Association of AluYb8 insertion in the MUTYH gene with the risk of decreased left ventricular diastolic function in elderly diabetic patients / 中华老年医学杂志

Objective:To explore the relationship between AluYb8 insertion in the MUTYH gene and the risk of decreased left ventricular diastolic function in the elderly.Methods:In the retrospective analysis, 498 elderly patients with decreased left ventricular diastolic function(the disease group)and 155 people without left ventricular diastolic function(the control group)were recruited.Polymerase chain reaction was employed to analyze the genotype distribution of AluYb8 insertion in MUTYH gene.Cardiac function was measured by high-resolution color Doppler ultrasound.Results:The frequencies of the A/A, A/P and P/P genotypes were 30.1%(150/498), 48.4%(241/498)and 21.5%(107/498)in patients with decreased left ventricular diastolic function, and 27.7%(43/155), 54.8%(85/155)and 17.5%(27/155)in the control group, respectively.There were no significant differences in genotype( χ2=2.162, P=0.339)and allele frequency( χ2=1.342, P=0.794)between the two groups.Further analysis after stratification revealed that there were statistically significant differences in genotype( χ2=7.173, P=0.028)and allele frequency( χ2=8.352, P=0.015). Multivariate Logistic regression analysis showed that, in elderly patients with diabetes, P-allele carriers had a higher risk of decreased left ventricular diastolic function than non-carriers( OR=3.450, 95% CI: 1.148-10.372, P=0.027). Conclusions:AluYb8 insertion in the MUTYH gene may be associated with the risk of decreased left ventricular diastolic function in the elderly with diabetes.

Change in corneal endothelial cell density and morphology in different stages of keratoconus / 中华实验眼科杂志

Objective:To assess the changes in corneal endothelial cell density (CD) and morphology in patients with different stages of keratoconus.Methods:A cross-sectional study was conducted.One hundred and nineteen patients (199 eyes) with keratoconus who were treated in the Eye Hospital of Shandong First Medical University were included from March 2018 to October 2021.The 199 eyes were classified into stage Ⅰ (111 eyes of 58 cases), stage Ⅱ (41 eyes of 30 cases), stage Ⅲ (47 eyes of 31 cases) keratoconus groups according to the Amsler-Krumeich classification.In the same period, 25 age- and sex-matched healthy subjects (50 eyes) were enrolled as a normal control group.Corneal topography and anterior segment parameters such as keratometry (K), central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior chamber depth (ACD), corneal diameter and corneal volume were obtained by Pentacam 3-dimensional anterior segment imaging and analysis system.The corneal endothelial CD, percentage of hexagonal cells (6A), average cell area (AVE), maximum cell area (MAX), minimum cell area (MIN), cell area standard deviation (SD) and cell area coefficient of variation (CV) in the central area were evaluated by non-contact specular microscopy.The correlation between corneal endothelial CD, morphological parameters and corneal topographic parameters was analyzed by Spearman rank correlation.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY201803). All patients were informed of the purpose and methods of the study and written informed consent was obtained before any medical examination.Results:The CD of the normal control group and stage Ⅰ, Ⅱ, Ⅲ keratoconus groups was 2 941(2 809, 3 072), 2 825(2 667, 3 030), 2 747(2 475, 2 903) and 2 370(2 142, 2 525) cells/mm 2, respectively.With the progression of keratoconus, CD decreased gradually, and there was a significant difference in CD among the four groups ( H=94.862, P<0.001). There were significant differences in CV and 6A among the four groups ( H=45.018, 20.421; both at P<0.001). CV was significantly higher in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ and Ⅱ keratoconus groups and 6A was significantly lower in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ keratoconus group (all at P<0.05). With the progression of keratoconus, MAX, MIN, AVE and SD increased gradually, and there were significant differences in MAX, MIN, AVE and SD among the four groups ( H=37.905, 32.437, 110.182, 72.941; all at P<0.001). MAX and MIN in stage Ⅲ keratoconus group were significantly higher than those in stage Ⅰ keratoconus groups and normal control group (all at P<0.05). AVE and SD in stage Ⅲ keratoconus group were significantly higher than those in normal control group and stage Ⅰ and Ⅱ keratoconus groups (all at P<0.05). In patients with keratoconus, CD was moderately positively correlated with CCT ( rs=0.47, P<0.001) and TCT ( rs=0.53, P<0.001), and was moderately negatively correlated with mean keratometry (Km) ( rs=-0.59, P<0.001).6A was weakly positively correlated with CCT ( rs=0.18, P=0.01) and TCT ( rs=0.22, P=0.002), and was weakly negatively correlated with Km ( rs=-0.32, P<0.001). CV was weakly negatively correlated with CCT ( rs=-0.35, P<0.001) and TCT ( rs=-0.37, P<0.001), and was moderately positively correlated with Km ( rs=0.48, P<0.001). There was no correlation between CD, CV, 6A and ACD, or corneal volume. Conclusions:As the keratoconus progresses, the cornea protrudes and becomes thinner with CD and 6A decreasing while CV increasing.Corneal topographic parameters are related to the density and morphology of corneal endothelial cells.

