Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Effect of cognitive behavioral group therapy on rehabilitation of community patients with schizophrenia:A short-term randomized control trial

BACKGROUND The efficacy of cognitive behavioral group therapy(CBGT)for cognitive dysfunction and negative symptoms of schizophrenia is established,but more evidence is required.AIM To assess the effectiveness of CBGT combined with mental health education as a treatment for schizophrenia compared with mental health education alone.METHODS In all,120 schizophrenia out-patients were randomized into CBGT combined with mental health education or single mental health education.The primary outcomes were positive and negative symptoms,cognitive function,excitatory factor,anxiety and depression symptom improvements on the positive and negative syndrome scale score.Secondary outcome measures included social function and drug compliance.RESULTS There were significant differences between CBGT combined with mental health education and single mental health education on measures of positive and negative symptoms,cognitive functions,excitatory factor,anxiety and depression symptoms,and social functions.No other significant difference in outcomes was observed.CONCLUSION CBGT combined with mental health education may be relevant beneficial treatment method in reducing symptoms,cognitive and social functions of patients with schizophrenia.

MiRNA profile in esophageal squamous cell carcinoma:Downregulation of miR-143 and miR-145

AIM:To investigate the expression profile of miRNA in esophageal squamous cell carcinoma(ESCC).METHODS:The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray.The expression levels of miR-143 and miR-145 in 86 ESCC patients were determined by real-time polymerase chain reaction(PCR) using TaqMan assay.The mobility effect was estimated by wound-healing using esophageal carcinoma cells transfected with miRNA expression plasmids.RESULTS:A set of miRNAs was found to be deregulated in the ESCC tissues,and the expression levels of miR-143 and-145 were significantly decreased in most of the ESCC tissues examined.Both miR-143 and miR-145 expression correlated with tumor invasion depth.The transfection of human esophageal carcinoma cells with miR-143 and miR-145 expression plasmids resulted in a greater inhibition of cell mobility,however,the protein level of the previously reported target of miR-145,FSCN1,did not show any significant downregulation.CONCLUSION:These findings suggest that the deregulation of miRNAs plays an important role in the progression of ESCC.Both miR-143 and miR-145 might act as anti-oncomirs common to ESCC.

Different histological subtypes of parotid gland tumors: CT findings and diagnostic strategy

AIM:To present computed tomography(CT) findings of different histological subtypes of parotid gland masses in detail and to establish diagnostic strategy.METHODS:From January 2009 to November 2011,56 patients were collected through the histopathology and Picture Archiving and Communication Systems records,which revealed 5 basal cell adenoma(BCA),16 pleomorphic adenoma(PA),25 Warthin's tumor(War-T),3 Kimura's disease(KD) and 7 parotid carcinoma(PCa) cases.All the CT images were retrospectively analyzed by two radiologists in consensus,based on their description of morphology(location,number,size,margin and fibrous capsule) and enhancement patterns of masses.In addition,the diagnostic efficiency of diagnostic strategy is tested.RESULTS:War-T and BCA patients' mean age was 59.9 ± 12.6 years and 58.4 ± 18.2 years;the significant difference was seen in War-T vs PA and BCA vs PA.About 40% of War-Ts presented with bilateral multifocal lesions,a higher ratio than others.Seventy two percent of War-Ts were limited to the superficial lobe,followed by BCA 60% and PA 40%.Vessel facing sign and enlarged lymph nodes were both frequent in War-T,which respectively accounts for 84% and 76% of cases.Rapid contrast enhancement and decreases were unique for War-T.BCA and PA showed obvious delayed enhancement.The diagnostic strategy of parotid gland tumor had a good diagnostic efficiency,with high accuracy,sensitivity and specificity.CONCLUSION:Determination of the histological subtypes of parotid gland masses might be possible based on CT findings and clinical data.A diagnostic strategy with high diagnostic efficiency was established.

