Objective:To investigate whether the lung specific X protein(LUNX)gene can serve as a prognostic biomarker for non-small cell lung cancer related to immune cell infiltration.Methods:A total of 280 non-small cell lung cancer patients admitted to Hengshui People's Hospital from January 2020 to January 2023 were selected to detect the expression of LUNX gene in cancer tissue and adjacent tissues,and to analyze the relationship between LUNX gene and immune cell infiltration and prognosis survival status in the tumor microenvironment.Results:Compared with adjacent tissues,the expression level and positive rate of LUNX gene in non-small cell lung cancer tissue were increased,which were related to differentiation degree,lymph node metastasis and tumor staging(P<0.05).GEPIA database analysis showed that the LUNX gene was only slightly expressed or not expressed in other tissues,while its expression was elevated in LUAD and LUSC(P<0.05).The copy number of LUNX gene and LUNX gene were related to the level of immune cell infiltration(P<0.05).Survival analysis showed that high expression of the LUNX gene was associated with patient survival prognosis(P<0.05).Conclusion:The LUNX gene is specifically expressed in non-small cell lung cancer tissue,affecting the level of immune cell infiltration in non-small cell lung cancer,leading to an imbalance in the immune microenvironment,and is an important mechanism for causing patients prognostic death,which can be used as a prognostic biomarker for evaluating immune cell infiltration.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To evaluate the prognostic accuracy of the sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria in predicting the mortality in patients with infection or suspected infection by using network Meta-analysis.Methods:Five databases including Wanfang Data, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), PubMed, Web of Science were searched from February 23, 2016 to September 5, 2020 to identify the relevant literatures comparing the prognostic accuracy of two or more scores for mortality in patients with infection or suspected infection. The literatures screening, data extraction and the quality assessment of the included studies were all conducted independently by two reviewers. Stata 14.0 software was used to test the heterogeneity between the original studies of pairwise comparison of each of the three scoring systems. Ring inconsistency test was used to judge the consistency between direct comparison and indirect comparison. Then network Meta-analysis was performed and the results were ranked. The predictive ability of the three scoring systems was evaluated by surface under cumulative ranking curve (SUCRA). A "comparison-correction" funnel plot was drawn to assess whether there was publication bias in the included studies.Results:A total of 38 studies were enrolled, the overall quality was high. Network meta-analysis showed that SOFA had a great prognostic performance in predicting mortality for patients with infection or suspected infection, which was followed by qSOFA [mean difference ( MD) = 0.07, 95% confidence interval (95% CI) was 0.05-0.09] and SIRS scores ( MD = 0.16, 95% CI was 0.14-0.18), and the qSOFA score was better than SIRS score ( MD = 0.09, 95% CI was 0.07-0.11). In the order of predicting the death risk of patients with infection or suspected infection, SOFA score had higher predictive value, followed by qSOFA score, and SIRS score was the lowest, with SUCRA values of 1.0, 0.5 and 0, respectively. Funnel plot showed that all the studies were distributed on both sides of the midline, but the distribution was not symmetrical, suggesting that there was a high possibility of publication bias and small sample effect. Conclusions:SOFA score had the best prognostic performance in predicting mortality of patients with infection or suspected infection as compared with qSOFA score and SIRS score. However, the funnel plot showed that included literatures may exist small sample effects or publication bias. So the final results should be validated by more prospective studies with multicenters and large samples.

