were predicted in China based on the geographical data and environmental variables using the ArcGIS 10.7 software and the maximum entropy model. RESULTS: Among the main climatic factors affecting the geographical distribution of R. microplus in China, the factors contributing more than 10% to the suitable habitats of R. microplus mainly include the annual mean precipitation (38.2%), the average temperature of the coldest quarter (28.4%) and the precipitation of the driest month (14.2%). The current suitable habitats of R. microplus were mainly found in southern China, and the high-, medium- and low-suitable areas accounted for 8.6%, 13.1% and 10.5% of the total land area of China, respectively. The suitable habitats of R. microplus were predicted to increase by 399 800 km2 in China using the maximum entropy model under the RCP 4.5 emissions scenario in 2070, and the emerging suitable habitats were mainly distributed in Gansu Province, Ningxia Hui Autonomous Region, Qinghai Province, Hebei Province, Shaanxi Province, Liaoning Province, Inner Mongolia Autonomous Region, Shandong Province, Sichuan Province and Tibeten Autonomous Region. In addition, the suitable habitats of R. microplus were predicted to show an overall expansion towards northward from present to 2070. CONCLUSIONS: Climate changes affect the distribution of suitable habitats of R. microplus in China, and annual mean precipitation may be a key factor affecting the distribution of suitable habitats of R. microplus.

Trypsin-like protease-active extracellular protein extracts from Porphyromonas gingivalis ATCC 33277 induce apoptosis in bovine aortic endothelial cells.

BACKGROUND AND OBJECTIVE: Certain virulence factors participating in periodontitis may relate to cardiovascular diseases. This study was to evaluate the pro-apoptotic effect of protein extracts from Porphyromonas gingivalis on bovine aortic endothelial cells (BAECs). MATERIAL AND METHODS: The BAECs were exposed to trypsin-like protease-active protein extracts from P. gingivalis, and apoptosis was examined by Hoechst 33342 staining, DNA fragmentation assay and cleaved caspase-3 detection. When BAECs were exposed to protein extracts pretreated with trypsin-like protease inhibitor (TLCK), the apoptosis rate was evaluated by Annexin V-propidium iodide staining. To further study the potential mechanism of the pro-apoptotic effect, immunoblotting was used to detect expression of alpha-tubulin, integrin beta1 and activated ERK1/2 in BAECs treated with protein extracts or cultured in suspension. RESULTS: After exposure to the protein extracts, BAECs exhibited loss of cell adhesion and apoptotic cell death. The pro-apoptotic effect could be delayed by TLCK pretreatment. In addition, BAECs treated with protein extracts showed decreased levels of alpha-tubulin, integrin beta1 and activated ERK1/2. When BAECs were cultured in suspension, ERK1/2 activation was also inhibited, but the percentage decrease in ERK1/2 activation was less than that induced by protein extracts. Moreover, no significantly altered expression of alpha-tubulin was detected in suspended cells. CONCLUSION: Trypsin-like protease-active protein extracts from P. gingivalis could induce apoptosis of BAECs. The destruction of alpha-tubulin and integrin beta1 and decrease of ERK1/2 activation might contribute to the pro-apoptotic effect of the protein extracts.

Effects of L-ascorbic acid, alpha-tocopherol and co-culture on in vitro developmental potential of porcine cumulus cells free oocytes.

The maturation and developmental potential on cumulus-cell-free oocytes is of great importance theoretically and practically. The present study was to investigate the effects of l-ascorbic acid, alpha-tocopherol and co-culture on in vitro developmental potential of porcine denuded oocytes (DOs). Porcine DOs were cultured in maturation medium supplemented with vitamin C (0, 50, 100, 250, 500, 750 microM) and vitamin E (0, 10, 20, 50, 100, 250 microm), respectively. And they were also co-cultured with dispersed cumulus cells (group CCscoculture), intact cumulus cells oocyte complexes (COCs) (group COCscoculture), and COCs whose oocytes were removed (group OOXcoculture), respectively. After 44 h incubation, the maturation rates, cleavage rates and blastocyst rates after parthenogenetic activation in three experiments mentioned above were collected and analysed, respectively. L-Ascorbic acid promoted porcine DOs in vitro maturation and blastocyt development after parthenogenetic activation while alpha-tocopherol did not increase the in vitro maturation rates, but improved the blastocyst rate. None of the three co-culture manner promoted the in vitro maturation and the cleavage of porcine DOs after parthenogenetic activation, but all the co-culture manners improved the blastocyst rates. Both Vitamin C and E enhance the in vitro developmental potential of porcine DOs. Co-culture increases the developmental potential of porcine DOs.

