AIM:To study the effects of N-palmitoylethanolamide ( PEA) on the anxiety-and depression-like behaviors of the mouse model induced by restraint stress , and to explore the possible mechanism of anxiolytic and antide-pressant effects of PEA .METHODS:The mice were intragastrically treated with 2.5, 5 and 10 mg/kg of PEA for 21 con-secutive days once daily .Thirty min after intragastric administration , the mice ( except the normal control group ) were placed in the glass tube to accept 4-h chronic restraint stress for 21 d.After the last administration , the mice were submit-ted to the forced stress test and the open field test (OFT) to observe the effects of PEA on the depression-like behaviors. The cumulative immobility time was recorded during the 4-min interval in the forced swimming test ( FST) or during the 5-min interval in the tail suspension test (TST).The elevated plus maze (EPM) test was used to investigate the effect of PEA on the mouse anxiety-like behaviors , and the water maze method was used to investigate the learning and memory abi-lities, spatial orientation and cognitive function of mice .After the behavior tests , the serum was collected and the hippo-campus was removed . The serum contents of adrenocorticotropic hormone ( ACTH ) , cortisol ( CORT ) and 5-hydroxytryptamine (5-HT) in the hippocampus were detected by ELISA .The changes of acetylcholinesterase ( AChE) ac-tivity in the hippocampal homogenate was measured by spectrophotometry .RESULTS:Compared with model group , in the FST or TST, the immobility time in the mice treated with PEA at 2.5~10 mg/kg and fluoxetine was significantly reduced . In the OFT, the total locomotion distance and total movement time were increased significantly in the mice , but only 10 mg/kg PEA and fluoxetine increased the numbers of rearing .In the EPM test , the percentage of the time spent in open arms, the entries into open arms and the total locomotion distance in 4 arms in the mice were significantly increased .In wa-ter maze test , PEA at 5 and 10 mg/kg and fluoxetine significantly shortened the latency to find the security zone in the mice, and PEA at 10 mg/kg and fluoxetine obviously shorten the swimming distance .Compared with model group , PEA at 10 mg/kg and fluoxetine reduced the mouse serum levels of ACTH and CORT , and the adrenal index , increased the 5-HT content and decreased the AChE activity in the hippocampus .CONCLUSION:PEA produces antagonistic effects on an-xiety-and depression-like behaviors in the mice induced by restraint stress .Its specific mechanism may be related to the re-gulation of the hypothalamic-pituitary-adrenal axis function by increasing the 5-HT level in hippocampus , thus participating in the regulation of central cholinergic system .

Objective:To investigate the relationship between blood lipid level and low birth weight infants in late pregnancy.Methods:Data of 303 low birth weight newborns delivered in ShengJing Hospital affiliated to China Medical University were collected from January 2018 to February 2020, and 303 cases of full-term normal birth weight infants delivered in our hospital during the same period (birth weight 2500 ~ 3999 g) for retrospective study.The general situation of puerpera was analyzed, including age, gestational age, times of pregnancy, times of labor, weight growth during pregnancy, pre pregnancy body mass index, and blood lipid indexes of puerpera within one week before termination of pregnancy, including triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B.Results:The normal birth weight group was (31.60±3.90) years old, the weight gain during pregnancy was (16.29±5.31) kg, and the triglyceride levels was(3.21±1.33) mmol/L.The low birth weight group was (30.30±4.65) years old, the weight gain during pregnancy was (14.45±8.08) kg, and the triglyceride level was(2.88±1.37) mmol/L, and there were differences between groups( P<0.01). In the low term birth weight group, birth weight was negatively correlated with maternal age ( r=-0.24, P=0.01), positively correlated with gestational age ( r=0.24, P=0.02), and negatively correlated with pregnancy weight gain ( r=-0.26, P<0.01), and was positively correlated with triglyceride ( r=0.15, P=0.01) and total cholesterol ( r=0.20, P<0.01). Conclusion:The incidence of full-term low birth weight infants is closely related to the blood lipid level, age, gestational age at delivery and the growth of body weight during pregnancy.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Adenocarcinoma ; metabolism ; pathology ; Chromogranin A ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; methods ; Proliferating Cell Nuclear Antigen ; metabolism ; Staining and Labeling ; methods ; Vimentin ; metabolism

