Augmented fluoroscopy-guided dye localization for small pulmonary nodules in hybrid operating room: intrathoracic stamping versus transbronchial marking.

PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.

[Modern research progress in external application of traditional Chinese medicine to acupoints].

Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.

Novel Inflammasome-Based Risk Score for Predicting Survival and Efficacy to Immunotherapy in Early-Stage Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICI) for early-stage non-small cell lung cancer (NSCLC) have been approved to improve outcomes and reduce recurrence. Biomarkers for patient selection are needed. In this paper, we proposed an inflammasome-based risk score (IRS) system for prognosis and prediction of ICI response for early-stage NSCLC. Cox regression analysis was used to identify significant genes (from 141 core inflammasome genes) for overall survival (OS) in a microarray discovery cohort (n = 467). IRS was established and independently validated by other datasets (n = 1320). We evaluated the inflammasome signaling steps based on five gene sets, which were IL1B-, CASP-1-, IL18-, GSDMD-, and inflammasome-regulated genes. Gene set enrichment analysis, the Kaplan-Meier curve, receiver operator characteristic with area under curve (AUC) analysis, and advanced bioinformatic tools were used to confirm the ability of IRS in prognosis and classification of patients into ICI responders and non-responders. A 30-gene IRS was developed, and it indicated good risk stratification at 10-year OS (AUC = 0.726). Patients were stratified into high- and low-risk groups based on optimal cutoff points, and high-risk IRS had significantly poorer OS and relapse-free survival. In addition, the high-risk group was characterized by an inflamed immunophenotype and higher proportion of ICI responders. Furthermore, expression of SLAMF8 was the key gene in IRS and indicated good correlation with biomarkers associated with immunotherapy. It could serve as a therapeutic target in the clinical setting of immunotherapy.

FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis.

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.

Protective Effect of Statins on Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease Patients: A Nationwide Retrospective, Matched Cohort Study.

In Taiwan, patients with pulmonary hypertension (PH) related to chronic obstructive pulmonary disease (COPD) are most common PH population (group 3). However, efficacy of medical treatments and optimal prevention methods in this group remain uncertain. Statins such as indirect RhoA/Rho-kinase inhibitors influence one of key signalling pathways that promote PH onset. In this study, we explored protective effects of statins against PH in COPD patients using database from Taiwan National Health Insurance programme from 2002 to 2017. The main outcome was the risk of PH. The Cox proportional-hazards model and the Fine and Gray model were used to adjust covariate and competing risks to estimate the subdistribution hazard ratios (sHRs). 553,617 newly diagnosed COPD patients were stratified by statin users (n = 41,168) and statin nonusers (n = 512,449). After 1:1 propensity score matching of statin users (n = 41,163), and 41,163 statin nonusers were included for outcome analysis. Statin users had a 22% lower risk of PH than nonusers (sHR: 0.78, 95% confidence interval: 0.65-0.94). During subgroup analysis, taking higher daily doses and for a longer duration displayed a more significantly reduced risk of PH (both P for trend <0.001). Statins may have a protective effect against PH that is dose- and time-dependent.

Statins for the Treatment of Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk for pulmonary hypertension (PH). The aim of our study was to investigate the benefit of statins for PH in patients with COPD. Methods: The study enrolled 23 million individuals from Taiwan's population database from January 1, 2002, to December 31, 2017. COPD patients who met the inclusion criteria were enrolled, and patients with lung cancer, less than one year of observation, specific drug therapy for PH and lung transplantation were excluded. Results: A total of 643,131 COPD patients were included in the study, and only 12,308 patients developed PH during follow-up. Based on the inclusion and exclusion criteria, 8,577 PH patients were included in the cohort of patients with PH related to COPD for analysis. According to the definition of statin exposure, the final study population had 1,487 statin users and 7,090 statin non-users. The statin user group had a lower mortality related to PH than the non-user group (3.87 vs. 5.55 per 100 person-years, p < 0.001). The mortality rate for PH in the multivariate analysis (aHR = 0.78, 95% CI = 0.62-0.98, p = 0.046) was significantly lower for statin users than for non-users. Conclusion: Statins seem to benefit patients with PH and COPD.

[Pharmaceutics research advances in oral administration of puerarin].

Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.

Needlescopic-assisted uniportal video-assisted thoracoscopic pulmonary anatomical segmentectomy.

