Chronic hepatitis B (CHB) is still a global public health problem, resulting in the high risk of decompensated cirrhosis and hepatocellular carcinoma.At present, there are no single available medications that can induce both potent HBV DNA suppression, and high rates of HBeAg and HBsAg clearance.Therefore, there is great interest in developing combination therapies for patients with chronic HBV infection, which can achieve sustained viral suppression and HBsAg negative inversion after a finite course of treatment leading to clinical cure.This article reviews the current status and advances of combination therapy for CHB.

Objective In the present study, we investigated the effects of advanced oxidation protein products(AOPP) on reactive oxygen species(ROS) production in murine osteoblastic MC3T3-E1 cells by NADPH oxidase enzymes pathway. Methods Experiments were divided into three groups, including control group, rats albumin(RSA) group, and AOPP group. Different concentrations of AOPP were added to the osteoblastic MC3T3-E1 cells culture medium. The production of ROS in MC3T3-E1 cells was measured by the fluorescence intensity of intracellular fluoroprobe ( DCFD ) . In order to verify the effect of enzyme of the production of ROS, the specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells which were cultured in the medium with AOPP. Finally, western blot and immunofluorescence were used to observe the changes of NADPH oxidase enzymes subunits. Results Different concentrations of AOPP (50,100,200μg/ml) induced MC3T3-E1 cells to produce different amount of ROS. The higher concentrations of AOPP were added, the more ROS were produced. Furthermore,200μg/ml AOPP induced the maximum amount of ROS production(P<0. 05). Meanwhile, AOPP induced MC3T3-E1 cells to produce different amount of ROS with a time-dependent manner. The peak amount of ROS production in MC3T3-E1 cells was observed in 3h when AOPP were added (P<0. 05). In addition, when specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells, the production of ROS were significantly suppressed by C-SOD, DPI, and apocynin(P<0. 05). On the other hand, AOPP can up-regulate the expression of Nox4 protein of the MC3T3-E1 cells, which is one of the subunits of NADPH oxidase enzymes. Meanwhile, AOPP can also induce the membrane migration of p47phox subunit. Conclusion AOPP induces osteoblastic MC3T3-E1 cells to produce ROS by NADPH oxidase enzymes pathway, and which may be one of the pathogenesis of AOPP involved in osteoporosis.

Objective To determine telmisartan and amlodipine assay in the compound tablet .Methods First derivative UV spectrophotometry was used at wavelength 236 nm for telmisartan and 390 nm for amlodipine .Results Telmisartan con-tent has a good linear relationship in the concentration range of (4~20) × 10-3 mg/ml .The standard curve equation is Y =0 .0043 X-0 .0005 and correlation coefficient R2 =0 .9993 .Amlodipine content has a good linear relationship in the concen-tration range of (10~90) × 10-3 mg/ml .The standard curve equation is Y =0 .0003 X+0 .0002 and correlation coefficient R2 =0 .9995 .Conclusion The assay results from this method are consistent with the results from HPLC .This procedure pro-vides a specific ,accurate and precise method to assay the amlodipine and telmisartan in compound tablet .

