Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues. We achieved a conjugation efficiency exceeding 98 % using a cosolvent system, with subsequent ester bond cleavage releasing the active Dex, as verified by liquid chromatography. Biodistribution and cellular uptake studies indicated the potential of the HA conjugate for cluster of differentiation 44 (CD44)-mediated targeting and accumulation. In a lipopolysaccharide-induced ALI mouse model, intravenous (IV) HA-Dex administration showed superior anti-inflammatory effects compared to free Dex administration. Flow cytometry analysis suggested that the HA conjugate preferentially accumulated in lung macrophages, suggesting the possibility of reducing clinical Dex dosages through this targeted delivery approach.

Plasma Cytokines Pattern as a Prognostic Marker for Esophageal Squamous Cell Carcinoma via Unsupervised Clustering Analyses.

INTRODUCTION: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed. RESULTS: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines. CONCLUSIONS: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

PURPOSE: Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. METHODS: The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. RESULTS: Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1ß in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. CONCLUSION: Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Corrigendum: Safety assessment of poly-ε-caprolactone in the treatment of primary spontaneous pneumothorax.

[This corrects the article DOI: 10.3389/fsurg.2024.1335144.].

Evaluating postoperative recovery in uniportal versus needlescopic video-assisted thoracoscopic surgery for primary spontaneous pneumothorax: a comparable study.

Objectives: Primary spontaneous pneumothorax (PSP) is a common disease in young and thin male. Operation has been regarded as definitive treatment for it. However, the operative methods for those patients are under dispute. This study aims to directly compare the outcomes of uniportal VATS vs. needlescopic VATS in the treatment of PSP, focusing on postoperative pain and safety outcomes. Methods: From July 2013 to December 2017, the patients who underwent video-assisted thoracic surgery for pneumothorax in National Taiwan University Hospital were retrospectively collected. The preoperative condition, surgical results, and postoperative outcomes was analyzed. Results: There were 60 patients undergoing needlescopic VATS and 91 undergoing uniportal VATS during the study period. There was no significant difference between the patients who underwent needlescopic VATS and those who underwent uniportal VATS in their demographic and clinical characteristics. The post-operative pain score was significantly lower in the uniportal VATS group compared to the needlescopic VATS group at day 1 (2.65 ± 1.59 vs. 1.74 ± 1.35, p = 0.001). Conclusion: Uniportal VATS offers an effective, safe alternative for PSP treatment, with benefits including reduced post-operative pain. Our findings support the use of uniportal VATS, supplemented by a wound protector, as a viable option for PSP patients.

Mechanical and biological properties of poly-ε-caprolactone membrane for pleurodesis: A preclinical study in pigs.

BACKGROUND/PURPOSE: Biomaterial implants are emerging as a treatment choice for pleurodesis; however, the optimal biomaterial and form for managing spontaneous pneumothorax, particularly post-video-assisted thoracic surgery, remain under investigation. This study evaluated the mechanical and biological properties of the poly-ε-caprolactone (PCL) membrane as a sclerosing agent for pleurodesis in Landrace pigs. METHODS: Twenty-four Landrace pigs were split into two groups for mechanical abrasion and PCL membrane pleurodesis, with the latter group's PCL meshes inserted using video-assisted thoracic surgery. The mechanical and biological properties of the PCL membrane were assessed in pigs at three, six, and 12 months after the procedure. This assessment involved a range of techniques, such as the T-Peel test, macroscopic evaluation with a scoring scale, microscopic examination, and biomechanical and molecular weight analysis. RESULTS: The PCL membrane group outperformed the traditional abrasion group, with stronger adhesions seen over longer implantation durations. This group also showed superior and more consistent results in both macroscopic and microscopic evaluations compared to the control group. The membrane-based method was easier and faster to perform than the control group's method, and importantly, no mortality occurred following membrane implantation. CONCLUSION: This study is the pioneering effort to present long-term findings regarding the mechanical and biological properties of the PCL membrane in an in vivo animal model. The membrane demonstrated better adhesion ability than that of traditional abrasion and showed reassuring biocompatibility in both the pig model, suggesting its potential as treatment for patients with primary spontaneous pneumothorax. Further clinical studies are needed to support these observations.

