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Can-Can Zhou,1,* Fang Huang,1,* Jing-Ming Zhang,1 Yu-Gang Zhuang2 1Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Emergency Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Gang Zhuang, Email zhuangyg07@sina.comAbstract: Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide tigecycline dosing in different patient subpopulations through comparing the published population pharmacokinetic models of tigecycline, as well as summarizing and determining the potential covariates that markedly influence tigecycline pharmacokinetics. In this review, literature was systematically searched from the PubMed database from inception to March 2022. The articles focusing on population pharmacokinetics for tigecycline in healthy volunteers or patients were included; finally, a total of eight studies were included in this review. NONMEM methods were used in five studies to generate the population pharmacokinetic models. Tigecycline pharmacokinetics were mostly described by a two-compartment model in these included studies. Estimated clearance and volumes of distribution of tigecycline at steady state (Vss) varied widely in different target patient populations, with a range of 7.5– 23.1 L/h and 212.7– 1087.7 L, respectively. Body-weight and creatinine clearance were the most important predictors of clearance in these studies, while other predictors include age, gender, bilirubin and aspartate aminotransferase. In conclusion, this review showed the large variability of tigecycline population pharmacokinetics, which can provide guide dosing in different target populations. For clinicians, the individual dosing adjustment should be based not only on the indication and pathogen susceptibility but also on the potential important predictors. However, more studies were needed to confirm the necessity of modified dosage regimens in different patient subpopulations.Keywords: tigecycline, population pharmacokinetics, modelling, NONMEM

Yayi He,1,2,* Sangtian Liu,1,* Jane Mattei,3 Paul A Bunn Jr,2 Caicun Zhou,1 Daniel Chan2 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China; 2Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Oncology Department, Moinhos de Vento Hospital, Porto Alegre, Brazil *These authors contributed equally to this work Background: The anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) monoclonal antibody has a good effect in the treatment of non-small cell lung cancer (NSCLC), but not all PD-1/PD-L1 positive patients can get benefit from it. Compensatory expression of other immune checkpoints may be correlated with the poor efficacy of anti-PD-1/PD-L1 monoclonal antibodies. The inhibitory human leukocyte antigen (HLA)/killer cell Ig-like receptor (KIR) can effectively block the killing effect of natural killer (NK) cells on tumors. Our previous studies have confirmed that high expression of KIR was correlated with poor prognosis of NSCLC. Inhibitory KIR expression was positively correlated with the expression of PD-1. Methods: The expressions of KIR 2D (L1, L3, L4, S4) (BC032422/ADQ31987/NP_002246/NP_036446, Abcam) and PD-1 (NAT 105, Cell marque) proteins was assessed by immunohis­tochemistry. Results: The expression of inhibitory KIR in tumor cells or tumor infiltrating lymphocytes (TILs) is associated with PD-1 expression. Among PD-1 positive patients, 76.3% were KIR 2D (L1, L3, L4, S4) positive on tumor cells, and 74.6% were KIR 2D (L1, L3, L4, S4) positive on TILs. We compared the expression of inhibitory KIR before and after treatment with nivolumab in 11 patients with NSCLC. We found that five (45.5%) patients had positive expression of inhibitory KIR in tumor tissue after being treated with anti-PD-1 monoclonal antibodies, two of whom exhibited a significant increase in expression of inhibitory KIR, and three showed no change. Conclusions: PD-1 expression was correlated with KIR 2D (L1, L3, L4, S4) on tumor cells or TILs. The resistance to anti-PD-1 monoclonal antibody treatment might be related to KIR. The inhibitory HLA/KIR could combine with the PD-1/PD-L1 signaling pathway negatively regulating NSCLC tumor immunity. Keywords: non-small cell lung cancer, immune therapy, HLA/KIR, PD-1/PD-L1, tumor immune escape

