CCN1 Is a Therapeutic Target for Reperfused Ischemic Brain Injury.

Ischemic stroke can lead to systemic inflammation, which can activate peripheral immune cells, causing neuroinflammation and brain injury. Meningeal lymphatics play a crucial role in transporting solutes and immune cells out of the brain and draining them into cervical lymph nodes (CLNs). However, the role of meningeal lymphatics in regulating systemic inflammation during the reperfusion stage after ischemia is not well understood. In this study, we demonstrated that brain infarct size, neuronal loss, and the effector function of inflammatory macrophage subsets were reduced after ischemia-reperfusion and disruption of meningeal lymphatics. Spatial memory function was improved in the late stage of ischemic stroke following meningeal lymphatic disruption. Brain-infiltrating immune cells, including neutrophils, monocytes, and T and natural killer cells, were reduced after cerebral ischemia-reperfusion and meningeal lymphatic disruption. Single-cell RNA sequencing analysis revealed that meningeal lymphatic disruption reprogrammed the transcriptome profile related to chemotaxis and leukocyte migration in CLN lymphatic endothelial cells (LECs), and it also decreased chemotactic CCN1 expression in floor LECs. Replenishment of CCN1 through intraventricular injection increased brain infarct size and neuronal loss, while restoring numbers of macrophages/microglia in the brains of meningeal lymphatic-disrupted mice after ischemic stroke. Blocking CCN1 in cerebrospinal fluid reduced brain infarcts and improves spatial memory function after ischemia-reperfusion injury. In summary, this study indicates that CCN1-mediated detrimental inflammation was alleviated after cerebral ischemia-reperfusion injury and meningeal lymphatic disruption. CCN1 represents a novel therapeutic target for inhibiting systemic inflammation in the brain-CLN axis after ischemia-reperfusion injury.

Minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for esophageal squamous cell carcinoma: case report.

Minimally invasive esophagectomy for cancer surgery remains associated with significant morbidity and surgical complications across the globe. Non-intubation video-assisted thoracic surgery (NIVATS) has been successfully employed in lung resection in recent years, but there are few reported cases with regard to the safety and feasibility of this approach in radical esophagectomy for patients with esophageal cancers. We present 4 consecutive cases with esophageal squamous cell carcinoma (ESCC) who received minimally invasive McKeown's esophagectomy under non-intubation general anesthesia from November 2022 to April 2023. All these patients were aged from 55 to 75 years old and were pathologically diagnosed with ESCC. All procedures of McKeown's esophagectomy in these patients were completed with non-invasive ventilation by laryngeal mask-assisted anesthesia. Operation duration ranged from 185 to 395 minutes and the estimated blood loss ranged from 25 to 60 ml in these 4 cases. No severe hypoxia was observed and transient hypercapnia was resolved intraoperatively. None of them was converted to endotracheal intubation with mechanical ventilation or to thoracotomy. The number of retrieved lymph nodes in mediastinum were 21-27 and all patients received R0 surgery with pathological stage as T1bN0M0 to T3N2M0. There was no serious complication (Clavien-Dindo grade III-IV) observed perioperatively and they were all discharged 11-14 days after the surgery with resumption of oral feeding. They are all alive without tumor recurrence at the date of data collection. The safety and efficacy of minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for patients with ESCC are warranted for explored in a larger cohort study.

Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis.