Clinical Efficacy of Guizhi Shaoyao Zhimutang Combined with Fire Needling in Treatment of Periarthritis of Shoulder with Wind-cold-dampness Impediment Syndrome by Stimulating Pain Points and "Shoulder Three Acupoints" / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Guizhi Shaoyao Zhimutang （GZSYZM） combined with fire needling in the treatment of periarthritis of shoulder with wind-cold-dampness impediment syndrome by stimulating pain points and "shoulder three acupoints". MethodA total of 120 patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome， admitted to Hainan General Hospital from August 2020 to August 2022， were randomly divided into two groups using a random number table. The control group （60 cases） received treatment with GZSYZM for two weeks， while the observation group （60 cases） received treatment with GZSYZM combined with fire needling at pain points and "shoulder three acupoints" for two weeks. The clinical efficacy， adverse reactions， shoulder pain intensity， shoulder joint function， and levels of calcitonin gene-related peptide （CGRP）， cyclooxygenase-2 （COX-2）， interleukin （IL）-2， and IL-17 before and after treatment were compared between the two groups. ResultThe total effective rate in the observation group was 88.33% （53/60）， significantly higher than 68.33% （41/60） of the control group （χ²=7.070， P<0.01）. Compared with the results before treatment， both groups showed significant reductions in pain rating index （PRI）， visual analog scale （VAS） scores， present pain intensity （PPI）， and Simplified McGill Pain Questionnaire （SF-MPQ） total scores， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 after treatment （P<0.01）， and improved pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. Compared with the control group after treatment， the observation group showed significantly reduced PRI， VAS score， PPI， SF-MPQ total score， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 （P<0.01）， and increased pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionGZSYZM combined with fire needling at pain points and "shoulder three acupoints" can effectively reduce the levels of serum inflammatory factors and pain mediators， alleviate pain， and improve shoulder joint function in patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome.

Research on the formulation and revision of standard limits for antimony,boron and vanadium in the "Standards for Drinking Water Quality (GB5749-2022)" in China / 中华预防医学杂志

China is rich in antimony, boron, and vanadium mineral resources, which have been detected in environmental water bodies and drinking water. During the revision process of the "Standards for Drinking Water Quality (GB5749-2006)", research and evaluation are focused on three indicators: antimony, boron and vanadium. Vanadium is added and the limit value of boron is adjusted. This study reviews and discusses the technical contents related to the revision of the antimony, boron and vanadium, including the environmental presence levels, exposure status, health effects, and the revision of the standard limits of these three indicators. Suggestions are also made for the implementation of this standard.

Clinical analysis of combined immunotherapy in patients with malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.

Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular Cl- concentration and activation of SGK1 signaling pathway.

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

Promoting effect of nicotinamide on generation of neural crest stem cells derived from human embryonic stem cells / 中华实验眼科杂志

