[Characteristics of the tumor microenvironment and therapeutic progress in malignant pleural effusion].

Malignant pleural effusion (MPE) can be secondary to various advanced malignant tumors. Although systemic anti tumor therapy may be effective in primary tumors, it cannot reduce the accumulation of MPE in proportion of the patients. The interaction of tumor cells, immune cells, and mesenchymal cells, as well as the abnormal proliferation of tumor-associated blood vessels, together create an immunosuppressive microenvironment for MPE, which promotes the abnormal proliferation of tumor cells and the accumulation of MPE. With the in-depth study of the tumor microenvironment, the application of local systemic anti-tumor therapy with local intrathoracic application of immune checkpoint inhibitors, immune cells, cytokines, and gene-mediated cytotoxic immunotherapy are able to alleviate the immunosuppressive tumor microenvironment and inhibit the accumulation of MPE. This article aimed to describe the tumor microenvironment in MPE and provide clues for identifying novel therapeutic targets.

Superconductivity in a unique type of copper oxide.

The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-T c cuprates crystallize into a layered perovskite structure featuring copper oxygen octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-T c cuprates are elongated along the c axis, leading to a 3dx 2-y 2 orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-T c cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba2CuO4-y , wherein the local octahedron is in a very exceptional compressed version. The Ba2CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (T c ) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the T c for the isostructural counterparts based on classical La2CuO4 X-ray absorption measurements indicate the heavily doped nature of the Ba2CuO4-y superconductor. In compressed octahedron, the 3d3z 2-r 2 orbital will be lifted above the 3dx 2-y 2 orbital, leading to significant 3D nature in addition to the conventional 3dx 2-y 2 orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high T c in cuprate materials.

Combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor clinical outcomes in patients with COVID-19: a multicentre retrospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for illness severity and adverse outcomes in patients with COVID-19. Alcohol drinking may also be a potential risk factor for disease severity. However, the combined and interactive effects of drinking and smoking on COVID-19 have not yet been reported. This study aimed to examine the combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor outcomes in patients with COVID-19. STUDY DESIGN: This was a multicentre retrospective cohort study. METHODS: This study retrospectively reviewed the data of 1399 consecutive hospitalised COVID-19 patients from 43 designated hospitals. Patients were grouped according to different combinations of drinking and smoking status. Multivariate mixed-effects logistic regression models were used to estimate the combined and interactive effects of drinking and smoking on the risk of severe COVID-19 and poor clinical outcomes. RESULTS: In the study population, 7.3% were drinkers/smokers, 4.3% were drinkers/non-smokers and 4.9% were non-drinkers/smokers. After controlling for potential confounders, smokers or drinkers alone did not show a significant increase in the risk of severe COVID-19 or poor clinical outcomes compared with non-drinkers/non-smokers. Moreover, this study did not observe any interactive effects of drinking and smoking on COVID-19. Drinkers/smokers had a 62% increased risk (odds ratio = 1.62, 95% confidence interval: 1.01-2.60) of severe COVID-19 but did not have a significant increase in the risk for poor clinical outcomes compared with non-drinkers/non-smokers. CONCLUSIONS: Combined exposure to drinking and smoking increases the risk of severe COVID-19, but no direct effects of drinking or smoking, or interaction effects of drinking and smoking, were detected.

[Development and thinking of Chinese expert consensus on diagnosis of pleural effusion].

The consensus published in this issue was developed over a period of 1.5 years, and it was discussed and revised by the expertpanel from pleural and mediastinal diseases working group (preparatory) of Chinese Thoracic Society and external experts in several meetings. This article introduced the purpose, process and thinking in the writing of the consensus, hoping to provide a reference for readers to understand the content of this consensus and to make reasonable application in clinical practice.

[Venous thromboembolism risk and prophylaxis status of cancer inpatient].

Objective: To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study. Methods: The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI). Results: A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95%CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95%CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95%CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions: Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don't receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.

[In situ semiconductor laser fenestration of type A aortic dissection during thoracic endovascular aortic repair].

Objective: To investigate the feasibility, efficacy and safety of semiconductor laser in situ fenestration of type A aortic dissection during thoracic endovascular aortic repair. Methods: The clinical data of 68 patients with type A aortic dissection treated by semiconductor laser in situ fenestration from June 2016 to January 2020 in Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University were analyzed retrospectively. Of the patients, 45 were male, 23 were female, the mean age was (52±14) years. The technical success rate and complication rates were assessed. Results: The technical success rate of 68 patients was 92.6% (63/68), only 5 patients failed due to the complex aortic arch type, 3 patients underwent chimney stent implantation, 2 patients underwent artificial vessel bypass. During the perioperative period, 1 patient died due to severe pulmonary infection, 4 patients developed neurological symptoms such as cerebral infarction after surgery, and the remaining patients had no related complications. Postoperative CTA follow-up indicated that the primary intercalation rupture was completely closed, and the main and branch stents were patency, 8 (8.8%) type Ⅰ leakage were occurred. Conclusion: It showed that in situ semiconductor laser fenestration is a feasible, effective and safe method to treat type A aortic dissection.