Surgery after neoadjuvant chemoradiotherapy remains the gold standard for the treatment of resectable esophageal cancer (EC); however, chemoradiotherapy without surgery has been recommended in specific cases. The aim of this meta-analysis is to analyse the survival between surgeries after neoadjuvant chemoradiotherapy compared with definitive chemoradiotherapy in order to provide a theoretical basis for clinically individualised differential treatment. We conducted an initial search of MEDLINE (PubMed), the Cochrane Library, and Embase for English-only articles that compared treatment regimens and provided survival data. According to the final I2 value of the two survival indicators, the random effect model or fixed effect model was used to calculate the overall hazard ratio (HR) and 95% confidence intervals (CI). Cochrane's Q test was used to judge the heterogeneity of the studies, and a funnel plot was used to evaluate for publication bias. A sensitivity analysis was performed to verify the stability of the included studies. A total of 38 studies involving 29161 patients (neoadjuvant therapy: 15401, definitive chemoradiotherapy: 13760) were included in the analysis. The final pooled results (HR = 0.74, 95% CI: 0.67-0.82) showed a statistically significant increase in overall survival with neoadjuvant chemoradiotherapy plus surgery compared with definitive chemoradiotherapy. Subgroup analyses were performed to determine the effects of heterogeneity, additional treatment regimens, study types, and geographic regions, as well as histologic differences, complications, and recurrence, on the overall results. For people with esophageal cancer that can be removed, neoadjuvant chemoradiotherapy combined with surgery improves survival compared to definitive chemoradiotherapy. However, more research is needed to confirm these results and help doctors make decisions about treatment.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

Thiolation of Terminal Alkynes with Thiuram Disulfide Reagents Using Water as the Hydrogen Source: Stereoselective Synthesis of (Z)-Vinyl Sulfides.

A stereoselective and environmentally friendly thiolation of terminal alkynes was reported. Thiuram disulfide reagents (tetramethylthiuram disulfide and tetraethylthiuram disulfide) that reacted with alkynes in dimethyl sulfoxide (DMSO)/H2O could give (Z)-vinyl sulfides in good yields (up to 88%). This protocol features broad substrate scope, good stereoselectivity, high atom economy, good yields, and is transition metal-free. Mechanistic studies revealed that water and DMSO served as hydrogen sources, which greatly highlighted the unique reactivity of this special reaction involving two H-atom donors.

Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma.

BACKGROUND: Macrophages play a critical role in tumor immune microenvironment (TIME) formation and cancer progression in lung adenocarcinoma (LUAD). However, few studies have comprehensively and systematically described the characteristics of macrophages in LUAD. METHODS: This study identified macrophage-related markers with single-cell RNA sequencing data from the GSE189487 dataset. An integrative machine learning-based procedure based on 10 algorithms was developed to construct a macrophage-related index (MRI) in The Cancer Genome Atlas (TCGA), GSE30219, GSE31210, and GSE72094 datasets. Several algorithms were used to evaluate the associations of MRI with TIME and immunotherapy-related biomarkers. The role of MRI in predicting the immunotherapy response was evaluated with the GSE91061 dataset. RESULTS: The optimal MRI constructed by the combination of the Lasso algorithm and plsRCox was an independent risk factor in LUAD and showed a stable and powerful performance in predicting the overall survival rate of patients with LUAD. Those with low MRI scores had a higher TIME score, a higher level of immune cells, a higher immunophenoscore, and a lower Tumor Immune Dysfunction and Exclusion (TIDE) score, indicating a better response to immunotherapy. The IC50 value of common drugs for chemotherapy and target therapy with low MRI scores was higher compared to high MRI scores. Moreover, the survival prediction nomogram, developed from MRI, had good potential for clinical application in predicting the 1-, 3-, and 5-year overall survival rate of LUAD. CONCLUSION: Our study constructed for the first time a consensus MRI for LUAD with 10 machine learning algorithms. The MRI could be helpful for risk stratification, prognosis, and selection of treatment approach in LUAD.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Surgical intervention after neoadjuvant therapy in esophageal cancer: a narrative review.