Safety assessment of poly-ε-caprolactone in the treatment of primary spontaneous pneumothorax.

Background/purpose: Biomaterial-based implants are gaining traction as an option for pleurodesis treatment, yet the search for the best biomaterial or the most suitable shape to handle spontaneous pneumothorax continues. This forward-looking research assessed the use of a poly-ε-caprolactone membrane for its safety when applied as a sclerosant in pleurodesis procedures in human patients. Methods: From July 2017 to February 2018, we conducted a Phase I trial in which 10 patients with primary spontaneous pneumothorax were treated using video-assisted thoracoscopic surgery with a poly-ε-caprolactone membrane. These procedures encompassed bleb resection and mechanical pleurodesis through parietal pleura scrubbing. After resection, a 150 × 150 mm poly-ε-caprolactone membrane was applied to the apex. The primary outcome measures were the adverse events and laboratory outcomes. Results: After surgery, we observed no cardiopulmonary-related adverse events or indications of systemic inflammation. Furthermore, no episodes of hypothermia or hyperthermia occurred. Chest radiographs showed no evident pneumonitis or effusion associated with tissue reactions. The average follow-up duration was 31.7 ± 17.7 months, during which two patients exhibited recurrence. Conclusion: This study is the first to show the biocompatibility of poly-ε-caprolactone in humans, suggesting its potential as a treatment option for patients with primary spontaneous pneumothorax. Despite the relatively small number of patients, we maintain confidence in the reliability and safety profile of the PCL membrane, bolstered by its previously established efficacy in applications involving other organs. Phase II and phase III clinical studies are needed to support these observations.

Advancing accuracy in breath testing for lung cancer: strategies for improving diagnostic precision in imbalanced data.

BACKGROUND: Breath testing using an electronic nose has been recognized as a promising new technique for the early detection of lung cancer. Imbalanced data are commonly observed in electronic nose studies, but methods to address them are rarely reported. OBJECTIVE: The objectives of this study were to assess the accuracy of electronic nose screening for lung cancer with imbalanced learning and to select the best mechanical learning algorithm. METHODS: We conducted a case‒control study that included patients with lung cancer and healthy controls and analyzed metabolites in exhaled breath using a carbon nanotube sensor array. The study used five machine learning algorithms to build predictive models and a synthetic minority oversampling technique to address imbalanced data. The diagnostic accuracy of lung cancer was assessed using pathology reports as the gold standard. RESULTS: We enrolled 190 subjects between 2020 and 2023. A total of 155 subjects were used in the final analysis, which included 111 lung cancer patients and 44 healthy controls. We randomly divided samples into one training set, one internal validation set, and one external validation set. In the external validation set, the summary sensitivity was 0.88 (95% CI 0.84-0.91), the summary specificity was 1.00 (95% CI 0.85-1.00), the AUC was 0.96 (95% CI 0.94-0.98), the pAUC was 0.92 (95% CI 0.89-0.96), and the DOR was 207.62 (95% CI 24.62-924.64). CONCLUSION: Electronic nose screening for lung cancer is highly accurate. The support vector machine algorithm is more suitable for analyzing chemical sensor data from electronic noses.

Panax quinquefolius polysaccharides ameliorate ulcerative colitis in mice induced by dextran sulfate sodium.

