Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

BACKGROUND Primary liver cancer is the sixth most common cancer worldwide,with hepato-cellular carcinoma(HCC)being the most prevalent form.Despite the current availability of multiple immune or immune combination treatment options,the prognosis is still poor,so how to identify a more suitable population is extremely important.AIM To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus(HBV)-related HCC in Barcelona Clinic Liver Cancer(BCLC)stages B/C,considering various body mass index(BMI)in diffe-rent categories.METHODS Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab.Patients were divided into two groups based on BMI:The non-overweight group(BMI<25 kg/m2,n=51)and the overweight/obese group(BMI≥25 kg/m2,n=75).Short-term prognosis was evaluated using mRECIST criteria,with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.with subgroup analyses for non-overweight(BMI:18.5-24.9 kg/m2),overweight(BMI:25-30 kg/m2),and obese(BMI≥30 kg/m2)patients.A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival(OS),leading to the development of a column-line graph model.RESULTS Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group.Similarly,the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group.The objective remission rate and disease control rate for the two groups of patients were,respectively,objective remission rate(5.88%vs 28.00%)and disease control rate(39.22%vs 62.67%).Fatigue was more prevalent in the obese/overweight group,while other adverse effects showed no statistically significant differences(P>0.05).Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients,with obese patients showing the best outcomes.Multifactorial regression analysis identified BCLC grade,alpha-fetoprotein level,portal vein tumor thrombosis,and BMI as independent prognostic factors for OS.The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis,followed by alpha-fetoprotein level,BCLC classification,and portal vein tumor thrombosis.CONCLUSION BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab,and obese/overweight patients have a better prognosis.

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy

Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human health.Owing to challenges in early diagnosis,most patients lose the opportunity for radical treatment when diagnosed.Nonetheless,recent advancements in cancer immunotherapy provide new directions for the treatment of HCC.For instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC.However,tumor cells can evade the immune system through various mechanisms.With the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor T cells,engineered cytokines,and certain cancer vaccines.This review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.

中国老年人左氧氟沙星用药错误报告分析及防范建议

目的分析中国老年人(≥60岁)左氧氟沙星用药错误(ME)及其影响因素,提出针对性防范建议。方法收集全国临床安全用药监测网2012年9月22日—2021年9月22日老年人左氧氟沙星(不包括局部使用制剂)ME报告,对ME的分级、内容、错误引发人员、发生场所、发现人员和错误因素等进行分析。结果老年人左氧氟沙星ME报告共计286例,其中男164例,女122例;中位年龄70(60~98)岁;B级ME 194例(67.83%);严重ME 10例(3.50%),包括3例出现药品不良反应后未及时停药,2例肾功能不全未进行剂量调整,2例有过敏史的患者使用左氧氟沙星,2例合用多索茶碱,1例患者输注速度过快。引发ME的人员主要是医生(220例,76.92%),错误内容前3位为频次、用量以及品种;引发因素主要是知识欠缺/培训不足和疲劳;其次是药师(41例,14.34%),错误内容前3位为品种、数量、规格,主要引发因素是药名相似/外观相似。发现ME的人员主要是药师(234例,81.82%)。结论老年患者使用左氧氟沙星重点需要关注处方、调配和使用环节用药错误;关注肾功能不全患者品种选择和剂量调整、左氧氟沙星的禁忌证与慎用情况、给药频次及药物相互作用。强化信息建设减少处方环节ME,同时需加强医务人员合理用药培训。

circRNA_0046366 inhibits hepatocellular steatosis by normalization of PPAR signaling

AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.

Entering the duodenal diverticulum:A method for cannulation of the intradiverticular papilla

Successful cannulation of the common bile duct may be difficult in patients in whom the papilla is located entirely within a diverticulum.In this study,we report successful biliary cannulation in three patients following intubation of the distal tip of the duodenoscope into the duodenal diverticulum and locating the major papilla.No complications occurred during the operation or during the postoperative period.This method didn't need second incubation an endoscope and might lower the burden of patients.So this skill is useful to deal with the papilla hidden inside the large diverticulum because of its safety and convenience.