Background and Objective: Esophageal cancer is one of the common malignant tumors in China. Previous studies have shown that surgery alone is less effective. Neoadjuvant therapy refers to preoperative chemoradiotherapy, which is the standard treatment for locally advanced and operable esophageal cancer. Selection of appropriate surgical methods and timing after neoadjuvant therapy is of great significance for improving the prognosis of patients and reducing postoperative complications. Methods: An online electronic search of all eligible literature through PubMed, Google Scholar, and the Cochrane Library database was conducted using a combination of the following keywords: esophageal cancer, neoadjuvant therapy, neoadjuvant chemotherapy, chemoradiotherapy, immunotherapy, targeting, surgery, complications. With a focus on the use of surgery after neoadjuvant therapy, Eligible articles were identified by one or both authors. Key Content and Findings: Neoadjuvant chemoradiotherapy combined with radical surgical resection remains the current standard of care for resectable esophageal cancer, significantly improving survival and pathologic complete response (PCR) compared with preoperative chemotherapy Recently, studies have also found that immunotherapy combined with chemotherapy has a more advantageous pathological response in patients with locally advanced disease. Although the emergence of targeted drugs has led to a change in treatment mode from traditional chemoradiotherapy to precision therapy, the postoperative progression-free survival (PFS) and overall survival (OS) need to be explored as well as how surgery-related risks caused by treatment can be reduced. Traditionally, surgery is performed 4-6 weeks after neoadjuvant therapy, and optimal timing for surgery after treatment is still being explored as research progresses, the surgical method also should be determined according to the specific situation of the patient. Postoperative complications should be dealt with in a timely manner, and of course, active preoperative intervention is equally important. Conclusions: Neoadjuvant therapy combined with surgery is the gold standard for resectable esophageal cancer. However, optimal timing of surgery after preoperative treatment remains unclear. Minimally invasive thoracoscopic surgery (including robotic surgery) has gradually replaced traditional open surgery. Active prevention before operation, accurate and meticulous operation during operation, and timely treatment after operation can minimize the incidence of adverse events.

Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study.

Background: Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer. However, there were few studies comparing nICT with nCRT. This study compared the efficacy and safety of nICT with that of nCRT administered prior to esophagectomy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: The study included patients with locally advanced resectable ESCC who were scheduled to receive neoadjuvant therapy at Gaozhou People's Hospital from January 1, 2019, to September 1, 2022. The enrolled patients were divided into 2 groups (nCRT or nICT) according to their neoadjuvant therapy regimen. The 2 groups were compared for their baseline data, the incidence of adverse events during neoadjuvant therapy, the clinical evaluation after neoadjuvant therapy, perioperative indicators, and the incidence of postoperative complications and postoperative pathological remission. Results: A total of 44 patients were enrolled; 23 in the nCRT group and 21 in the nICT group. There were no significant differences between the 2 groups in the baseline data. In the nCRT group, leukopenia occurred more often than in the nICT group, and hemoglobin-decreasing events were rarer (P=0.03<0.05). A significantly higher proportion of patients in the nICT group experienced erythema following neoadjuvant therapy compared to the nCRT group (23.81% vs. 0%; P=0.01<0.05). Neoadjuvant therapy showed no significant difference between the 2 groups for adverse event rates, surgery-related indicators, postoperative pathological remission rates, and postoperative complications. Conclusions: nICT was a safe and feasible treatment for locally advanced ESCC and it may be a potential new treatment modality.

A revamped MIC-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk.

BACKGROUND: The purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery. METHODS: This revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed. RESULTS: All patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation. CONCLUSIONS: Merit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.

Modulatory Effects of Heat-Inactivated Streptococcus Thermophilus Strain 7 on the Inflammatory Response: A Study on an Animal Model with TLR3-Induced Intestinal Injury.