Objective:To investigate the role of nicotinamide (NIC) in the differentiation of neural crest cells from human embryonic stem cells (hESCs), and lay the foundation for the induction of hESC-derived corneal endothelial cells.Methods:hESCs line H1 cultured for 5-7 days was used for induction.According to the different components of the neural crest induction medium, cells were assigned into different groups for 7-days induction, including group treated without NIC cultured in induction medium only, group treated with NIC cultured in induction medium containing 10 mmol/L NIC, NIC+ resveratrol (Res) group cultured in induction medium containing 10 mmol/L NIC and 10 μmol/L Res and Sirtinol group cultured in induction medium containing 10 μmol/L Sirtinol.Res and Sirtinol were used as SIRT1 activity agonist and inhibitor, respectively.The relative mRNA expression levels of hESCs and neural crest cell markers were detected by real-time fluorescence quantitative PCR at 1, 3, 5 and 7 days during the induction.The expression of neural crest cells markers after 7 days of induction was assayed by immunofluorescence staining.The induction efficiency of NIC and the effect of SIRT1 regulation on human natural killer 1 (HNK-1) positive cells expression were evaluated through flow cytometry analysis of percentages of nerve growth factor receptor (P75) and HNK-1 + cells. Results:Compared with the group treated without NIC, the mRNA expressions of totipotent genes octamer transcription factor 4 (OCT4) and homeodomain proteins (NANOG) were significantly decreased, and the mRNA expression levels of neural crest cell markers P75, HNK-1, SRY-related HMG box (SOX) 9 and SOX10 were significantly increased in the group treated with NIC after 5 days of induction (all at P<0.05). In the group treated without NIC, P75 was weakly expressed, and HNK-1 was sporadically expressed, and transcription factor AP-2β (AP-2β) and paired-like homeodomain transcription factor 2 (PITX2) were not detected.In the group treated with NIC, P75, HNK-1, AP-2β and PITX2 were strongly expressed.The proportion of P75 + HNK-1 + cells and P75 + cells were both significantly higher in the group treated with NIC than without NIC ( t=8.481, P=0.001; t=2.987, P=0.041). The percentage of HNK-1 + cells in groups treated without and with NIC, NIC+ Res group and Sirtinol group were (34.267±12.522)%, (89.633±1.358)%, (64.667±6.429)% and (86.300±3.460)%, respectively, with a statistically significant overall difference ( F=36.799, P<0.001). The proportion of HNK-1 + cells in NIC+ Res group was significantly lower than that in the groups treated with NIC and Sirtinol (all at P<0.05). Conclusions:NIC promotes the differentiation of hESCs-derived neural crest cells by inhibiting the activity of SIRT1 to enhance the expression of HNK-1.NIC treatment may provide a new strategy for source of seed cells in the treatment of neural crest cell-related diseases, such as corneal endothelial transplantation.

Association between non-thyroidal illness syndrome and pre-sarcopenia in elderly patients / 中华老年医学杂志

Objective:To explore the association between non-thyroid illness syndrome(NTIS)and pre-sarcopenia in the elderly.Methods:In the retrospective study, a total of 219 patients aged 60-85 years in Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University from April 2018 to March 2021, included 60 patients with NTIS and 159 patients without NTIS.Clinical data, laboratory results and body composition data were collected.Pre-sarcopenia was diagnosed based on human composition determination data and diagnostic criteria of pre-sarcopenia.Logistic regression analysis, Pearson's correlation analysis and the area under receiver operator characteristic curve(ROC)were used to explore the correlation between serum thyroid hormone levels and diagnostic data level of pre-sarcopenia.Results:Of 54 pre-sarcopenia patients, 30.3%(36/119)were male, 18.0%(18/100)were female with statistically significantly differences( P<0.01). Mean age was higher in both male and female patients in the NTIS group than in the non-NTIS group( P<0.01). The body mass index, levels of triiodothyronine(T3), free triiodothyronine(FT3), hemoglobin, and albumin were lower in NTIS group than in non-NTIS group( P<0.05). The prevalence of presarcopenia in female patients was higher in the NTIS group than in the non-NTIS group[42.9%(10/17) vs.10.6%(8/83), χ2=9.564, P<0.01]. Multivariate logistic regression analysis showed that the risk of pre-morbidity of sarcopenia was significantly higher in NTIS patients than in non-NTIS patients.FT3 was positively correlated with skeletal muscle mass index, fat-free body weight, and phase angle, and negatively correlated with visceral fat area( r=-0.17, P<0.05). While, free thyroxine(FT4)was negatively correlated with skeletal muscle mass index( r=-0.21), fat-free body weight( r=-0.16)and phase Angle( r=-0.2, P<0.01 or P<0.05), and was positively correlated with body fat percentage and visceral fat area( r=0.20 and 0.22, respectively, P<0.01). The use of area under ROC curve(AUC)of FT3 predicting sarcopenia stage showed that the AUC was 0.768(95% CI: 0.691~0.844). Conclusions:In elderly patients, NTIS is correlated with the pre-sarcopenia in the elderly, and FT3 and FT4 are related to muscle mass.The low level of FT3 can predict the pre-validation of pre-sarcopenia.

