Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.

Objectives:To evaluate the tricuspid valve(TV)geometric remodeling in patients with idiopathic pulmonary arterial hypertension(IPAH)by three-dimensional transthoracic echocardiography. Methods:Two-dimensional and three-dimensional transthoracic echocardiography were performed in 30 IPAH patients and 15 healthy controls,and the geometry parameters of TV were obtained by four-dimensional auto tricuspid valve quantitative(4D Auto-TVQ)in the right ventricular-focused apical view.Pulmonary arterial hypertension was determined by right heart catheterization within 48 hours of echocardiography. Results:The 4-chamber diameter,tricuspid annular(TA)perimeter,TA area,maximal tenting height,coaptation point height and tenting volume were larger in IPAH patients than those in healthy controls(all P＜0.05),2-chamber diameter was similar between two groups.In IPAH group,maximal tenting height and coaptation point height were moderately correlated with right ventricular end-diastolic volume(r=0.710,r=0.515,both P＜0.05),while TA perimeter,4-chamber diameter and TA area were moderately correlated with right atrial end-systolic volume(r=0.712,r=0.558,r=0.545,all P＜0.05). Conclusions:IPAH patients have larger maximal tenting height,coaptation point height and tenting volume,TA enlargement is mainly visible in 4-chamber diameter.TV tenting height is associated with right ventricular volume,but TA size is associated with right atrial volume in IPAH patients.

Objective To explore the action of Bufei Jianpi formula(BJF)on mitochondrial damage to skeletal muscle in chronic obstructive pulmonary disease(COPD)rats via its regulation of the IRS-1/PI3K signaling axis.Methods 60 SPF SD rats were randomly divided into Control group,Model group(COPD stable stage group),aminophylline(Am)group,BJF group,pioglitazone(PIO)group and BJF+PIO group,with 10 rats per group.A stable COPD rat model was established via forced smoking and Klebsiella pneumoniae nasal drip method.Samples were taken from the 9th week to the end of the 20th week,and the weight of the rats was measured every week.Routine sectioning and HE staining were performed on lung and skeletal muscle tissue,and corresponding pathological changes were observed under a light microscope.The lung function of the rats was observed by whole-body plethysmography in weeks 0,8,and 20,including tidal VT,PEF,and EF50.The mRNA expression of IRS-1,leptin,PGC1-α,and PI3K in rat skeletal muscle was detected by qPCR.The expression of PGC-1α,TFAM,IRS-1,PI3K,AKT,p-AKT,and leptin in rat skeletal muscle tissue was detected by Western blot.Results The Model group,but not the Control group,showed a large number of inflammatory cells infiltrating the alveolar interstitium and bronchus,indicative of lung disease;some alveolar walls had broken and fused to form air cavities,and fiber networks were destroyed.After drug treatment,the rats showed improved alveolar wall and fiber network integrity and reduced inflammatory cell infiltration in the bronchus,especially those in the BJF and Am groups.In the drug treatment groups,the skeletal muscle pathology of each group showed improved spatial arrangement,the atrophy and fracturing of muscle fibers were ameliorated to different degrees,and cytoplasmic staining of muscle cells was uneven,and the BJF group showed the most significant effects.Compared with the Control group,the Model group's PEF,VT,and EF50 significantly decreased from week 8(P＜0.01),while the BJF,BJF+PIO and Am groups had significantly increased PEF and EF50(P＜0.01).Compared with Control group,the Model group's mRNA and protein expression levels of IRS-1,PGC-1α,and PI3K were significantly decreased(P＜0.05,P＜0.01),the level of leptin was significantly increased(P＜0.01).Compared with the Model group,the mRNA and protein expressions of IRS-1,PGC-1α and PI3K in the BJF group were significantly increased(P＜0.05,P＜0.01),and the mRNA expression of IRS-1 in the PIO group was significantly increased(P＜0.01).The BJF+PIO group's mRNA levels of PGC-1α(P＜0.01)and mRNA and protein levels of IRS-1 and PI3K were significantly increased(P＜0.05,P＜0.01).The mRNA and protein expression levels of PI3K in the Am group were significantly increased(P＜0.01).The expression levels of leptin mRNA were significantly decreased in the four treatment groups(P＜0.01),and the expression of leptin protein was significantly decreased in all treatment groups except the Am group(P＜0.01).Compared with the Control group,the Model group's quadriceps femoris tissue showed a significant decrease in TFAM and p-AKT expression.TFAM and p-AKT expression in all the treatment groups showed an increasing trend,but the difference was not statistically significant(P＞0.05).Conclusions By regulating the IRS-1/PI3K signaling axis,Bufei Jiempi reduces mitochondrial damage to skeletal muscle,increases the expression of PGC-1α and mitochondrial transcription factor TFAM,enhances mitochondrial biosynthesis,and reduces pathological damage to lung and skeletal muscle tissue.

AIM:To investigate the effects of the three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanisms.METHODS:SPF-grade SD rats were randomly divided into control,COPD,pyrrolidinedithiocarbamate ammonium(PDTC),Bufei-Jianpi formula(BJF),Bu-fei-Yishen formula(BYF),Yiqi-Zishen formula(YZF),BJF combined with PDTC(BJF+PDTC),BYF combined PDTC(BYF+PDTC),and YZF combined PDTC(YZF+PDTC)groups.Cigarette smoke exposure combined with bacterial infec-tion were used to develop a stable-phase rat model of COPD,and kidney-injured rats were screened for subsequent treat-ment.Pulmonary and renal functions,pathological changes in lung and kidney tissues,24 h urine volume,urine biochem-ical indexes,aquaporin(AQP)levels,ratio of inflammatory cells in the bronchoalveolar lavage fluid(BALF),serum in-flammatory factor levels,and mRNA and protein expressions of IκB kinase(IKK)and nuclear factor-κB(NF-κB)were observed at the end of the 16th week.RESULTS:Compared with control group,the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity(FVC),forced expiratory volume in 0.1 second(FEV0.1)and FEV0.1/FVC(P<0.05).The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration.The renal function indexes serum creatinine,blood urea nitrogen and serum cystatin C(Cys-C)were signifi-cantly increased(P<0.01).The renal histopathology showed swollen and disorderly arranged tubular epithelial cells.The 24 h urine volume decreased(P<0.01).The urinary biochemical indexes 24 h urinary total protein,urinary kidney injury molecule-1(KIM-1),urinary Cys-C,and urinary N-acetyl-β-D-glucosaminidase significantly increased(P<0.01).The protein levels of AQP1～4 were significantly increased(P<0.01).The ratio of neutrophils and lymphocytes in the BALF were increased(P<0.01).The ratio of monocytes was decreased(P<0.01).The serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-13,IL-1β,and transforming growth factor-β1(TGF-β1)were significantly increased(P<0.01).And the mRNA and protein expression levels of IKK,NF-κB were significantly elevated in the renal tissue(P<0.05).Compared with COPD group,the above symptoms and indexes of the rats were improved to different degrees after the intervention in treatment groups,among which BJF,BYF and YZF demonstrated similar effects to PDTC,and BJF+PDTC,BYF+PDTC and YZF+PDTC exhibited better improvements than the corresponding monotherapy.CONCLU-SION:The three Tiao-Bu Fei-Shen therapies can reduce the airway and systemic inflammatory response,improve renal function and attenuate renal injury in COPD rats.The mechanism may be related to the inhibition of NF-κB signaling path-way.