Liver sinusoidal endothelial cells (LSECs) are crucial to the maintenance of hepatic homeostasis under physiologic conditions, while under the conditions of pathological liver damage, LSEC can respond to the damage by changing their structure through the process called capillarization, thereby aggravating liver damage. In addition, the interaction between LSEC and other cells in the liver plays a certain role in the development and progression of liver fibrosis, especially the interaction between LSEC and hepatic stellate cells, which are the primary effector cells of liver fibrosis. This article mainly elaborates on the role of LSEC in the development and progression of liver fibrosis during chronic liver injury.

Objective:To develop a single-tube one-step multiplex nested real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the simultaneous detection of 2019-nCoV, influenza A virus, influenza B virus and internal-control with human-derived gene.Methods:This study included 30 positive specimens for 2019-nCoV nucleic acid detection and 336 screening specimens collected from the arrivals at Guangzhou Baiyun Airport between February 2020 and February 2022. Sixty-four positive specimens of other respiratory pathogens were also collected from the arrivals at Guangzhou Baiyun Airport during the three-year period before the occurrence of COVID19 outbreak in 2020, and 7 positive viral strains of respiratory pathogens were provided by collaborative laboratories. In order to establish a set of multiplex nested real-time RT-PCR assay, a group of primers and probe combinations for a multiplex nested real-time RT-PCR was designed and screened according to a selection of nucleotide conserved regions of the ORF and N genes of 2019-nCoV and the M gene of influenza A and B viruses, while nested amplification primers and probe for the internal-control with human-derived gene were introduced. Then the prepared pseudovirus-positive quality control and sample discs were applied to evaluate the sensitivity and specificity. Clinical specimens were performed to validate the applicability of the method.Results:The results show that the established one-step multiplex nested real-time RT-PCR assay can specifically detect 2019-nCoV and influenza A and B viruses, with the limit-of-detection of about 125 copies/ml for 2019-nCoV and about 250 copies/ml for influenza A and B viruses. Totally 101 positive samples of various respiratory pathogens were detected, showing that the detection sensitivities of 2019-nCoV and influenza A and B viruses were 96.67%, 92.86% and 96.15%, respectively, with the specificity of 100%. No false-positive detection was found in the applied detection of more than 300 clinical samples.Conclusions:A one-step multiplex nested real-time RT-PCR assay for 2019-nCoV, influenza A and B viruses and human-derived gene internal-control was developed. The assay has good sensitivity and specificity and can be used for rapid screening of 2019-nCoV and influenza A and B viruses in high-volume samples.

OBJECTIVE To sy stematically evaluate the relations hip between immune-related adverse events （irAEs） and efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical application of ICIs and safety evaluation. METHODS PubMed，Embase，Cochrane Library ， Web of Science ，CNKI，Wanfang database ，VIP and CBM were searched to collect prospective or retrospective cohort studies on the correlation between irAEs and efficacy of ICIs in the treatment of NSCLC. The retrieval time was from the inception to June 30th，2021. After literature screening and data extraction ，Newcastle-Ottawa scale was used to evaluate the quality of included literatures. Meta-analysis and publication bias analysis were performed by using RevMan 5.3 software；Stata 15.0 software was used for sensitivity analysis. RESULTS A total of 7 957 patients were included in 31 studies. Meta-analysis showed that the objective response rate （ORR）[RR＝2.34，95％CI（1.98，2.76），P＜0.000 01]，progression-free survival （PFS）[HR＝0.49，95％CI （0.44，0.55），P＜0.000 01] and overall survival （OS）[HR＝0.45，95％CI（0.39，0.53），P＜0.000 01] of irAEs group as well as ORR[RR＝1.88，95％CI（1.57，2.25），P＜0.000 01]，PFS [HR ＝0.59，95％CI（0.50，0.69），P＜0.000 01] and OS [HR ＝0.58，95％CI （0.48，0.70），P＜0.000 01] of this group at 6th week were all significantly higher or longer than non irAEs group. According to organ specificity ，severity and quantity of irAEs，subgroup analysis showed that skin ，gastrointestinal and endocrine system ，mild irAEs（grade 1-2）and one or more than 2 kinds of irAEs were significantly correlated with the improvement of PFS and OS （P＜ 0.05），while liver and lung ，severe irAEs（≥ grade 3）were not significantly correlated with the improvement of PFS and com OS （P＞0.05）. Sensitivity analysis results showed that the results of the above-mentione d meta-analysis were relatively robust. The results of publication bias showed that there was may be some possibility of publication bias in this study. CONCLUSIONS For NSCLC patients treated with ICIS ，the occurrence of irAEs may be related to their good prognosis. The irAEs may be a predictor of the efficacy of ICIs.

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Animals ; Brain ; Cocaine ; Conditioning, Operant ; Extinction, Psychological ; Lipidomics ; Male ; Mice ; Simvastatin/therapeutic use*