Objective: Surgery remains the first line treatment for meningiomas and can benefit from fluorescence-guided surgical techniques such as second-window indocyanine green (SWIG). In the current study, we compared the use of the standard SWIG dose of 5.0 mg/kg relative to 2.5 mg/kg indocyanine green (ICG) in meningioma patients., Methods: Patients were prospectively enrolled in an IRB-approved study of SWIG and received either the standard dose of 5.0 mg/kg or a reduced dose of 2.5 mg/kg of ICG around 24 h prior to their surgery. Intraoperative near-infrared fluorescence imaging was performed with exo- and endoscopic systems. Signal-to-background ratio (SBR) was calculated to quantify fluorescence and was compared between 5.0 mg/kg and 2.5 mg/kg ICG. All patients received pre-operative MRI and, in select cases, the pre-operative MRI was correlated to intraoperative fluorescence imaging., Results/discussion: In the current study, we found no significant difference in the SBR of meningiomas in patients that were administered with either 5.0 mg/kg or 2.5 mg/kg ICG. However, in five patients that received the standard-dose SWIG regimen of 5.0 mg/kg ICG we observed dose-related fluorescence quenching - referred to as "inversion" - that interfered with tumor visualization during fluorescence-guided surgery (FGS). When correlated to pre-operative MRI, a similar rim pattern was observed around the primary tumor on T 2 FLAIR, which, in retrospect, could be used as a predictor for inversion during FGS in meningioma patients receiving standard-dose ICG., Conclusion: This study demonstrated that a reduced ICG dose was as effective as standard-dose SWIG in meningioma patients. We therefore recommend to adjust the standard ICG dose for meningioma patients to 2.5 mg/kg particularly when rim enhancement is observed on pre-operative T 2 FLAIR., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram., Methods: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA)., Results: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance., Conclusion: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making., (© 2024. Huazhong University of Science and Technology.)

To investigate the dynamic homing process and characteristics of macrophages in different organs of immune-mediated aplastic anemia (AA) model mice. Macrophages in donor lymph nodes were sorted by magnetic beads and labeled with PKH67. After modeling according to the preparation method of the AA model, peripheral blood rountine analysis, bone marrow biopsy and HE staining results were analyzed to verify the modeling effect. On days 4, 8, and 12 of modeling, the bone marrow, spleen, and lymph node mononuclear cells were collected, and dynamic changes of PKH67-labeled macrophages in donor mice were analyzed by flow cytometry. In this study, dynamic changes in PKH67-labeled macrophages in the pathogenesis of AA model mice were explored. Macrophages in donor mice homed to the lymph nodes, expanding and differentiating in the lymph nodes, and finally transported to the bone marrow and spleen. Through proteomics mass spectrometry analysis, the related immune inflammatory response pathway of macrophages involved in the activation of the AA bone marrow microenvironment was preliminarily revealed, which provides a basis for the pathological macrophages involved in the pathogenesis of AA model mice.

Introduction and Hypothesis: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia., Methods: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia., Results: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828)., Conclusions: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery., (© 2024. The International Urogynecological Association.)

Objectives: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity., Methods: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity., Results: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I 2 =96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I 2 =94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I 2 >50 %)., Conclusions: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Currently, there is no specific perioperative nursing standard for RARC based on the ERAS concept. This retrospective study investigates to analyze the effect of RARC-ERAS nursing program on VTE and other clinical outcomes in patients undergoing RARC surgery. This retrospective study included 216 patients undergoing RARC surgery From January 1, 2022 to December 30, 2023, and propensity score adjustment analysis was applied. The study compares a control group receiving traditional nursing and an observation group receiving RARC-ERAS nursing program. Perioperative variables and other postoperative complications were retrieved from the hospital medical records. After propensity score matching, there were no significant differences in the demographic and clinical characteristics between the two groups (p > 0.05). The ERAS group exhibited aa significantly higher rate of postoperative unobstructed venous blood flow in the lower extremities by color Doppler ultrasound as compared to the control group (94.6% VS 80.4%, p = 0.042). Before anesthesia induction, lower preoperative anxiety and surgical information needs scores were observed in the ERAS group than in the control group (p < 0.05). Compared to the control group, the ERAS group demonstrated a shorter surgical duration, a lower incidence of perioperative hypothermia, less time needed for getting out of bed, anal exhaust, and for defecation after returning to the ward (p < 0.05). RARC-ERAS nursing program significantly increased the rate of postoperative unobstructed venous blood flow in the lower extremities by color doppler ultrasound, lower preoperative anxiety and intraoperative hypothermia in patients undergoing RARC. This nursing approach presents a valuable strategy for enhancing patient outcomes and merits further exploration in clinical practice.Trial registration:ChiCTR2400081118; http://www.chictr.org.cn , Principal investigator: Mang-mang He, Date of registration: Feb 22, 2024., (© 2024. The Author(s).)