[Efficacy comparison of primary percutaneous coronary intervention by drug-coated balloon angioplasty or drug-eluting stenting in acute myocardial infarction patients with de novo coronary lesions].

Objective: To compare the safety profile, angiographic and clinical outcomes between drug-coated balloon(DCB) only strategy versus drug eluting stent(DES) implantation in primary percutaneous coronary intervention(PCI) for acute myocardial infarction(AMI) patients. Methods: A total of 380 AMI patients who underwent primary PCI in Beijing Chaoyang Hospital from January 2016 to May 2019 were enrolled. They were allocated into DEB group(n=180) or DES group(n=200). The Primary endpoint was the major adverse cardiac events(MACE) in hospital and within 3 months after discharge, the composite event of cardiac death, non-fatal myocardial infarction(MI), target vessel revascularization(TVR) and in stent thrombosis. The secondary endpoints included: (1)TIMI blood flow grade and myocardial perfusion grade (TMP grade) of infarct-related vessels before and after PCI. (2)The degree of ST segment resolution(STR) between half hour and two hours after PCI, and STR was represented by percentage of summed ST-segment reduction between baseline and post-PCI. Using the most significant lead of ST segment elevation, calculating the rate of decline in the ST segment after treatment; or the most significant lead of the ST segment depression, to calculate the rate of recovery in the ST segment after treatment. STR<50% was defined as incomplete STR. (3)The occurrence of coronary artery dissection during operation. (4)The peak value of myocardial enzymes. (5)The incidence of bleeding in hospital and within 3 months after discharge. The inverse probability weighting method based on propensity score (IPTW) was used to compare the effects of the two treatments on MACE occurrence in the logistic regression model. Results: There was no significant difference in sex, age, risk factors of coronary heart disease, type and site of AMI, interventional therapy data(P>0.05) between the two groups. The ratio of bifurcation lesions in DCB group was significantly higher than that in DES group, and the diameter of the DCB was smaller while the length was longer than that of DES (all P<0.05). One death occurred in each group during hospitalization. Compared with the DES group, the incidence of MI ï¼»2.8%(5/180) vs. 0.5% (1/200), P=0.10ï¼½ and TVR ï¼»2.8%(5/180) vs. 0.5%(1/200), P=0.10ï¼½ in the DCB group during hospitalization showed an increasing trend, and were mostly associated with delayed coronary dissection. The incidence of MACE was similar between the two groups (3.3%(6/180) and 1.0%(2/200), P=0.15) during hospitalization. There was no MACE occurred in the two groups within 3 months after discharge. There was no significant difference between the two groups in TIMI grade, TMP grade, incomplete STR rate and peak value of myocardial enzyme (all P>0.05). The incidence of coronary artery dissection was significantly higher in DCB group than in DES group (8.3%(15/180) and 3.0%(6/200), P=0.02), but most of them were type B or A dissection and did not need special treatment. There was no significant difference in bleeding event between the two groups(P=0.91). Logistic regression analysis showed that there was no difference in the risk of MACE during hospitalization between DES and DCB groups for AMI patients receiving PCI (compared with DCB, OR=0.35, 95%CI 0.08-1.43, P=0.13). Conclusions: The initial safety and efficacy profiles of DCB are similar with those of DES for the AMI patients during PCI. The study highlights that the incidence of coronary dissection (type A or B) is higher post DCB treatment than post DES, but it does not affect blood flow. However, the incidence of in-hospital MI due to delayed coronary dissection trends to be higher post DCB. So we should pay close attention to the risk of delayed coronary dissection after DCB in AMI patients with de novo lesion.

[De novo Assembly and Analysis of Sumac (Toxicodendron vernicifluum (Stokes) F.A. Barkley) Transcriptomes Provides Insights into the Biosynthesis of Urushiol].

