Objective To investigate the effects of raddeanin A(RA)on the proliferation and apoptosis of HCT116 cells and on the β-catenin/c-Myc pathway.Methods Human colon cancer HCT116 cells were divided into four groups:Control group,experimental-L group,experimental-M group and experimental-H group.Experimental-L,experimental-M,experimental-H groups were treated with 5,10 and 20 μmol·L-1raddeanin A,and the control group was given the same amount of normal saline,respectively.The inhibitory effect of RA on the proliferation of HCT116 cells of colon cancer was detected by cell counting kit-8(CCK-8)method.Cell nucleus morphology change was observed with the fluorescence;the apoptosis rate was detected by flow cytometry;and the expression of related proteins of β-catenin/c-Myc signaling pathway was detected by western blot.Results After 48 h,the cell inhibitory rates of the control group,experimental-L,experimental-M,experimental-H groups were 0,(19.15±0.65)％,(35.11±0.40)％and(49.93±1.13)％,respectively;the cell apoptosis rates were(0.16±0.18)％,(9.26±0.42)％,(17.87±2.54)％and(38.10±2.70)％,respectively;the protein expression levels of β-catenin were 0.74±0.03,0.69±0.01,0.33±0.02 and 0.16±0.04,respectively;the protein expression levels of c-Myc were 0.89±0.01,0.54±0.03,0.29±0.03 and 0.13±0.04,respectively;the protein expression levels of Cyclin D1 were 0.84±0.04,0.66±0.01,0.48±0.06 and 0.21±0.03,respectively;the expression levels of Cleaved-Caspase3 protein were 0.19±0.03,0.26±0.04,0.45±0.04 and 0.78±0.01,respectively.The above indicators in the experimental-L,experimental-M,experimental-H groups showed statistically significant differences compared to those of control group(all P＜0.05).Conclusion RA can inhibit the proliferation of HCT116 cells and induce apoptosis,which may be related to the inhibition of β-catenin/c-Myc signaling pathway.

Objective To investigate the effects of acetylshikonin on proliferation,invasion and migration of oxaliplatin-resistant human colon cancer HCT116 cells(HCT116/L-OHP).Methods HCT116/L-OHP cells were divided into blank group,control group,experimental-L group,experimental-M group and experimental-H group.The control group was treated with 10 μmol·L-1 oxaliplatin.The experimental-L,experimental-M,experimental-H groups were treated with 1.25,2.50 and 5.00 μmol·L-1 acetylshikin and 10 μmol·L-1 oxaliplatin,respectively.The blank group was given routine culture.The changes of HCT116/L-OHP cell proliferation were detected by cell counting kit-8(CCK-8)method;flow cytometry was used to evaluate the apoptosis of cells;Transwell assay was used to detect the changes of cell migration and invasion ability;Western blot was used to detect the expressions of P-glycoprotein(P-gp),matrix metallo-proteinases 2(MMP2),nuclear factor kappa-B(NF-κB)/and hypoxia induced factor-1 α(HIF-1α)proteins.Results The cell inhibition rates of the blank group,control group and experimental-L,-M,-H groups were 0,(8.27±0.01)％,(10.53±0.02)％,(34.17±0.01)％and(48.47±0.05)％;cell apoptosis rates were(0.13±0.02)％,(1.37±1.04)％,(9.73±0.87)％,(26.71±4.26)％and(40.75±4.70)％;invading cells were 130.70±9.81,127.10±9.21,71.83±3.57,28.83±1.87 and 19.63±6.11;the number of migration cells was 150.50±10.17,148.40±8.13,94.58±4.09,63.98±5.09 and 31.85±5.50;the relative expression levels of P-gp protein were 0.91±0.01,0.89±0.02,0.75±0.04,0.61±0.07 and 0.25±0.03;the relative expression levels of MMP2 protein were 1.24±0.01,1.22±0.02,0.96±0.01,0.53±0.01 and 0.16±0.02;the relative expression levels of NF-κB-p65 were 1.12±0.12,1.07±0.01,0.78±0.01,0.64±0.02 and 0.31±0.03;the relative expression levels of HIF-1 α were 0.65±0.04,0.52±0.03,0.41±0.02,0.35±0.03 and 0.09±0.01,respectively.The above indicators in the experimental-L,-M,-H groups showed statistically significant differences compared to those of blank group(all P＜0.05).Conclusion Acetylshikonin combined with oxaliplatin can significantly inhibit the proliferation,invasion and migration of HCT116/L-OHP cells,and induce cell apoptosis,which may be related to the inhibition of P-gp and MMP2 expression and the activation of NF-κB/HIF-1 α signal.

Pasteurella multocida and Aeromonas hydrophila are rare human pathogens,and zoonotic infections caused by bites of big cats are rarely reported.This paper reported the first case of wound infection caused by Pas-teurella multocida and Aeromonas hydrophila after tiger bites in China.Strain identification and drug susceptibility testing were conducted by BD PHOENIXTM100 automatic microbial analyzer.The patient was discharged with a good prognosis after wound debridement,surgical intervention and combined antimicrobial treatment.This paper aims to advise emergency physicians to consider the possibility of co-infection of Pasteurella multocida and Aero-monas hydrophila when encountering rare big cat bites.