Changes of plasma C-reactive protein in patients with craniocerebral injury before and after hyperbaric oxygenation: A randomly controlled study

Changes of plasma C-reactive protein in patients with craniocerebral injury before and after hyperbaric oxygenation： A randomly controlled study BACKGROUND： Plasma inflammatory factor, such as C-reactive protein, whose content is regarded as a sensitively pathological marked protein and quantitative indexes of central nervous system injury, has been paid more and more attention in clinic. OBJECTIVE： To observe the effects and clinical significance of C-reactive protein in patients with craniocerebral injury after hyperbaric oxygenation. DESIGN： Randomized controlled study. SETTING： Departments of Neurosurgery, Laboratory and Hyperbaric Oxygen, the Second Affiliated Hospital, Medical College of Shantou University. PARTICIPANTS： A total of 60 patients with craniocerebral injury were selected from Department of Neurosurgery, the Second Affiliated Hospital, Medical College of Shantou University from October 2006 to April 2007. There were 37 males and 23 females and the mean age was 26 years. All subjects were certainly diagnosed as history of craniocerebral injury. Patients hospitalized at 24 hours after injury, Glasgow Coma Score ranged from 3 to 12 points, and all patients were certainly diagnosed with CT or MR scanning. Patients and their relatives provided confirmed consent. All the subjects were randomly divided into hyperbaric oxygenation group and control group with 30 in each group. METHODS： Patients in the control group were treated with routinely neurosurgical therapy after hospitalization; however, based the same basic treatment in the control group, patients in the hyperbaric oxygenation group received hyperbaric oxygenation by using iced-wheel four-door 2-cabin air-compression chamber （made in Yantai） from 24 hours to 10 days after operation or injury. After entering the cabin, patients who had a clear consciousness breathed the oxygen by using face mask; contrarily, patients directly breathed the oxygen. Therapeutic project： Expression was increased for about 15–20 minutes, maintained for about 70–80 minutes, and decreased for 20 minutes. Otherwise, pressure was maintained from 0.2 to 0.25 MPa. Hyperbaric oxygenation took an hour for once a day and 10 times were regarded as a course. Venous blood was collected before treatment and on the next day of the first course end. Content of C-reactive protein in plasma was measured with immune turbidimetry in hyperbaric oxygenation group; in addition, content of C-reactive protein in plasma was directly measured with the same method at the corresponding time in the control group. If the content was less or equal to 8 mg/L, it was regarded as normal value. Effects of the two groups were evaluated based on Glasgow Coma Score before and after treatment. MAIN OUTCOME MEASURES： Content of plasma C-reactive protein and Glasgow Coma Score in the two groups before and after treatment. RESULTS： All 60 patients were involved in the final analysis. ① Content of plasma C-reactive protein： The two contents were obviously higher than normal value after craniocerebral injury. There was no significant difference in the two groups before treatment （P 〉 0.05）, but both contents were decreased after treatment, and there was significant difference between HBOT group and control group after treatment （t =4.756, P 〈 0.01）. In addition, there was significant difference in hyperbaric oxygen therapy group before and after treatment （t =5.236, P 〈 0.01）. ② Glasgow Coma Score： There was no significant difference in the two groups before treatment （P 〉 0.05）, but scores were increased in both groups after treatment （t =9.92, 2.51, P 〈 0.01, 0.05）; on the other hand, therefore, there was significant difference between the two groupsafter treatment （t =9.21, P 〈 0.01）. CONCLUSION： Hyperbaric oxygenation can remarkably decrease content of plasma C-reactive protein in patients with craniocerebral injury at the phase of stress.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China

AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the genealcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence in- terval (CI): 2.76-5.67]. Signif icant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00,95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/ Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis

Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.

Risk Factors of Low Back Pain among the Chinese Occupational Population:A Case-control Study

Objective To explore the risk factors of low back pain among the Chinese occupational population in several major industries. Methods A total of 7200 subjects （3600 cases and 3600 controls） were randomly sampled from a cross-sectional study, and they were investigated for individual and occupational factors of low back pain. The potential risk factors were first selected by using chi-square tests. Secondly, collinearity diagnosis proceeded by using the Kendall＇s rank correlation. Finally, binary logistic regression model was used for multi-factor analysis. Results Collinearity diagnosis showed that there was a severe collinearity problem among the potential risk factors of low back pain. Logistic regression model included 20 variables with statistical significance. Bending neck forward or holding neck in a forward posturefor long periods （0R=1.408） was the most important risk factor inducing low back pain in this study, followed by bending heavily with the trunk （0R=1.402）, carrying out identical work almost for the whole day （0R=1.340）. Additionally, suHicient normal break was a protective factor of low back pain. Conclusion Low back pain among the Chinese occupational population was associated with body height, occupation, work organization, physical work, working posture, and others. All these risk factors could be regarded as the indicators of low back pain, and some relevant preventive measures should be taken to reduce low back pain risk.