Sumac is universally known for its abundance of raw lacquer. Toxicodendron vernicifluum (Stokes) F.A. Barkley is one of the widely distributed native sumac cultivars. To accelerate sumac breeding for more prolific, high-quality, and robust cultivars, it is essential to explore its lacquer metabolism. However, transcriptomic and genomic data available for sumac are still limited. In this study, we generated the transcriptomic profiles of triploid Toxicodendron vernicifluum CV. Dahongpao (Dahongpao) and diploid T. vernicifluum and Toxicodendron vernicifluum CV. Huoyanzi (Huoyanzi), with 87856 unigenes. About 53% of these unigenes were annotated using Nr, Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Cluster of Orthologous Groups (COG) and Gene Ontology (GO). We identified nine differentially expressed candidate genes associated with type III polyketide synthase formation, which is the first step in urushiol biosynthesis. Additionally, a number of simple sequence repeats (EST-SSRs) were identified in T. vernicifluum for further molecular marker-assisted breeding. This study is the first report of Toxicodendron species transcriptome.

[The effect of extending proximal landing zone in thoracic endovascular aortic repair on the prognosis of Stanford type B aortic dissection].

With the continuous development of endovascular surgery, thoracic endovascular aortic repair (TEVAR) has gradually replaced traditional open surgery and has become the preferred treatment strategy for Stanford type B aortic dissection. However, the disadvantage of the short proximal landing zone greatly limited the indication of TEVAR surgery and affected the prognosis. In recent years, many strategies such as hybrid surgery, in vitro fenestrated and branched aortic endo-graft, chimney technique, in-situ fenestration technique, etc., have been developed, which greatly broadens the TEVAR indication and improved the prognosis.

The adverse effects of perinatal exposure to nonylphenol on carbohydrate metabolism in male offspring rats.

BACKGROUND: We sought to investigate the adverse effects of perinatal exposure to nonylphenol (NP) on carbohydrate metabolism of male offspring rats. METHODS: Thirty-two healthy pregnant Sprague Dawley rats were randomly divided into four groups, control normal diet group (C), NP normal diet group (NPN), control high-energy diet group (CH), and NP high-energy diet group (NPH). Both of the control groups were received a gavage of corn oil and the NP-groups were received NP (200 mg/kg/day) from gestational days 6 to post-natal day (PND) 21. The concentrations of NP in pancreatic tissues were measured by high-performance liquid chromatography (HPLC). The key genes of glucose metabolism expression were detected by reverse transcription-polymerase chain reaction (RT-PCR). The pancreatic tissues were stained with hematoxylin/eosin (HE). RESULTS: On PND 1, the body weights of male pups in the NPN and NPH groups were lower than those of the CH group (p = 0.012 and 0.001, respectively). On PND 30, the body weight of male pups from the NPH group was elevated compared with the C group (p = 0.019), while the body weights of male pups in the NPN and NPH groups were elevated compared to the CH group (p = 0.034 and 0.004, respectively). On PND 60, the body weights of NPN and NPH pups were higher than those in the C (p < 0.001) and CH groups (p < 0.001). The levels of fasting blood glucose (FBG) were increased significantly in the animals treated with NP compared to control animals (F = 29.14, p < 0.001). The FBG levels in the treatment groups are ranked as follows: NPH > NPN > CH > C (p < 0.05). The concentrations of NP in pancreas tissues in both the NPN (2045.0 ± 130.1 µg/L) and NPH groups (2038.0 ± 104.2 µg/L) were higher than those in the C (499.5 ± 27.4 µg/L) and CH groups (494.2 ± 22.4 µg/L; p < 0.05). Morphological examination of tissues from rats exposed to NP shown that the NP-treated groups appeared to have a higher degree of inflammatory injury, edema, and focal necrotic cells in the pancreatic tissues. Compared with C group, expression of glucokinase (GCK) was down-regulated, while Uncoupling protein-2 (UCP-2) was up-regulated in the NP-treated groups (FGCK = 218.89, p < 0.001; FUCP-2 = 18.82, p < 0.001). CONCLUSIONS: Prenatal exposure to NP could induce glucose metabolism disorder in male F1 rats, which may be due to the fact that NP induces abnormal expression patterns of GCK and UCP-2.

[The clinical analysis of frontline nilotinib vs imatinib therapies for newly diagnosed chronic myeloid leukemia in chronic phase].