This study aimed to investigate the ameliorative effect of the polysaccharides of Panax quinquefolius (WQP) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice and to explore its mechanism. Male C57BL/6J mice were randomly divided into the control group (C), model group (DSS), positive control mesalazine (100 mg/kg, Y) group, and low (50 mg/kg, L), medium (100 mg/kg, M) and high dose (200 mg/kg, H) of WQP groups. The UC model was induced by free drinking water with 2.5% DSS for 7 days. During the experiment, the general condition of the mice was observed, and the disease activity index (DAI) was scored. The conventional HE staining was used to observe pathological changes in mice's colon, and the ELISA method was used to detect the levels of interleukin-6 (IL-6), IL-4, IL-8, IL-10, IL-1ß and tumor necrosis factor-α (TNF-α) in mice's colon. The changes in gut microbiota in mice were detected by high-throughput sequencing; the concentration of short-chain fatty acids (SCFAs) was determined by gas chromatography; the expression of related proteins was detected by Western blot. Compared with the DSS group, the WQP group showed a significantly lower DAI score of mice and an alleviated colon tissue injury. In the middle- and high-dose polysaccharides groups, the levels of pro-inflammatory cytokines IL-6, IL-8, IL-1ß and TNF-α in the colonic tissue were significantly decreased (P<0.05), while the levels of IL-4 and IL-10 were significantly increased (P<0.05). The 16S rRNA gene sequencing results showed that different doses of WQP could regulate the composition and diversity of gut microbiota and improve its structure. Specifically, at the phylum level, group H showed an increased relative abundance of Bacteroidetes and a decreased relative abundance of Firmicutes compared with the DSS group, which was closer to the case in group C. At the family level, the relative abundance of Rikenellaceae in L, M and H groups increased significantly, close to that in group C. At the genus level, the relative abundance of Bacteroides, Shigella and Oscillospira in the H group increased significantly, while that of Lactobacillus and Prevotella decreased significantly. The high-dose WQP group could significantly increase the contents of acetic acid, propionic acid, butyric acid, and total SCFAs. Different doses of WQP also increased the expression levels of tight junction proteins ZO-1, Occludin and Claudin-1. To sum up, WQP can regulate the gut microbiota structure of UC mice, accelerate the recovery of gut microbiota, and increase the content of Faecal SCFAs and the expression level of tight junction proteins in UC mice. This study can provide new ideas for the treatment and prevention of UC and theoretical references for the application of WQP.

Prognostication and optimal criteria of circumferential margin involvement for esophageal cancer after chemoradiation and esophagectomy.

Purpose: Circumferential radial margin (CRM) involvement by tumor after resection for esophageal cancer has been suggested as a significant prognostic factor. However, the prognostic value of CRM involvement after surgery with neoadjuvant concurrent chemoradiotherapy (CCRT) is unclear. This study aimed to evaluate the prognostic value of and survival outcomes in CRM involvement as defined by the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) for patients with esophageal cancer undergoing neoadjuvant CCRT and esophagectomy. Methods: A total of 299 patients with esophageal cancer who underwent neoadjuvant CCRT followed by esophagectomy between 2006 and 2016 were enrolled in our study. The CRM status of the specimens obtained was determined pathologically according to both the CAP and RCP criteria. Survival analyses were performed and compared according to the two criteria. Results: Positive CRM was found in 102 (34.1%) and 40 (13.3%) patients according to RCP and CAP criteria, respectively. The overall and progression-free survival rates were significantly lower in the CRM-positive group than in the CRM-negative group according to both the RCP and CAP criteria. However, under multivariate analysis, in addition to pathological T and N staging of the tumor, only CAP-defined CRM positivity was a significant prognostic factor with adjusted hazard ratios of 2.64 (1.56-4.46) and 2.25 (1.34-3.78) for overall and progression-free survival, respectively (P < 0.001). Conclusion: In patients with esophageal cancer undergoing neoadjuvant CRT followed by esophagectomy, CAP-defined CRM positivity is an independent predictor of survival. Adjuvant therapy should be offered to patients with positive CRM.

Comparison between non-surgical and surgical management of rib fractures in major trauma patients without brain injuries.

BACKGROUND: This study aimed to evaluate the different outcomes between the non-surgical and surgical groups in patients with major trauma without brain injuries. METHODS: This study prospectively collected data from patients with traumatic rib fractures without brain injuries from June 2017 to November 2019. The primary outcomes were the pain score at admission and discharge and the length of hospital stay. We performed multiple regression analysis to compare the outcomes and surgical risk as the severity of chest trauma between both groups. RESULTS: Fifty-three patients were enrolled. There was no statistically significant difference in baseline characteristics between both groups. However, the surgical group had more severe chest trauma than the non-surgical group. After the analysis, the pain score improved significantly in the surgical group. The hospital stay of the surgical group was four days shorter than that of the non-surgical group, and there was severe chest trauma in the surgical group. CONCLUSIONS: Surgical management of rib fractures can reduce pain and hospital stay in major trauma patients.

