Bowel habits were associated with mortality in chronic kidney disease: results from a nationwide prospective cohort study.

PURPOSE: Bowel habits may affect the prognosis in the chronic kidney disease (CKD) patients. This study aimed to explore the association of bowel habits with cardiovascular and all-cause mortality in CKD. METHODS: 2460 CKD patients in the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2010 without missing data for bowel habits and mortality were enrolled. Bowel habits including bowel movements (BMs) per week and stools consistency were obtained by standard interview. Mortality status and cause of death were determined by NHANES-linked National Death Index records through 31 December 2015. Cox proportional hazard models and Kaplan-Meier analysis were used to evaluate the association of bowel habits with cardiovascular and all-cause mortality. RESULTS: A total of 2460 CKD patients with an average age of 60.80 ± 0.57 years were enrolled. During an average follow-up of 87.47 ± 0.98 months, 144 cardiovascular and 669 all-cause deaths were documented. Reporting 3 or fewer BMs per week was associated with cardiovascular (HR = 1.83, 95% CI: 1.06, 3.17) and all-cause mortality (HR = 1.71, 95% CI: 1.20, 2.43). More than 10 BMs per week also increased the risk of all-cause mortality (HR = 1.21, 95% CI: 1.01, 1.45). Hard stools consistency increased the risk of all-cause mortality (HR= 2.00, 95% CI: 1.48, 2.70) compared with those reporting normal stools. CONCLUSION: Low stool frequency and hard stool consistency were associated with an increased risk of mortality in patients with CKD.

The use of multiplex imaging techniques to characterize tuberculous granuloma heterogeneity.

Caseous granulomas are pathological hallmarks of tuberculosis (TB), and increasing evidence suggests that TB granuloma composition is highly temporally and spatially heterogenous in both animal models and humans. Traditional pathological techniques are limited in their ability to reveal the heterogeneity present in TB granulomas. Multiplex tissue imaging tools combined with powerful, high resolution spatial analysis have enabled the detection of various cell phenotypes, aiding in the visualization of the granuloma complex and revealing the interactions between immune cells and nonimmune cells. This updated understanding of tuberculous granuloma heterogeneity offers vital insights for researchers aiming to uncover the immunoregulatory mechanisms underlying granuloma formation during TB pathogenesis. More detailed granuloma classification systems will also be of use for precision medicine, and for identifying biological targets for host-directed therapeutics in TB patients. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Biomedical Engineering Infectious Diseases > Molecular and Cellular Physiology.

Potential biomarkers and resistance mechanisms of atezolizumab in a patient with lung squamous cell carcinoma.

Background: At present, only a small fraction of patients with cancer benefit from treatment with immune checkpoint inhibitors, the reasons for which are not fully understood. Monitoring molecular and immunologic changes during treatment with immune checkpoint inhibitors would help to identify potential biomarkers and mechanisms associated with resistance and guide subsequent treatment. Methods: The authors report on a patient previously treated for lung squamous cell carcinoma who received atezolizumab-based therapy for 24 months. Results & Conclusion: Analysis of samples before and after atezolizumab treatment suggested that genetic mutations in EGFR exon 20 insertion, phosphatase and PTEN and NOTCH1 as well as changes in tumor immune microenvironment may be associated with acquired resistance to immune checkpoint inhibitor therapy.

Lay abstract The authors aimed to figure out potential biomarkers and mechanisms associated with immune checkpoint inhibitor resistance by monitoring changes during treatment in a lung squamous cell cancer patient. Interestingly, EGFR exon 20 insertion, decreased PTEN copy number and NOTCH1 mutation as well as changes in CD8⁺ T cells and macrophages were observed after disease progression. Thus, the authors suggest that these changes may be associated with atezolizumab resistance.

Long-Term Survival After Salvage Thoracic Surgery on a Patient with ALK-Rearranged Metastatic Lung Adenocarcinoma After Progression on Targeted Therapy.

Targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) is often challenged by the arising of drug resistance. After progression to targeted therapy, treatment options include continued targeted therapy, definitive local therapy, and the combination of both. While there is evidence that local ablative radiotherapy may prolong the disease control by targeted therapy, little is known regarding the relevance of salvage thoracic surgery in this setting. Herein, we presented a case of stage IV lung adenocarcinoma with concurrent EML4-ALK and TAC1-ALK fusion who had long-term survival after salvage thoracic surgery. The patient underwent a multidisciplinary treatment scheme that consisted of radiotherapy, ALK inhibitor crizotinib, and surgery, with blood-based genomic profiling for monitoring disease progression. Notably, salvage thoracic surgery was performed after progression on the crizotinib therapy and acquired ALK F1174C mutation was identified, which has been shown to be resistant to crizotinib and possibly sensitive to ceritinib. The patient benefited from salvage thoracic surgery with a remarkable progression-free survival of 31 months at last follow-up, and the patient maintained high-performance status throughout the course of management. To the best of our knowledge, this is the first case reporting on the long-term survival outcome from salvage thoracic surgery after crizotinib treatment in an NSCLC patient carrying double ALK fusion.

Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p.

BACKGROUND: Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. METHODS: The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as CCK-8, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis. RESULTS: We found that circ_0002483 was upregulated in LUAC tissue samples and associated with Tumor Node Metastasis (TNM) stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively regulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. CONCLUSIONS: Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

Thermal treatment decreases resistance to osimertinib in non-small cell lung cancer through the EGFR/PI3K/AKT pathway.

Osimertinib (OSI) resistance commonly occurs during the treatment of non-small-cell lung cancer (NSCLC). This study aims to investigate whether the thermal effects of radiofrequency ablation (RFA) can increase the sensitivity of OSI-resistant NSCLC to OSI treatment and whether OSI effectively inhibits the recurrence of OSI-resistant NSCLC following RFA treatment and improve survival of NSCLC patients. In vitro, OSI-resistant NCI-H1975 (NCI-H1975/OSIR) cells and thermotolerant NCI-H1975/OSIR (NCI-H1975/OSIR-a-h) cells were established using human NSCLC cell line NCI-H1975. Cell viability, apoptosis, sensitivity to OSI, threonine-methionine amino acid substitution at position 790 (T790M) mutation levels, and protein expression of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), hypoxia-inducible factor-1 alpha (HIF-1a) were detected using different methods. In vivo, a nude mouse model of metastatic human lung cancer was developed and subjected to RFA treatment. The tumor growth, apoptosis, sensitivity to OSI, expression of EGFR/PI3K/AKT/HIF-1a, and CD34 levels were detected in the micrometastases of the transition zone (TZ) around the central ablation zone, and the reference zone (RZ) far from central ablation zone. NCI-H1975/OSIR and thermotolerant NCI-H1975/OSIR cell models were successfully established. Thermotolerant NCI-H1975/OSIR cells show higher sensitivity to OSI than NCI-H1975/OSIR cells and NCI-H1975 cells. OSI treatment can inhibit the EGFR/PI3K/AKT pathway and induce apoptosis in both NCI-H1975 cells and thermotolerant NCI-H1975/OSIR cells, but not in NCI-H1975/OSIR cells. In vivo, RFA treatment increases sensitivity to OSI in NCI-H1975/OSIR cell micrometastases in the TZ but not in the RZ. OSI intervention effectively inhibits the over-proliferation of micrometastases and activation of the EGFR/PI3K/AKT pathway, and induces apoptosis of micrometastases in the TZ, but shows little effects on the micrometastases in the RZ. The thermal effects can increase the sensitivity of OSI-resistant NSCLC cells to OSI through the EGFR/PI3K/AKT/HIF-1a signaling pathway, indicating that RFA combined with OSI might be a clinically effective and comprehensive therapy for the treatment of OSI-resistant NSCLC.

Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P-glycoprotein expression level in non-small lung cancer.