Objective: To compare the clinical efficacy and safety of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase(CML-CP). Methods: Until December 31st 2016, 18 patients using nilotinib and 83 using imatinib were recruited in our study. The efficacy and safety of two groups were evaluated. Results: A total of 101 patients with CML-CP included 18 receiving nilotinib and 83 imatinib. The optimal response rates at 3, 6, 12 and 18 months in nilotinib and imatinib group were 88.9% (16/18) vs 57.3% (47/82) (P=0.012), 82.4% (14/17) vs 55.7% (44/79) (P=0.041), 9/12 vs 63.9% (39/61) (P=0.460), 6/9 vs 68.9% (31/45) (P=0.896) respectively. The optimal response rates by 3 months in low sokal risk group on nilotinib and imatinib were 9/9 vs 76.5%(26/34) (P=0.107), in intermediate and high sokal risk group were 7/8 vs 45.2%(14/31) (P=0.032). At the end of follow-up, the rate of major molecular response (MMR) in nilotinib group was 72.2%, which was higher than 56.6% in imatinib group (P=0.021). The rate of complete cytogenetic response (CCyR) in nilotinib group was 100%, which was higher than 71.1% in imatinib group (P = 0.002). Progression free survival (PFS) rates in nilotinib and imatinib groups were 94.4% and 98.8% (P=0.019) respectively; whereas event free survival (EFS) rates were 88.9% and 48.2% (P=0.045). The incidence of drug related adverse reactions in nilotinib and imatinib was similar with only minor proportion of grade 3/4 adverse reactions. Conclusions: Nilotinib achieves a deeper molecular response in a shorter time than imatinib in newly diagnosed patients with CML-CP, especially in patients with high risk outcome. Good safety is obtained in both groups so as to ensure a long-term administration and improving prognosis.

[Implantation of the irradiation stent system intoportal vein: studies on normal beagles].

Objective: To assess the feasibility and safety of the irradiation stent system in portal vein on normal beagles. Methods: A portal vein irradiation stent system was composed of an Iodine-125 seeds-carrier and a conventional stent.Twenty beagle dogs were randomly assigned to receive treatment with a conventional stent (5 beagle dogs) or an irradiation stent system (15 beagle dogs in three groups received 11.1, 22.2, 33.3 MBq radioactivity, n=5 in each dose group). Follow-up methods included blood biochemical test, color Doppler sonographyand CT scan at 0, 15, 30, 60, and 120 days after implantation of irradiation stent system.Pathological tissues were obtained from sacrificed beagle dogs on the 120th day. Results: The portal vein irradiation stent systems and the conventional stents were successfully deployed into the targeted portal vein segment in all beagles, none was dislodged during the deployment or the follow-up period.Differences of blood biochemical indexes and portal vein flow volume measured by color Doppler sonography were not significant (P>0.05). Stent systems were morphologically intact and patent.None of the peripheral organs had hemorrhage, necrosis or perforation.Pathological tissues revealed that the systems were surrounded by fibrous tissues and a few inflammatory cells, but with no significant differences in all groups. Conclusion: It indicates that portal veinirradiation stent system is safe in all dose groups, and it is feasible to design a special irradiation stent system for each patient according to the size of the portal vein tumor thrombus.

CCL20-CCR6 Cytokine Network Facilitate Treg Activity in Advanced Grades and Metastatic Variants of Hepatocellular Carcinoma.

Tumour immunity regulates tumour restriction to the site of occurrence. Failure of this balance facilitates tumour spread beyond the primary organ of origin. Tregs are known to be recruited in infections, including viral infections like hepatitis B and hepatitis C. Thus, they form a continuum of initial viral infection, an environment of immune suppression by recruitment of Tregs, intrinsic viral-mediated nuclear transformation and carcinogenesis, and thereafter worsening of progress, including metastasis due to the Tregs suppressing the cell-mediated destruction of tumour cells. In this study, we obtained advanced grades of hepatocellular carcinoma (HCC) and examined the cytokines that is potentially known to recruit Tregs. We examined the expression of CCL20, the cytokine that recruits Tregs. We isolated Tregs from HCC samples and examined expression of CCR6, the receptor for CCL20 and compared expression in control tissues obtained mainly from subjects with cirrhosis, but no evidence of cancer. The findings of this study indicate that mRNA expression of CCL20 is significantly enhanced, along with expression of mRNA for the cytokines IL17 and IL6. Furthermore, tissue expression of Gamma-interferon was reduced in HCC. When Tregs were isolated from the liver cancer samples, the expression of CCR6, the only and specific receptor for CCL20, was upregulated in the cancer tissue derived Tregs . Furthermore, STAT3 levels were significantly increased in these tumour-derived Tregs. This study demonstrates that immune evasion mechanisms are operant in hepatocellular carcinoma through a transcriptional network of CCL20-IL17-IL6 cytokines that facilitate immune suppression-mediated cancer cell elimination and metastasis.

[Effects of tetrahydrobiopterin on the angiogenesis in hepatocellular carcinoma].