TMEM16A ameliorates vascular remodeling by suppressing autophagy via inhibiting Bcl-2-p62 complex formation.

Rationale: Transmembrane member 16A (TMEM16A) is a component of calcium-activated chloride channels that regulate vascular smooth muscle cell (SMC) proliferation and remodeling. Autophagy, a highly conserved cellular catabolic process in eukaryotes, exerts important physiological functions in vascular SMCs. In the current study, we investigated the relationship between TMEM16A and autophagy during vascular remodeling. Methods: We generated a transgenic mouse that overexpresses TMEM16A specifically in vascular SMCs to verify the role of TMEM16A in vascular remodeling. Techniques employed included immunofluorescence, electron microscopy, co-immunoprecipitation, and Western blotting. Results: Autophagy was activated in aortas from angiotensin II (AngII)-induced hypertensive mice with decreased TMEM16A expression. The numbers of light chain 3B (LC3B)-positive puncta in aortas correlated with the medial cross-sectional aorta areas and TMEM16A expression during hypertension. SMC-specific TMEM16A overexpression markedly inhibited AngII-induced autophagy in mouse aortas. Moreover, in mouse aortic SMCs (MASMCs), AngII-induced autophagosome formation and autophagic flux were blocked by TMEM16A upregulation and were promoted by TMEM16A knockdown. The effect of TMEM16A on autophagy was independent of the mTOR pathway, but was associated with reduced kinase activity of the vacuolar protein sorting 34 (VPS34) enzyme. Overexpression of VPS34 attenuated the effect of TMEM16A overexpression on MASMC proliferation, while the effect of TMEM16A downregulation was abrogated by a VPS34 inhibitor. Further, co-immunoprecipitation assays revealed that TMEM16A interacts with p62. TMEM16A overexpression inhibited AngII-induced p62-Bcl-2 binding and enhanced Bcl-2-Beclin-1 interactions, leading to suppression of Beclin-1/VPS34 complex formation. However, TMEM16A downregulation showed the opposite effects. Conclusion: TMEM16A regulates the four-way interaction between p62, Bcl-2, Beclin-1, and VPS34, and coordinately prevents vascular autophagy and remodeling.

Endophilin A2 regulates calcium-activated chloride channel activity via selective autophagy-mediated TMEM16A degradation.

TMEM16A Ca2+-activated chloride channel (CaCC) plays an essential role in vascular homeostasis. In this study we investigated the molecular mechanisms underlying downregulation of TMEM16A CaCC activity during hypertension. In cultured basilar artery smooth muscle cells (BASMCs) isolated from 2k2c renohypertesive rats, treatment with angiotensin II (0.125-1 µM) dose-dependently increased endophilin A2 levels and decreased TMEM16A expression. Similar phenomenon was observed in basilar artery isolated from 2k2c rats. We then used whole-cell recording to examine whether endophilin A2 could regulate TMEM16A CaCC activity in BASMCs and found that knockdown of endophilin A2 significantly enhanced CaCC activity, whereas overexpression of endophilin A2 produced the opposite effect. Overexpression of endophilin A2 did not affect the TMEM16A mRNA level, but markedly decreased TMEM16A protein level in BASMCs by inducing ubiquitination and autophagy of TMEM16A. Ubiquitin-binding receptor p62 (SQSTM1) could bind to ubiquitinated TMEM16A and resulted in a process of TMEM16A proteolysis in autophagosome/lysosome. These data provide new insights into the regulation of TMEM16A CaCC activity by endophilin A2 in BASMCs, which partly explains the mechanism of angiotensin-II-induced TMEM16A inhibition during hypertension-induced vascular remodeling.

Evaluation of Residual Stepping Ability in Monkeys with Spinal Cord Injury / 中国康复理论与实践

Objective:To evaluate the residual stepping ability in monkeys with spinal cord injury longitudinally. Methods:Four adult female monkeys were studied. Right hemisection of 10 mm spinal cord tissue was performed at the T7-9 segment. Gait tests of bipedal locomotion were performed before, and six weeks and twelve weeks after injury by VICON system. Gait cycle duration, amplitude of knee and ankle angles, and ratio of united parameters were obtained from successive stepping and were quantitative analyzed. Results:The coordination of bilateral hindlimbs was destroyed after spinal cord injury, and the right hindlimb showed obviously dragging. The gait cycle duration of the left hindlimb increased significantly (P < 0.001), and the amplitudes of knee and ankle angle significantly increased (P < 0.001) after spinal cord injury. The ratio of united parameters was not statistically different among all the time points (P > 0.05). The gait cycle duration of the left hindlimb was correlated with step length (r = 0.838, P = 0.001), step height (r = 0.726, P = 0.007) and amplitude of ankle angle (r = 0.766, P = 0.004), and the amplitude of ankle angle was correlated with step length (r = 0.627, P = 0.029). Conclusion:The gait pattern of monkey with spinal cord injury has been changed. The gait strategy of the uninjured side was adjusted compensatively after spinal cord injury to adapt the functional impairment of contralateral hindlimb.

