BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Atractylodes macrocephala, a plant of the Asteraceae family, as a commonly used traditional Chinses medicine in clinic, has the efficacy of invigorating spleen and supplementing qi, eliminating dampness and inducing diuresis, and expelling wind and dispersing cold. Moreover, it was proved that it has many pharmacological effects such as anti-inflammation, anti-tumor, and improving immunical ability based on the scientific researches. Atractyloside is one of its active ingredients and characteristic ingredients. In this paper, using the search terms of Baizhu lactone, sesquiterpene lactone, quality evaluation, quality control, and chemical composition, the CNKI, Weipu and PubMed literature database were searched. And relevant literature results were compared and summarized. The catagories, structural formula of atractyloside and their transformation mechanism were summarized. It was found that the content of lactone components could be affected by different processing methods, different producing locations, different harvesting season, and different growth years. It was found that for the quality evaluation of Atractylodes macrocephala, the multivariate statistical analysis combined with content determination or fingerprint establishment could be more accurate, reliable and comprehensive, among which the supervised PLS-DA with OPLS-DA analysis was better than the unsupervised PCA analysis. This literature summary could provide a beneficial reference for the quality evaluation and utilization of Atractylodes macrocephala.

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.
Animals ; Cattle ; Neocallimastigales/metabolism* ; Anaerobiosis ; Rumen/microbiology* ; Propionates/metabolism* ; Isobutyrates/metabolism* ; Cellulose/metabolism* ; Fungi ; Starch/metabolism* ; Glucose/metabolism* ; Acetates ; Sucrose/metabolism* ; Cellulases ; Cellulase

Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.

To investigate the clinical efficacy of extended thymectomy by subxiphoid approach video-assisted thoracoscopic surgery(VATS) for myasthenia gravis. Methods We retrospectively analyzed the clinical date of 64 cases of myasthenia gravis treated by subxiphoid approach VATS in the same surgical team from September 2015 to April 2018. The patients were equally divided into 4 groups(A, B, C and D) according to the date of operation. Comparisons were made among the four groups in operation time, blood loss during operation, rate of conversion to thoracotomy, postoperative complications, postoperative hospital stay, duration and amount of postoperative chest tube drainage, frequenlly of surgery. The operative effect of different stage was analyzed. Results There were no intraoperative deaths. 1 patient(group A) was converted to thoracotomy. 3 patients(2 cases of group A; 1 case of group D) had lung infection. 1 patient(group B) developed myasthenia crisis after surgery, and the rest patients showed obvious improvement in postoperative myasthenia symptoms. No significant differences were found in postoperative complications, rate of conversion to thoracotomy, postoperative hospital stay, duration and amount of postoperative chest tube drainage among the 4 groups(P >0. 05). The operation time was significantly longer in group A(186. 25 ± 25. 79) min than the other 3 groups [B(128. 75 ± 16. 28) min, C(135. 00 ± 21. 29) min, D(128. 75 ± 19. 62)min], P <0. 05. The blood loss in surgery was significsntly more in group A(110. 00 ±38. 82)ml than that in the other 3 groups[B(63. 75 ±28. 26)ml, C(58. 13 ±27. 86)ml, D(58. 75 ±25. 00)ml], P <0. 05, while no statistical difference was found among group B, C and D. The frequency of surgery was increased from 1. 6 cases in group A to 2. 3, 2. 7 and 2. 7 cases one month in B, C and D, respectively. Conclusion The results of the present study have shown that subxiphoid approach VATS thymectomy is safe and feasible for the treatment of MG patients. For thoracic surgeons with certain experience in thoracoscopic technique, a plateau of the surgical skill of the subxiphoid opproach can be reached after learning curve procedures.

Objective To investigate the clinicopathological characteristics and postoperative prognosis analysis of intra-thoracic localized Castleman disease (LCD).Methods The clinical data of 9 patients with intra-thoracic LCD who accepted surgical treatment were retrospectively analyzed.There were 5 males and 4 females,with age of (32.8 ± 10.9) years.Two patients complained of chest pain,1 patient suffered from paraneoplastic pemphigus,and the rest were diagnosed by physical examination.Four cases were diagnosed with LCD by preoperative CT examination.Results All patients underwent surgical resection.Four patients were performed open surgery and 5 patients had video assisted thoracic surgery.All patients accepted radical surgery.But 2 of these patients had postoperative complications.One patient was the injury of phrenic nerve and another was pericardial effusion.Patho-histological showed hyaline vascular type of Catleman disease in all patients.All patients survived without recurrence during the follow-up for 2-53 months.Conclusions Intra-thoracic is rare and liable to misdiagnosed.For increasing the preoperative diagnosis rate of LCD,the combined application of imaging tests is important,and clinicians and radiologists should also enhance the awareness of this disease.Complete surgical resection of the tumor is the best therapeutic alternative for intra-thoracic LCD.