Tumour drug resistance is one of the most urgent issues faced by anti-tumour therapies. P-glycoprotein (P-gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real-time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P-gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug-resistant cell lines A549/ADR in nude mice by down-regulating the mRNA and protein expression of P-gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P-gp in lung cancer.

miR­10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway.

Circulating tumor cells (CTCs) that are shed from the primary tumor invade the blood stream or surrounding parenchyma to form new tumors. The present study aimed to explore the underlying mechanism of cisplatin resistance in lung adenocarcinoma CTCs and provide clinical treatment guidance for lung cancer treatment. CTCs from the blood samples of 6 lung adenocarcinoma patients were treated with different concentrations of cisplatin along with A549 and H1299 cells. The sensitivity of CTCs to cisplatin was explored by detecting the inhibitory rate via CCK­8 assay. The related molecular mechanism was investigated by western blot analysis. miR­10a expression was detected using quantitative real­time PCR (RT­qPCR). The relationship between miR­10a and phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit α (PIK3CA) was verified and further confirmed by luciferase reporter assay, western blotting and RT­qPCR assay. The results revealed that CTCs exhibited lower cisplatin sensitivity than A549 and H1299 cells. Moreover, CTCs treated with cisplatin demonstrated higher miR­10a expression and lower PIK3CA expression than that in A549 and H1299 cells (P<0.01). Expression of phosphoinositide 3­kinase (PI3K) and protein kinase B (Akt) phosphorylation were also decreased in A549 and H1299 cells compared with CTCs after cisplatin treatment. PIK3CA is a target of miR­10a, and both miR­10a overexpression and PIK3CA knockdown obviously decreased the sensitivity of A549 and H1299 cells to cisplatin as well as the expression of PI3K and phosphorylation of Akt. PIK3CA overexpression attenuated the cisplatin resistance of A549 and H1299 cells induced by miR­10a. In conclusion, miR­10a suppressed the PI3K/Akt pathway to strengthen the resistance of CTCs to cisplatin via targeting PIK3CA, providing a new therapeutic target for lung cancer treatment.

Independent prognostic value of HIF-1α expression in radiofrequency ablation of lung cancer.

Radiofrequency ablation (RFA) is widely used in the treatment of lung cancer. Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor regulating oxygen homeostasis that is involved in tumor cell metastasis. The present study investigated the impact of HIF-1α expression and other factors, such as postoperative blood CD4+/CD8+ ratio, on the prognosis of patients with lung cancer who had received RFA treatment. A total of 80 patients with lung cancer were recruited between January 2011 and October 2016 at The Shenzhen People's Hospital. Lung cancer was confirmed following pathological or histological examination. All patients underwent RFA treatment. Patients were followed up for 6-66 months. HIF-1α expression in lung cancer tissues was assessed by immunohistochemistry. Multivariate survival analysis was performed using Cox proportional hazards model. The results demonstrated that HIF-1α level was low in 36 patients and overexpressed in 44 patients with lung cancer. Kaplan-Meier (KM) curve analysis demonstrated that the overall survival time of patients with high HIF-1α expression was significantly shorter compared with patients with low HIF-1α expression (P<0.05). Furthermore, the results from the KM model and log-rank test revealed that age, Union for International Cancer Control stage, primary or metastatic cancer, chemotherapy, postoperative blood CD4+/CD8+ ratio, Eastern Cooperative Oncology Group performance status and HIF-1α expression had significant effects on overall survival of patients with lung cancer. The results from Cox analysis demonstrated that high HIF-1α expression, advanced age, clinical staging and chemotherapy were independent risk factors for the prognosis of lung cancer following RFA treatment, and that high HIF-1α expression was associated with the increased risk (5.91-fold) of mortality. In conclusion, the present study demonstrated that HIF-1α expression was increased in lung cancer tissues and was associated with the prognosis of patients with lung cancer who were treated with RFA. These findings suggest that HIF-1α expression may be considered as a marker for evaluating the prognosis of these patients.

Case report: HER2 amplification as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping.

Patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping can benefit from crizotinib treatment. Currently, the main resistance mechanisms to crizotinib are MET D1228N and Y1230C mutations. We reported a case of a Chinese NSCLC patient with MET exon 14 skipping detected by targeted next-generation sequencing (NGS) achieved clinical and imaging remission after crizotinib treatment. Then, amplification of multiple genes such as erb-b2 receptor tyrosine kinase 2 (HER2) was detected when disease progressed, indicating novel resistance mechanisms to crizotinib. Ultimately the patient died from cancer-related factors. This was the first NSCLC case with MET exon 14 skipping which reported the HER2 gene amplification at the time of progression during crizotinib treatment, indicating that bypass mechanisms contribute to the development of acquired resistance to MET inhibitors.

miR-142-5p regulates CD4+ T cells in human non-small cell lung cancer through PD-L1 expression via the PTEN pathway.

The present study aimed to evaluate the function of microRNA (miR)-142-5p on cancer immunity to induce apoptosis in human non-small cell lung cancer (NSCLC) and its mechanism. miR-142-5p expression was upregulated, and CD4+ T cell levels were reduced in patients with NSCLC. Overexpression of miR-142-5p expression inhibited the cancer effects of CD4+ T cells on NSCLC cell lines, and downregulation of miR-142-5p increased the cancer effects of CD4+ T cells on NSCLC cell lines, compared with the control group. In addition, we found that overexpression of miR-142-5p suppressed PTEN protein expression and induced PI3K, p-Akt and PD-L1 protein expression in an in vitro model of NSCLC. Downregulation of miR-142-5p induced PTEN and PD-L1 protein expression and suppressed PI3K and p-Akt and protein expression in an in vitro model of NSCLC. The suppression of PD-L1 reduced the cancer effects of CD4+ T cells on NSCLC cell lines following miR-142-5p downregulation. The inhibition of PTEN also reduced the cancer effects of CD4+ T cells on NSCLC cell lines following miR-142-5p downregulation. Therefore, our study demonstrated that miR-142-5p regulated CD4+ T cells in human NSCLC through PD-L1 expression via the PTEN pathway.

Efficacy generated by afatinib in a lung adenocarcinoma patient harboring HER2 S310Y mutation.

Afatinib exhibits therapeutic efficacy for lung adenocarcinoma patients harboring HER2 exon 20 insertions. HER2 S310Y single site substitution was discovered in recent years and afatinib efficacy for adenocarcinoma patients harboring S310Y mutation has not been reported. We presented a case of a 41-year-old male patient with lung adenocarcinoma harboring the HER2 S310Y mutation obtained clinical response to the treatment of afatinib, an oral HER family blocker. After the treatment of afatinib, the patient achieved partial response (PR) in chest lesions and almost complete response (CR) in intracranial lesions. He experienced progressive disease (PD) with liver metastasis and achieved a progression-free survival (PFS) of 5 months. He continually treated with afatinib after CT guided percutaneous radiofrequency ablation to eradicate the hepatic tumor cells and achieved stable disease (SD). In this study, we reported the first clinical evidence of efficacy generated by afatinib, the irreversible HER family inhibitor, targeting HER2 S310Y single site mutation in lung adenocarcinoma.

MiR-186 inhibits proliferation, migration, and invasion of non-small cell lung cancer cells by downregulating Yin Yang 1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the main type of lung cancer. While miR-186 is significantly reduced in lung cancer tissues and cells, its role in NSCLC has not been completely elucidated. MATERIAL AND METHODS: We used qRT-PCR and western blot methods to investigate the levels of miR-186 and YY1 in 21 pairs of NSCLC tissues. Dual luciferase reporter gene assays were performed to detect whether miR-186 directly targets YY1. Next, the roles of miR-186 and its target gene (YY1) in determining the proliferation, apoptosis and migration capabilities of selected cell lines (A549 and HCC827) were investigated by using miR-186 mimics or YY1 siRNA. RESULTS: Our results showed that miR-186 was downregulated and YYI was upregulated in NSCLC tissue, and miR-186 expression was negatively associated with YY1. Similarly, miR-186 was also downregulated and YY1 expression also was upregulated in both A549 and HCC827 cells; furthermore, miR-186 was found to directly target YY1. Cell proliferation, invasion, and migration, as well as apoptosis induction were more strongly inhibited by YY1 siRNA than by miR-186. CONCLUSION: Our results suggest that miR-186 and its target gene (YY1) could possibly serve as new prognostic biomarkers and therapeutic targets for treating NSCLC in humans.

