ObjectiveTo investigate the synergistic inhibitory effect of chidamide （CHI） combined with compound Kushen injection （CKI） on breast cancer MCF-7 cells and to elucidate the potential molecular mechanisms based on transcriptomics analysis. MethodsCell proliferation was detected by the methyl thiazolyl tetrazolium （MTT） assay， and the "one belt and one line" method was adopted to screen the optimal mass concentration for synergistic effect. According to the combination index （CI） values， cells were allocated into the blank， CHI （1.6 mg·L^-1）， CKI （0.4 g·L^-1）， and CHI+CKI （1.6 mg·L^-1+0.4 g·L^-1） groups. Transwell assay was employed to examine cell migration， and flow cytometry to measure cell cycle distribution and apoptosis rate. Transcriptome sequencing （RNA-seq） and weighted gene co-expression network analysis （WGCNA） were performed to screen the key modules highly correlated with the cell inhibition rate. Candidate genes were identified by intersecting module genes with differentially expressed genes （DEGs）， followed by functional enrichment analysis. Western blot was employed to quantify the protein levels of histone deacetylase 1 （HDAC1）， protein kinase A （PKA）， cyclin-dependent kinase inhibitor 1 （p21）， cAMP response element-binding protein （CREB） and its phosphorylated form （p-CREB）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in cells of each group. ResultsCompared with the blank group， both CHI and CKI monotherapies inhibited the proliferation of MCF-7 cells in a mass concentration-dependent manner. Compared with the blank and monotherapy groups， CHI+CKI inhibited cell migration， increased the proportion of cells arrested in the G₀/G₁ phase， and elevated the apoptosis rate （P<0.01）. WGCNA identified the MEred module strongly correlated with the inhibition rate （r=0.90， P<0.01）， yielding 97 candidate genes upon intersection with DEGs. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis indicated significant enrichment of the cAMP signaling pathway. Western blot results showed that compared with the blank group， all treatment groups down-regulated the expression of HDAC1， up-regulated the expression of PKA and p21， and increased the p-CREB/CREB and Bax/Bcl-2 ratios （P<0.01）. Compared with the monotherapy groups， CHI+CKI further up-regulated the PKA and p21 expression and increased the p-CREB/CREB and Bax/Bcl-2 ratios （P<0.01）. ConclusionThe combination of CHI and CKI exerts a significant synergistic anti-tumor effect. CHI exerts epigenetic regulation by inhibiting HDAC1， which， in combination with CKI， may further contribute to the activation of the cAMP/PKA/CREB signaling pathway， leading to up-regulation of p21 expression and the Bax/Bcl-2 ratio， thereby promoting cell cycle arrest and apoptosis.

Sleep disorders caused by neuropathic pain（NP）are a type of neurological disorder with difficulties in treatment， which greatly affects the quality of life of patients.Studies have shown that NP-related brain regions are involved in the regulation of sleep disorders， such as the thalamus，the hypothalamus， and the basal forebrain and the two diseases are closely associated with each other in terms of central and peripheral pathogeneses， but there is still a lack of sufficient research. This article reviews the main pathogenesis and therapeutic drugs for sleep disorders caused by NP in recent years， in order to provide a reference for the clinical search for effective drugs.

Objective To explore the possibility of rhabdomyolysis and related organ damage in new recruits training in high temperature and high humidity environment by comparing the effects of different training environments on the laboratory indicators and electrocardiogram.Methods A total of 250 new recruits from a unit in Beijing and another 250 ones from a unit in Hainan were recruited and assigned into conventional environment group and high temperature and high humidity environment group,respectively.All of them were male,with an average age of 21.36±2.59 years.Before and in 4 weeks after training in the same subjects,their general information,blood and urine indicators,and electrocardiogram were collected.All data were statistically analyzed.Results The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,and kidney injury were 45.76％,3.39％,12.71％,25.42％,and 12.71％,respectively,in the high temperature and high humidity environment group,which were all significantly higher than those in the conventional environment group(P＜0.05).The former group had an incidence rate of 6.78％,5.93％,8.47％,6.78％,and 2.54％,respectively,in sinus bradycardia,atrial premature beats,unspecific ST-T changes,left ventricular hypertension and short PR interval,and all of the rates were higher than those of the conventional environment group(P＜0.05).Conclusion The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,kidney injury,and ECG abnormalities are more common in new recruits after military training in high temperature and high humidity environment.

AIM:To investigate the regulatory ef-fects and mechanisms of glycyrrhizin on morphine-induced neurotoxicity.METHODS:A neurotoxicity model was established by intracerebroventricular injection of morphine.Glycyrrhizin was adminis-tered intraperitoneally for 5 and 10 days.Pathologi-cal observation,protein immunoblotting,cell viabil-ity,apoptosis,and primary neuron differentiation were assessed.RESULTS:After morphine treat-ment,neuronal loss,decreased cell viability,in-creased apoptosis,axonal breakage,and cell shrink-age were observed in cortical tissue.Glycyrrhizin administration significantly improved cell viability,and axonal,dendritic,and cell body structures gradually became intact,with reduced apoptosis.The phosphorylation levels of protein Akt at posi-tion 473 and PKA at position 197 decreased,while autophagy-related proteins Beclin and LC3B1/2 re-mained unchanged.CONCLUSION:Glycyrrhizin sig-nificantly inhibits morphine-induced neuronal dif-ferentiation suppression and neuronal apoptosis,which may be mediated through the synergistic ef-fects of glycyrrhizin and morphine on the Akt path-way.

OBJECTIVE:To study the mechanism of action of grape seed proanthocynidins extract(GSPE)in treating acetic acid-induced colitis gravis in rats.METHODS:Rats model with acetic acid-induced colitis was built,the animals were di-vided into normal control group,model group,positive control group and GSPE group(which were subdivided into low,medium and high dose subgroups by intragastric administration).On the8th day of administration of drugs,the changes of myeloperoxidase(MPO),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)in colonic tissue were detected,respectively.RESULTS:The model group had a significantly higher level of MPO content than did the normal control group(P