Objective To evaluate the economic value of fluticasone furoate/umeclidinium/vilanterol(FF/UMEC/VI)powder for inhalation in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk from the perspective of the Chinese health system.Methods Based on subgroup analysis of the China cohort in the IMPACT trial,a four-state lifetime Markov model was established with a 3-month cycle.The model simulation period was 11 years.Clinical efficacy,health benefits,and cost data were obtained through published literature.The health outcomes included quality adjusted life year(QALY).Using 3 times Chinas per capita gross domestic product(GDP)in 2023 as the willingness-to-pay threshold,the cost-utility analysis method was used for analysis the economic viability of FF/UMEC/VI.The scenario analysis,one-way sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the results.Results Compared with fluticasone furoate/vilanterol(FF/VI),FF/UMEC/VI in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk saved costs 8 118.66 yuan and obtained an additional 0.000 06 QALYs,giving it an economic advantage.Compared with umeclidinium/vilanterol(UMEC/VI),FF/UMEC/VI treatment paid 2 784.41 yuan more and received 0.000 45 QALYs less,making UMEC/VI more cost-utility.The scenario analysis results further confirmed the robustness of the model.The sensitivity analysis results showed that when the drug cost of FF/UMEC/VI per cycle decreases to 637.29 yuan,FF/UMEC/VI had economic benefits under a willingness-to-pay threshold of 3 times China's per capita GDP in 2023.Conclusion For patients with symptomatic chronic obstructive pulmonary disease at risk of acute exacerbation,FF/UMEC/VI is more cost-utility than FF/VI.Compared with UMEC/VI,FF/UMEC/VI has economic viability after price reducing.

AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

OBJECTIVE To analyze the compatible stability of commonly used intravenous drugs in the intensive care units （ICU）， and to provide a reference for improving medication safety in clinic. METHODS The commonly used intravenous drugs in the ICU of Hebei General Hospital were investigated and confirmed in April 1-30， 2022， and used as keywords to retrieve the relevant literature about compatible stability from PubMed， CNKI， Wanfang Data and other databases， and manually filtered with Micromedex database at the same time. Then， the compatible stability results of the included literature were analyzed descriptively. RESULTS Totally 32 commonly used intravenous drugs and 39 mixed infusion combinations were collected from ICU of this hospital. A total of 40 studies were included， only 2 studies followed all quality requirements； 18 studies validated their methods to guarantee correct reproducibility； 33 studies evaluated physical stability， including precipitate formation and pH changes； 32 studies evaluated chemical compatibility， mainly content/concentration changes. A total of 666 possible two-drug combinations were obtained from the included literature， of which 254 combinations of stability data were available， including 176 were stable， 68 were unstable， and 10 were contradictory. Totally 412 combinations had no stability results. Among two-drug combinations in ICU of this hospital， 42 combinations were stable， 14 combinations were unstable， and 2 combinations were contradictory. CONCLUSIONS The pH， solvent， excipients and preparation concentration are the factors that affect the stability. There are drug combinations with unstable compatibility of commonly used intravenous drugs in ICU of this hospital. The stability study methods are limited， and the stability data cannot meet the actual clinical needs.

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Drug-drug interactions (DDI) of tyrosine kinase inhibitors (TKIs) mediated by metabolic enzymes and transporters have become an important issue in clinical practice recently. In addition to CYP450 enzymes, uridine diphosphate glucuronidases (UGTs) are another class of metabolic enzymes involved in the metabolism of TKIs, and most TKIs can inhibit the UGTs in vitro. Potential clinically meaningful DDIs may occur with the co-administration of TKIs and substrates or inhibitors of UGTs. This paper will mainly focus on the UGTs-mediated drug-drug and the effect of UGT1A genotype on the drug interactions of TKIs and explores strategies to address, aiming to provide clinicians and pharmacists with references for the safe and rational application of TKIs.

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ² = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.