Objective To evaluate the effect of video- assisted thoracoscopic pulmonary segmentectomy in patients with isolated pulmonary arteriovenous fistula (PAVF). Methods A retrospective analysis was performed on 10 patients with PAVF in the department of thoracic surgery of the first affiliated hospital of Nanjing Medical University between January 2010 and December 2016. Computed tomography angiography (CTA) and three-dimensional reconstruction were performed before operation, and all patients accepted video-assisted thoracoscopic pulmonary segmentectomy. Results The diagnosis of PAVF was identified by CTA, with maximum diameter of tumor of 3.0- 5.0 cm. No perioperative mortality or postoperative complications were observed including bleeding, hemoptysis, serious air leakage, and bronchopleural fistula. The lesions were completely removed in all 10 patients, and no patients converted to open surgery intraoperatively. Blood gas analysis showed that oxygen partial pressure before operation, in the first day after operation and the third month after operation was (62.5 ± 6.7), (70.2 ± 4.8) and (75.4 ± 4.8) mmHg (1 mmHg = 0.133kPa) respectively; which was significantly increased successively (P<0.05). After a follow-up time of 3-30 months, no recurrences were observed. Conclusions Video- assisted thoracoscopic pulmonary segmentectomy guided by preoperative CTA and three-dimensional reconstruction is a very effective method for the treatment of isolated PAVF.

Objective Based on the different physiological characteristics of the mastoid skin and soft tissue in congenital microtia malformation ,the different ear reconstructivemethod were respectively applied for the individuals with microtia .And the feasibility of personalized treatment to microtia patients was explored in this study .Method Considering different thickness and tightness in mastoid hairless skin and soft tissue,2129 microtia patients were received the skin expansionmethod of ear reconstruction surgery , while 1321 cases were treated with Nagata ' s technique, and 330 cases with skin and fascia expansionmethod . Result With average 10-month follow-up,1944 ( 91.31％) cases using the mastoid skin expansionmethod were satisfied with the outcome of the reconstructed ear including three dimensional position and subunit appearance.305(92.42％)cases using the skin and fascia expansionmethod were satisfied with theresult .1264 (95.69％) cases using Nagata ' s two—stagemethod received satisfactory outcomes .49 ( 3.71％) cases showed partial exposure of the cartilage framework .There were no postoperative complications , such as chest wall deformity or affected normal physical function .Conclusion Based on the different physiological characteristics of the mastoid skin and soft tissue ,it's beneficial to select individualized operationalmethod in ear reconstruction for congenital microtia among Chinese patients .

Objective Based on the different physiological characteristics of the mastoid skin and soft tissue in congenital microtia malformation ,the different ear reconstructivemethod were respectively applied for the individuals with microtia .And the feasibility of personalized treatment to microtia patients was explored in this study .Method Considering different thickness and tightness in mastoid hairless skin and soft tissue,2129 microtia patients were received the skin expansionmethod of ear reconstruction surgery , while 1321 cases were treated with Nagata ' s technique, and 330 cases with skin and fascia expansionmethod . Result With average 10-month follow-up,1944 ( 91.31％) cases using the mastoid skin expansionmethod were satisfied with the outcome of the reconstructed ear including three dimensional position and subunit appearance.305(92.42％)cases using the skin and fascia expansionmethod were satisfied with theresult .1264 (95.69％) cases using Nagata ' s two—stagemethod received satisfactory outcomes .49 ( 3.71％) cases showed partial exposure of the cartilage framework .There were no postoperative complications , such as chest wall deformity or affected normal physical function .Conclusion Based on the different physiological characteristics of the mastoid skin and soft tissue ,it's beneficial to select individualized operationalmethod in ear reconstruction for congenital microtia among Chinese patients .

Objective: To analyze the risk factors of acute kidney injury (AKI) after isolated heart valve prosthesis implantation (HVPI) in relevant patients. Methods: We retrospectively studied 400 patients who received isolated HVPI in our hospital. The demographic characteristics and pre-, intra-, post-operative information were collected to conduct uni- and multi-variantanalysis. Results: The pre-operative serum creatinine level in 400 patients was 85.0 (72.0, 98.0) μmol/L and post-operative level was 104.5 (80.0, 146.3) μmol/L, the elevation was 20.9% (1.6%, 57.9%),P<0.05. Multi Logistic regression analysis indicated that age>50years (OR=2.12, 95% CI 1.13-3.95),hypertension history (OR=4.07, 95% CI1.23-13.47), cardiopulmonary bypass time>180 minutes (OR=5.38, 95% CI 1.63-17.77), post-operative hemoglobin<70 g/L (OR=0.20, 95% CI 0.06=0.74), serum glutamic-pyruvic transaminase>100 u/L (OR=12.10, 95% CI 2.28-64.23), pleural fluid drainage at the day of operation> 500 ml (OR=2.12, 95% CI 1.13-3.95), extubation after 24 hours of operation (OR=3.94, 95% CI 2.07-7.52), combining low cardiac output syndrome (OR=4.64, 95% CI 1.06-20.29) were the independent risk factors for AKI occurrence in patients after HVPI, allP<0.05. Conclusion: Post-HVPI AKI was associated with many factors. At prior operation, it was mainly related to the age and hypertension; during theoperation, it was mainly related to cardiopulmonary bypass time; at post-operation, it was mainly related to delayed extubation, low cardiac outputsyndrome, anemia, increased pleural lfuid drainage and serum glutamic-pyruvic transaminase.