Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.
Apoptosis ; Humans ; Mitogen-Activated Protein Kinases/metabolism* ; Reactive Oxygen Species/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats. METHODS: Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry. RESULTS: Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05). CONCLUSION EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms.

METHODSCardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca]) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively. The mRNA expressions of atrial natriuretic factor (ANF), calcineurin (CaN), extracellular signal-regulated kinase-2 (ERK-2), and endothelial nitric oxide synthase (eNOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit (CnA) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by Western blot analysis.

RESULTSCompared with the control group, Ang II induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF mRNA expression; increased intracellular free calcium ([Ca]) concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but decreased MKP-1 protein expression (P<0.05 or P<0.01). Compared with Ang II, Evo (0.3, 3 μmol/L) significantly attenuated Ang II-induced cardiomyocyte hypertrophy, decreased the [Ca] concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but increased MKP-1 protein expression (P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the eNOS mRNA expression (P<0.05).

CONCLUSIONEvo signifificantly attenuated Ang II-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.

Angiotensin II ; Animals ; Atrial Natriuretic Factor ; metabolism ; Calcineurin ; genetics ; metabolism ; Calcium ; metabolism ; Dual Specificity Phosphatase 1 ; genetics ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Hypertrophy ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Quinazolines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley

OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute-olin-7-O-β-D-glucuronide (LGU) against focalcerebral ischemic injury. METHODS The focal cerebral ischemic injury model was established by middle cerebral artery occlusion (MCAO). Male Sprague Dawley rats were randomly divided into sham group,model group(MCAO),LGU group(0.24,0.72 and 2.16 mg·kg-1)and positive control group(Edaravone at 5 mg·kg-1).LGU was injected intravenously 30 min after MCAO.Neurological severity score,infarct volume and brain water content were detected 24 h after MCAO and the levels of Na+-K+ATPase,Ca2+ATPase,TNF-α and IL-1β were detected to explore the possible mechanisms.For the therapeutic time window test,LGU(0.72 mg·kg-1)was injected intrave-nously 0.5, 2, 4, 6, 8, 10 and 12 h respectively after MCAO. To evaluate motion behavior, LGU were injected intravenously 30 min after MCAO and once per day during detection period. The changes of motor coordination were detected by rotating rod method and grip strength analysis, and the changes of gaits were detected using DigiGait Imaging System. RESULTS LGU improved the neurological severity score, infarct volume ratio and brain water content. The therapeutic time window of LGU for cerebral infarction and brain edema was at least 6 h and for neurological dysfunction was 12 h.LGU also prolonged the latency on rotarod, increased the forelimb tension and improved 8 gait parameters, including stance duration,stride length,stance width,paw area,paw area variability,gait symmetry,ataxia coefficient and tau propulsion.Furthermore,LGU increased Na+-K+-ATPase and Ca2+-ATPase levels in the cortex and hippocampus in the ischemic side,reduced the levels of TNF-α and IL-1β in the serum. CONCLUSION LGU has a significant neuroprotective effect against cerebral ischemic injury via improving energy metabolism and reducing inflammation.

OBJECTIVE To investigate the protective effect and mechanisms of luteolin-7-O-β-d-glucuronide (LGU) on oxygen glucose deprivation (OGD)-induced H9C2 cardiomyocytes injury. METH-ODS The protective effect of LGU on OGD-induced H9C2 cardiomyocytes death were investigated by MTT assay. The microfilament change of H9C2 cardiomyocytes was detected by phalloidin staining and the lactate dehydrogenase (LDH) leakage rate was also detected by LDH kit. In order to explore the possible mechanisms of LGU, ATP content, intracellular Ca2+fluorescent intensity and concentra-tion, mitochondrial membrane potential (MMP)and the expressions of apoptosis-related proteins were detected by ATP kit,CLSM(Fluo-3/AM probe),Ca2+kit,CLSM(JC-1 probe)and western blotting meth-od, respectively. RESULTS The inhibition of H9C2 cardiomyocyte survival rate inducedby OGD was improvedby pretreated with LGU in a concentrationdependent manner. The microfilaments injury as well as the increase of LDH leakage rate were also improvedby pretreated with LGU.The ATP content was significantly decreased,intracellular Ca2+fluorescent intensity and concentration were significantly increased and the MMP was significantly decreased 4 hafter OGD. LGU significantly reversed the de-crease of intracellular ATP content,the increase of Ca2+fluorescent intensity and concentration and the decrease of MMP.The release of cytochrome C,the expressionsof caspase-9 and caspase-3 in H9C2 cardiomyocytes were increased 16 h after OGD.LGUsignificantly inhibited the changes of these apop-tosis-related proteins. CONCLUSION LGU has a significant protective effect against OGD-induced H9C2 cardiomyocytes injury through inhibiting calcium overload,increasing ATP content,improving mi-tochondrial function and inhibiting apoptosis.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