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N -oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N -oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N -oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

Osteoarthritis (OA) is a prevalent joint disorder pathologically correlated to chondrocyte ferroptosis. Gamma-oryzanol (γ-Ory), as a first-line drug for autonomic disorders, aroused our interest because of its antioxidant, lipid-lowering, and hypoglycemic potential. The purpose of this study was to investigate the potential impact and mechanism of γ-Ory in treating OA. And the inhibition of γ-Ory in extracellular matrix molecule (ECM) degradation, ferroptosis, and Keap1-Nrf2 binding in IL-1β-exposed chondrocytes was detected via immunoblotting, immunofluorescence, and co-immunoprecipitation. Micro-CT, SO staining, and immunofluorescence have been conducted to assess the impact of γ-Ory treatment on ACLT-mediated OA in rats at both imaging and histological stages. We found that γ-Ory dose-dependently suppressed IL-1β-induced ECM deterioration and chondrocyte ferroptosis. Our animal experiments revealed that γ-Ory delayed ACLT-mediated OA development. Mechanistically, γ-Ory interfered with the binding of Keap1 to Nrf2 to promote the latter's nuclear import, thereby increasing the expression of detoxification enzymes. Summarily, our works support γ-Ory's potential as a candidate drug for the treatment of OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Membrane-bound organelles as well as membrane-free compartments exist in eukaryotic cells, which divide the nucleus and cytoplasm into distinct subregions and allow specific biochemical reactions to occur. The physiological mechanisms of membrane-bound organelles have been extensively characterized, but the formation and function of membrane-free compartments have not been thoroughly studied. Over the past decade, significant progress had been made in the studies about the role of liquid-liquid phase separation (LLPS) in the formation of membrane-free organelles. LLPS which serves as an aggregated separation mechanism for cellular biochemical reactions, is associated with a variety of physiological processes such as signal transduction and gene transcriptional regulation; while aberrant LLPS may contribute to the occurrence of developmental diseases. The present review investigates the role of LLPS as a mechanism of aggregation and segregation of cellular biochemical responses. The mechanisms of LLPS development and recent advances in the relationships between aberrant LLPS and developmental diseases are forward discussed, as well as how these advances may aid in the development of LLPS-based therapies.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Zhou, Jiang, Lan, Zhang, Tao and Chen.)

Background: Although the decreasing rate of hospital admission in the omicron wave has led countries to loosen control, still the patients requires ICU admission. It is common for viral respiratory infections to be co-infected with bacteria. However, the difference between co-infection and ICU-acquired infection on their clinical characteristics and outcomes during the Omicron wave was little reported., Methods: Clinical and microbiological data were collected from ICU patients with omicron infection between April 1st, 2022, and May 31th, 2022 and a comprehensive comparative study of the clinical characteristics and endpoint were conducted., Results: The Omicron SARS-CoV-2 variants-infected patients requiring intensive care had high rates of co-infection (42.55%). Additionally, the ICU COVID-19 patients with co-infection showed more severe clinical features compared to those with ICU-acquired infection. Furthermore, Multivariate Cox analysis demonstrated that co-infection (hazard ratio: 4.670, p  = 0.018) was a significant risk factor for poor outcomes in ICU patients with COVID-19. Besides, Kaplan-Meier survival curve analysis revealed that COVID-19 patients with co-infection had a significantly shorter 28-Day survival time compared to those with ICU-acquired infection ( p  < 0.001). Finally, our investigation identified a significant association between the presence of Candida app. in the broncho-alveolar lavage and an elevated risk of mortality (OR: 13.80, p  = 0.002) and invasive ventilation (OR: 5.63, p  = 0.01)., Conclusion: Co-infection is prevalent among patients requiring intensive care and is linked to unfavorable outcomes in the Omicron wave. Consequently, more attention may be needed for the empirical antibacterial treatment in ICU patients within the COVID-19 Omicron variant, especially anti-fungi., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhou, Huang, Shen and Li.)

Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system., Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact., Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively., Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Purpose: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study., Methods: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety., Results: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively., Conclusion: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified., Clinical Trial Number: NCT02474355., (© 2023. The Author(s).)

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3A high subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3A high cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3A high tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC., Competing Interests: None., (AJCR Copyright © 2023.)

Inflammasomes are important components of the innate immune system. They are assembled by cytoplasmic pattern recognition receptors and play a critical role in the pathogenesis and progression of various inflammatory diseases through regulating the release and activation of inflammatory cytokines and inducing cell prytosis. NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome has been widely studied and has been shown to be closely associated with cardiovascular diseases and metabolic disorders. Bone and joint diseases, such as osteoarthritis and rheumatoid arthritis show high prevalence worldwide and can cause bone and cartilage damage, pain, and dysfunction, adversely affecting the patients' quality of life. The reported findings of some studies indicate that the pathogenesis of various bone and articular diseases is associated with NLRP3 inflammasome. Small molecule antagonists targeting NLRP3 inflammasome have shown considerable therapeutic potentials, but their clinical application still needs further exploration. Herein, we reviewed the composition and function of NLRP3 inflammasome and its association with bone and articular diseases., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background and Objective: Neonatal jaundice is a common clinical disease in neonates. Pathologic jaundice is more harmful to neonates. There are a few studies on the biomarkers of pathologic jaundice and the correlation between gut microbiota and clinical indices. Therefore, we aimed to reveal the characteristics of gut microbiota in pathologic jaundice, provide potential biomarkers for the diagnosis of pathologic jaundice, and find the correlation between gut microbiota and clinical indices., Methods: Fourteen neonates with physiologic jaundice were recruited into a control group (Group A). Additionally, 14 neonates with pathologic jaundice were recruited into a case group (Group B). The microbial communities were analyzed using 16S rDNA sequencing. LEfSe and the differences in the relative abundance of gut microbiota were used to identify different bacteria among the two groups. The ROC curve was used to assess effective biomarkers for pathologic jaundice. Spearman's rank-sum correlation coefficient was used to evaluate the correlation between gut microbiota and clinical indices., Results: There were no differences in the total richness or diversity of gut microbiota between the two groups. At the phylum and genus levels, compared with the control group, Bacteroidetes ( p = 0.002) and Braydrhizobium ( p = 0.01) were significantly higher, while Actinobacteria ( p = 0.003) and Bidfldobacterium ( p = 0.016) were significantly lower in the case group. Bacteroidetes were valuable in differentiating pathologic jaundice from physiologic jaundice by the ROC curve, and the area under the ROC curve (AUC) value was 0.839 [95%CI (0.648-0.995)]. In the case group, Bacteroidetes were negatively associated with total bilirubin (TBIL) ( p < 0.05). In the control group, Bacteroidetes were positively associated with TBIL ( p < 0.05)., Conclusion: Bacteroidetes could be used as biomarkers to identify pathologic jaundice and Bacteroidetes are positively associated with bilirubin levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 You, Qiu, Li, Peng, Ma, Zhou, Fang, Huang and Xiao.)

Background: The use of cervical strain elastography for nulliparous women during late-term pregnancy remains unclear. This study assesses the predictive value of late-term cervical strain elastography for successful induction of labor (IOL) in nulliparous women., Methods: This single-centered, prospective study included 86 patients undergoing IOL between January 2020 and March 2022. Univariate and multivariate analyses were conducted to identify predictive factors for successful IOL. The predictive values were assessed using the area under receiver operating characteristic (ROC) curves., Results: IOL was successful in 58 patients. The hardness ratio and cervical length were significantly associated with successful late-term IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone., Conclusions: The hardness ratio and cervical length assessed by cervical strain elastography during late-term pregnancy are predictors of the success of IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone., (© 2023. The Author(s).)