Axonal autophagy during regeneration of the rat sciatic nerve

BACKGROUND： The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE： To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model. DESIGN, TIME AND SETTING： Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS： Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS： Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES： Ultrastructure （axon body, autophagic body, and cystoskeleton） of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS： The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma surrounding the axon body was derived from the neuronal cell membrane; the condensed axoplasm contained many autophagic vacuoles at all levels. A large number of neurofilaments, microtubules, and microfilaments were arranged in a criss-cross pattern. The autophagic vacuoles exhibited acidic phosphatase activity. Axonal bodies were absorbed after degradation from day 7 onwards, and macrophages were observed rarely in the formative cavity. CONCLUSION： The degenerating axons were cleared mainly by axonal autophagy and Schwann cell phagocytosis during regeneration of the rat sciatic nerve, and macrophages exhibited only an assisting function.

Preemptive analgesic effects of low-dose ketamine on growth-associated protein expression in dorsal root ganglion of chronic constriction injury model rats

BACKGROUND： Ketamine is a noncompetitive N-methyl-D-aspartate （NMDA） receptor antagonists and plays an important role in the treatment of pain. OBJECTIVE： To analyze the preemptive analgesic effects of different doses of ketamine on growth-associated protein-43 （GAP43） expression in dorsal root ganglion in a rat model of chronic sciatic nerve constricted injury, and to study the differences between high-dose and low-dose ketamine DESIGN： Randomized controlled animal study. SETTING： Medical College of Shantou University. MATERIALS： Thirty-five adult male Sprague Dawley rats were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Ketamine hydrochloride injection was provided by Hengrui Pharmaceutical Co., Ltd., Jiangsu. METHODS： This study was performed at the Immunological Laboratory, Medical College of Shantou University from September to December 2006. Model of chronic sciatic nerve constricted injury： after anesthesia, the right sciatic nerve was exposed and ligated l-cm distal to the ischiadic tuberosity with a No. 3-0 cat gut suture. Grouping and intervention： 35 rats were randomly divided into 4 groups： normal control group （n = 5）, chronic constriction injury （CCI） group （n = 10）, low-dose ketamine group （n = 10）, and high-dose ketamine group （n = 10）. Rats in the normal control group did not undergo any surgery or drug intervention. Rats in the CCI group received intraperitoneal injection of saline （1 mL）, and their sciatic nerves were ligated after 10 minutes. Rats in the low-dose ketamine group underwent intraperitoneal injection of ketamine （25 mg/kg） 10 minutes prior to ligation of sciatic nerve; while, rats in the high-dose ketamine group were given intraperitoneal injection of ketamine （50 mg/kg） 10 minutes prior to ligation of sciatic nerve. On the third and the seventh days after surgery, dorsal root ganglion were resected from the sciatic nerve and cut into sections. MAIN OUTCOME MEASURES： GAP-43 expression in dorsal root ganglion was detected by immunohistochemistry and image analysis system, as well as semi-quantitative analysis. RESULTS： Thirty-five Sprague Dawley rats were included in the final analysis. Qualitative analysis： GAP-43 expression in the CCI group was higher than in the normal control group. Quantitative analysis： after three post-operative days, GAP-43 expression in the CCI group was significantly higher than in the normal control group （t = 22.919, 7.319, P 〈 0.05）. GAP-43 expression in the low-dose and high-dose ketamine group was significantly lower than in the CCI group （t = 11.166, 26.474, P 〈 0.05）. After seven postoperative days, GAP-43 expression in the low-dose and high-dose ketamine groups was significantly lower than in the CCI group （t = 2.382, 5.016, P 〈 0.05）. CONCLUSION： Preoperative administration of ketamine inhibited the increased GAP-43 expression in dorsal root ganglion during neuropathic pain.

Neuronal differentiation effects of vascular endothelial factor on bone marrow stromal cells