Objective:To explore the clinical value of adenosine stress myocardial contrast echocardiography in detecting myocardial blood perfusion abnormalities in patients with type 2 diabetes mellitus.Methods:Twenty-six patients with type 2 diabetes mellitus clinically diagnosed from May 2019 to January 2020 in the endocrinology department of Fuwai Central China Cardiovascular Hospital and 28 healthy examinees with gender and age matched during the same period were enrolled. Routine echocardiography, rest and adenosine stress myocardial contrast echocardiography were performed, the plateau signal intensity(A value), curve rising slope(K value) and A×K value of the myocardial perfusion time-intensity curve were obtained by offline analysis. And general data such as age, gender, disease course, body mass index and glycated hemoglobin were collected, and results of the two groups were compared statistically.Results:In the rest state, the A value of the myocardial perfusion parameter in the diabetic group was not significantly different from that of the control group, both in whole and in segments ( P>0.05), while the K value and A×K value of the myocardial perfusion parameters in the diabetic group were significantly lower than those in the control group ( P<0.05). In the stress state, the A value, K value and A×K value of myocardial perfusion parameters in the diabetic group were significantly lower than those in the control group, both in whole and in segments ( P<0.05). The detection rate of myocardial perfusion abnormality in the stress state was significantly higher than that in the rest state, and the difference was statistically significant ( P<0.05). The myocardial blood flow reserve in the diabetic group was negatively correlated with the course of disease and the level of glycated hemoglobin ( r=-0.580, P=0.020; r=-0.481, P=0.013). Conclusions:Adenosine stress myocardial contrast echocardiography can be used for detection of left ventricular myocardial perfusion abnormalities in patients with type 2 diabetes mellitus, which has great clinical application value.

OBJECTIVE：To optimize ultrasonic-assisted ethanol-（NH4）2SO4 aqueous two-phase extraction technology of citru- sinol from Desmodium caudatum . METHODS ：Using the content of citrusinol as indexes ，with ethanol volume fraction ， solid-liquid ratio ，（NH4）2SO4 addition amount ，ultrasonic time and ultrasonic temperature as factors ，based on the single factor tests，Box-Behnken design-response surface methodology was used to optimize the extraction technology of citrusinol. RESULTS ： The optimized extraction technology of citrusinol included that ethanol volume fraction was 95.35％，the solid-liquid ratio was 1∶50.35 （g/mL），（NH4）2SO4 addition amount was 4.49 g，ultrasonic time was 48.7 min，ultrasonic temperature was 57.6 ℃. In 3 times of validation tests ，the extraction rates of citrusinol were 0.637 8，0.638 4，0.625 4 mg/g，respectively，which was close to predicted value（0.630 5 mg/g）. CONCLUSIONS ：The optimized ultrasonic-assisted ethanol- （NH4）2SO4 aqueous two-phase extraction technology is stable and feasible ，and can be used for the extraction of citrusinol from D. caudatum .

The study was designed to investigate the effects and mechanism of a calcium-sensing receptor (CaSR) polymorphism at E942K on the proliferation of gastric cancer cells. Single nucleotide polymorphisms (SNPs) were detected between gastric cancers group and normal controls group by DNA sequence analysis. The cell model was constructed by transfection of E942K mutant plasmid and wild-type (WT) plasmid into SGC-7901 and HEK-293 cells. The effect of E942K mutation on cell proliferation ability was detected by CCK8 and cell clone formation experiments. The effect of E942K mutation on calcium signaling was detected by calcium imaging. Western blot experiments were used to detect changes in phosphorylation levels of key proteins ERK1/2 and β-catenin in downstream signaling pathways after E942K mutation. The results showed that the mutation rate of E942K in gastric cancer group was significantly higher than that in normal control group (P < 0.05). CCK8 and cell clone formation experiments showed that E942K mutation significantly improved the proliferation ability of SGC-7901 gastric cancer cells and HEK-293 cells. E942K mutation enhanced calcium signaling in SGC-7901 and HEK-293 cells. E942K mutation enhanced ERK1/2 phosphorylation without affecting β-catenin phosphorylation. The results suggest that E942K mutation in CaSR may ultimately promote the proliferation of gastric cancer cells by enhancing intracellular calcium signaling and ERK1/2 phosphorylation. These results have potential clinical implications for the diagnosis and targeted therapy of gastric cancer.
Calcium ; Cell Proliferation ; HEK293 Cells ; Humans ; MAP Kinase Signaling System ; Mutation ; Receptors, Calcium-Sensing ; genetics ; Stomach Neoplasms ; genetics

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK(+) and 9 ones (27.3%) ALK(-). Of them, 25 patients (19 ALK(+) and 6 ALK(-)) underwent auto-HSCT and 8 cases (5 ALK(+) and 3ALK(-)) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion: ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.
Adolescent ; Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large-Cell, Anaplastic/therapy* ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