Rotavirus infections result in severe gastroenteritis with a detrimental inflammatory response in the intestine. Because probiotics have an anti-inflammatory effect and can modulate the gut microbiota profile, they can be used as a biotherapy for inflammatory intestinal diseases. In this study, we isolated Streptococcus thermophilus strain 7 (ST7) from cow milk and examined the effect of heat-inactivated ST7 on the intestinal histopathological score, inflammatory cytokine levels, T-cell activation and effector function, and microbiome profile in a mouse model with intestinal injury induced by polyinosinic-polycytidylic acid (poly I:C), a Toll-like receptor 3 agonist. The results indicated that ST7 treatment prevented weight loss and intestinal injury and prevented the upregulation of serum interleukin-6 (IL-6), tumor necrosis factor-α, and IL-15 levels in intestinal epithelial cells; prevented the upregulation of inflammation-associated Gammaproteobacteria and Alistipes; and increased the levels of Firmicutes in fecal microbiota after poly I:C stimulation. ST7 treatment also increased the serum interferon-γ (IFN-γ) level and promoted the expression of IFN-γ in both CD8 and CD4 T cells. In summary, ST7 prevented the inflammatory response, promoted the T-cell effector function, and modulated the microbiota profile of mice with poly I:C-induced small intestine injury.

Sweet's syndrome with adenocarcinoma of lung: a rare case report.

Background: Sweet's syndrome is a rare inflammatory disease of unknown etiology, and its relationship with tumors is unknown at present. Sweet's syndrome in patients with solid tumors, especially adenocarcinoma of the lung, is extremely rare. At present, only 1 case of an operative patient has been reported in the literature. Diagnosing lung cancer with Sweet's syndrome is not easy, when there is a fever with an unknown cause and erythemas, especially when the erythemas do not disappear after antibiotic treatment, a skin biopsy is much important. Although the exact mechanism of the disease and its link to lung cancer are unknown, our case shows that the active surgical treatment of the primary disease and appropriate glucocorticoid therapy are effective means. Case Description: We report the first case of a patient with Sweet's syndrome and lung adenocarcinoma with a decrease in peripheral whole blood cells. A 66-year-old male patient presented, who had been suffering from a fever for >10 days and had multiple tender erythemas, erythemas were mainly on the limbs and upper chest. He was treated with a variety of antibiotics, but his symptoms did not improve significantly. The routine blood tests results show a decline in peripheral blood cells, a chest computed tomography (CT) examination showed a space occupying lesion in the middle lobe of the right lung, which was considered peripheral lung cancer. Sweet's syndrome was diagnosed after a skin biopsy, a pathological examination showed that a large number of neutrophils were infiltrating. The patient then underwent video-assisted thoracoscopic lobectomy associated with the systematic dissection of the mediastinal lymph node, and glucocorticoids were administered. After the operation, the tender erythemas and fever disappeared, at the 1-month follow-up, the chest CT showed no obvious tumor recurrence or metastasis. Conclusions: To the best of our knowledge, this is the first report of Sweet's syndrome in a patient with lung adenocarcinoma with 3 cell lines reduced. The active surgical treatment of the primary disease and appropriate glucocorticoid therapy proved to be an effective treatment for this syndrome.

Lymph node metastasis-related lncRNA GAS6-AS1 facilitates the progression of esophageal squamous cell carcinoma.

Background: Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the adventitia layer (T3 stage), the incidence of lymph node metastasis increases sharply. Abnormal expression of long non-coding RNAs (lncRNAs) has been confirmed in ESCC, but there are still many unknown connections between lncRNAs and lymph node metastasis. Methods: We used transcriptome sequencing (RNA-seq) to analyze 10 pairs of ESCC tissues with primary tumor stage T3 and their paired normal epithelium. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to further verify the sequencing results, and survival curve analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate its clinical application value. We investigated the growth and metastasis effects of lncRNA GAS6-AS1 on ESCC cell lines TE-1 and KYSE410 in vitro and in vivo. Other functional experiments included cell apoptosis and cell cycle experiments. Results: Based on our RNA-seq data, lncRNA GAS6-AS1 is highly expressed in ESCC tissues, especially in cancer tissues with lymph node metastasis. The qRT-PCR experiment analysis showed that high expression of GAS6-AS1 was related to poor tumor differentiation and tumor stage. Logistic regression analysis showed that it was an independent risk factor for lymph node metastasis, and ROC analysis validated that it could predict lymph node metastasis. Further survival analysis suggested that high expression of GAS6-AS1 was associated with patients' poor prognosis. In vitro experiments, knocking down GAS6-AS1 inhibited the growth and metastasis of ESCC cells and inhibited tumor growth in vivo. In addition, knocking down GAS6-AS1 can inhibit cell cycle and promote cell apoptosis. Conclusions: Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.