OBJECTIVE:To study the time-effect and dose-effect of paeonol on the apoptosis of knee osteoarthritis(OA)artic-ular chondrocyte in rabbits and the mRNA expression of its related protein Bcl-2 and Bax. METHODS:60 big-ear rabbits were ran-domly divided into normal (normal saline) group,model (normal saline) group,paeonol high-dose,medium-dose and low-dose groups and triamcinolone acetonide(positive drug)group,with 10 rabbits in each group. Except for normal group,OA model was induced by right knee anterior cruciate ligament (ACLT) and the medial meniscus 1/3 resection in those groups. After modeling, different doses of paeonol(0.8,0.4,0.2 mg/kg),triamcinolone acetonide 0.2 mg/kg were injected into right articular cavity twice a week. 4 weeks and 8 weeks after administration,articular cartilage specimens were collected. Ultrapathological structure changes of articular chondrocytes were observed by electron microscope. Apoptosis of cartilage cell was observed by TUNEL and apoptotic index was calculated. mRNA expression of apoptosis related genes of Bcl-2 and Bax in articular cartilage tissue of rabbits were de-tected by in situ hybridization technique. RESULTS:Compared with normal group,articular chondrocyte of model group showed early and middle stage apoptosis morphology change after 4 and 8 weeks,and apoptosis index increased significantly and the mRNA expression of Bcl-2 and Bax was up-regulated (P<0.01);4 and 8 weeks later after administration,compared with model group,apoptosis index decreased and mRNA expression of Bax was down-regulated in paeonol groups,while mRNA expression of Bcl-2 was up-regulated(P<0.05 or P<0.01). Electron microscopy ultrastructural observation showed articular chondrocyte of pae-onol high-dose and middle-dose groups were in early stage of apoptosis.CONCLUSIONS:Paeonol can slow down articular chondro-cyte degeneration and destroy in OA model rabbits in time and dose dependently. Its mechanism may be associated with expression up-regulation of Bcl-2 and expression down-regulation of Bax.

Sarcopenia is common in chronic heart failure. The pathogenesis of chronic heart failure-related sarcopenia is complex and diverse. Resistance training, as the main intervention for chronic heart failure-related sarcopenia, is widely applicated as effective and safe therapy.

Objective To investigate clinical characteristics, diagnosis, treatment and prognosis of thyroid carcinoma in childhood. Methods Sixty patients under 14 years of age with thyroid carcinoma were retrospectively reviewed. Results Forty-nine suffered from papillary carcinoma, eight were with follicular carcinoma and three with medullary carcinoma. Cervical lymph node metastasis was found in 36 cases (60%). Operations included unilateral total thyroidectomy and isthmectomy in 20 cases (33.3%), unilateral total thyroidectomy and contralateral subtotal thyroidectomy in 36 cases (60%) and total thyroidectomy in 4 cases (6.7%). The follow-up period was 1 to 20 years (mean 10.5 years), and the survival rate of 5 and 10 years were 93% and 87.1% respectively. Conclusions Most thyroid carcinoma in children is well differentiated and the prognosis is good. A proper surgical procedure and postoperative comprehensive therapy are important for good outcome.

Objective To investigate the clinical effect of large dosage of Methylprednisolone on epilespy combined with electrical status epilepticus during sleep(ESES) in children.Methods Forty-six epielpsy patients with ESES were treated with additive large dosage of Methylprednisolone.The seizures and video electroencephalogram discharges were observed before and after using Methylprednisolone.The Methylprednisolone effect in eliminating the methylprednisolone of ESES and controlling of clinical seizures and improving cognitive function were analyzed.Results Two cases were lost and 44 cases were included,male 30,female 14,the age at onset was (5.37 ±2.52) (2-9) years old.The duration of follow-up was (4.12 ± 2.00)(1-9) years old.The age at diagnosis of ESES was (8.17 ± 2.09) (4.0-12.5) years old.The efficacy of Methylprednisolone on seizures was 72.7％ (32/44 cases),while the efficacy of Methyl prednisolone on electroencephalograph (EEG) was 59.1％ (26/44 cases).For patients who were resistant to Levetiracetam or Clonazepam,Methylprednisolone was still effective.Intelligence quotient had no significant changes before and after treatment(P ＞ 0.05).The earlier onset age,the worse effect of Methylprednisolone.The efficacy of methylprednisolone for atypical benign epilepsy with cento-temporal spike(BECT) was higher than other syndromes.Conclusions Large dosage of Methyl prednisolone therapy for children with ESES,especially for those resistant to traditional or new antiepileptic drug for ESES,was effective and safe.The onset age and syndrome classification may have a certain value for prognosis and prediction of the effect of Methylprednisolone treatment.