Transcription Factor YY1 Modulates Lung Cancer Progression by Activating lncRNA-PVT1.

Lung cancer is the leading cause of cancer-related death worldwide. Despite the advancement in surgery and chemotherapy, the prognosis of patients with advanced lung cancer is still poor. Yin Yang-1 (YY1) is a multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes. In this study, we showed that the expression of YY1 is upregulated in lung cancer tissues as compared to adjacent normal tissues. Patients with higher expression of YY1 had larger tumor size, poor differentiation, higher TNM stage, and lymph node metastasis. Ectopic expression of YY1 in lung cancer cells promoted cell proliferation and invasion. Inversely, siRNA-mediated silencing of YY1 inhibited cell proliferation and induced apoptosis. These results suggested that YY1 may function as an oncogene in lung cancer. Moreover, through luciferase reporter assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we showed that YY1 could directly bind to the promoter region of (long noncoding RNA-plasmacytoma variant translocation 1 [lncRNA-PVT1]) and activated its transcription through the consensus YY1 motif. Knockdown of the expression of YY1 reduced cell proliferation in vivo, consistent with the results obtained from silencing the expression of YY1 in lung cancer cells. Collectively, our study showed a critical role of YY1 in the regulation of tumorigenesis, partly through its downstream target PVT1.

Inhibition of Skp2 sensitizes lung cancer cells to paclitaxel.

S-phase kinase-associated protein 2 (Skp2) is an E3 ubiquitin ligase and plays an important role in the control of cell cycle progression. Skp2 is upregulated in several cancers, including lung cancers, but the role of Skp2 in the tumorigenesis and anticancer drug resistance in human lung cancer remains to be determined. We report here that Skp2 positively regulated mitotic arrest deficient 2 (MAD2) expression and that inhibition of Skp2 sensitizes human lung cancer cells to paclitaxel. Knockdown of Skp2 by small interfering RNA (siRNA) decreased Mad2 messenger RNA (mRNA) and protein levels in A549 and NCI-H1975 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb). In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while it decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression and prevented the increase of Mad2 expression by Skp2. Most importantly, pharmacological inhibition of Skp2 sensitized A549 and NCI-H1299 cells to paclitaxel. Our results demonstrated that SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway and that inhibition of Skp2 sensitizes A549 and NCI-H1299 cells to paclitaxel, suggesting that small molecule inhibitors of Skp2 are potential agents for the treatment of lung cancer with upregulation of Skp2.

Upregulated lncRNA H19 promotes non-small cell lung cancer cell proliferation through miR-138/PDK1 axis.

Long non-coding RNA (lncRNA) H19 was reported to be aberrantly expressed and implicated in non-small cell lung cancer (NSCLC). However, the regulation of NSCLC progression by H19 was not well understood. In this study, we found that the expression level of H19 was obviously increased, but miR-138 was decreased in NSCLC tissues and NSCLC cells including A549, H1299 and H460 cells. Upregulation of H19 promotes cell proliferation ability in A549 and H460 cells, while downregulation of H19 did the opposite. H19 represses miR138 expression and H19 expression level was negatively correlated with miR-138 expression level in NSCLC tissues. Moreover, overexpression of mutant H19 (Mut-H19) has no effect on miR-138 expression in A549 and H460 cells. Dual luciferase reporter assay showed that PDK1 was a target gene of miR-138. Overexpression of H19 attenuated the inhibitory effect of miR-138 on PDK1 protein expression. The inhibition of NSCLC cell proliferation induced by H19 knockdown required the activity of miR-138, and could be reversed by overexpression of PDK1. Overall, we concluded that H19 upregulates the expression of PDK1 through downregulation of miR-138 to promote NSCLC cell proliferation. H19 could potentially be employed as a therapeutic target for the treatment of NSCLC.