Objective To evaluate the clinical efficacy of interferon(IFN) α-2b,adefovir dipivoxil (ADV),granulocyte-macrophage colony stimulating factor (GM-CSF) and hepatitis B vaccine in the treatment of patients with HBeAg-positive chronic hepatitis B (CHB).Methods Two hundredand forty HBeAg-positive CHB patients admitted in the First Affiliated Hospital,Zhejiang University School of Medicine during November 2013 and December 2015 were retrospectively reviewed.They were randomly assigned to four groups with 60 cases in each group,to receive IFNα-2b (group A),IFNα-2b + ADV (group B),IFNα-2b + ADV + GM-CSF (group C) or IFNoα-2b + ADV + GM-CSF + hepatitis B vaccine (group D) for treatment,respectively.All patients were treated for 48 wks and then followed up for 24 wks.The HBsAg serological response,HBeAg serological response,virological response,biochemical response,histological response and adverse effects were compared among 4 groups.Results After 48-wk treatment,the HBsAg negative conversion rate of group D was significantly higher than that of group A and B (x2 =8.634 and 8.634,both P ＜ 0.01);the seroconversion rate of HBsAg in group D was significantly higher than that in group A and group B (x2 =7.149 and 7.149,both P ＜0.01).The baseline drop rate of HBsAg in group C and D was higher than that in group A (t =4.194 and 4.508,both P ＜0.01).In 24-wk follow-up,HBsAg negative conversion rate was as same as that after 48-wk treatment;the seroconversion rate of HBsAg in group D was significantly higher than that in group A and B (x2 =8.634 and 8.634,both P ＜0.01).The baseline drop rate of HBsAg in group C and group D was higher than that in group A (t =4.546 and 4.969,both P ＜0.01).After 48-wk treatment,the HBeAg negative conversion rate in group D was significantly higher than that in group A (x2 =8.792,P ＜ 0.01);the HBeAg seroconversion rate of group C and D was higher than that of group A (x2 =7.064 and 10.159,P ＜0.01).In 24-wk follow-up,the HBeAg negative conversion rate in group C and D was higher than that in group A (x2 =10.159 and 13.713,P ＜0.01);the HBeAg negative conversion rate in group D was higher than that in group B (x2 =8.155,P ＜0.01);the seroconversion rate of HBeAg in group C and D was higher than that in group A (x2 =10.506 and 12.857,P ＜ 0.01).After 48-wk treatment,the negative rate of HBV DNA in group B,C and D was significantly higher than that in group A (x2 =12.452,17.062 and 20.670,all P ＜0.01).In the 24-wk follow-up,the negative rate of HBV DNA in group B,C and D was also significantly higher than that in group A (x2 =21.121,26.880 and 33.611,all P ＜ 0.01).After 48-wk treatment,the alanine aminotransferase (ALT) normalization rate of the group of C and D was significantly higher than that in group A (x2 =8.711 and 8.711,both P ＜0.01).In the 24-wk follow-up,the ALT normalization rate in group C and D was significantly higher than that in group A (x2 =8.076 and 9.624,P ＜0.01).After 48-wk treatment,the improvement rate of inflammation or fibrosis in the group of A,B and C was significantly higher than that in the group A (x2 =8.543,13.348 and 16.205,all P ＜ 0.01).There were no half-way withdrawal and no serious adverse reactions.The main adverse reactions were fever,headache and fatigue,and no significant difference of above reaction was observed among 4 groups (P ＞ 0.05).Conclusion The new anti-virus/immunoregulation therapy containing IFNα-2b + ADV + GM-CSF + hepatitis B vaccine has a better therapeutic effect for patients with HBeAg-positive CHB.

Objective:To investigate the changes of liver pathology and its influencing factors in patients with chronic hepatitis B viral (HBV) infection and low level of serum alanine aminotransferase (ALT).Methods:The clinical data of 135 with chronic HBV infection patients, in whom the serum ALT levels were less than two times of the upper limit of normal (ULN), were collected from the Affiliated Hospital of Medical School of Ningbo University and the First Affiliated Hospital, Zhejiang University School of Medicine during July 2017 and July 2019. The result of hepatic histological examination was reviewed, and the risk factors of obvious liver inflammation (G≥2) or fibrosis (S≥2) in patients were analyzed with Logistic regression analysis.Results:The pathological examination of liver tissue revealed G≥2 or S≥2 in 52 cases (38.5%). The univariate analysis showed that age, family history of HBV infection, ALT 1-<2×ULN, aspartate aminotransferase(AST)≥1×ULN, low platelet count(PLT)and prolongation of prothrombin time(PT)were associated with G≥2 or S≥2 in chronic HBV infection patients with low level ALT ( P<0.05 or <0.01). Multivariate Logistic regression analysis showed that age( OR=1.052, 95% CI 1.007-1.100), family history of HBV infection( OR=5.448, 95% CI 2.191-13.548)and AST( OR=1.042, 95% CI 1.005-1.081)were independent risk factors of G≥2 or S≥2 in chronic HBV infection patients with low level ALT ( P<0.05 or <0.01). Conclusion:Age, family history of HBV infection and AST level can be used to judge the severity of liver pathological changes and necessity of antiviral treatment for patients with chronic HBV infection having ALT<2×ULN.