Cytomegalovirus seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients: a retrospective cohort study.

BACKGROUND: Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients. METHODS: The clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China. RESULTS: A total of 308 patients were analyzed. The CMV serostatus was donor positive (D+) recipient negative (R-) in 19 (6.17%) patients, D+/R+ in 233 (75.65%), D-/R+ in 36 (11.69%), and D-/R- in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D+/R- serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05-6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92-9.42) were risk factors of CMV disease. CONCLUSION: CMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.

Mining Database to Identify Aging-Related Molecular Subtype and Prognostic Signature in Lung Adenocarcinoma.

Background: Lung cancer is emerging as one of most deadly diseases, and the mortality rate was still high with 5-year overall survival rate less than 20%. Aging is referred as protumorigenic state, and it plays a significant role in cancer development. Methods: Molecular subtype of lung cancer was identified by consensus cluster analysis. Prognostic signature was constructed using LASSO cox regression analysis. CeRNA network was constructed to explore lncRNA-miRNA-mRNA regulatory axis. Results: A total of 27 differentially expressed aging-related genes (ARGs) were obtained in LUAD. Three clusters of TCGA-LUAD patients with significant difference in prognosis, immune infiltration, chemotherapy, and targeted therapy were identified. We also developed an aging-related prognostic signature that had a better performance in predicting the1-year, 3-year, and 5-year overall survival of LUAD. Further analysis suggested a significant correlation between prognostic signature gene expression and clinical stage, immune infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also identified the lncRNA UCA1/miR-143-3p/CDK1 regulatory axis in LUAD. Conclusion: Our study identified three clusters of TCGA-LUAD patients with significant difference in prognosis, immune infiltration, chemotherapy, and targeted therapy. We also developed an aging-related prognostic signature that had a good performance in the prognosis of LUAD.

KI Essence extract (a spleen-tonifying formula) promotes neurite outgrowth, alleviates oxidative stress and hypomyelination, and modulates microbiome in maternal immune activation offspring.

Mushrooms and Chinese traditional herbs have bioactive nutraceuticals with multiple therapeutic functions, including antioxidant and antibacterial activities and microbiome modulation properties. Mushroom-derived bioactive compounds are used in medicines for the treatment of neurological disorders with abnormal brain-gut-microbiome axis. This study examined the effects of KI Essence extract, a spleen-tonifying formula, on neurite growth, antioxidant activity, hypomyelination modulation, and the microbiome profile in lipopolysaccharide (LPS)-induced maternal immune activation (MIA) offspring. The KI Essence extract induced PC12 cell neurite growth by increasing extracellular signal-regulated kinase (ERK) phosphorylation, promoting 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing the level of tert-butylhydroperoxide-induced lipid peroxidation in brain homogenates, protecting PC12 cells from H2O2-induced cell death (through the inhibition of ERK phosphorylation), alleviating hypomyelination, and downregulating interleukin-1ß through LPS-activated microglia production; moreover, the numbers of Enterobacteriaceae, Actinobacteria, Peptostreptococcaceae, Erysipelotrichaceae, and Bifidobacterium bacteria in MIA offspring increased. In summary, the KI Essence extract promotes neurite outgrowth, alleviates oxidative stress and hypomyelination, and modulates microbiota dysbiosis in MIA offspring.

Modified McKeown vs. traditional McKeown minimally invasive esophagectomy in improving short-term efficacy and the quality of life of esophageal cancers: a retrospective comparative cohort study.