Uniportal video-assisted thoracoscopic anatomic segmentectomy for small-sized lung cancer.

Increasing evidences prove video-assisted thoracic surgery (VATS) segmentectomy is accepted as a valid alternative to lobectomy esp. a greater number of small lung nodules have been detected. Uniportal VATS segmentectomy for small-sized lung cancer is more challenging not only for technical issues in simple or complex uniportal segmentectomy, but also considering oncological efficacy in terms of localization, safe margin, the extent of lymph node dissection and pathological analysis. In this work, we evaluated our evolving uniportal experience, the surgical technique and decision-making of uniportal VATS segmentectomy for small-sized lung cancer.

Uniportal complete video-assisted thoracoscopic surgery lobectomy with partial pulmonary arterioplasty for lung cancer with calcified lymph node.

Now, more and more complete video-assisted thoracoscopic surgery (cVATS) surgeons are capable of performing lobectomy by uniportal approach. However, concerns regarding the safety of uniportal procedures for complex cases such as neoadjuvant chemotherapy, bronchial sleeves or vascular reconstructions still remains. As experience with uniportal VATS has increased, its application toward more technically demanding operations has also expanded. This article describes a uniportal cVATS left upper lobectomy with partial pulmonary arterioplasty for lung cancer with calcified lymph nodes. In order to reduce the risk of bleeding, we looped the left main pulmonary artery and applied two-stage maneuvering for left upper lobe (LUL) bronchus, cut the bronchus at the distal end and close the stump using a stapler at the end, which are conducive to maximal safety.

[A study on the relationship between single nucleotide polymorphisms of interleukin-22 and susceptibility to pulmonary tuberculosis].

OBJECTIVE: To study the association between single nucleotide polymorphisms (SNPs) of interleukin-22 (IL-22) gene and pulmonary tuberculosis. METHODS: From January 2009 to December 2010, clinical data of 479 patients with pulmonary tuberculosis in Shenzhen Third People's Hospital were collected. There were 212 males, and 267 females, aging from 18 to 69 (mean 36 ± 17) years, as well as 358 healthy controls (162 males and 196 females), aging from 18 to 60 (mean 34 ± 13) years. The genotype of SNPs (rs1182844, rs2227473, rs2227476, rs2227480, rs2227485, rs2227508) in IL-22 gene were determined with MassARRAY assay, after Hardy-Weinberg equilibrium test, and the allelic frequency and odds ratio were calculated. Peripheral blood mononuclear cells (PBMCs) from patients with different rs2227473 genotypes were stimulated with anti-CD3 and CD28, and then the IL-22 concentration in supernatant was determined with ELSIA. The SNP allelic frequencies between 2 groups were analyzed by chi-square and IL-22 concentration by t-test. RESULTS: The frequency of allele G of rs2227473 SNP was significantly higher in tuberculosis group than that in the control group (χ(2) = 7.448, P < 0.01, OR = 1.509, 95%CI= 1.121 - 2.030). The other 5 SNPs allele frequency were not statistically significant between the 2 groups (χ(2) = 0.528 - 3.571, all P > 0.05). The secretion of IL-22 was significantly lower in PBMCs with genotype GG of rs2227473 SNP as compared to that in the others (GA/AA) (t = 2.686, P < 0.01). CONCLUSIONS: The results suggested that the rs2227473 SNP in IL-22 was associated with the risk of pulmonary tuberculosis. The allele G was the risk factor of pulmonary tuberculosis. The SNP (rs2227473) may play an important role in the protective immune process against tuberculosis by affecting the IL-22 expression of PBMCs.