Objective To discuss the security and reliability of preoperative thoracoscopic pericardial exploratory and to evaluate of the surgical indications.Methods Video full-assisted thoracoscopic pericardioscopy has been implemented in 41 central type lung cancer cases before radical resection.Results Video assisted pericardioscopy group underwent thoracotomy lung resection with procession of intrapericardial pulmonary artery in 8 cases (partial pericardial resection in 2 cases),with pulmonary vein in 10 cases,and out-pericardial lung resection in 9 cases.Spiral CT projections were consistent with surgery was only 65.8 ％.The average time of explorationa was (23±10) min.Conclusion Except for widely used in pulmonary wedge resection and lobectomy,video-assisted thoracoscopic pericardial exploration can improve resection rate and survival rate in central type lung cancer patients which can reduce the need for exploratory thoracotomy.

Objective:To investigate the intervention effect of ventricular zone expressed PH domain-containing 1 (VEPH1) on epithelial mesenchymal transition (EMT) and proliferation of human cutaneous melanoma (CM) cells based onthe transforming growth factor-β (TGF-β) signaling pathway.Methods:The melanoma cells were cultured in vitro. After transfecting the melanoma cells with overexpression or interference plasmids of VEPH1 or TGF-β overexpression plasmids, or treating the cells with SB-431542 (TGF-β pathway inhibitor), we detected the expression of genes and proteins relevant to VEPH1, TGF-β, and EMT by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot to observe the effect of these proteins on CM cell proliferation. Results:qRT-PCR results showed that the expression of VEPH1 in melanoma cells (B16-BL6, B16 and A375 cells) was significantly lower than that in HaCaT cells, and the lowest expression was found in A375 cells, so A375 cells were selected for follow-up experiments. After transfection with VEPH1 overexpression plasmid or SB-431542, the mRNA and protein expression of E-cadherin in A375 cells were significantly increased, the mRNA and protein expressions of TGF-β, Smad4, N-cadherin and vimentin were significantly decreased, and the cell proliferation was significantly decreased ( P<0.05). Compared with the VEPH1 vector group, the expression of TGF-β, Smad4 and N-cadherin in the VEPH1 vector+ SB-431542 group was significantly reduced ( P<0.05); the expression of E-cadherin was increased, and the cell proliferation was also significantly decreased ( P<0.05). The expression of TGF-β, Smad4, N-cadherin and vimentin were increased after co-transfection with VEPH1 vector, while the expression of E-cadherin was decreased, and the cell proliferation was also enhanced ( P<0.05). The expression of VEPH1 in A375 cells was significantly decreased after transfection with si-VEPH1 plasmid, while that in SB-431542 and TGF-β vector group was not significantly decreased. Conclusions:VEPH1 can inhibit human CM cells by the intervention on TGF-β signaling pathway. This study reveals the potential of VEPH1 as a diagnostic, prognostic and therapeutic target for CM.

Objective:To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF).Methods:This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke.Results:Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion:Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

OBJECTIVE：To study the improvement ef fects of sanggenone C on lipid accumulation in human liver cancer HepG2 cells induced by free fatty acid （FFA）. METHODS ：HepG2 cells were divided into control group ，model group ， fenofibrate group （10 μmol/L），sangerone C low ，medium and high concentration groups （2，4，8 μmol/L）. Except for control group，other groups were treated with 1 mmol/L FFA to induce lipid accumulation model ，and administration groups were cultured with relevant medium containing drugs. The lipid accumulation was observed by oil red O staining ，and lipid level and triglyceride （TG） content were also determined. Real-time PCR and Western blot assay were adopted to detect the mRNA and protein expression of PPARα，CPT-1，SREBP-1c，FAS，SIRT1 and PGC- 1α in HepG2 cells. RESULTS ：Compared with control group ， the nucleus was atrophied significantly and the volume became smaller ，and the number of lipid droplets was significantly increased；the level of lipid ，TG content ，mRNA and protein expression of SREBP- 1c and FAS were significantly increased （P＜ 0.05 or P＜0.01），mRNA and protein expression of PPARα，CPT-1，SIRT1 and PGC- 1α were decreased significantly（P＜0.01）. Compared with model group ，no obvious nucleus atrophy and normal volume were observed in sangerone C groups ，and the number of lipid droplets was significantly reduced ；the levels of lipid ，TG content ，mRNA and protein expression of PPARα pathway related genes （except for SREBP- 1c protein in saggenone C low concentration group ）were significantly reversed （P＜ 0.05 or P＜0.01）. CONCLUSIONS ：Sangenone C can significantly improve the lipid accumulation of HepG 2 cells，and its mechanism may associated with regulating PPAR α signaling pathway，improving cell lipid oxidation ability and inhibiting lipid synthesis.

OBJECTIVE To provide references for the safe use of lorlatinib in clinical practice. METHODS The reporting odds ratio （ROR） method， Medicines and Healthcare Products Regulatory Agency comprehensive standard method （referred to as “MHRA method”） and the Bayesian confidence propagation neural network （BCPNN） method were used to detect adverse drug events （ADEs） signals of lorlatinib in the FDA Adverse Event Reporting System from the first quarter of 2019 to the fourth quarter of 2022. RESULTS & CONCLUSIONS Totally 114 overlapping ADEs signals of lorlatinib were detected by the three methods， among which there were 73 new suspicious ADEs signals which were not covered in the instruction of lorlatinib. When using loratinib in clinical practice， special attention should be paid to ADEs with a high number of cases and signals， such as various neurological diseases， psychiatric diseases， respiratory system， thoracic and mediastinal diseases； clinical manifestations included cerebral edema， cerebral infarction， pulmonary hypertension， mutism， decreased sexual desire， pleural effusion. The signals of mobile thrombophlebitis， radiation necrosis， mutism， vesicoureteral reflux not mentioned in the instructions were all strong in BCPNN detection with high specificity， to which we should pay attention in clinical application.

OBJECTIVE To mine and analyze severe cutaneous adverse reaction signals of 5 commonly used immune checkpoint inhibitors （ICIs）， and to provide reference for clinically safe use of drugs. METHODS Based on the FDA adverse events reporting system （FAERS） database，adverse drug events （ADEs） reports about severe cutaneous adverse reactions related to ipilimumab， nivolumab， pembrolizumab， atezolizumab and durvalumab were collected from listing in the United States to the fourth quarter of 2022. The ADE signals were mined and analyzed with reporting odds ratio （ROR） and Bayesian confidence propagation neural network （BCPNN）. RESULTS A total of 5 726 reports of severe cutaneous adverse reactions were collected， including 3 037 reports for nivolumab，1 465 reports for pembrolizumab， 130 reports for durvalumab， 429 reports for atezolizumab and 665 reports for ipilimumab. All 5 kinds of ICIs caused positive signals， the correlation degree of which was as follows： pembrolizumab＞atezolizumab＞nivolumab＞ipilimumab＞durvalumab. Stevens-Johnson syndrome（SJS） and toxic epidermal necrolysis （TEN） have been reported for all 5 ICIs， and the association was the strongest with pembrolizumab. CONCLUSIONS All 5 kinds of ICIs are associated with the risk of severe skin adverse reactions， and close attention should be paid to their clinical use， especially being cautious when using pembrolizumab. The combination of ICIs should be avoided as much as possible.