Objective: To investigate the effect and mechanism of tetrahydrobiopterin (BH4) on the angiogenesis in hepatocellular carcinoma (HCC). Methods: BALB/c-nu mice were subcutaneously injected with HepG-2 cells and randomly divided into control and BH4 groups. The BH4 group and control group received 20 mg/kg BH4 or saline by intraperitoneal injection daily for two weeks, respectively. The level of BH4 was measured by high performance liquid chromatography (HPLC), the level of nitric oxide (NO) was measured by Griess test array, the transcriptional level of K-ras was measured by quantitative RT-PCR, and the protein expressions of guanosine triphosphate cyclohydrolase Ⅰ(GTPCH), endothelial nitric oxide synthase (eNOS), phospho-Akt and Akt were determined by Western blot. Results: BH4 level in the tumor tissues of BH4 group was (0.24±0.02) µg/ml, significantly higher than the (0.17±0.01) µg/ml in the control group (P<0.01). The level of NO in the tumor tissues of BH4 group was (51.44±2.90) mmol/L, significantly higher than the (24.77±0.54) mmol/L in the control group (P<0.01). The tumor volume of BH4 group was (191.05±8.70) mm3, significantly higher than the (103.10±5.03) mm3 in the control group (P<0.01). The expressions of CD34, K-ras, phospho-eNOS, phospho-Akt and GTPCH were significantly up-regulated in the tumor tissues of BH4 group when compared with those of the control group (P<0.01). Conclusions: BH4 recognized as an essential cofactor of eNOS can increase tumor-produced NO by activating the wild-type Ras-PI3K/Akt pathway, thus induces angiogenesis. This might provide a novel and promising way to control the progression of hepatocellular carcinoma through targeting BH4 synthesis pathway and inhibiting angiogenesis.

[The effect and safety of tirofiban on acute ST segment elevation myocardial infarction patients receiving no early reperfusion therapy].

OBJECTIVE: To study the efficacy and safety of tirofiban on acute ST segment elevation myocardial infarction (STEMI) in patients who do not receive early reperfusion therapy. METHODS: A total of 153 STEMI patients without early reperfusion therapy were randomly distributed into tirofiban group (therapeutic group, n=78) and non-tirofiban group (control group, n=75). Coronary angiography was performed on the 5(th) and 10(th) day after treatment, and percutaneous coronary intervention (PCI) was conducted when necessary. The differences of initial patency of the infarct related artery (IRA), bleeding complication and clinic events within 30 days between these two groups were compared. RESULTS: Tirofiban did not increase the percentage of patients with initial patency of IRA (60.3% vs 64.0%, P=0.63). The percentage of patients with thrombolysis in myocardial infarction (TIMI) 3 after PCI was 100.0% in tirofiban group and 97.1% in the control group (P=0.09). However, application of tirofiban significantly decreased poor myocardial perfusion rate after PCI (1.4% vs 8.8%, P=0.04). No significant differences were observed in major adverse cardiovascular events (MACE) (3.8% vs 2.7%, P=0.68) between therapeutic and control group. The same is true for mild (5/78 vs 4/75 cases, P=0.78) and severe hemorrhage (2/78 vs 1/75 cases, P=0.58), and severe thrombocytopenia (2/78 vs 0/75 cases, P=0.10) between these two groups within 30 days. CONCLUSIONS: Tirofiban did not increase initial patency in STEMI patients without early reperfusion therapy. However, it can improve myocardial perfusion after PCI.

Self-priming on the plant viral RNAs during reverse transcription-PCR.

The occurrence of the primer-independent cDNA synthesis during RT-PCR analysis of human and animal RNA viruses has been well documented. Conversely, there is scant knowledge about this event in plant RNA viruses. Here we show that the primer-independent cDNA synthesis occurs in all eight different plant RNA viruses tested in this study, suggesting a common phenomenon for RT-PCR analysis of plant RNA viruses. Additional experiments indicate that the event is likely contributed to by RNA self-priming, and can be effectively reduced or eliminated through increasing temperature of the RT reaction.

Chemical probes for the functionalization of polyketide intermediates.

A library of functionalized chemical probes capable of reacting with ketosynthase-bound biosynthetic intermediates was prepared and utilized to explore in vivo polyketide diversification. Fermentation of ACP mutants of S. lasaliensis in the presence of the probes generated a range of unnatural polyketide derivatives, including novel putative lasalocid A derivatives characterized by variable aryl ketone moieties and linear polyketide chains (bearing alkyne/azide handles and fluorine) flanking the polyether scaffold. By providing direct information on microorganism tolerance and enzyme processing of unnatural malonyl-ACP analogues, as well as on the amenability of unnatural polyketides to further structural modifications, the chemical probes constitute invaluable tools for the development of novel mutasynthesis and synthetic biology.