BACKGROUND：Studies have demonstrated that bone marrow stromal cells （BMSCs） undergo neuronal differentiation under certain in vitro conditions.However,very few inducers of BMSC differentiation have been used in clinical application.The effects of vascular endothelial growth factor （VEGF） on in vitro neuronal differentiation of BMSCs remain poorly understood.OBJECTIVE：To investigate the effect of VEGF on neuronal differentiation of BMSCs in vitro,and to determine the best VEGF concentration for experimental induction.DESIGN,TIME AND SETTING：In vitro comparative study was performed at the Central Laboratory and Laboratory of Male Reproductive Medicine,Shenzhen Hospital of Peking University from October 2008 to August 2009.MATERIALS：Recombinant human VEGF165 was purchased from Peprotech Asia,Rehovot,Israel.Neuron-specific enolase （NSE） was purchased from Beijing Biosynthesis Biotechnology,China.METHODS：BMSCs were harvested from adult Sprague Dawley rats.The passaged cells were pre-induced with 10 ng/mL basic fibroblast growth factor for 24 hours,followed by differentiation induction with 0,5,10,and 20 ng/mL VEGF,respectively.MAIN OUTCOME MEASURES：Morphological changes in BMSCs prior to and following VEGF induction.Expression of NSE following induction was determined by immunocytochemistry.RESULTS：Shrunken,round cells,with a strong refraction and thin bipolar or multipolar primary and secondary branches were observed 3 days after induction with 5,10,and 20 ng/mL VEGF.However,these changes were not observed in the control group.At 10 days after induction,the number of NSE-positive cells was greatest in the 10 ng/mL VEGF-treated group （P〈 0.05）.The number of NSE-positive cells was least in the control group at 3 and 10 days post-induction （P〈 0.05）.Moreover,the number of NSE-positive cells was greater at 10 days compared with at 3 days after induction （P〈 0.05）.CONCLUSION：Of the VEGF concentrations tested,10 ng/mL induced the greatest number of neuronal-like cells in vitro from BMSCs.

Morphology of spinal cord extracellular matrix-derived acellular scaffolds fabricated in rats

Acellular peripheral allograft scaffolds can be fabricated using chemical extraction techniques,but methods for producing acellular scaffold derived from spinal cord tissue are not currently available.The present study demonstrated that chemical extraction using Triton X-100 and sodium deoxycholate could be used to completely remove the cells,axons and neural sheaths in spinal cord extracellular matrix-derived scaffolds.The matrix fibers were longitudinally arranged in a wave-like formation,and were connected by fiber junctions.Lattice-shaped fiber cages appeared and developed into bone trabecula-like changes.The natural structure of matrix fibers in the scaffolds was maintained;this helps to guide the differentiation and migration of implanted stem cells.Decellularized spinal cord extracellular matrix-derived scaffolds can provide an ideal substance for fabricating tissue-engineered spinal cord.

Human umbilical mesenchymal stem cell and its adipogenic differentiation:Profiling by nuclear magnetic resonance spectroscopy

AIM: To study the metabolic profile of human umbilical mesenchymal stem cells (HUMSC) and adipogenic differentiation by nuclear magnetic resonance (NMR) spectroscopy.

Effects of Local Testicular Heating on Bcl-2 and Bax Protein Expression in Spermatogenic Cells in Rats

Objective To investigate the expression of Bcl-2 and Bax in spermatogenic cells induced by local testicular heating in rats Methods Forty adult male SD rats were divided into experimental group and control group at random. According to day 0.5, 1, 3 and 6 after local testicular heating, each group was divided into 4 subgroups： experimental subgroup （n=6） and control subgroup （n=4）. The expression of Bcl-2 and Bax in the spermatogenic cells was detected on day 0.5, 1, 3 and 6 after heat exposure by using immunohistochemistry. Results Compared with control groups, the ratio of positive cells and content of Bcl-2 positive cells significantly decreased in all experimental subgroups （P〈0.01）. The content of Bax positive cells increased in all experimental subgroups （P〈0.01）, the ratio of positive cells which had no significant difference （P〉0.05） except 6 d group decreased （P〈0.01 ）. Redistribution of Bax from a cytoplasmic to perinuclear or nuclear localization could be observed after heating. Conclusions Expression of Bcl-2 would decrease and Bax would increase with redistribution in spermatogenic cells in rats after heating. The change of Bcl-2 and Bax expression in spermatogenic cells would be correlated with the spermatogenic cell apoptosis induced by heating.