BACKGROUND: Pulmonary segmentectomy can be an oncologic equivalent of lobectomy for small non-small cell lung cancer. Uniportal video-assisted thoracoscopic surgery (VATS) has recently showed favorable surgical outcomes, but remains technical demanding, especially in a complex procedure like anatomic segmentectomy. This manuscript demonstrates the surgical techniques for uniportal VATS segmentectomies with the assistance of additional needlescopic instruments. METHODS: Data of 22 consecutive patients who underwent 24 needlescopic-assisted uniportal VATS segmentectomies between December 2016 and June 2017 was analyzed. RESULTS: There were 12 uni-segmentectomies, 10 bi-segmentectomies, and 2 tri-segmentectomies. The mean operation time was 178.3 minutes. The mean duration of chest tube drainage was 5.2 days, and the mean duration of hospital stay was 7.4 days. There were two episodes of major bleeding and one case that required conversion to lobectomy. CONCLUSIONS: Under the assistance of additional needlescopic instruments, segmentectomy can be performed more easily and safely with uniportal VATS.

Lacking of palladin leads to multiple cellular events changes which contribute to NTD.

BACKGROUND: The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects. However, the mechanism how palladin regulates the process of cranial neural tube closure (NTC) remains unknown. METHODS: In this paper, we use gene knockout mouse to elucidate the function of palladin in the regulation of NTC process. RESULTS: We initially focuse on the expression pattern of palladin and found that in embryonic brain, palladin is predominantly expressed in the neural folds at E9.5. We further check the major cellular events in the neural epithelium that may contribute to NTC during the early embryogenesis. Palladin deficiency leads to a disturbance of cytoskeleton in the neural tube and the cultured neural progenitors. Furthermore, increased cell proliferation, decreased cell differentiation and diminished apical cell apoptosis of neural epithelium are found in palladin deficient embryos. Cell cycle of neural progenitors in Palladin -/- embryos is much shorter than that in wt ones. Cell adhesion shows a reduction in Palladin -/- neural tubes. CONCLUSIONS: Palladin is expressed with proper spatio-temporal pattern in the neural folds. It plays a crucial role in regulating mouse cranial NTC by modulating cytoskeleton, proliferation, differentiation, apoptosis, and adhesion of neural epithelium. Our findings facilitate further study of the function of palladin and the underlying molecular mechanism involved in NTC.

[Report on induction efficacy of protocol ALL-2005 and middle term follow-up of 158 cases of childhood acute lymphoblastic leukemia].

OBJECTIVE: To reduce the risk of infection during the induction therapy while to ensure remission rates, and to evaluate the protocol ALL-2005. METHODS: The minimal residual disease (MRD) was detected by flow cytometry on day 35 and 55 of induction therapy. The efficacy of induction and the clinic grouping were evaluated by MRD level. From May 1, 2005 to April 30, 2007, 158 children with newly diagnosed ALL were enrolled in this study. According to clinic grouping criteria of ALL-2005, patients were stratified into 3 groups: low-risk( LR), intermediate-risk (MR) and high-risk (HR). The remission rates, therapy related complication during induction, and the relationship between MRD level on day 35 and 55 of induction and prognosis were analyzed. The endpoints are disease-free survival (DFS), relapse and death of any cause. Patients lost to follow-up were censored at the time of their withdrawal. RESULTS: Of the 158 patients, 59 were LR, 93 MR and 6 HR. The CR rate on day 35 was 98.1%. There were detectable MRD in 139 (88.0%) patients. In 94 patients (68.6%) MRDs were < or = 0.01% on day 35 being 73.1% (49/67) for LR and 63.4% (45/71) for MR (P = 0.219). During induction therapy, 43 patients (27.2%) developed infection and among them 1.3% (2/158) suffered serious infection and 0.6% (1/158) died of complication. Four patients (2.5%) in CR were lost follow-up, 17 patients (10.8%) relapsed, including 4 patients (4.3%) with MRD < or = 0.01% and 10 (23.3%) >0.01% on day 35 (P = 0.003). One died of severe malnutrition and infection in CR. With a median follow-up of 20 (12-35) months, the estimated 30 month DFS for whole group was (81.6 +/- 4.5)% including (94.1 +/- 3.3)% for LR, (82.8 +/- 4.4)% for MR, and (91.0 +/- 5.4)% for MRD < or = 0.01%, (67.1 +/- 9.5)% for MRD >0.01% on day 35 and (89.1 +/- 5.3)% for MRD < or = 0.01% and (46.9 +/- 15.6)% for MRD >0.01% on day 55. CONCLUSION: The risk of infection and therapy related death during induction with protocol ALL-2005 are lower, while the remission rate and quality of the induction are better. Longer follow-up is needed to estimate the long-term result.