Objective: Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts (AVGs), but the factors mediating this process are unclear. The purpose of this study was to investigate the role of endoplasmic reticulum stress (ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet (HFD) mice., Methods: CCAAT-enhancer-binding protein-homologous protein (CHOP) knockout (KO) mice were created. Mice were fed with HFD to produce HFD model. AVGs model were applied in the groups of WT ND, WT HFD, and CHOP KO HFD. Human umbilical vein endothelial cells (HUVECs) were cultured with oxidized low density lipoprotein (ox-LDL) (40 mg/L) for the indicated time lengths (0, 6, 12, 24 h). ERS inhibitor tauroursodeoxycholic acid (TUDCA) was used to block ERS. Immunohistochemical staining was used to observe the changes of ICAM1. Changes of ERS were detected by real-time RT-PCR. Protein expression levels and ERS activation were detected by Western blotting. Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay., Results: HFD increased neointima formation in AVGs associated with endothelial dysfunction. At the same time, ERS was increased in endothelial cells (ECs) after AVGs in mice consuming the HFD. In vitro, ox-LDL was found to stimulate ERS, increase the permeability of the EC monolayer, and cause endothelial dysfunction. Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL. In vivo, knockout of CHOP (CHOP KO) protected the function of ECs and decreased neointima formation after AVGs in HFD mice., Conclusion: Inhibiting ERS in ECs could improve the function of AVGs., (© 2023. Huazhong University of Science and Technology.)

Sorafenib, a multiple kinase inhibitor, is widely used in cancer patients. Recently, clinical studies highlighted the relationship between cognitive deficits and sorafenib exposure. Zinc abundant in the body has been reported to exert neuroprotective activities. However, the effects of zinc supplementation on sorafenib-induced cognitive impairment are still unknown. In the current study, we verified that mice challenged with sorafenib displayed characteristic features of cognitive impairment. However, zinc treatment effectively improved these changes. Histopathological staining also showed that zinc significantly alleviated hippocampal microstructural and ultrastructural damages induced by sorafenib. Meanwhile, zinc significantly reduced sorafenib-induced ROS production and neuronal cells apoptosis in vivo and vitro. Additionally, we also investigated whether zinc protected against sorafenib-induced neuronal cells apoptosis via ROS/JNK pathway through treating SH-SY5Y cells with the NAC or the specific JNK activator anisomycin. The results indicated that NAC performed the same protective effects as zinc in sorafenib-challenged SH-SY5Y cells and activation of JNK by anisomycin partly abolished the protective effects of zinc. Collectively, the present study suggested that inhibition of oxidative stress and the JNK pathway might contribute to the protective effects of zinc against sorafenib-caused cognitive impairment in vivo and vitro., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored., Methods and Results: FNDC5/irisin was reduced in natural ageing, senescence, and angiotensin II (Ang II)-treated conditions. The deletion of FNDC5 shortened lifespan in mice. Additionally, FNDC5 deficiency aggravated vascular stiffness, senescence, oxidative stress, inflammation, and endothelial dysfunction in 24-month-old naturally aged and Ang II-treated mice. Conversely, treatment of recombinant irisin alleviated Ang II-induced vascular stiffness and senescence in mice and vascular smooth muscle cells. FNDC5 was triggered by exercise, while FNDC5 knockout abrogated exercise-induced protection against Ang II-induced vascular stiffness and senescence. Intriguingly, FNDC5 was detected in human and mouse blood-derived EVs, and exercise-induced FNDC5/irisin-enriched EVs showed potent anti-stiffness and anti-senescence effects in vivo and in vitro. Adeno-associated virus-mediated rescue of FNDC5 specifically in muscle but not liver in FNDC5 knockout mice, promoted the release of FNDC5/irisin-enriched EVs into circulation in response to exercise, which ameliorated vascular stiffness, senescence, and inflammation. Mechanistically, irisin activated DnaJb3/Hsp40 chaperone system to stabilize SIRT6 protein in an Hsp70-dependent manner. Finally, plasma irisin concentrations were positively associated with exercise time but negatively associated with arterial stiffness in a proof-of-concept human study., Conclusion: FNDC5/irisin-enriched EVs contribute to exercise-induced protection against vascular ageing. These findings indicate that the exerkine FNDC5/irisin may be a potential target for ageing-related vascular comorbidities., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Current standard treatment includes lifestyle change, oral pharmacological agents, and surgical modalities. However, the efficacy of current therapies is less than satisfactory. Clinical evidence has shown that acupuncture is effective for regulating hormone levels, promoting ovulation, and attenuating insulin resistance in patients with PCOS. Acupuncture may affect the production of β-endorphin, which may lead to gonadotropin-releasing hormone secretion and then affect ovulation, menstrual cycle, and fertility. The mechanism of acupuncture for patients with PCOS has not been comprehensively reviewed so far. Better understanding of the mechanisms of acupuncture would help popularize the use of acupuncture therapy for patients with PCOS. In this narrative review, we aimed to overview the potential mechanisms and evidence-based data of acupuncture on PCOS, and analyze the most frequently used acupoints based on animal and clinical studies. The results of this study will contribute to a better understanding of the current situation in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Zhou, Hu, Fukuzawa and Zhang.)