AFG, an important maillard reaction product in red ginseng, alleviates D-galactose-induced brain aging in mice via correcting mitochondrial dysfunction induced by ROS accumulation.

Red ginseng is a classical processed product from Panax ginseng. C.A Meyer with many bioactive components formed through the Maillard reaction called Maillard reaction products. Maillard reaction refers to complex reversible reactions between amino acids or proteins and glycosides, which are used in food processing and storage, as well as in tobacco development, traditional Chinese medicine processing, and wine brewing. Arginyl-fructosyl-glucose (AFG) is a main non-saponin (ginsenoside) component produced in red ginseng processing, with high antioxidant, anti-apoptotic and neuroprotective efficiencies. However, its effects and mechanisms against oxidation stress in on the brain remain elusive. Therefore, this study aimed at exploring the therapeutic effect exerted by AFG on murine subacute brain aging induced by D-galactose (D-gal) and its potential molecular mechanism in the murine model, finding that AFG (40 and 80 mg/kg) significantly ameliorated D-gal-resulted changes in pathology. Besides, according to the transmission electron microscopy (TEM) and Western blot, AFG corrected the mitochondrial dysfunction resulted from ROS, thereby delaying the mice brain aging caused by D-gal.

Uniportal versus multiportal nonintubated thoracoscopic anatomical resection for lung cancer: A propensity-matched analysis.

BACKGROUND/PURPOSE: No studies have compared between uniportal and multiportal nonintubated thoracoscopic anatomical resection for non-small cell lung cancer (NSCLC). We aimed to compare short- and long-term postoperative outcomes concerning these two methods. METHODS: Our retrospective dataset comprised patients with NSCLC who underwent uniportal or multiportal nonintubated thoracoscopic anatomical resection between January 2011 and December 2019. The primary outcome was recurrence-free survival. Propensity scores were matched according to age, sex, body mass index, pulmonary function, tumor size, cancer stage, and surgical method. RESULTS: In total, 1130 such patients underwent nonintubated video-assisted thoracoscopic surgery (VATS), and 490 consecutive patients with stage I-III NSCLC underwent nonintubated anatomical resection, including lobectomy and segmentectomy (uniportal, n = 158 [32.3%]; multiportal, n = 331 [67.7%]). The uniportal group had fewer dissected lymph nodes and lymph node stations. In paired group analysis, the uniportal group had shorter operation durations (99.8 vs. 138.2 min; P < 0.001), lower intensive care unit (ICU) admission rates and ICU admission intervals (7.0% vs. 27.8%; P < 0.001), and shorter postoperative hospital stays (4.1 days vs. 5.2 days; P < 0.001). The most common postoperative complication was prolonged air leaks. No surgical mortality was observed. The multiportal group had higher complication rates for grades ≥ II NSCLC; however, this difference was not significant (4.4% vs. 1.3%, respectively; P = 0.09). CONCLUSION: Nonintubated uniportal VATS for anatomical resection had better results for some perioperative outcomes than multiportal VATS. Oncological outcomes such as recurrence-free and overall survival remained uncompromised, despite fewer dissected lymph nodes.

20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.

Cisplatin-loaded gold nanoshells mediate chemo-photothermal therapy against primary and distal lung cancers growth.

Lung cancer is the most common cause of cancer mortality worldwide. The advances in surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs have progressed in the past decades, but the prognosis of lung cancer is still poor. In this study, we developed cisplatin (CDDP)-loaded human serum albumin (HSA)-based gold nanoshells (HCP@GNSs) for synergistic chemo-photothermal therapy (chemo-PTT). The HCP@GNSs not only acted as drug nanocarriers for chemotherapy but also serve as a superior mediator for PTT, which could exhibit a temperature increase upon a near infrared (NIR) laser exposure that was sufficient for photothermal ablation. HCP@GNSs were highly biocompatible and hemocompatible nanocarriers, while the synergistic chemo-PTT resulting from HCP@GNSs plus NIR exposure displayed stronger cytotoxicity effect than HCP@GNSs or PTT alone, especially at a low CDDP concentration. In vivo analysis demonstrated that HCP@GNSs-mediated chemo-PTT increased necrosis in tumors to achieve a high tumor clearance rate with no adverse side effects. Moreover, HCP@GNSs-medicated chemo-PTT induced the recruitment of dendritic cells, B-cells, and natural killer T-cells in distal tumors to inhibit the growth of the tumors. Therefore, the CDDP-loaded HCP@GNSs may be a potential nanomedicine candidate for curative lung cancer treatment in the future.