Effects of leptin on lipid metabolism and inflammatory factors in diabetic rats / 中国应用生理学杂志

To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 μg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Compared with the control group, the blood glucose levels of other groups were increased significantly (P＜0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P＜0.05, P＜0.01). The insulin level of high dose leptin group decreased significantly (P＜0.01). There was no significant difference in FBG and INS among the three groups (P＞0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P＜0.05, P＜0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P＜0.05), HDL-C level of high dose group was increased significantly (P＜0.01). Compared with different dose groups, the high dose of leptin (100 μg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P＜0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 μg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.

Effect of Duhuo Jisheng Tang on PERK/Bip Signaling Pathway in Knee Osteoarthritis Model Rats / 中国实验方剂学杂志

Objective: To explore the possible mechanism of Duhuo Jisheng Tang in relieving knee osteoarthritis based on protein kinase R-like endoplasmic reticulum kinase (PERK)/immunoglobulin-binding protein (Bip) signaling pathway.Method: A model of knee osteoarthritis was established by cold stimulation.Rats were randomly divided into blank group,model group,celecoxib group (0.021 g·kg-1),low,medium and high-dose Duhuo Jisheng Tang groups (8.37,16.72,33.48 g·kg-1).Blank group and model group were given equal volume of physiological saline.The changes of knee joint diameter were recorded.The pathological changes of rat articular cartilage were observed by hematoxylin-eosin (HE) staining.The expressions of tumor necrosis factor-alpha (TNF-α),interleukin-1β(IL-1β) and hyaluronic acid (HA) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The mRNA and protein expression levels of PERK,Bip and cysteinyl as parates pecific protein-9(Caspase-9) in cartilage were detected by Real-time PCR and Western blot.Result: The knee joint redn ess and the joint diameter of celecoxib group and high-dose Duhuo Jisheng Tang group were improved,and the joint diameter was reduced significantly (Pα,IL-1β and HA were increased in model group (PPPα,IL-1β and HA in serum of celecoxib group and high-dose Duhuo Jisheng Tang group were decreased (PPPPConclusion: Duhuo Jisheng Tang can alleviate the symptoms of knee osteoarthritis model rats,and its mechanism may be related to the regulation of PERK/Bip signaling pathway in rat cartilage.

Advances in the application of portable perimetry in glaucoma / 中华实验眼科杂志

Glaucoma is the irreversible blind eye disease and many glaucoma patients have severe optic nerve and visual field defect in their initial diagnosis.Therefore,visual field is critical to the evaluation of glaucoma damage.However,the testing time is too long and the conventional standard automatic perimetry is not convenient to carry,which limits its application in the diagnosis of glaucoma.At present,a variety of portable perimetries and softwares have been developed,and its rapid,effective and portable features are convenient for the diagnosis of glaucoma.This article summarized the advances in the application of various portable perimetry,which have been used to evaluate the glaucomaous visual field defect.

Effects of 12-week brisk walking training on exercise blood pressure in elderly patients with essential hypertension: a pilot study.