Analysis of DNA Content of Various Types of Spermatogenic Cells in Rat after Testicular Heating with Flow Cytometry

To measure DNA contents of spermatogenic cells and analyze the efficiency of spermatogenesis after testicular heating in rat Methods Eighty adult male Sprague-Dawley rats were randomly divided into experimental group （43 ℃, 30 min） and control group （22 ℃, 30 min）. According to day 0.5, 1, 3, 6, 10, 25, 35 and 50 after local testicular heating, every group was divided into 8 subgroups： experimental subgroups （n=6） and control subgroups （n=4）. DNA contents of various types of germ cells were observed with flow cytometry （FCM） in all groups. Results Compared with control groups, percentages of 4C cell （primary spermatocyte） in 0.5-35 d groups and percentages of 1C cell （spermatid and sperm） in 6-50 d groups significantly decreased in experimental groups （P〈0.05）, and percentages of 2C cell （spermatogonium and second spermatocyte） in 3 -35 d experimental groups increased significantly after heating （P〈0.05）. 4C：2C in all of 8 experimental groups and 1C：2C in 3-35 d experimental groups were down （P〈0. 05）, and in 1 d experimental group 1C：4C was up after heating （P〈0.05）. Conclusions After being heated, the number of spermatocyte firstly decreased, and then that of spermatid and sperm decreased too. Heat influences several stages in spermatogenesis and results in suppression of spermatogenesis. Flow cytometry is an effective method for researching on the change of spermatogenesis and has significance on mechanism about changing of spermatogenic cells induced by heat.

Protective Effects of Tetramethylpyrazine on Glutamate-Induced Neurotoxicity in Mice

The aim of this study was to investigate the potential protective effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, on glutamate-induced neurotoxicity in mice and its possible mechanism. Mice, except for controls, received simultaneously intragastric (ig) administration of monosodium glutamate [MSG, 4.0 g/(kg·d)] or/and intraperitoneal (ip) administration of TMP [10, 20, 40 mg/(kg·d)] for 10 d, and then behavioral tests, as well as histopathological and immunohistochemical examination of hippocampi were performed to analyze the glutamate-induced functional and morphological changes and the possible protective effect of TMP. The results showed that ip administration of TMP countered the effects of ig administration of MSG on behavior and histopathology, suggesting that TMP was a neuroprotective agent. This study provides evidence that TMP possesses obviously neuroprotection against glutamate-induced neurotoxicity, and the neuroprotection effect may result from its inhibiting expression of NMDARs, consequently blocking-up Ca2+ influx through the receptor’s associated ion channel, which can be neurotoxic.

The serum levels of MMP-9, sICAM-1, CRP and WBC increased in patients with acute coronary syndrome

Objective：To evaluate the association of the peripheral levels of the defined inflammatory markers with different types of acute coronary syndrome （ACS） and stable angina, and the role inflammation played in the pathogenesis of ACS. Methods ：For understanding the variation of serum concentrations of matrix metalloproteinase-9 （MMP-9）, soluble intercellular adhesion molecule-1 （sICAM-1） ,C-reactive protein （CRP）, and white blood cell count （WBC） and their association with ACS, 90 patients with coronary heart disease （CHD） and 30 healthy volunteers were recruited. The enrolled people were assigned into four equal groups, including acute myocardial infarction （AMI） group, unstable angina pectoris（UAP） group, stable angina pectoris（SAP） group and healthy control group. The serum levels of MMP-9 and sICAM-1 were measured with ELISA kits, CRP were measured with im munoturbidimetric assay, and WBC number were assessed all before any treatment was administrated. Results： （1）The serum levels of MMP-9 ,sICAM-1 ,CRP and WBC in the patients with ACS were significantly higher than those in the control group （P 〈 0.01 ）. （2）Compared with control group, patients with SAP only had higher serum level of sICAM-1 （P 〈 0.01 ）. While the levels of MMP-9, CRP, and WBC had no significant difference between them （P 〉 0.05 all）. （3）Significant positive correlation between the serum levels of MMP-9 and sICAM-1 and CRP and WBC all were observed in the patients with ACS （P 〈 0.05）. Conclusion： The elevation of serum concentrations of inflammatory markers including MMP-9, slCAM-1, CRP and WBC were associated with initiation and progression of ACS, and they may help predicting cardiovascular events.

