Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: The pathogenic variants responsible for Birt-Hogg-Dubé syndrome (BHDS) in folliculin (FLCN) gene mostly consist of point mutations. Although large intragenic deletions/duplications have been reported in several case reports, the relationship between large intragenic deletions/duplications and phenotype in BHDS remains unclear. METHODS: We retrospectively identified and reviewed patients with a large intragenic deletion spanning exons 1-3 and analyzed their phenotypic features to compare with those of point mutation carriers in our hospital from January 1, 2017 to August 31, 2022. RESULTS: Twenty unique point mutations (including 4 novel mutations) were detected in 62 patients from 45 families (90%). Exons 1-3 deletion were identified in 8 patients from 5 families (10%) that resided in the same region, Feidong County of Anhui Province, China. Breakpoint analysis indicated that all the deletion breakpoints were flanked by Alu repeats. The prevalence of exons 1-3 deletion carriers in Feidong County was 8.1-times higher than that for BHDS in Anhui Province, suggesting a clustered phenomenon of exons 1-3 deletion. Significantly increased risk of pneumothorax was observed in those with exons 1-3 deletion compared with point mutations (91% vs. 58%, p value 0.047). The risk of renal cancer may be higher in those with exons 1-3 deletion than for those with point mutations (18% vs. 4%, p > 0.05). CONCLUSIONS: Large intragenic deletion of exons 1-3 in FLCN was identified as a local aggregation phenomenon in Feidong County, China, and was associated with a significantly higher risk of pneumothorax compared to those with point mutations.

Birt-Hogg-Dubé syndrome encountered at rare lung disease clinic in Anhui province, China.

BACKGROUND: Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China. METHODS: After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021. RESULTS: There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far. CONCLUSIONS: Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.

SQM-LRU: A Harmony Dual-Queue Management Algorithm to Control Non-Responsive LTF Flow and Achieve Service Differentiation.

The increase in network applications diversity and different service quality requirements lead to service differentiation, making it more important than ever. In Wide Area Network (WAN), the non-responsive Long-Term Fast (LTF) flows are the main contributors to network congestion. Therefore, detecting and suppressing non-responsive LTF flows represent one of the key points for providing data transmission with controllable delay and service differentiation. However, the existing single-queue management algorithms are designed to serve only a small number of applications with similar requirements (low latency, high throughput, etc.). The lack of mechanisms to distinguish different traffic makes it difficult to implement differentiated services. This paper proposes an active queue management scheme, namely, SQM-LRU, which realizes service differentiation based on Shadow Queue (SQ) and improved Least-Recently-Used (LRU) strategy. The algorithm consists of three essential components: First, the flow detection module is based on the SQ and improved LRU. This module is used to detect non-responsive LTF flows. Second, different flows will be put into corresponding high or low priority sub-queues depending on the flow detection results. Third, the dual-queue adopts CoDel and RED, respectively, to manage packets. SQM-LRU intends to satisfy the stringent delay requirements of responsive flow while maximizing the throughput of non-responsive LTF flow. Our simulation results show that SQM-LRU outperforms traditional solutions with significant improvement in flow detection and reduces the delay, jitter, and Flow Completion Time (FCT) of responsive flow. As a result, it reduced the FCT by up to 50% and attained 95% of the link utilization. Additionally, the low overhead and the operations incur O(1) cost per packet, making it practical for the real network.

MiR-34c regulates the proliferation and apoptosis of lung cancer cells.

PURPOSE: As miR-34c acts as a tumor suppressant for multiple cancers, the purpose of this study was to investigate that role that miR-34c plays in the proliferation and apoptosis of lung cancer. METHODS: The expression of miR-34c in 600 patients with lung cancer was quantitatively analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology and correlated to clinical pathological parameters. The CCK-8 analysis and flow cytometry were carried out to detect cell proliferation and apoptosis in miR-34c-mimic transfected cell lines. Moreover, the regulation of miR-34c to interleukin-6 (IL-6) in cell lines was detected by western blot, qRT-PCR and dual-luciferase reporter assay. RESULTS: The expression of miR-34c was downregulated in lung cancer compared with adjacent normal tissues. The expression level of miR-34c was linked to stromal invasion. Furthermore, overexpressing miR-34c played an active role in effectively inhibiting cell proliferation and inducing apoptosis. In addition, a significant inverse relationship was exhibited between the expression of miR-34c and IL-6 in tumor tissues. CONCLUSION: At the molecular level, IL-6 can be used as a direct target of miR-34c in the treatment of lung cancer cells and miR-34c can be used as an effective biomarker and therapeutic target for lung cancer.

Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age.