Objective To explore the role of viral infection in the development of drug eruption in patients with HIV infection, and to evaluate the efficacy of antiviral treatment. Methods This study enrolled 87 HIV-positive patients, including 11 with and 76 without drug eruption, all of whom received highly active antiretroviral therapy(HAART). Clinical data on, baseline CD4+ and CD8+ T cell counts and CD4/CD8 ratio in these subjects were retrospectively analyzed. Results The severity of drug eruption was mild in the 11 HIV-positive patients, with a mean latency period of (14.00 ± 8.10)(range, 8 - 34)days. Of the 11 patients with drug eruption, 7 had liver function impairment, which was not in accordance with the severity of skin lesions. Drug eruption was controlled in all the 11 patients after anti-anaphylactic treatment without withdrawal of antiviral drugs. Compared with 75 HIV-positive patients without drug eruption, the 11 HIV-positive patients with drug eruption showed significantly increased baseline CD4 + T cell counts (493.00 ± 245.68 (range, 42 - 810)/μl vs. 347.81 ± 167.00 (range, 11 - 814)/μl, t = 647.50, P < 0.05), but decreased proportion of patients with baseline CD4+ T cell counts below the lower limit of normal(3/11 vs. 48/75(64.00%), X2 = 3.95, P < 0.05). There were no significant differences between 10 patients with drug eruption and 69 patients without drug eruption in the baseline CD8+ T cell count(1472.30 ± 858.55/μl vs. 1356.59 ± 684.06/μl, P > 0.05), CD4/CD8 ratio(0.40 ± 0.27 vs. 0.29 ± 0.16, P > 0.05), or percentage of patients with a CD4/CD8 ratio below the lower limit of normal (9/10 vs. 68/69 (98.55%), P >0.05). Conclusions The latency period of drug eruption seems to be long in HIV-positive patients receiving HAART, and mild drug eruption can be complicated by liver function impairment in the patients. Relatively high CD4 + counts may be a risk factor for the development and aggravation of drug eruption in HIV-positive patients.

OBJECTIVETo observe the effect of SIRT1 on intestinal barrier function of epithelial Caco-2 cells under hypoxia and investigate its mechanism.

METHODSCaco-2 cells were randomly divided into three groups: normoxia group (Nx), hypoxia group (Hx,1%O2 for 6 h) and hypoxia plus 40 μmol/L Resveratrol (agonist of SIRT1) group (Hx+Res). Transepithelial electrical resistance (TER) was determined. mRNA and protein expressions of SIRT1 and tight junctions (ZO-1, Occludin, Claudin-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.

RESULTSBoth mRNA and protein expressions of SIRT1 were significantly reduced in Hx group as compared with Nx group (0.40±0.02 vs. 0.70±0.07, P=0.001; 0.37±0.03 vs. 0.76±0.03, P=0.001). The mRNA and protein expressions of SIRT1 were significantly increased in Hx+Res group as compared with Hx group(0.50±0.02 vs. 0.40±0.02, P=0.026; 0.54±0.02 vs. 0.37±0.03, P=0.011). The expression levels of ZO-1, Occludin and Claudin-1 in Hx group were lower than those in Nx group (P<0.05), however, pretreatment with Resveratrol could attenuate the decreased expression of above 3 molecules under hypoxia(P<0.05). TERs of Nx group, Hx group and Hx+Res group were (142±7) Ohm/cm(2), (94±3) Ohm/cm(2) and (119±7) Ohm/cm(2) respectively. Compare with the Nx group, the TER of Hx group was significantly decreased(P<0.05). TER of Hx+Res group was significantly increased compare with Hx group, but it was still significantly lower than that in Nx group(P<0.05).

CONCLUSIONSExpression of SIRT1 is significantly reduced under hypoxia. Activation of SIRT1 can maintain the epithelial barrier function through regulating the expression of tight junctions under hypoxia.

Caco-2 Cells ; Cell Hypoxia ; Claudin-1 ; metabolism ; Epithelial Cells ; metabolism ; Humans ; Intestinal Mucosa ; cytology ; Occludin ; metabolism ; Sirtuin 1 ; metabolism ; Zonula Occludens-1 Protein ; metabolism