OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Sarcopenia,also known as"oligomyositis""hypomyositis"and"muscle wasting",is an age-related geriatric syndrome characterized by decreased muscle mass,muscle strength and function decline.It can increase the risk of adverse out-comes such as physical disability,poor quality of life,and death.The pathogenic factors of sarcopenia mainly include older age,diseases,lack of exercise,malnutrition,etc.As one of the key factors affecting sarcopenia,the nutritional status of the body play an important role in the development of sarcopenia.Therefore,this paper reviews the role of nutrition in sarcopenia and nutritional interventions for patients with common chronic diseases combined with sarcopenia,aiming to provide a basis for the developing more scientific and rationalized nutritional intervention program for elderly patients with sarcopenia.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Abstract Vaccination is the most effective prevenative measure against infectious diseases. As guardians of minor children, parental attitudes have a decisive influence on children s vaccination. Therefore, it is very important to understand parental attitudes and preference towards the vaccination of minor children in COVID-19 for the successful implementation of vaccination. In this study, the current situation and associated factors of parental COVID-19 vaccine hesitancy for children. It was found that parental vaccine hesitation was mainly influenced by factors related to parents, children, vaccination and information process. Parents should be guided to obtain information through authoritative channels and treat vaccination correctly. At the same time, medical staff should play an important role in health education, submit correct immunisation information, reduce vaccine hesitancy, and promote herd immunity.

Polymorphism of chemical drugs has become a hot topic in pharmaceutical research at home and abroad. In this review, the phenomena, causes and significance of polymorphism were introduced briefly. The international drug development process and characteristics of the polymorphic drug development in our country were analyzed. Finally, the present situation and development in China was summarized from four aspects including the basic theory, technical methods, intellectual property rights and supervision. This paper can provide a reference for correct understanding the research level of polymorphic drugs in China and clarifying the direction of polymorphic drug research.

Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both and , which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially the AKT/FOXO3a/BIM pathway.

Objective To evaluate the efficacy and safety of short-term deep sedation strategy in patients with spontaneous intracerebral hemorrhage (ICH) after surgery. Methods A perspective, randomized, parallel-group study was conducted. Adult patients with spontaneous ICH and undergoing craniotomy admitted to Daxing Teaching Hospital of Capital Medical University from December 2015 to November 2016 were enrolled. The patients who received surgery were randomly divided into a short-term deep sedation and a slight and middle sedation group. Sufentanil was used as an analgesic drug in all patients and midazolam was used as a sedative after the operation. The patients in the slight and middle sedation group received midazolam 0.05-0.10 mg/kg with a goal of mild sedation [Richmond agitation and sedation scale (RASS) score of -2-1]. The patients in the short-term deep sedation group received midazolam 0.1-0.2 mg/kg with a goal of deep sedation (RASS score of -4 to -3) and a duration of no more than 12 hours. Postoperative sedation, blood pressure changes, laboratory indexes, residual hematoma and clinical outcomes were recorded in two groups. Results During the study, a total of 183 patients with spontaneous ICH were collected, excluding who was older than 65 years, with shock, and with preoperative Glasgow coma score (GCS) of 3. 106 patients were enrolled in this study, and 53 patients were assigned to the short-term deep sedation group and slight and middle sedation group, respectively. In the slight and middle sedation group, 4 patients received reoperation because of repeated hemorrhage and no patient operated repeatedly in the short-term deep sedation group, and there was a significant difference between the two groups (χ2= 4.000, P = 0.045). The number of patients undergoing tracheotomy in the short-term deep sedation group was significantly lower than that in the slight and middle sedation group (9 cases vs. 21 cases,P < 0.05). RASS score within 12 hours after operation of the patients in the short-term deep sedation group was lower than that in slight and middle sedation group [-4 (-4, -2) vs. -2 (-3, -1) at 4 hours, -4 (-4, -2) vs. -1 (-2, 0) at 8 hours,-3 (-4, -2) vs. 0 (-2, 1) at 12 hours, all P < 0.01], sudden restlessness was significantly reduced [times: 1 (0, 1) vs. 3 (2, 3), P < 0.01], and postoperative sedation duration was significantly prolonged [hours: 14.0 (8.3, 20.8) vs. 8.9 (3.4, 15.3), P < 0.05]. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) within 12 hours after operation in the short-term deep sedation group were significantly lower than those of the slight and middle sedation group [SBP (mmHg, 1 mmHg = 0.133 kPa): 136.8±30.5 vs. 149.1±33.5, DBP (mmHg): 85.0 (70.8, 102.3) vs. 89.0 (69.2, 116.7), both P < 0.05]. There were no significant differences in the arterial blood gas, routine blood test or coagulation function between the two groups at 24 hours after operation. The volume of residual hematoma at 2, 7 and 14 days after operation in the short-term deep sedation group was significantly decreased as compared with slight and middle sedation group (mL: 16.4±15.6 vs. 38.2±22.2 at 2 days, 9.6±8.7 vs. 20.6±18.6 at 7 days, 1.2±1.0 vs. 4.4±3.6 at 14 days, all P < 0.05), number of deaths in 3 months were significantly less (5 cases vs. 13 cases), and the patients with favorable prognosis were increased significantly (39 cases vs. 12 cases, both P < 0.05). Conclusion The study results showed that short-term deep sedation strategy after surgery can reduce the incidence of adverse events and improve the prognosis of patients with spontaneous ICH, so it is safe and effective.

The Economists Intelligence Unit pointed out that the global ranking of Chinese people's death quality index falls behind and once again causes people's attention and discussion of death and related legal issues.Palliative Care can make people go to death as far as possible with dignity,ready and calm.So it is gradually being concerned,and the importance of legislation related to it is also becoming increasing.Palliative Care has emerged in our country,but because of the lack of legislative regulation,relatives of patients and medical staff are at risk being accounted for legal liability.Through the analysis of the legitimacy and feasibility of palliative care,this paper put forward some suggestions of relevant legislation and current corresponding countermeasures;it should clarify the legal validity of living will signed by patients,strengthen the supervision in the implementation process and exempt responsibility of relevant personal.

OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.