BACKGROUND Lung cancer has become a leading disease for the tumor-induced mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The present research aimed to evaluate the correlation between the anaplastic lymphoma kinase/oncogene or c-ros oncogene 1 (ALK/ROS1) fusions or mutations of epidermal growth factor receptor (EGFR) and ages or gender of patients. MATERIAL AND METHODS Among 1449 NSCLC patients, 457 patients who were diagnosed as consecutive EGFR mutations or ALK/ROS1 fusions between November 2016 and February 2018 were involved in the present study. EGFR genes or ALK/ROS1 mutations were detected by using DNA sequencing technique and amplification-refractory mutation system (ARMS). The mRNAs of ROS1 and ALK fusion were examined by using polymerase chain reaction technique and fusion gene detection kit. RESULTS Females were more often inflicted by the EGFR mutations, especially for the exon 19 deletion and L858R mutation. There were significantly more ALK/ROS1 fusions in females compared to males (P<0.05) and significantly more ALK/ROS1 fusions in <60 years of age patients compared to patients older than 60 years of age (P<0.05). Exon 21 L858R and L861Q dominantly occurred in patients ≥60 years of age and exon 19 deletion in patients <60 years of age. EML-ALK-1 mainly existed in the female NSCLC patients. CONCLUSIONS EGFR mutations and ALK/ROS1 fusions mainly occurred in the NSCLC female patients who were older than 60 years of age.

Histone deacetylase inhibitor SAHA-induced epithelial-mesenchymal transition by upregulating Slug in lung cancer cells.

SAHA, a member of histone deacetylase inhibitors (HDACIs), which emerged as a class of novel antitumor drug, has been used in clinical treatment of cancers. However, clinical experience of SAHA in solid tumors has been disappointing. Nevertheless, the underlying mechanism of this deficiency is not clearly understood. In the present study, we found that SAHA could induce epithelial-mesenchymal transitions (EMT) in lung cancer A549 cells, which was associated with increased migration capability and cellular morphology changes. We showed that SAHA decreased epithelial marker E-cadherin's expression and increased the expression of mesenchymal marker vimentin. SAHA upregulated the protein and mRNA expression of transcription factor Slug in a time-dependent manner and promoted its nuclear translocation. We further demonstrated that SAHA upregulated Slug expression by promoting Slug acetylation but not influencing the phosphorylation of GSK-3ß, a main kinase-controlled Slug expression. Finally, silencing of Slug by siRNA reversed EMT marker expressions and cellular morphology change induced by SAHA, suggesting that Slug plays a crucial role in SAHA-mediated EMT in A549 cells. Our research study provided a better understanding of treatment failure of SAHA in patients with solid tumors. Therefore, more attention should be paid to cancer treatment using SAHA and strategies for reversing EMT before using SAHA would be better if the value of SAHA in the treatment of solid tumors, especially lung cancer, is realized.

[Establishment of A Clinical Prediction Model of Prolonged Air Leak 
after Anatomic Lung Resection].

BACKGROUND: Prolonged air leak (PAL) after anatomic lung resection is a common and challenging complication in thoracic surgery. No available clinical prediction model of PAL has been established in China. The aim of this study was to construct a model to identify patients at increased risk of PAL by using preoperative factors exclusively. METHODS: We retrospectively reviewed clinical data and PAL occurrence of patients after anatomic lung resection, in department of thoracic surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, from January 2016 to October 2016. 359 patients were in group A, clinical data including age, body mass index (BMI), gender, smoking history, surgical methods, pulmonary function index, pleural adhesion, pathologic diagnosis, side and site of resected lung were analyzed. By using univariate and multivariate analysis, we found the independent predictors of PAL after anatomic lung resection and subsequently established a clinical prediction model. Then, another 112 patients (group B), who underwent anatomic lung resection in different time by different team, were chosen to verify the accuracy of the prediction model. Receiver-operating characteristic (ROC) curve was constructed using the prediction model. RESULTS: Multivariate Logistic regression analysis was used to identify six clinical characteristics [BMI, gender, smoking history, forced expiratory volume in one second to forced vital capacity ratio (FEV1%), pleural adhesion, site of resection] as independent predictors of PAL after anatomic lung resection. The area under the ROC curve for our model was 0.886 (95%CI: 0.835-0.937). The best predictive P value was 0.299 with sensitivity of 78.5% and specificity of 93.2%. CONCLUSIONS: Our prediction model could accurately identify occurrence risk of PAL in patients after anatomic lung resection, which might allow for more effective use of intraoperative prophylactic strategies.
.

Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomsis.

We retrospectively analyzed the clinical data of 112 patients who underwent esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity from October 2011 to June 2013. First, the gastric tube was created with the aid of linear stapling device by removing the stomach and dissecting lymph nodes under laparoscopy and making a 3-4 cm incision through the subxiphoid area in the upper abdomen. Second, the thoracic esophagus and lymph nodes were dissected during thoracoscopic procedure. Gastric tube was inserted into the chest cavity and placed in the posterior mediastinum. The thoracic gastro-esophageal anastomosis was stapled with a circular stapler. Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis is technically feasible and safe, with minimized trauma, less operative blood loss and quick recovery.