AIM:To detect the endogenous expression of B-cell leukemia/lymphoma 6 member B (BCL6B) in FHC and LoVo cells, and to investigate the effects of BCL6B on proliferation and migration of LoVo cells for further explo-ring the underlying mechanism .METHODS:The endogenous expression of BCL 6B in the FHC and LoVo cells was detec-ted by RT-PCR and Western blot .The methods of MTT assay , colony formation assay , wound healing assay and Transwell chamber experiment were employed to examine the biological functions of BCL 6B in the LoVo cells.The mRNA and protein levels of BCL6B, cyclin D1 and matrix metalloproteinase-9 ( MMP-9) were determined by RT-PCR and Western blot , re-spectively.The level of phosphorylated protein kinase B (p-AKT) was detected by Western blot.RESULTS:BCL6B ex-pression was notably repressed in the LoVo cells as compared with the FHC cells , which were significantly increased by transfection with pcDNA3.1-BCL6B.The abilities of proliferation and migration of the LoVo cells at 72 h were inhibited by 28.33%(P<0.01) and 36.11%(P<0.05) in BCL6B group.The mRNA levels of cyclin D1 and MMP-9 in the cells of BCL6B group were decreased by 39.90%(P<0.01) and 77.36% (P <0.05), and the protein levels of cyclin D1, MMP-9 and p-AKT were reduced by 44.00%(P<0.05), 47.06%(P<0.01) and 32.88% (P<0.05), respectively. CONCLUSION:BCL6B inhibits proliferation and migration of the LoVo cells , and the PI3K/AKT signaling pathway is in-volved in this process .

Objective To investigate the prevalence of thyroid nodules and thyroid dysfunction in southern mountainouss areas of Ningxia.Methods A cross-sectional study was conducted among a representative sample of 10 639 adults in Jingyuan county with a population proportionate sampling method.High-resolution ultrasound was used to examine the thyroid and fasting blood specimens were collected in the morning for measurement of TSH,FT4,FT3.Chi-square test and spearman rank correlation analysis were used for statistical analysis.Results The prevalence of thyroid nodules was 29.08％,the sex-and age-adjusted rate was 27.17％.The prevalence of thyroid nodules was higher in women than in men (32.68％ vs.24.88％,x2=76.029 2,P＜0.001) and age was positively associated with thyroid nodules (r=0.272,P＜0.001).The rate of thyroid dysfunetion,subclinical hypothyroidism,subclinical hyperthyroidism,hypothyroidism,hyperthyroidism were 17.39％,13.00％,0.42％,0.96％,3.01％,respectively.The prevalence of thyroid nodules was higher in abnormal TSH group than in normal TSH group (39.44％ vs.27.24％,x2=95.624 0,P＜0.001).The level of THS,FT3,FT4 in thyroid nodules group differed fromn control group (Z=-9.144,P＜0.001;Z=-6.140,P＜0.001;Z=-1.997,P=0.046).Conclusion The prevalence of thyroid nodules and thyroid dysfunction were higher in southern mountainous areas of Ningxia.The relationship between thyroid nodules and thyroid function needs further research.We should pay attention to the early screening and diagnosis of thyroid nodules in mountainous areas.

OBJECTIVETo investigate the effect of high-intensity focused ultrasound (HIFU) on tumor metastasis in mouse model bearing melanoma xenograft.

METHODSMice bearing murine melanoma B16-F10 cell xenograft were randomized for sham-HIFU or HIFU exposure when the tumors grew to a maximum diameter of 7-10 mm, and the tumor size was measured every 3 days. The cumulative survival rate of the mice and tumor metastasis rate were calculated, and the circulating melanoma cells were detected using qRT-PCR. At 14 days after HIFU treatment, B16-F10 cells were retransplanted via the tail vein and the pulmonary metastatic nodules were counted.

RESULTSThe median survival time of the mice was 19.00 days (95% CI 17.14-20.86 days) in the sham group and 26.00 days (95%CI 24.76-27.25 days) in HIFU group. The cumulative survival rate in the HIFU group was significantly higher than that in sham-HIFU group (P<0.01), and the tumor size was significantly smaller in HIFU group at 20, 23, and 26 days after HIFU treatment (P<0.05). Compared with the sham-HIFU group, HIFU group had significantly lower levels of MAGE-A3, MART1 and PAX3 at 7 days after HIFU (P<0.05) with still lower MAGE-A3 level at 14 days (P<0.05). HIFU group showed a significantly smaller number of pulmonary metastatic nodules following tumor cell retransplantation than in sham-HIFU group (P<0.01) with a metastasis inhibition rate of 42.4%.

CONCLUSIONHIFU treatment can inhibit tumor metastasis in melanoma-bearing mice possibly by reducing tumor cell detachment from the primary tumor site and suppressing colonization of the circulating melanoma cells.