Objective:To evaluate the impact of the reform of the county medical community on the expenditure of medical insurance funds, and to provide references for maintaining the stability of the medical insurance fund and deepening the reform of the medical community.Methods:Medical insurance data of urban and rural residents in M County, Yunnan province from 2016 to 2019 were collected, and a discontinuous time series model was used to analyze the impact of county medical community reform on medical insurance fund expenditures.Results:Since the reform, the number of patients discharged from county-level hospitals has shown a downward trend, averaging a decrease of 25.996 people per month; yet increases have emerged with the average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure, averaging a monthly increase of 90.931 yuan, 50.014 yuan and 1.528 yuan respectively. The average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure of the township hospitals all showed an upward trend, averaging a monthly increase of 31.191 yuan, 38.678 yuan and 0.085 yuan respectively. The flow of external medical insurance funds of the medical community has shown a continuous upward trend, averaging a monthly increase of hospitalization fund expenditures of 33.005 yuan, and a monthly increase of outpatient overall fund expenditures of 4.896 yuan overall.Conclusions:The M County medical community should further strengthen the top-level design, explore the reform of medical insurance payment methods, improve the regional information platform, standardize the referral system, and strengthen supervision to deepen the construction of the medical community to ensure the sustainable operation of medical insurance funds.

OBJECTIVE To compare efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， Wanfang， CNKI， CBM and VIP database， randomized controlled trial （RCT） and cohort study about 24 h continuous pump （trial group） versus intermittent infusion （control group） of amphotericin B were collected from the inception to Jan. 2023. After literature screening and data extraction， the quality of RCT was evaluated with modified Jadad scale， and the quality of cohort study was evaluated with Newcastle-Ottawa scale. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software. RESULTS A total of 7 literature were included， involving 1 RCT and 6 cohort studies with a total of 767 patients. The results of meta-analysis showed that the clinical effective rate [RR＝1.44， 95%CI （1.13，1.83）， P＝0.003] of trial group was significantly higher than that of control group， and all-cause mortality rate [RR＝0.37， 95%CI（0.19，0.72），P＝0.003] and the incidence rate of infusion reaction [RR＝0.28，95%CI（0.18，0.43）， P＜0.000 01] were significantly lower than control group； there was no statistical significance in the incidence rate of renal impairment between 2 groups [RR＝0.71，95%CI（0.45，1.11），P＝0.13] . The sensitivity analysis results showed that the results obtained in this study were robust. CONCLUSIONS The efficacy and safety of 24 h continuous pump of amphotericin B are better than those of intermittent infusion in the treatment of invasive fungal infection.

In recent years, PET-CT has an increasing importance in the diagnosis and treatment of breast cancer. PET-CT scan can be used as a noninvasive method for molecular subtyping of breast cancer, and prediction of therapeutic effect and prognosis of patients. Studies have revealed that luminal A subtype has a significantly lower maximum standard intake value (SUVmax) than the other subtypes; triple-negative and human epidermal growth factor receptor 2 (HER2) positive tumors have relatively high SUVmax than luminal B subtype, but the specificity and sensitivity of SUVmax in diagnosis of molecular subtypes are very low, so its clinical application is limited. In predicting the effectiveness of the treatment and the prognosis of the patients, the decreased uptake of fluorodeoxyglucose (FDG) is correlated with better therapeutic effect. In addition, patients with high FDG uptake have worse survival outcomes. New tracers, such asF-fluoroestradiol (F-FES) and[89Zr]trastuzumab play an important role in molecular subtyping of breast cancer.F-FES PET-CT can effectively evaluate the estrogen receptor (ER) status of breast cancer and the response to endocrine therapy.[89Zr]trastuzumab PET-CT can evaluate the expression of HER2 and localization of HER2-overexpressing tumors, but their specificities and sensitivities are also low. In this article, we review the recent advances on the correlation of PET-CT findings with molecular subtypes, treatment response and prognosis of breast cancer.