Meta-analysis of curative effect of Sacubitril valsartan combined with Qiliqiangxin capsule in the treatment of patients with chronic cardiac failure

Objective:To systematically review the effect of Sacubitril valsartan combined with Qiliqiangxincapsule on clinical effect,serological index,cardiac function,quality of live,and adverse reactions in patients with heart failure.Methods:Search the databases of CNKI,VIP,WanFang,CBM,DuXiu,ChiCTR,Web of science,The Cochrane Library,PubMed and Embase to collect the randomized controlled trial(RCT)of Sacubitril valsartan combined with Qiliqiangxin capsule in the treatment of patients with heart failure,The search time limit is from the establishment of the database to May 2021.After the literatures were screened,evaluated and extracted by two researchers independently,Meta analysis was carried out with Stata 16.1 software.Results:A total of 18 RCTs,were included,including 1613 patients.The results of the Meta-analysis showed that there was statistical significance in improving the effective rate(OR=2.60,95%CI[2.09,3.24],P<0.00001),N-terminal pro-brain natriuretic peptide(MD=-468.36,95%CI[-606.80,-329.92],P<0.00001),left ventricular ejection fraction(MD=5.41,95%CI[4.93,5.89],P<0.00001),left ventricular end-diastolic diameter(MD=-3.27,95%CI[-3.65,-2.90],P<0.00001),left ventricular end-systolic diameter(MD=-3.60,95%CI[-4.99,-2.21],P<0.00001),6-minute walking distance(MD=61.42,95%CI[50.04,72.80],P<0.00001),Minnesota living with heart failure questionnaire(MD=-11.39,95%CI[-14.50,-8.28],P<0.00001),and traditional Chinese medicine syndrome score scale(MD=-3.62,95%CI[-6.45,-0.80],P=0.01),but there was no significant difference in cardiac output(MD=0.26,95%CI[-0.02,0.54],P=0.07)and adverse reactions.Conclusion:The current evidence shows that Sacubitril Valsartan combined with Qiliqiangxin capsule can better improve cardiac function,TCM symptoms and quality of life in patients with heart failure than simple Sacubitril Valsartan.However,there was no significantdifference in improving cardiac output between the two groups.However,higher quality RCTs are needed to verify.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs

Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase(MCT) in asthmatic guinea pigs.Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group(group A),asthmatic group(group B).and 1,25-dihydroxyvitamin D3 group(group C),with 20 cases in each group.To establish asthmatic guinea pig models,1ml peanut oil was tilled into stomach in the morning in group A and group B.and 1 ml peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C.Airway resistance(Re) of asthmatic guinea pigs was detected,and the bronchoalveolar lavage fluid(BALF) cells were counted.Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT.Results:After injection of different concentration of acetylcholine chloride,the Re in group B and group C were increased significantly compared with group A(P<0.05):compared with group B.the Re in group C were decreased significantly(t=-5.385.-5.761.-6.184.-13.574.P<0.05):the total number of BALF cells and eosinophils were increased significantly in group B and C(t=19.618.9.598.10.854.5.388.P<0.05);compared with group B.the total number of BALF cells and eosinophils in group C was decreased significantly(t=-5.555.-5.392.P<0.05):the number of tryptase positive cells in group B was increased significantly than that in group A(t=21.312,P<0.05),and in addition to the alveolar septum and submucosa,the cells were also distributed around blood vessels and outside the cells:the number of tryptase positive cells in group C was decreased significantly compared with group B.and the difference was statistically significant(t=5.043.P<0.05).Conclusions:After the asthmatic guinea pigs arc treated with 1,25-dihydroxyvitamin D3,their BALF.Re.infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly.1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

Expression of Sirt1 and Sirt2 in the Injured Optic Retina of Calorie-Restricted Rats

Purpose:To investigate retinal ganglion cell (RGC) survival after optic nerve injury in calorie-restricted (CR) rats,and analyze the potential role of Sirtuins.Methods:Ten-month old male Sprague-Dawley rats (n=14) were divided into calorie restricted (CR) and ad libitum (AL) groups.In the CR group (n=7),the rats were denied access to food every other day.Animals in the AL group (n=7) had had free access to food.PN-ON grafting was carried out on the right eye of all subjects after 5 months of feeding.Three weeks postoperatively,retina samples were collected,half of which were fixed in 4% paraformaldehyde (PFA) and subjected to standard immunofluorescence staining for TUJ-1.The remaining samples were subjected to total RNA analysis and RT-PCR for Sirt1 and 2 expression.Results:Comparing the amount of TUJ-1 staining between the groups,the mean density and the total number of RGCs showed no significant difference.RT-PCR results indicated that mRNA expression of Sirtuin2 in the CR group was significantly lower than that in the AL group,whereas no statistically significant difference was observed between the two groups regarding the mRNA expression of Sirt1.Conclusion:Calorie restriction had no impact on the survival of injured RGCs.The down-regulated mRNA expression of Sirt2 in the CR group may indicate an improved capacity for regeneration among these animals,but more work is needed to explore this possibility.