This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Objective To explore the effect of Qingre Xiaoyanning tablets on chronic toxicity in SD rats.Methods A total of 120 SD rats were randomly divided into blank group(water)and experimental-L,-M,-H groups(2.63,5.25 and 10.50 g·kg 1 Qingre Xiaoyanning dry paste powder),with 30 rats per group.Four groups were administered continuously for 4 weeks with a recovery period of 4 weeks.SD rats were dissected as planned.The general condition,weight gain,hematological and biochemical indexes,major organ coefficients,macroscopic and microscopic tissue morphology were observed.Results There were no significant differences in the general condition,body mass growth,coagulation index and histopathology of rats between the experimental-L,-M,-H groups and the blank group.End of administration,the mean hemoglobin concentrations of experimental-H and blank groups were(370.70±3.78)and(365.90±5.77)g·L-1,glucose were(5.98±0.63)and(6.61±0.93)mmol·L-1,blood urea nitrogen(BUN)were(4.72±1.01)and(5.78±1.64)mmol·L-1,liver coefficients were 3.05±0.17 and 2.89±0.19,and the differences were statistically significant(P≤0.05,P≤0.01).Resumption of the final,direct bilirubin of experimental-L and blank groups were(0.38±0.18)and(0.19±0.18)pmol·L 1,BUN of experimental-M and blank groups were(4.45±0.56)and(5.65±1.16)mmol·L-1,and the differences were statistically significant(all P≤0.05).Conclusion Repeated administration of Qingre Xiaoyanning tablets showed no significant toxicity in SD rats.

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.

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q₁, Q₃) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q₁, Q₃) of 42 (20, 55) and the median exposure period (Q₁, Q₃) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
Male ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology* ; Incidence ; Family Characteristics

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.
China/epidemiology* ; Early Detection of Cancer ; Female ; Hepatitis B Surface Antigens ; Humans ; Incidence ; Liver Neoplasms/epidemiology* ; Male ; Mass Screening ; Risk Factors

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans