ARID1A loss induces P4HB to activate fibroblasts to support lung cancer cell growth, invasion, and chemoresistance.

Loss of AT-interacting domain-rich protein 1A (ARID1A) frequently occurs in human malignancies including lung cancer. The biological consequence of ARID1A mutation in lung cancer is not fully understood. This study was designed to determine the effect of ARID1A-depleted lung cancer cells on fibroblast activation. Conditioned media was collected from ARID1A-depleted lung cancer cells and employed to treat lung fibroblasts. The proliferation and migration of lung fibroblasts were investigated. The secretory genes were profiled in lung cancer cells upon ARID1A knockdown. Antibody-based neutralization was utilized to confirm their role in mediating the cross-talk between lung cancer cells and fibroblasts. NOD-SCID-IL2RgammaC-null (NSG) mice received tumor tissues from patients with ARID1A-mutated lung cancer to establish patient-derived xenograft (PDX) models. Notably, ARID1A-depleted lung cancer cells promoted the proliferation and migration of lung fibroblasts. Mechanistically, ARID1A depletion augmented the expression and secretion of prolyl 4-hydroxylase beta (P4HB) in lung cancer cells, which induced the activation of lung fibroblasts through the ß-catenin signaling pathway. P4HB-activated lung fibroblasts promoted the proliferation, invasion, and chemoresistance in lung cancer cells. Neutralizing P4HB hampered the tumor growth and increased cisplatin cytotoxic efficacy in two PDX models. Serum P4HB levels were higher in ARID1A-mutated lung cancer patients than in healthy controls. Moreover, increased serum levels of P4HB were significantly associated with lung cancer metastasis. Together, our work indicates a pivotal role for P4HB in orchestrating the cross-talk between ARID1A-mutated cancer cells and cancer-associated fibroblasts during lung cancer progression. P4HB may represent a promising target for improving lung cancer treatment.

Preoperative risk factors for prolonged length of stay after bullectomy: A single-center retrospective study.

Objective: Prolonged length of stay (LOS) increases the economic burden on patients, therefore, optimizing LOS is a critical clinical challenge for physicians. This study aims to examine the correlation between the postoperative LOS and surgery-related adverse events after bullectomy. We defined prolonged postoperative LOS after bullectomy and analyzed the preoperative risk factors linked to prolonged LOS. Methods: In this retrospective study, we analyzed patient data from thoracoscopic bullectomy performed at our hospital between January 2018 and December 2023. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off values defining prolonged LOS after bullectomy. It was then characterized as prolonged LOS. Patients were divided into prolonged and normal LOS groups based on their postoperative duration. Further, univariate and multivariate logistic regression analyses were performed to identify preoperative risk factors associated with prolonged postoperative LOS after bullectomy. Results: Among the 152 patients analyzed, binary logistic regression revealed a significant effect of surgery-related adverse events after bullectomy on the LOS (P < 0.001). A postoperative LOS exceeding 3 days was considered prolonged. Among the 152 patients, 38.2 % (58/152) experienced a prolonged LOS out of which 20.4 % (31/152) developed surgery-related adverse events. Multivariate regression analysis revealed that preoperative risk factors associated with prolonged LOS included age ≥60 years (OR = 3.052, 95%CI 1.226-7.586, P = 0.016), current smoking status (OR = 2.754, 95%CI 1.482-6.346, P = 0.025), and ASA grade 3 (OR = 4.783, 95%CI 2.356-9.131, P = 0.003). Conclusion: In summary, the postoperative length of stay beyond 3 days after bullectomy was considered prolonged. The preoperative risk factors associated with prolonged postoperative stays after bullectomy included age (over 60), current smoking, and grade 3 ASA. Therefore, quick identification and intervention in patients with these high-risk factors may promote rapid recovery.

V6 vein-preserving superior segmentectomy: A potentially preferable option.

Objective: The increasing identification of pulmonary nodules has led to a growing emphasis on segmentectomy. Nevertheless, the surgical process for segmentectomy is complex and optimizing segmentectomy is a critical clinical concern. This study aimed to evaluate the safety and short- and long-term efficacy of V6-preserving superior segmentectomy. Methods: We performed a retrospective analysis of patients who underwent thoracoscopic superior segmentectomy at our hospital between January 2019 and June 2020. Eligible patients were categorized into an V6 vein-preserving segmentectomy (VVPS) group and a Non V6 vein-preserving segmentectomy (NVVPS) group depending on the preservation of V6. Primary outcome measures encompassed the evaluation of surgical safety (surgical margins, 3-year overall survival, and disease-free survival), whereas secondary measures included postoperative complication rates, operative time, estimated intraoperative blood loss, length of hospital stay, and associated costs. Results: The analysis included a final cohort of 78 patients. In the NVVPS group (n = 43), 95.3 % of patients exceeded the tumor diameter, and no positive surgical margins were observed. The 3-year overall survival (OS) and disease-free survival (DFS) rates for the NVVPS group were 95.3 %, with no significant differences in OS (p = 0.572) and DFS (P = 0.800) compared with the VVPS group. Additionally, the median total hospitalization cost for the NVVPS group was 41,400 RMB (IQR, 38,800-43,400), which was significantly lower than that of the VVPS group, showing statistical significance (P < 0.05). No statistically significant differences were observed in the incidence of postoperative complications and length of stay between the two groups (P > 0.05). Conclusion: V6-preserving superior segmentectomy is a secure and optimized surgical alternative. Its streamlined procedure facilitates easier adoption in primary healthcare facilities, rendering it a superior choice for superior segmentectomy.

PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1.

Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression Omnibus (GEO) datasets that contain RNA sequencing data from ARID1A-depleted cancer cells. PLAU was identified as a common gene that was induced in different cancer cells upon ARID1A depletion. Overexpression of PLAU positively modulated NSCLC cell growth, colony formation, cisplatin resistance, and survival under serum deprivation. Moreover, enforced expression of PLAU enhanced tumorigenesis of NSCLC cells in nude mice. Mechanistically, PLAU interacted with TM4SF1 to promote the activation of Akt signaling. TM4SF1-overexpressing NSCLC cells resembled those with PLAU overepxression. Knockdown of TM4SF1 inhibited the growth and survival and increased cisplatin sensitivity in NSCLC cells. The interaction between PLAU and TM4SF1 led to the activation of Akt signaling that endowed ARID1A-depleted NSCLC cells with aggressive properties. In addition, treatment with anti-TM4SF1 neutralizing antibody reduced the growth, cisplatin resistance, and tumorigenesis of ARID1A-depleted NSCLC cells. Taken together, PLAU serves as a target gene of ARID1A and promotes NSCLC growth, survival, and cisplatin resistance by stabilizing TM4SF1. Targeting TM4SF1 may be a promising therapeutic strategy for ARID1A-mutated NSCLC.

Sub-axillary cosmetic incision versus single-incision thoracoscopic surgery for primary spontaneous pneumothorax.

BACKGROUND: In recent years, single-incision thoracoscopic surgery (SITS) has been increasingly applied as an optimal treatment option for primary spontaneous pneumothorax (PSP). However, most SITS techniques are used in the fourth to sixth intercostal space between the anterior axillary and mid axillary lines. To find out more concealed incisions, this study performed PSP surgery via the sub-axillary cosmetic incision (SACI) technique. METHODS: A total of 128 PSP patients were subjected to video-assisted thoracoscopic surgery (VATS) between January 2017 and January 2019 at our institution. These patients were evaluated and assigned into SACI (n = 21) and SITS (n = 57) groups. Propensity score matching (PSM) was performed based on patients' backgrounds, and the enrolled cohort was divided into 21 pairs. The incision satisfaction was assessed at 2 weeks and 6 months post-surgery. RESULTS: The 21 pairs with matching baseline characteristics in the two groups did not exhibit significant differences in their backgrounds and surgical results. However, compared with the SITS group, the operation time was longer in the SACI group (p = 0.013). There were no post-operative complications in both groups. At 2 weeks and 6 months, incision satisfaction scores in the SACI group were significantly lower than those in the SITS group (p = 0.022 and p = 0.039, respectively). There were no recurrences of ipsilateral pneumothorax in both groups. CONCLUSIONS: SACI is a safe and feasible surgical method for PSP treatment. In addition, incision concealment can be used for patients with incision needs.

Identification of preoperative risk factors associated with prolonged length of stay after lobectomy.

Objective: To examine the association between length of stay (LOS) after lobectomy and operative adverse events and define the best predictors and risk factors associated with prolonged LOS after lobectomy. Methods: Data from patients undergoing thoracoscopic lobectomy in the Thoracic Surgery Department of our center between January 2015 and December 2021 were retrospectively analyzed. The association between operative adverse events and LOS after lobectomy was explored using receiver operating characteristic (ROC) curves, and multivariate logistic regression analyses were used to identify preoperative risk factors associated with prolonged LOS after lobectomy. Results: Prolonged LOS after lobectomy was defined as a LOS after lobectomy that is > 3.5 days based on an optimal diagnostic value for operative adverse events (AUC = 0.882). Of the included patients, 20.9% (91/435) exceeded this threshold, of whom 52.7% (48/91) exhibited operative adverse events. The preoperative risk factors associated with prolonged LOS after lobectomy were age≥60 years old (OR = 9.632, 95%CI 1.126-75.66, p = 0.03), being a current smoker (OR = 2.702, 95%CI 1.547-4.72, P < 0.001), an American Society of Anesthesiology (ASA) classification of 2 or higher (OR = 1.845, 95%CI 1.06-3.211, P = 0.03), ASA = 3 (OR = 9.133, 95%CI 3.281-25.425, P < 0.001), and Stage IIIA disease (OR = 6.565, 95%CI 2.823-15.271, P < 0.001). Prolonged LOS after lobectomy was significantly associated with the incidence of different operative adverse events, including conversion to thoracotomy, an operative duration of ≥300 min, blood transfusion events, chest tube drainage time, postoperative complications, and postoperative interventions (P < 0.001). Conclusion: The risk of prolonged LOS after lobectomy is higher in patients that are ≥60 years old, current smokers, exhibit an ASA classification of 2 or higher, and have a stage IIIA disease. Early identification of these risk factors can enhance the treatment offered to high-risk patients, thereby reducing the rates of operative adverse events and optimizing resource utilization.

Lymph node metastasis risk factors in clinical stage IA3 lung adenocarcinoma.

Background: Lymph node metastasis is a poor prognostic factor for lung cancer. However, the risk of lymph node metastasis has not yet been clarified. This study was conducted to analyze the predictive factors for lymph node metastasis in patients with clinical-stage IA3 lung adenocarcinoma. Methods: We retrospectively analyzed all surgical patients with clinical stage IA3 lung adenocarcinoma admitted to our hospital from January 2017 to January 2022. Three hundred and thirty-four patients underwent lobectomy combined with systematic lymph node dissection. Univariate and multivariate logistic regression analyses were used to predict the risk factors of lymph node metastasis. Results: Of the 334 patients eligible for this study, the overall lymph node metastasis rate was 15.3%. There were 45 cases with N1 metastasis, 11 cases with N2 metastasis, and five cases with both N1 and N2 metastasis. The lymph node metastasis rate was 18.1% in patients with a consolidation tumor ratio (CTR) of >0.75, 57.9% in those with >5 ng/mL carcinoembryonic antigen (CEA), and 18.0% in those with a maximum standardized uptake value of >5. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for CTR and CEA was 0.790 [95% confidence interval (CI): 0.727-0.853, P < 0.001] and 0.682 (95% CI: 0.591-0.773, P < 0.001), respectively. According to multivariate regression analysis, CEA (>5 ng/mL) [odds ratio (OR) = 3.05, P = 0.016] and CTR (>0.75) (OR = 2.75, P = 0.025) were significantly correlated with lymph node metastasis of clinical stage IA3 lung adenocarcinoma. Conclusions: CEA (>5 ng/mL) and CTR (>0.75) are two important predictors of lymph node metastasis in patients with clinical stage IA3 lung adenocarcinoma.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

Gene Targets Network Analysis for the Revealing and Guidance of Molecular Driving Mechanism of Lung Cancer.

The objective was to explore the function of gene differential expressions between lung cancer tissues and the interaction between the relevant encoded proteins, thereby analyzing the important genes closely related to lung cancer. A total of 120 samples from the GEO database (including two groups, i.e., 60 lung cancer in situ specimens and 60 normal specimens) were taken as the research objects, which were submitted to the analysis of signaling pathway, biological function enrichment, and protein interactions to reveal the molecular driving mechanism of lung cancer. Results: A total of 875 differentially expressed genes were obtained, including 291 up-regulated genes and 584 down-regulated genes. The up-regulated genes were mainly involved in biological processes such as protein metabolism, protein hydrolysis, mitosis, and cell division. Down-regulated genes were mainly involved in neutrophil chemotaxis, inflammatory response, immune response, and angiogenesis. The protein expression of high expression genes and low expression genes in patients were higher than those in the control group. The protein corresponding to the high expression gene was highly expressed in the patient group. Meanwhile, the proteins corresponding to the low expression genes were also expressed in the patient group, which showed that although the proteins corresponding to the low expression genes were low in the patients, they were still the target genes related to lung cancer. In conclusion, the molecular driving mechanism in lung cancer was mainly related to protein metabolism, proteolysis, mitosis, and cell division. It was found that TOP2A, CCNB1, CCNA2, CDK1, and TTK might be the critical target genes of lung cancer.

Clinical Characteristics of Patients With Re-admitted of Novel Coronavirus 2019 (nCOVID-19) in Wenzhou, China.

Background: During the COVID-19 pandemic, many patients admitted to hospital for treatment have recovered and been discharged; however, in some instances, these same patients are re-admitted due to a second fever or a positive COVID-19 PCR test result. To ascertain whether it is necessary to treat these patients in hospitals, especially in asymptomatic cases, we summarize and analyze the clinical and treatment characteristics of patients re-admitted to hospital with a second COVID-19 infection. Methods: Of the 141 COVID-19 cases admitted to the Wenzhou Central Hospital between January 17, 2020, to March 5, 2020, which were followed until March 30, 2020, 12 patients were re-admitted with a second COVID-19 infection. Data was collected and analyzed from their clinical records, lab indexes, commuted tomography (CT), and treatment strategies. Results: Most of the 141 patients had positive outcomes from treatment, with only 12 (8.5%) being re-admitted. In this sub-group: one (8.3%) had a fever, a high white blood cell count (WBC), and progressive CT changes; and one (8.3%) had increased transaminase. The PCR tests of these two patients returned negative results. Another 10 patients were admitted due to a positive PCR test result, seven of which were clinically asymptomatic. Compared to the CT imaging following their initial discharge, the CT imaging of all patients was significantly improved, and none required additional oxygen or mechanical ventilation during their second course of treatment. Conclusions: The prognoses of the re-admitted patients were good with no serious cases. We conclude that home treatment with concentrated medical observation is a safe and feasible course of treatment if the patient returns a positive PCR test result but does not display serious clinical symptoms. During medical observation, patients with underlying conditions should remain a primary focus, but most do not need to be re-admitted to the hospital.

microRNA-381 suppresses the growth and increases cisplatin sensitivity in non-small cell lung cancer cells through inhibition of nuclear factor-κB signaling.

microRNA (miR)-381 is downregulated and exhibits anti-invasive activity in non-small cell lung cancer (NSCLC). In this study, we investigated the role of miR-381 in proliferation, tumorigenesis, and cisplatin resistance of NSCLC cells. The effects of miR-381 overexpression on proliferation, tumorigenesis, cell cycle progression, and cisplatin sensitivity were examined. Overexpression of miR-381 significantly inhibited cell proliferation and colony formation in vitro and tumorigenesis in vivo. Ectopic expression of miR-381 arrested NSCLC cells at G0/G1 phase, which was accompanied by increased expression of p21 and p27 and decreased expression of cyclin D1 and CDK4. Compared to A549 parental cells, cisplatin-resistant equivalents (A549/CDDP) had reduced levels of miR-381. miR-381 re-sensitized A549/CDDP cells to cisplatin and potentiated cisplatin-induced apoptosis. Mechanistically, miR-381 interfered with the activation of nuclear factor (NF)-κB through repression of inhibitor of differentiation 1 (ID1). Co-expression of ID1 reversed the suppression of proliferation and enhancement of cisplatin cytotoxicity by miR-381. Taken together, miR-381 can induce growth suppression and chemosensitization in NSCLC, largely through inactivation of NF-κB via downregulation of ID1. Restoration of miR-381 represents a potential therapeutic strategy for NSCLC.

MicroRNA-485-5p suppresses growth and metastasis in non-small cell lung cancer cells by targeting IGF2BP2.

miR-485-5p serves as a tumor suppressor in several types of cancers. However, its prognostic and biological significance in non-small cell lung cancer (NSCLC) have not been determined yet. In the present study, we checked the expression of miR-485-5p in 87 pairs of paraffin-embedded lung cancer and matched non-cancerous specimens. The associations of miR-485-5p expression with aggressive parameters and survival in NSCLC were investigated. In addition, the function of miR-485-5p in controlling tumor growth and metastasis was clarified. We found that miR-485-5p was significantly downregulated in NSCLC, relative to adjacent non-cancerous lung tissues. Low miR-485-5p expression was significantly associated with advanced TNM stage, lymph node metastasis, and reduced patient survival. Overexpression of miR-485-5p significantly suppressed the growth and invasion, while knockdown of miR-485-5p had an opposite effect. Moreover, miR-485-5p overexpression caused a G0/G1 cell-cycle arrest and impaired TGF-ß-induced epithelial-mesenchymal transition. Mechanistically, IGF2BP2 was identified as a novel direct target of miR-485-5p. Depletion of IGF2BP2 significantly inhibited NSCLC cell proliferation and invasion. Enforced expression of IGF2BP2 reversed the tumor suppressive activity of miR-485-5p. In vivo studies further demonstrated that overexpression of miR-485-5p interfered with the growth and metastasis of A549 cells in mice and reduced the expression of IGF2BP2. In conclusion, low miR-485-5p expression predicts poor prognosis in NSCLC patients. The miR-485-5p/IGF2BP2 axis orchestrates the growth and metastasis of NSCLC and represents a potential therapeutic target for this disease.