Follow-up management strategy for patients undergoing peritoneal dialysis during novel coronavirus pneumonia epidemic.

OBJECTIVE: The study aimed to explore the best follow-up management strategy for patients undergoing peritoneal dialysis (PD) during the novel coronavirus pneumonia (NCP) epidemic. PATIENTS AND METHODS: Patients undergoing PD who were followed up during the NCP epidemic by our hospital were enrolled in this study. Because of the need to control the epidemic, a follow-up system was established during the epidemic period, with WeChat, QQ, and the telephone as the main methods of communication. Outpatient and emergency follow-ups were carried out to ensure the safety of dialysis and the prevention and control of the epidemic. The follow-up strategy included response measures related to the epidemic situation, prevention of peritonitis related to PD, water and salt control, exercise guidance, and psychological care. According to the patient's condition, the appointment system was implemented, with one consulting room and one process for each patient. The emergency patients were isolated in accordance with the epidemic situation. RESULTS: Since January 2020, among the 580 patients undergoing PD who were followed up in our department and their families, none had NCP infection. During the epidemic period, the standard hemoglobin level and the inpatient rate decreased. Complications related to PD, such as peritonitis, cardiovascular complications caused by volume overload, and pulmonary infection, did not significantly increase, and the withdrawal rate and mortality rate decreased compared with those in the same period last year. CONCLUSIONS: The patient follow-up strategy during the epidemic period had a significant positive effect on preventing and controlling the epidemic. Furthermore, during the epidemic period, encouraging patients and caregivers to pay attention to protection at home, avoid going out, strengthen self-management, and other measures were beneficial to the control of kidney disease itself, which is worth promoting. The close relationship between doctors and patients during the epidemic had a positive effect on the occurrence of complications related to patients undergoing PD.

LncRNAp21 promotes osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis by the Wnt/ß-catenin signaling pathway.

OBJECTIVE: The aim of this study was to explore the promoting effect of long non-coding ribonucleic acid p21 (lncRNAp21) on the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis (OP) through the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: A total of 30 healthy female rats were selected and randomly divided into three groups, including the lncRNAp21 group, OP model group (model group) and normal group. Rats in the lncRNAp21 group were given a certain quantity of lncRNAp21 inhibitors for gavage. Rats in the model group were regularly given 0.9% NaCl for gavage every day after the removal of bilateral ovaries. Meanwhile, rats in the normal group were fed normally without any changes. Bone mineral density (BMD) was measured after 12 weeks of modeling. The levels of procollagen type I N-terminal propeptide (PINP), serum estradiol (E2), osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal cross-linking telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the bone and serum of rats were measured by enzyme-linked immunosorbent assay (ELISA). Besides, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were adopted to detect the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues, respectively. RESULTS: Compared with the normal group and lncRNAp21 group, the serum level of E2 in the model group decreased significantly (p<0.05). BMD and phosphorus (P) content in the model group were both markedly lower than those of the normal group and lncRNAp21 group. However, calcium (Ca) content was remarkably higher than that of the normal group and lncRNAp21 group (p<0.05). The serum levels of bone resorption markers (including TRACP-5b and CTX) in the model group were prominently higher than those of the normal group (p<0.05). However, the levels of the two markers in the lncRNAp21 group were significantly lower than the model group (p<0.05). Additionally, bone formation markers (including OC, PINP and BALP) in the serum of rats in the model group were notably higher than those in the normal group and lncRNAp21 group (p<0.05). QRT-PCR and Western blotting results revealed that the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues of the model group were markedly lower than those of the normal group. However, the mRNA and protein expressions of Wnt1 and ß-catenin in the lncRNAp21 group were remarkably higher than the model group (p<0.05). CONCLUSIONS: Low expression of lncRNAp21 activates the Wnt/ß-catenin signaling pathway by increasing E2 secretion, eventually stimulating bone formation and increasing osteogenic differentiation of mesenchymal stem cells in OP model rats.