Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels， but their effectiveness is limited. The mechanisms underlying its onset are complex， and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression， involving multiple pathways， including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 （TLR4/NLRP3）， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， brain-derived neurotrophic factor/tyrosine kinase receptor B （BDNF/TrkB）， cyclic AMP/protein kinase A/cAMP response element-binding protein （cAMP/PKA/CREB）， and others. Traditional Chinese medicine（TCM） is based on a holistic approach and the principle of treatment based on the differentiation of syndromes， regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems， involving liver Qi stagnation， heart spirit deficiency， kidney essence depletion， and spleen dysfunction. TCM compound treatments focus on soothing the liver， strengthening the spleen， calming the heart， and replenishing essence， with formulas such as Xiaoyaosan， Zishui Qinggan Yin， and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi， such as salidroside， ginsenoside Rb₁， astragaloside， and muscone. External TCM treatments， primarily acupuncture， aim to open the orifices and invigorate the spirit. Acupoints such as Baihui， Shenting， and Yintang are commonly used. Additionally， massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression， aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Objective The aim of the study was to investigate how morphine(Mor)effects mitochondrial dynamics change of H9c2 induced by hypoxia/reoxygenation(H/R).Methods Myocardial H9c2 cells were divided into blank group(without treatment),model group(H/R treatment),control group(5 μmol·L-1 Mor treatment)and experimental group(H/R+5 μmol·L-1 Mor treatment).The content of reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and complex of Ⅰ and Ⅲ activity were detected using ROS,tetramethylrhodamine ethyl ester(TMRE),and mitochondrial complex of Ⅰ and Ⅲ activity detection kits,respectively.The morphology of mitochondria and lysosomes was observed by transmission electron microscope electron microscopy(TEM);Western blot was used to detect the expression of GTPase kinetic protein 1(Drp1),cytochrome c oxidase Ⅳ(COX Ⅳ)and transporters of the outer mitochondrial membrane(TOM20).Results The nuclear membrane was smooth and complete;the mitochondrial size was consistent;the crest arrangement was neat;vacuolization was reduced or even disappeared;the mitochondrial matrix electron density was increased;the number of autophagosomes was decreased in the experimental group.The contents of ROS in blank group,model group,control group and experimental group were 1.03±0.04,1.53±0.10,1.06±0.06 and 1.10±0.11;MMP were 1.00±0.15,0.80±0.16,1.06±0.19 and 1.00±0.19;the activities of complex of Ⅰ were 1.00±0.08,2.28±0.82,1.05±0.26 and 1.13±0.37;the activities of complex of Ⅲ were 1.00±0.09,2.13±0.38,0.83±0.22 and 0.96±0.11;the expression of Drp1 protein were 1.00±0.14,1.27±0.07,0.97±0.21 and 0.93±0.17;the expression of fission protein 1(Fis1)protein were 1.00±0.16,1.33±0.18,1.17±0.25 and 0.99±0.05;the expression of COX Ⅳ protein were 1.00±0.25,0.62±0.08,0.79±0.26 and 0.97±0.16;the expression of TOM20 protein were 1.00±0.13,0.67±0.15,0.75±0.13 and 0.89±0.05.The above indexes of model group were significantly different from those of blank group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).The above indexes of experimental group were significantly different from those of model group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).Conclusion Morphine may inhibit mitophagy and fission,and alleviated mitochondrial oxidative stress damage by decreasing the activity of respiratory chain complex of Ⅰ and Ⅲ,thus maintaining mitochondrial dynamic homeostasis and alleviating H/R-induced myocardial cell damage.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.