BACKGROUND: Essential hypertension (EP) is characterized by blood pressure (BP) elevations, which often lead to target organ damage and cardiovascular illness. The following study investigates whether aerobic exercise programs with different intensities could reduce the magnitude of BP rise. METHODS: Patients with essential hypertension were recruited from the Baoshan Community Health Service Center. A total of 46 patients were finally selected and randomly assigned into two groups: control group (CON) included patients who did not participate in exercise intervention training; treatment group (TRG) included patients who participated in 12-week brisk walking training (60-min of brisk walking, three times a week for a total of 12 weeks). 3-minute step tests of low and high intensity were conducted pre- and post-intervention. To compare the effects of exercise intervention, 23 subjects with normal blood pressure (NBP) who did not participate in 12-week brisk walking training, were recruited. RESULTS: After 12 weeks of brisk walking, SBP of TRG during resting, low and high-intensity exercise was significantly reduced by 8.3mmHg, 15.6mmHg, and 22.6mmHg, respectively; while HR of TRG's during resting, low and high intensity was significantly reduced by 3.6beats/minute, 8.7beats/minute and 11.3beats/minute, respectively. Meanwhile, after 12 weeks of brisk walking, TRG's steps per day, [Formula: see text]o2max, moderate physical activity time and physical activity energy expenditure significantly increased by 6000 steps, 2.4 ml/kg/m, 40 minutes and 113 kcal, respectively. At the same time, TRG's body fat rate and sedentary time significantly reduced by 2% and 60 minutes per day. CONCLUSION: Brisk walking can reduce the magnitude of BP rise during exercise of different intensities and may be reduced the risk of acute cardiovascular incidents in elderly patients with essential hypertension. ABBREVIATIONS: EP: Essential hypertension; BP: blood pressure; CON: control group; TRG: treatment group; NBP: normal blood pressure; PA: physical activity.

Ca2+/Calmodulin-Dependent Protein Kinase II γ-Dependent Serine727 Phosphorylation Is Required for TMEM16A Ca2+-Activated Cl- Channel Regulation in Cerebrovascular Cells.

BACKGROUND: TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, ß, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Cl-current and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Cl-current was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Cl-current. Phosphomimetic mutation S727D markedly decreased TMEM16A Cl-current and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice. CONCLUSIONS: Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

Diagnostic value of D-dimer combined with Wells score for suspected pulmonary embolism / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the value of conventional and age-adjusted D-dimer cut-off value combined with 2-level Wells score for diagnosis of suspected pulmonary embolism.@*METHODS@#In the study, 335 patients with suspected pulmonary embolism who visited Peking University People's Hospital were enrolled retrospectively, then 274 patients with age over fifty years were chosen. The 2-level Wells score was applied to evaluate the clinical probability of pulmonary embolism, the diagnostic value of traditional D-dimer cut-off value (500 μg/L) and age adjusted D-dimer cut-off value (age×10 μg/L above 50 years) combined with Wells score no greater than 4 were compared. Computed tomography pulmonary arteriography (CTPA) was considered as the gold standard for diagnosis of pulmonary embolism.@*RESULTS@#(1) The area under a receiver operating characteristic (ROC) curve (AUC) in analysis of the combination of Wells score no greater than 4 and traditional D-dimer cut-off value was 0.764 (95%CI: 0.703-0.818). On the other hand, the AUC in a ROC analysis of the combination of Wells Score no greater than 4 and age-adjusted D-dimer cut-off value was 0.814 (95%CI:0.756-0.863). These two results did not differ statistically (Z=0.05, P=0.121). (2) The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of traditional D-dimer cut-off value and 2-level Wells Score were 100%, 48.9%, 28.8%, 100%, and 0.49, respectively. Meanwhile, the sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of age-adjusted D-dimer cut-off value and 2-level Wells Score were 97.4%, 62.3%, 35.5%, 99.1%, and 0.60, respectively. Compared with using traditional D-dimer cut-off value, using age-adjusted D-dimer cut-off value could improve the diagnosis specificity (traditional D-dimer cut-off value group: 48.9%, age-adjusted D-dimer cut-off value group: 62.3%) of pulmonary embolism without reducing the sensitivity (traditional D-dimer cut-off value group: 100%, age-adjusted D-dimer cut-off value group: 99.1%). (3) Among the 222 patients with Wells Score no greater than 4, 90 patients were with D-dimer less than traditional cut-off value (500 μg/L), and 25 patients (account for 11.3% of all 222 patients) were with D-dimer between traditional cut-off value and age-adjusted cut-off value.@*CONCLUSION@#The application of age-adjusted D-dimer cut-off value can improve the diagnostic specificity of pulmonary embolism in patients over 50 years, without reducing the sensitivity. It can be used for ruling out suspected pulmonary embolism safely.