Objective:To explore the application value of skin lead marker combined with iSCOUT image-guided positioning system in monitoring and correcting the setup error of intensity-modulated radiotherapy (IMRT) for breast cancer and calculate the PTV margin, aiming to provide reference for clinical practice.Methods:25 breast cancer patients treated with IMRT after modified radical mastectomy in Fujian Medical University Union Hospital from April to August 2019 were enrolled in this study. The skin lead marker combined with iSCOUT image-guided positioning system was employed for image-guided positioning based on the gold standard registration algorithm. Initial setup errors on the x (lateral), y (craniocaudal) and z (anteroposterior) axis and residual errors after the position correction were recorded and analyzed. The effect of the errors before and after image-guided correction upon the plan dose was compared and the reasonable PTV margin was calculated.Results:25 patients received 150 times of positioning verification using skin lead marker combined with iSCOUT image-guided positioning system. The absolute residual errors on the x-, y-and z-axis were (1.53±0.96), (1.30±0.99) and (1.34±0.92) mm, significantly smaller than the initial setup errors of (2.63±2.12), (2.41±2.45) and (3.07±2.77) mm (all P<0.001). The percentage of dose deviation due to residual errors was also smaller than that of the initial errors. Significant differences were observed in D 98%, D 2%, D max of PTV, D max of the heart, D max of the healthy breast, and D mean of the affected lung and both lungs. The percentage deviation from the original plan was decreased from 2.18%, 3.19%, 10.66%, 8.75%, 48.21%, 10.50%, and 3.66% to 0.38%, 0.23%, 2.31%, 0.04%, 13.78%, 6.35% and 0.41%, respectively (all P<0.05). PTV margins on the x-, y-and z-axis after correction were calculated as 1.87, 1.75 and 1.69 mm, respectively. Conclusion:It is feasible and valuable to apply the skin lead marker combined with iSCOUT image-guided positioning system in the positioning verification and correction of breast cancer radiotherapy position, providing novel reference for clinical PTV margin.

Objective:To construct a comprehensive, systematic and quantifiable quality evaluation index system for blood purification care in ICU.Methods:The contents of the evaluation index system for blood purification care in ICU were determined by reviewing the literature, discussion of the research group and two rounds of Delphi expert consultation.Results:The response rate of the two rounds of experts was 100%. The authoritative coefficients of the two rounds of experts were 0.908 and 0.965 respectively. The coordination coefficient of the indicators of the second round of consultation results was 0.210-0.292, P<0.05 or 0.01. The quality evaluation index system for blood purification care included 3 first-class indicators, 16 second-class indicators, and 56 third-class indicators. Conclusions:The enthusiasm, authority, concentration of opinions and degree of coordination of the consulting experts are relatively high. The constructed evaluation system for the quality of blood purification care indicators can be used for reference in the implementation, training and quality control.

Objective: To analyze the risk factors of cancer recurrence in stomach after non-curative endoscopic resection for early gastric cancer (EGC). Methods: Data of 59 patients with early gastric cancer, who underwent non-curative resection at endoscopy center of Shanghai Renji Hospital from October 2008 to June 2018, were analyzed with the univariate Logistic regression for the risk factors of cancer recurrence in the stomach. Results: The follow-up period ranged from 4 to 77 months, with the median time of 40 months. There were 11 cases of cancer recurrence in the stomach. The univariate Logistic regression analysis showed lymphatic vessel invasion (OR=8.63, 95%CI: 1.24-60.04, P=0.030) and eCura high-risk grading (OR=7.31, 95%CI: 1.05-51.10, P=0.045) were risk factors for cancer recurrence in the stomach. Conclusion The routine eCura grading assessment can be considered after non-cure resection. Patients with lymphatic vessel invasion or high-risk eCura category are not recommended for follow-up; patients with low-risk eCura grading can be followed up by regular endoscopy and attention should be paid to whether there are abnormalities around the original lesion.

Objective To investigate the safety and efficacy of wide local excision surgery combined with 5-aminolaevulinic acid(ALA)-photodynamic therapy(PDT)in treating Paget's disease of the scrotum in elderly people.Methods Patients with an average age of 68.4 ± 4.7 years undergoing wide local excision surgery combined with ALA-PDT for Paget's disease of the scrotum from June 2014 to February 2018 were followed up.All patients underwent wide local excision surgical treatment first and were then enrolled in ALA-PDT study after the diagnosis of Paget's disease of the scrotum was confirmed.Four cases were eliminated as a result of two patients refusing photodynamictherapy for various reasons and two patients lost during follow-up after ALA-PDT.A total of 16 patients were included in the study,of whom 6 cases were in Ray stage A1,7 cases in stage A2 and 3 cases in stage B.Patients underwent 3 courses of ALA-PDT after operation.Then the efficacy,shortand medium-term complications were followed up.Results The duration of disease among the 16 patients ranged from 4 to 76 months before diagnosis,with an average of 35.7 months.Surgery was performed immediately after diagnosis.Ten patients underwent resection and suture and 6 patients were treated with skin flap transfers.Of the patients treated with surgery,3 patients received suspicious lymph node dissection and 1 patient underwent reoperation due to skin flap necrosis.Patients were followed up for 3 months to 3 years and 6 months after ALA-PDT.Recurrence and distant metastasis occurred in 2 cases,with 1 case of brain metastasis and 1 case of systemic metastasis,and the overall recurrence rate was 12.5％.During the follow-up,there were no other serious complications except for 1 case(6.3 ％)with lower limb movement disorders.Conclusions Wide local excision surgery combined ALA-PDT has good clinical outcomes,low recurrence rates and few complications for the treatment of Paget's disease of the scrotum in elderly people.

Local and/or regional recurrence is a common cause of the failure of primary radical radiotherapy for nasopharyn-geal carcinoma,and it is also a clinically existing treatment problem. Re-radiation therapy is one of main effective means of treatment for recurrent nasopharyngeal carcinoma. The article summarizes the recent domestic and abroad literatures on radiotherapy in vitro(in-cluding conventional two-dimensional,three-dimensional conformal,intensity-modulated radiotherapy),stereotactic radiotherapy, brachytherapy,proton beam and heavy ion therapy for recurrent nasopharyngeal carcinoma,and summarized the advantages and disad-vantages of different radiotherapies as well as their efficacies.