Background and purpose: Researches demonstrated that the butyric acid sodium salt (sodium butyrate, NaB) has effect on the inhibition of tumor cell proliferation, differentiation and apoptosis-promoting, while the mechanism on salivary adenoid cystic carcinoma(SACC) is still uncertain. This study mainly probed into the impact of different concentration of sodium butyrate on the migration and invasion of SACC cell line ACC-M, and its mechanism of action. Methods:MTT assay explored the optimal concentration of sodium butyrate on the cell ACC-M and the observation of cell growth. Transwell assay was used to detect the effects of sodium butyrate on the ACC-M cells on the aspact of invasion and migration ability. Fluorescence real-time quantitative PCR (RT-PCR) and Western blot were used to test respectively the expression of HMGB1, TLR4 mRNA and protein in ACC-M after functioned by 5 group drugs with different concentrations. Results:Compared with the control group, on the one hand, the concentration 0.625, 1.25, 2.5, 5 and 10 mmol/L of sodium butyrate could effectively inhibit cell proliferation and apparently showing concentra-tion-dependence (P<0.05);On the other hand, 5 sets concentration of sodium butyrate could also effectively inhibit invasion and migration ability of ACC-M cells in vitro (P<0.05), as well as reducing the expression of HMGB1, TLR4 mRNA and protein in ACC-M cells (P<0.05). Furthermore related analysis showed that the decline of TLR4 protein expression was positively correlated with inhibition of HMGB1 (r=0.810, P<0.05). Conclusion:Sodium butyrate has an effect on inhibiting ACC-M cell proliferation, signiifcantly reducing ACC-M cell invasion and migration capabilities, and reducing expression of HMGB1, TLR4 mRNA and protein, and both expression amount are positively correlated, Meanwhile the positively correlation suggests that sodium butyrate probably achieve the inhibition ability by lowering the expression of HMGB1, TLR4 mRNA and protein in ACC-M cell.

Objective To observe the effect of sodium butyrate on the invasion and migration of human salivary gland ade‐noid cystic carcinoma cell line ACC‐2 in vitro and to investigate the underlying mechanisms .Methods The cultured ACC‐2 cells were treated with different concentrations of sodium butyrate for 24 h ,and detected the viability rate of the cells by methyl thiazolyl tetrazolium(MTT) assay ;the drug′s influence on invasion and migration on ACC‐2 were detected by Transwell experiment ,while the protein and mRNA expression of HMGB1 and TLR4 explored by Western‐blot and RT‐PCR assay ;the relationship between TLR4 expression and HMGB1 was investigated .Results Compared with control group ,0 .625 ,1 .250 ,2 .500 ,5 .000 ,10 .000 mmol/L groups of sodium butyrate inhibited the proliferation of ACC‐2 cells(P<0 .05);the influence of sodium butyrate on the in‐vasion of ACC‐2 cells of all groups had no significant difference(P>0 .05);only 2 .500 ,5 .000 and 10 .000 mmol/L groups inhibited ACC‐2 cells migration and down‐regulated the protein and mRNA of HMGB1 and TLR4(P<0 .05) .Correlation analysis showed a positive correlation between the TLR4 protein and HMGB1 protein(r=0 .810 ,P<0 .05) .Conclusion Sodium butyrate could inhib‐it ACC‐2 cells proliferation and high concentration gropes inhibit ACC‐2 cells migration ,while reducing HMGB1 and TLR4 mRNA and protein expression ,suggesting that NaB might inhibite ACC‐2 cells migration through down‐regulated the mRNA and protein expression .