Impairment of Weight Support of Lower Limbs after Spinal Cord Hemisection in Rhesus Monkeys / 中国康复理论与实践

@#Objective To observe the influence of spinal cord injury on lower limbs weight support capacity,and the changes with time. Methods Six adult female rhesus monkeys with thoracic(T7-9)right spinal cord hemi-section were measured the plantar pressure ratio of both lower limbs with Foot-Scan system before,and six and twelve weeks after operation. Results There was no statistical difference between both sides of limbs before operation(Z=-1.330,P>0.05),while the plantar pressure ratio was more on the left limbs six and twelve weeks after operation(Z>4.783,P<0.001).The plantar pressure ratio of right lower limb became less and less during observation(Z=3.191,P<0.001). Conclusion The weight support capacity of affected limbs is injured after spinal cord hemi-section in monkeys, and would become worse without intervention.

Determination of eight components in Lamiophlomis rotate by UPLC method and preliminary study on influencing factors of contents / 中国中药杂志

To establish a method for simultaneous determination of the contents of sesamoside, menthyl chloride, chlorogenic acid, caffeic acid, 8-O-acetyl-phloridzin methyl ester, forsythiaside B, luteolin, and ergosterol, the LIPLC analysis was performed on a Kinetex XB-C₁₈ (4.6 mm×50 mm,2.6 μm)column with acetonitrile (A)-0.1% phosphoric acid solution (B) as the mobile phase. The flow rate is 1.0 mL min⁻¹. The detection wavelength was 238, 320 and 350 nm and column temperature was 30 ℃. The results showed that the eight components could be completely separated with good linear relationships (r≥0.999 8) in the linear range. The average recoveries were 96.61%-100.4%. The method was simple with strong specificity and high precision. It can be used for the identification and quality evaluation of the Lamiophlomis rotate.The results also showed that there was a correlation between the various components, and the habitat was the main factor affecting the content of the eight components. However, the degradation gradient had no obvious effect on the contents, while the content of sesamoside was significantly decreased after one year of storage.

Affecting factors of corneal epithelial healing following de-epithelized corneal collagen cross linking in keratoconus patients / 中华实验眼科杂志

Background Corneal collagen cross-linking (CXL) shows good clinical effects for keratoconus,and de-epithelized CXL appears to be benefit to the distribution and absorption of riboflavin in cornea stroma.However,de-epithelization of CXL will increase the infective risk and corneal healing time.It is very important to understand and control the affecting factors of corneal repair after de-epithelization of CXL.Objective This study was to evaluate the characteristics of corneal epithelial repair and analyze the relevant factors affecting corneal healing time after de-epithelized CXL.Methods A series-cases observational study was performed.De-epithelized CXL was performed on 77 eyes of 68 keratoconus patients in Shandong Eye Hospital from September 2013 to September 2015 under the approval of Ethic Committee of this hospital and informed consent of each patient.The age,corneal curvature,corneal thickness,breakup time of tear film (BUT),corneal front astigmatism (Astig) and epithelial healing time of the patients were recorded after surgery.The correlations between corneal epithelium healing time and above-mentioned factors were analyzed.Results De-epithelized CXL was smoothly finished in all the eyes.The corneal epithelium healing time was 2-12 days after surgery,with the average healing time 5 (4,6) days.The mean age,thickness at corneal thinnest point,minimal cornea curvature (Kf),maximal corneal curvature (Ks),corneal average curvature (Km) and Astig was 22.00 (18.00,25.00) years,436 (412,470) μm,47.40 (44.70,50.45) D,52.10 (49.00,54.55) D,50.00 (47.15,53.15) D and-3.30 (-5.45,1.70) D,respectively.Spearman rank correlation analysis showed significant negative correlations between corneal epithelium healing time and BUT or the thickness at corneal thinnest point (BUT:rs =-0.334,P =0.003;corneal thickness:rs =-0.417,P =0.000),and thesignificant positive correlations were found between corneal epithelium healing time and Km,Kf and Ks (Km:rs =0.449,P =0.000;Kf:rs =0.300,P =0.008;Ks:rs =0.432,P =0.000).There were no considerable correlarions between corneal epithelium healing time and age or Astig (age:rs =0.023,P =0.845;Astig:rs =-0.190,P =0.098).Multiple linear regression analysis were carried out to study the dependent variable and independent factors.Because of the multiple co-linearity between variables,this paper corrects the model by using ridge regression.There is significant negative correlation between BUT,corneal thickness and corneal healing time,respectively (both at P＜0.05),corneal curvature Km and Kf is positively correlated with corneal healing time (both at P ＜ 0.05).Conclusions The corneal thickness,Kf,Km,as well as BUT are influencing factors of epithelial healing after CXL.