Objective To study the clinical efficacy and safety of edaravone in the treatment of traumatic cerebral infarction.Methods A total of 72 patients with traumatic cerebral infarction were randomly divided into the control group (n =36) and the treatment group (n =36).The control group received conventional treatments including intracranial pressure control,nerve nutrition and microcirculation regulation.The patients in treatment group were given intravenous infusion of edaravone 20 mL + 0.9％ NaC1 200 mL on the basis of the conventional treatment,bid,14 d.The changes of hemorheologic parameters were measured and compared between the two groups respectively.The total effective rate were evaluated according to the Glasgow scores,and the safety of clinical medication was evaluated.Results The total effective rate of the treatment group was 91.67％ (33/36 cases) while that of the control group was 72.22％ (26/36 cases),with statistically significant difference between the two groups (P ＜ 0.05).Mter treatment,high shear whole blood viscosity in the treatment group and the control group were (4.73 ± 0.56),(5.36 ± 0.78) mPa · s respectively,while low shear whole blood viscosity were (8.15 ± 1.03),(9.54 ± 1.26) mPa · s,plasma viscosity were (1.41 ± 0.15),(1.76 ± 0.19) mPa · s,red blood cell pressure were (37.15 ± 3.21) ％,(43.17 ± 4.03)％,fibrin deposition were (3.58 ± 0.45),(4.67 ±0.54)g· L-1,and the differences of all the parameters above between the two groups were statistically significant (P ＜ 0.05).The incidence of adverse drug reactions in the treatment group and control group were 5.56％ (1/36 cases) and 2.78％ (2/36 cases) respectively,while no statistical significance was observed (P ＞ 0.05).Conclusion Edaravone is able to improve hemorheology indexes in patients with traumatic brain injury complicated with cerebral infarction.The treatment effect is better than the routine nervous medical treatment,and edaravone has a positive effect on the clinical treatment of traumatic brain injury complicated with cerebral infarction.

OBJECTIVETo observe the change of intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) patients, and to study the effect of Qingyi Chengqi Decoction (QCD) on it.

METHODSEighty-six SAP patients from Department of General Surgery and Department of Digestive Diseases, Qingyang People's Hospital, Gansu Province, who were in line with diagnosis standard of SAP, were assigned to the treatment group (44 cases) and the control group (42 cases) from March 2012 to May 2013. All patients received routine Western medicine. Those in the treatment group took QCD additionally. Main clinical symptoms and APACHE II were observed. The serum levels of amylase (AMY), C-reactive protein (CRP), and IAP were examined. The incidence of secondary infection rate (SIR), drainage rate (percutaneous catheter drainage and operation), mortality, and mean days in ward were also recorded.

RESULTSMain clinical symptoms were significantly improved in the treatment group. APACHE II score, serum levels of AMY, CRP, and IAP obviously decreased in the treatment group. The incidence of SIR, drainage rate, and the mortality were also significantly lower in the treatment group than in the control group. The mean days in ward were also markedly shortened (P < 0.01).

CONCLUSIONQCD could relieve inflammatory response, lower IAP, SIR, and mortality, increase the curative rate and improve the prognosis of SAP.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; drug therapy ; Phytotherapy ; Treatment Outcome