Robotic-Assisted Thoracoscopic (RATS) Enucleation of Esophageal Mesenchymal Tumors and Foregut Cysts.

Background: Esophageal mesenchymal tumors and foregut cysts are mostly benign lesions of the esophagus. Tumor enucleation is recommended for lesions with a risk of malignancy, or for the relief of clinical symptoms. Although robotic-assisted thoracoscopic enucleation of esophageal tumors and cysts has been demonstrated in sporadic case reports, its clinical role is yet to be elucidated. Methods: This study aimed to present the first case series in the literature for the perioperative and long-term clinical outcomes of robotic-assisted thoracoscopic enucleation. Results: A total of 19 patients who underwent robotic-assisted thoracoscopic enucleation of esophageal tumors and cysts from 2012 to 2019 were included in the study. The mean tumor/cyst size was 5.5 cm (1.5-22 cm). There were two cases shifting to minimally invasive esophagectomy (10.5%) due to intraoperative pathological confirmation of malignant gastrointestinal stromal tumors with mucosal invasion. Perioperative complication was detected in three (15.8%) cases, without 30-day or surgical mortality. There was no recurrence of tumor or symptoms in all patients during the clinical follow-up period (mean = 35 months). Conclusions: Robotic-assisted thoracoscopic enucleation of esophageal submucosal benign tumors is technically feasible and effective. Given its advantage in overcoming spatial limitations, it can become a widely accepted surgical option for such diseases.

Computed Tomography-Guided Localization and Extended Segmentectomy for Non-Small Cell Lung Cancer.

Background: Lung cancer is one of the most devastating cancers. Low-dose computed tomography (LDCT) can detect lung cancer at an early stage of the disease when a minimally invasive surgical procedure using video-assisted thoracoscopic surgery is the best strategy. Herein, we discuss the treatment of deep lung tumors between segments or lesions located near the margin of a segment. Patients and Methods: This was a retrospective study conducted from January 2013 to January 2020 using the National Taiwan University Hospital data bank. We included early-stage non-small cell lung cancer (NSCLC) patients who underwent lung surgery and screened out those who received CT-guided localization for extended segmentectomy. Outcome measurements were safety margin, complication rate, and postoperative course. Results: During the study period, 68 patients with early-stage NSCLC received CT-guided localization followed by extended segmentectomy. The mean surgery time was 92.1 ± 30.3 min, and the mean blood loss was 32.8 mL. Mean drainage time was 2.3 ± 1 days, and the total hospital stay was 4.9 ± 1.1 days. Pathological reports showed tumor-free resection margins >2 cm. Sixty-one patients had adenocarcinoma at stage IA and two patients at stage IB. One patient had squamous cell carcinoma at stage IA. Conclusion: CT-guided localization followed by extended segmentectomy allows lung volume preservation with clean safety margins and good clinical outcomes.

Evaluating the effects of mitochondrial autophagy flux on ginsenoside Rg2 for delaying D-galactose induced brain aging in mice.