A self-management application“painhousekeeper”to control cancer pain:a randomized controlled trial study protocol

Objective:Pain is a prevalent and distressing symptom in patients with cancer which has a significant impact on patients’physical health,psychological well-being,and quality of life(QOL).Deficiency of pain care,inadequate pain communication,and reluctance toward pain medication contribute to the difficulties in improving the situation of patients with cancer pain.Fortunately,the integration of self-management and professional healthcare provides new opportunities for patients with cancer pain.Methods:A two-arm randomized controlled trial will be conducted to assess the effectiveness of self-management application compared with routine care among patients with cancer pain.Based on Orem’s self-care theory and Naylor’s transitional care theory,cancer pain self-management application“Pain-housekeeper”was developed with dual client:patient client and medical client.A total of 120 patients with cancer pain are recruited from two university-affiliated tertiary public hospitals in China.They are randomly assigned to the control group and the intervention group.The patients in the control group get routine care while the patients in the intervention group get routine care and Pain-housekeeper App.The intervention is delivered by registered doctors,nurses,and postgraduate nursing students specialized in pain care.Effect measurements for both groups are carried out with questionnaires at baseline(T0),after 4 weeks(T1)and after 12 weeks(T2).The primary outcomes include pain condition,self-efficacy,and QOL.The secondary outcomes include pain medication adherence,satisfaction,anxiety,and depression.Compliance of data submission,economic evaluation,usage,and clinical data are also considered in the test.Data for the evaluation are gathered continuously during the study period.Discussion:This article provides insight into the effectiveness of a theory-based self-management mobile application intervention delivered to patients with uncontrolled cancer pain.The results are used to help patients to improve cancer pain control,self-efficacy,and QOL.Conclusions:The findings of this article provide evidence to support the implementation of an innovative and easily accessible intervention that enhances health outcomes.

Engineering layered/spinel heterostructure via molybdenum doping towards highly stable Li-rich cathodes

Li-rich layered oxide(LLO),e.g.,Li_(1.12)[Mn_(0.56)Ni_(0.16)Co_(0.08)]O_(2)(LRMO),is considered as a promising cathode material due to its superior Li-storage capability.However,the poor cycling stability and large voltage decay,which are related to the phase transition,limit its industrialization process.Herein,a Mo-doped LRMO(Li_(1.12)[Mn_(0.56)Ni_(0.16)Co_(0.08)]_(0.98)Mo_(0.02)O_(2),LRMO-Mo2.0%)was successfully synthesized via a simple combination of co-precipitation with high-temperature calcination for solving the mentioned above-disadvantages.Compared with the pristine counterpart,the as-prepared LRMO-Mo2.0%shows more excellent electrochemical performance in terms of rate capability(reversible capacity of 118 mA·h·g^(−1) at 5 C),cyclic ability(94.3%capacity retention after 100 cycles at 0.2 C)and discharge midpoint voltage decay(0.11 V after 100 cycles).Systematic investigation of structural evolution and electrochemical kinetics elucidate that the synergic effect of robust oxygen framework and layered/spinel heterostructure is the key to its performance improvement.Such synergy helps to stabilize the layered structure by curbing the structural transformation and oxygen escaping during the electrochemical cycling.This work paved the way for the simple and efficient preparation of highly stable LLO cathode materials.

Chemical Constituents from Mycelia and Spores of Fungus Cordyceps cicadae

Objective To isolate and identify the chemical constituents from mycelia and spores of the fungus Cordyceps cicadae,respectively.Methods The chemical constituents were isolated and purified by repeated silica gel,Sephadex LH-20,and reversed phase HPLC.The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis,including 1 D and 2D NMR.Results Nine known sterols such as ergosterol（1）,ergosterol peroxide（2）,9,11-dehydroergosterol peroxide（3）,3β,5α,9α-trihydroxy-（22E,24R）-ergosta-7,22-dien-6-one（4）,3β,5α,9α,14α-tetrahydroxy-（22E,24R）-ergosta-7,22-dien-6-one（5）,5 α,6α-e poxy-（22 E,,24 R）-e rgosta-8（14）,22-diene-3α,7α-diol （6）, 3β,5α,6β-（22E,24R）-ergosta-7,22-dien-3,5,6-triol （7）, 3β,5α,6α-6- methoxyergosta-（22E,24R）-7,22-diene-3,5-diol （8）, 4-hydroxy-17R-methylincisterol （9）, together with a resorcinol derivative, 5-n-nonadecylresorcinol （10）, a cydo- desipeptide, beauvericin （11）, and a nucleoside, N^6-（2-hydroxyethyl）adenosine （12） were successively isolated from the cultivated C. cicadaemycelia and spores. Conclusion Compounds 3-10 are reported for the first time from the title sample, beauvericin exhibits significant cytotoxicity against human leukemia cell line and human lung cancer cell line.