Background: Traditional McKeown minimally invasive esophagectomy (MIE-McKeown) with resection of the thoracic and abdominal branches of vagus nerve, the azygos vein and the bronchial artery, is notorious for high complications incidence and sharply decreased quality of life (QoL) postoperatively in esophageal cancer (EC). Recently, reports of preservation of azygos vein arch or the vagus nerve have shown the advantages of decreasing postoperative complication incidence. However, the modified MIE-McKeown with preservation of azygos vein arch, vagus nerve and the bronchial artery has never been investigated in EC. In the present study, we aimed to compare the short-term efficacy and postoperative QoL between modified MIE-McKeown and traditional MIE-McKeown. Methods: A total of 218 eligible patients with esophageal squamous cell carcinoma (ESCC) who met our inclusion criteria between October 2018 and January 2022 in our center were retrospectively enrolled and divided into modified MIE-McKeown group (N=48) and the control group with traditional MIE-McKeown (N=170) according to their surgical procedure. We compared the perioperative parameters (e.g., operation time and postoperative complications) between the two groups. The core quality of life questionnaire (QLQ-C30) (version 3.0) and the EC-specific QoL assessment form (QLQ-OES18) were used to evaluate the QoL in the 2 groups at 1 and 3 months after operation. Results: There were no significant differences in baseline characteristics between modified MIE-McKeown group and the control group. Compared with the control group, the modified MIE-McKeown group had significantly lower postoperative drainage volume (551.46±249.45 vs. 812.96±405.82; P<0.001) and a lower incidence of thoracic stomach syndrome (TSS; P=0.001). The bleeding loss in the modified MIE-McKeown group was lower than that in the control group (56.88±20.44 vs. 83.18±97.93; P=0.066), but not significantly. There were no significant differences observed in postoperative complications and other perioperative parameters between the two groups. The results of QLQ-C30 and QLQ-OES18 questionnaire revealed that the modified MIE-McKeown group was associated with better physical function, better global health status and milder symptoms of gastroesophageal reflux and cough. Conclusions: The modified MIE-McKeown is a safe and efficient procedure and has the potential to improve postoperative health status of patients with EC.

Conversion Surgery Following Immunochemotherapy in Initially Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma-A Real-World Multicenter Study (RICE-Retro).

Purpose: The present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario. Materials and Methods: In this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared. Results: One hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery. Conclusion: Our results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Effects of Predictive Nursing Intervention among Patients with Acute Stroke.

BACKGROUND: To explore the effects of predictive nursing intervention among patients with acute stroke. METHODS: One hundred and sixty participants were included. They were hospitalized in the Department of Neurology of a third-level first-class hospital in Changsha, Hunan Province, from January to August 2019. They were categorized into control group and intervention group by random number table, with 80 patients in each group. General nursing for patients in Neurology Department was offered to the control group. On the basis of general nursing, predictive nursing intervention was offered to the intervention group. The effectiveness of predictive nursing intervention were evaluated by disparity in neurologic function, movement function, daily life ability and sleep quality before intervention and 2 weeks after intervention. The neurologic function, movement function, daily life ability and sleep quality were evaluated by National Institute of Health acute stroke scale (NIHSS), Fugl-Meyer scale, Barthel indicator, and Pittsburgh sleep quality indicator (PSQI), respectively. RESULTS: There was no significant difference in gender, age, complications and treatment methods between two groups. There was no significant difference in the scores of NIHSS, Fugl-Meyer scale, Barthel indicator, and PSQI before intervention. The scores of NIHSS and PSQI were significantly lower in the intervention group than those in the control group, and the scores of Fugl-Meyer scale and Barthel indicator were significantly higher in the intervention group than those in the control group (P <0.05). CONCLUSION: Predictive nursing intervention could help improve not only neurologic function, movement function, and daily life ability, but also sleep quality among patients with acute stroke.