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

OBJECTIVE: The purpose of this study was to determine the serum uric acid levels and the prevalence of hyperuricemia among Chinese adults in 2015 and compare the differences between urban and rural areas, as well as the differences between eastern, central, and western regions. METHODS: A national representative sample of 180,208 participants were included using a stratified, multistage, and random sampling method. The demographic characteristics and blood samples were collected to determine the serum uric acid levels and prevalence of hyperuricemia among subgroups using complicated sampling weight. A t-test or ANOVA was used for normally-distributed data. The Kruskal-Wallis rank test was used for skewed-distributed data. The Mantel-Haenszel chi-square test was used to compare the difference in categorical variables. RESULTS: The weighted mean uric acid level in Chinese adults was 310.4 μmol/L (317.5 μmol/L in urban areas and 302.9 μmol/L in rural areas). The weighted average values of uric acid in eastern, central, and western China were 315.5 μmol/L, 303.5 μmol/L, and 310.4 μmol/L, respectively. The weighted prevalence of hyperuricemia in Chinese adults was 14.6%, with a prevalence of 16.5% in urban areas and 12.5% in rural areas. The weighted prevalence of hyperuricemia in eastern, central, and western China was 16.0%, 12.5%, and 14.8%, respectively. CONCLUSION The uric acid level in Chinese adults is relatively high. Effective actions are warranted to improve this metabolic abnormality.
Adult ; Humans ; Hyperuricemia/epidemiology* ; Uric Acid ; Nutritional Status ; Asian People ; China/epidemiology*

Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule（FTZ） on hemoglobin A1c（HbA1c）in patients with type 2 diabetes mellitus （T2DM） based on real-world data. Method:T2DM patients who were provided with FTZ （FTZ group） and those receiving conventional hypoglycemic drugs （control group） were extracted from the hospital information system （HIS） of the First Affiliated Hospital of Guangdong Pharmaceutical University， followed by propensity score matching （PSM） for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index， the difference in efficacy between the two groups was compared using t-test and χ² test. For repeated measurement data of the same patient， the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation （GEE）. The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis （MLRA）， and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation， ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time， the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover， the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c ［β=-0.530，95% confidence interval（CI） -0.850～-0.209，P<0.01］ or those who were complicated with hypertension （β=-0.918，95%CI -1.614～-0.222，P<0.05）. Conclusion:In the real world， FTZ is able to control the blood sugar， and its effect is similar to those of conventional hypoglycemic drugs. Besides， it is capable of stabilizing the blood sugar for a long time.

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

This study aims to systematically evaluate the clinical efficacy and safety of Toutongning Capsules in the treatment of tension-type headache(TTH), so as to provide a corresponding basis for clinical treatment. Eight commonly used medical research databases and two clinical trial registration systems were retrieved with the time interval from the establishment of the database or system to November 2020. The randomized controlled trials of Toutongning Capsules in the treatment of TTH were screened out according to the pre-set criteria. The quality of the included papers was evaluated by the bias risk assessment tool in Cochrane Reviewers Handbook 6.1 and the data were statistically analyzed by RevMan v5.4 provided by Cochrane collaboration. A total of 13 studies were included and the quality of methodology was generally low. Meta-analysis showed that Toutongning Capsules assisted with western medicine therapy can effectively reduce the pain intensity(MD_(VAS)=-1.94,95%CI[-2.50,-1.38],P<0.000 01;MD_(NRS)=-0.83,95%CI[-0.86,-0.80],P<0.000 01), headache duration(SMD=-0.98,95%CI[-1.17,-0.79],P<0.000 01), headache frequency(MD=-1.01,95%CI[-1.16,-0.85],P<0.000 01), headache index(MD=-11.13,95%CI[-12.10,-10.16],P<0.000 01), anxiety and depression scale score(MD_(HAMA)=-4.02,95%CI[-6.58,-1.46],P=0.002;MD_(HAMD)=-2.67,95%CI[-4.04,-1.29],P=0.000 1), while Toutongning Capsules as monotherapy only reduced the headache score(MD=-2.24,95%CI[-2.97,-1.51],P<0.000 01). The available clinical studies demonstrate that Toutongning Capsules combined with western medicine in the treatment of TTH can improve the related outcome indicators, but the clinical safety and efficacy of Toutongning Capsules alone remain unclear. Due to the small number and low quality of the included studies, large-sample, multi-center, high-quality and strictly designed randomized controlled trials are still needed to verify the clinical efficacy in the future.
Capsules ; Databases, Factual ; Drugs, Chinese Herbal ; Humans ; Tension-Type Headache/drug therapy* ; Treatment Outcome

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Purpurogallin, a natural phenol obtained from oak nutgalls, has been shown to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, in addition to ultraviolet B (UVB) radiation that induces cell apoptosis via oxidative stress, particulate matter 2.5 (PM(2.5)) was shown to trigger excessive production of reactive oxygen species. In this study, we observed that UVB radiation and PM(2.5) severely damaged human HaCaT keratinocytes, disrupting cellular DNA, lipids, and proteins and causing mitochondrial depolarization. Purpurogallin protected HaCaT cells from apoptosis induced by UVB radiation and/or PM(2.5). Furthermore, purpurogallin effectively modulates the pro-apoptotic and anti-apoptotic proteins under UVB irradiation via caspase signaling pathways. Additionally, purpurogallin reduced apoptosis via MAPK signaling pathways, as demonstrated using MAPK-p38, ERK, and JNK inhibitors. These results indicate that purpurogallin possesses antioxidant effects and protects cells from damage and apoptosis induced by UVB radiation and PM(2.5).
Antioxidants ; Apoptosis Regulatory Proteins ; Apoptosis ; DNA ; Humans ; Keratinocytes ; Oxidative Stress ; Particulate Matter ; Phenol ; Reactive Oxygen Species