ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Objective To explore the mechanism of Wumei pill on ulcerative colitis(UC)in mice based on the anti oxidative stress pathway of nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE).Methods Seventy SPF male C57BL/6 mice were randomly divided into the control group,the UC group,the mesalazine group(MES group,0.82 g/kg MES),the low dose Wumei pill group(WMW-L group,5 g/kg crude drug),the middle dose Wumei pill group(WMW-M group,10 g/kg crude drug),the high dose Wumei pill group(WMW-H group,20 g/kg crude drug)and the high dose Wumei pills+Nrf2 inhibitor ML-385 group(WMW-H+ML-385 group,Wumei pills crude drug 20 g/kg+20 mg/kg ML-385),with 10 rats in each group.The disease activity index(DAI)score and colonic mucosa injury score were performed in mice after the last administration.Pathological changes of colonic mucosa in mice were observed by HE staining.The levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α)and IL-6 in serum and colon tissue of mice were measured by enzyme-linked immunosorbent assay(ELISA).The content of malondialdehyde(MDA)in serum and colon tissue of mice was determined by thiobarbituric acid colorimetry(TBA).The activity of superoxide dismutase(SOD)in serum and colon tissue of mice was measured by xanthine oxidase method.The activity of glutathione peroxidase(GSH-px)in serum and colon tissue of mice was determined by direct method with dithiodinitrobenzoic acid(DTNB).The positive expression of Nrf2 in colon tissue of mice was observed by immunohistochemistry.The expression of heme oxygenase-1(HO-1)and NAD(P)H:quinone oxidoreductase-1(NQO1)proteins in colon tissue of mice were detected by Western blot assay.Results Compared with the control group,the DAI score,colonic mucosa injury score,colonic histopathology score,levels of IL-1β,TNF-α,IL-6 and MDA in serum and colonic tissue,and expression levels of Nrf2,HO-1 and NQO1 protein in colonic tissue of mice were increased in the UC group,levels of SOD and GSH-px in serum and colon tissue decreased(P＜0.05),the colon mucosa of mice was seriously damaged.Compared with the UC group,changes of corresponding indexes were contrary to the above in the MES group,the WMW-M group and the WMW-H group.However,the expression levels of Nrf2,HO-1 and NQO1 proteins in colon tissue were increased(P＜0.05),and the damage of colon mucosa in mice was alleviated.Changes of the above indexes were dose-dependent in the WMW-L group,the WMW-M group and the WMW-H group.There were no significant differences in the above indexes between the WMW-H group and the MES group.ML-385 attenuated the improvement effect of high dose Wumei pill on colon mucosa injury.Conclusion Wumei pill may alleviate the colon mucosal damage of UC mice by activating Nrf2/ARE antioxidant stress pathway.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Scientific and rigorous selection of theories,models or frameworks is the premise of high-quality nursing research.This work introduces the development process,basic information,application in nursing of T-CaST(Theory Comparison and Selection Tool,T-CaST),and shows the specific application process of this tool through examples,to provide evaluation methods for nursing scholars to choose appropriate guiding theories in the research process,and has guiding significance for developing high-quality nursing research under the guidance of theories,models or frameworks.

Objective:Evaluate the effects of brief mindfulness meditation training on improving negative e-motions,mindfulness attention awareness,and sleep quality in patients after percutaneous coronary intervention(PCI)for coronary heart disease.Methods:Eighty-four patients with coronary heart disease after PCI admitted to the cardiology department were selected.According to the principle of simple randomization,they were divided into an intervention group of 42 cases and a control group of 42 cases.The Self Rating Anxiety Scale/Self Rating De-pression Scale,Mindfulness Attention Awareness Scale,and Pittsburgh Sleep Quality Index Scale were used as eval-uation indicators before and after intervention.Results:The difference in total scores of anxiety,depression,and mindfulness attention awareness before and after intervention in the intervention group was higher than that in the control group(P＜0.05).The difference in total sleep score,sleep quality,time to fall asleep,sleep duration,use of hypnotic drugs,daytime dysfunction,and total sleep score before and after intervention was higher than that of the control group(P＜0.05).Conclusion:It suggests that brief mindfulness meditation training could alleviate negative emotions in patients with coronary heart disease after PCI,improve mindfulness awareness,and improve sleep quali-ty.

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti–tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

ObjectiveTo understand the concentration levels of benzene， toluene and xylene in the workplaces of enterprises involved in benzene and benzene series in Jinshan District， and to provide the basis for the government to formulate key occupational disease prevention and control strategies. MethodsFrom 2016 to 2021， enterprises involved in benzene and benzene series were sampled individually， and the monitoring results of benzene and benzene series were statistically analyzed through workplace air sampling and laboratory detection. ResultsFrom 2016 to 2021， a total of 80 enterprises were monitored， and the total passing rate of individual monitoring was 87.50%， which decreased first and then increased. The difference was not statistically significant. A total of 387 individuals were sampled with a total passing rate of 95.61% and a detection rate of 73.38% （284 individuals）. The detection rates of benzene， toluene and xylene were 6.46%， 29.97% and 36.95%， respectively. The exceedance rates were 1.03%， 0.26% and 3.10%， respectively. Among the companies exceeding the standard， the metal products industry had the highest rate of exceedance （19.05%）. For individuals， those working in the printing and recording media reproduction industry had the highest rate of exceedance （10.26%）. ConclusionThe passing rate and detection rate of benzene and benzene series are relatively high in Jinshan District. The metal products industry and the printing and recording media reproduction industry have a higher exceedance rate of benzene and benzene series.

The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl₂) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl₂ was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl₂ in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
Animals ; Male ; Mice ; Antioxidants/pharmacology* ; Apoptosis ; Endoplasmic Reticulum Stress ; Melatonin/pharmacology* ; Mice, Inbred C57BL ; Nickel/adverse effects* ; Selenoproteins/genetics* ; Heart/drug effects*

Humans ; Soft Tissue Neoplasms ; Mesenchymoma/diagnostic imaging* ; Paraneoplastic Syndromes/pathology*