Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Objective To investigate the characteristics of gut flora related to dampness syndrome in the population at risk of cerebrovascular disease and to explore their influencing factors.Methods Based on the results of epidemiological investigation of damp syndrome in at-risk population of cerebrovascular disease in Guangdong from October 2021 to February 2023,60 subjects(including 41 at-risk cases of cerebrovascular disease and 19 healthy controls)were included in the study.The identification of dampness syndrome and the risk rating of stroke were carried out for the subjects,and fecal samples were collected.High-throughput 16S rRNA sequencing technology and bioinformatics methods were used to analyze the characteristics of gut flora.Results(1)A total of 53 cases(88.33％)were identified as dampness syndrome.There was significant difference in the quantitative score of dampness syndrome between the risk group and the healthy group,and between the low-,medium-and high-risk groups(P=0.016;P=0.041).(2)There was no statistical difference in the species and abundance of gut flora between the dampness syndrome group and the non-dampness syndrome group.(3)In the population identified as dampness syndrome,there was no significant difference in Alpha diversity between the healthy group and the risk group,but there was significant difference in Beta diversity analysis;LEfSe analysis found that Fusobacterium and Lactobacillus were enriched in the risk group;correlation analysis showed that the differential bacteria were related to the three risk factors of diabetes,dyslipidemia and obesity and carotid intima-media thickness(IMT).(4)In the population identified as dampness syndrome and having the risk of cerebrovascular disease,there was no significant difference in Alpha diversity among three groups with different levels of risks,while significant difference in Beta diversity was observed;LEfSe analysis showed that Acidaminococcaceae,Phascolarctobacterium and Butyricimonas were enriched in the low-risk group,Veillonellaceae was enriched in the medium-risk group,and Ruminococcus 2 and Alloprevotella were enriched in the high-risk group;correlation analysis showed that the differential bacteria were associated with high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),white blood cell count(WBC),and neutrophil count(NEUT).Conclusion In the Guangdong population predominated by dampness syndrome,the severity of dampness syndrome is related to the risk of stroke,and the specific flora associated with sub-clinical atherosclerosis,inflammatory response and lipid metabolism are presented.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

Aim To explore and verify the possible mechanism of Jiawei Duhuo Jisheng Mixture(JDJM)in the treatment on Knee Osteoarthritis(KOA)via using network pharmacology and animal experiment. Methods The ingredients of JDJM and relevant targets were collected from TCMSP and BATMAN-TCM database. The KOA-related targets were collected from GeneCard, OMIM and GEO databases. The common targets were acquired by intersecting ingredients-related and KOA-related targets, and then the Ingredient-Disease-Target Network and PPI network were constructed by Cytoscape 3.7.2 software and STRING platform. GO and KEGG enrichment analysis were performed based on Metascape database. Finally, the key targets and relevant mechanism were validated via animal experiment. Results In the network pharmacology study, 180 active ingredients related to treatment on KOA by JDJM were collected, and 152 common targets were confirmed. PPI network analysis showed that AKT1 might be the key targets of JDJM in the treatment on KOA. GO and KEGG enrichment analysis revealed that the key target mainly concentrated on inflammatory response and apoptosis. Animal experiment confirmed that JDJM could improve lesion in KOA rabbits, and suppress the expression levels of IL-1β, TNF-α, Caspase 3 and BAX in serum and articular fluid. AKT1 expression(including mRNA and protein)in articular cartilage was also down-regulated. Conclusions Based on the results of network pharmacology and animal experiment, JDJM may relieve KOA severity by anti-inflammatory and anti-apoptotic effects through a variety of molecular signaling pathways.

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg^-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.