BACKGROUND: Aging is an inevitable gradual process of the body, which can cause dysfunction or degeneration of the nervous or immune system, thus becoming a critical pathogenic factor inducing neurodegenerative diseases. Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C.A. Meyer exerted obvious memory-enhancing and anti-aging effects, and the simpler the structure of ginsenosides, the better the biological activity. Ginsenoside Rg2 (Rg2) is a prominent and representative panaxatriol-type ginsenoside produced during ginseng processing, which has been reported to have pretty good neuroprotective activity. PURPOSE: The work was aimed at exploring the therapeutic effects and possible molecular mechanisms of Rg2 by establishing the subacute brain aging model induced by D-galactose (D-gal) in mice. METHODS: The anti-aging activity of G-Rg2 (10, 20 mg/kg for 4 weeks) was assessed using the D-gal induced brain aging model (800 mg/kg for 8 weeks). The Morris water maze (MWM) and histopathological analysis were used to evaluate the cognitive function and pathological changes of the brain in mice, respectively. The protein expression levels of p53, p21, p16ink4α, IL-6, CDK4, ATG3, ATG5, ATG7, LC3, p62, LAMP2, and TFEB were quantified through western blot analysis. The degree of mitochondrial damage and the number of mitochondrial autophagolysosomes in hippocampal neurons were monitored using TEM analysis. RESULTS: The results showed that Rg2 could significantly restore D-gal-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Rg2 treatment also considerably decreased the over-expression of aging-related proteins such as p53/p21/p16ink4α induced by D-galactose, which demonstrated that Rg2 possessed good anti-aging activity. Meanwhile, Rg2 could evidently reduce the pathological changes caused by D-gal exposure. Moreover, the results from transmission electron microscopy and western blot analysis indicated that Rg2 could delay the brain aging induced by D-gal in mice via promoting the degradation of the autophagy substrate p62 while increasing the protein expression level of LAMP2/TFEB to maintain mitochondrial function. CONCLUSION: These results indicate that Rg2 could postpone brain aging by increasing mitochondrial autophagy flux to maintain mitochondrial function, which greatly enriched the research on the pharmacological activity of ginsenosides for delaying brain aging.

Selection of minimally invasive surgical approaches for treating esophageal cancer.

Minimally invasive esophagectomy has gradually been accepted as an active treatment option for surgery of esophageal cancer. However, there is no consensus about how to perform the procedures in the thoracic and abdominal phase including anastomosis in the neck (McKeown) or chest (Ivor Lewis), VATS, robotic-assisted or reduced port approaches or various endoscopic abrasion techniques. Further studies to investigate the roles of these novel techniques are required to treat the various patient populations.

Non-Intubated Versus Intubated Video-Assisted Thoracic Surgery in Patients Aged 75 Years and Older: A Propensity Matching Study.

Introduction: In most developed countries, lung cancer is associated with the highest mortality rate among all cancers. The number of elderly patients with lung cancer is increasing, reflecting the global increase in aging population. Patients with impaired lung or cardiac function are at a high risk during intubated general anesthesia, which may preclude them from surgical lung cancer treatment. We evaluated the safety and survival of non-intubated video-assisted thoracoscopic surgery (VATS) versus those of intubated thoracoscopic surgery for surgical resection for lung cancer in older patients. Methods: Patients aged ≥75 years who underwent non-intubated and intubated VATS resection with pathologically confirmed non-small cell lung cancer, using a combination of thoracic epidural anesthesia or intercostal nerve block and intra-thoracic vagal block with target-controlled sedation, from January 2011 to December 2019 were included. Ultimately, 79 non-intubated patients were matched to 158 patients based on age, sex, body mass index, family history, comorbidity index, pulmonary function (forced expiratory volume in one second/ forced vital capacity [%]), and disease stage. The endpoints were overall survival and recurrence progression survival. Results: All patients had malignant lung lesions. Data regarding conversion data and the postoperative result were collected. Both groups had comparable preoperative demographic and cancer staging profiles. The anesthetic duration in the non-intubated group was shorter than that in the intubated group, which showed a significantly higher mean number of lymph nodes harvested (intubated vs non-intubated, 8.3 vs. 6.4) and lymph stations dissected (3.0 vs. 2.6). Intensive care unit (ICU) admission rate and postoperative ICU stay were significantly longer in the intubated group. The complication rate was higher and hospital stay were longer in the intubated group, but these differences were not significant (12% vs. 7.6%; p = .07, respectively). Conclusions: In the elderly, non-intubated thoracoscopic surgery provides similar survival results as the intubated approach, although fewer lymph nodes are harvested. Non-intubated surgery may serve as an alternative to intubated general anesthesia in managing lung cancer in carefully selected elderly patients with a high risk of impaired pulmonary and cardiac function.