Abdominal aortic aneurysm (AAA) is defined as a dilated aorta in diameter at least 1.5 times of a normal aorta. Our previous studies found that activating α7 nicotinic acetylcholine receptor (α7nAChR) had a protective effect on vascular injury. This work was to investigate whether activating α7nAChR could influence AAA formation and explore its mechanisms. AAA models were established by angiotensin II (Ang II) infusion in ApoE - /- mice or in wild type and α7nAChR -/- mice. In vitro mouse aortic smooth muscle (MOVAS) cells were treated with tumor necrosis factor-α (TNF-α). PNU-282987 was chosen to activate α7nAChR. We found that cell pyroptosis effector GSDMD and NLRP3 inflammasome were activated in abdominal aorta, and inflammatory cytokines in serum were elevated in AAA models of ApoE -/- mice. Activating α7nAChR reduced maximal aortic diameters, preserved elastin integrity and decreased inflammatory responses in ApoE -/- mice with Ang II infusion. While α7nAChR -/- mice led to aggravated aortic injury and increased inflammatory cytokines with Ang II infusion when compared with wild type. Moreover, activating α7nAChR inhibited NLRP3/caspase-1/GSDMD pathway in AAA model of ApoE -/- mice, while α7nAChR deficiency promoted this pathway. In vitro, N-acetylcysteine (NAC) inhibited NLRP3 inflammasome activation and NLRP3 knockdown reduced GSDMD expression, in MOVAS cells treated with TNF-α. Furthermore, activating α7nAChR inhibited oxidative stress, reduced NLRP3/GSDMD expression, and decreased cell pyroptosis in MOVAS cells with TNF-α. In conclusion, our study found that activating α7nAChR retarded AAA through inhibiting pyroptosis mediated by NLRP3 inflammasome. These suggested that α7nAChR would be a potential pharmacological target for AAA., (© 2022. The Author(s).)

Background: Hypoxemia is a common complication in older patients during postoperative recovery and can cause pulmonary complications. Therefore, reducing the incidence of postoperative hypoxemia is a clinical concern., Aim: To investigate the clinical efficacy of high-flow nasal cannula oxygen (HFNCO) in the resuscitation period of older orthopedic patients., Methods: In this prospective randomized controlled trial, 60 older patients who underwent orthopedic surgery under general anesthesia were randomly divided into two groups: those who used conventional face mask and those who used HFNCO. All patients were treated with 60% oxygen for 1 h after extubation. Patients in the conventional face mask group were treated with a combination of air (2 L) and oxygen (2 L) using a traditional mask, whereas those in the HFNCO group were treated with HFNCO at a constant temperature of 34 °C and flow rate of 40 L/min. We assessed the effectiveness of oxygen therapy by monitoring the patients' arterial blood gas, peripheral oxygen saturation, and postoperative complications., Results: The characteristics of the patients were comparable between the groups. One hour after extubation, patients in HFNCO group had a significantly higher arterial partial pressure of oxygen (paO 2 ) than that of patients in conventional face mask group ( P < 0.001). At extubation and 1 h after extubation, patients in both groups showed a significantly higher arterial partial pressure of carbon dioxide (paCO 2 ) than the baseline levels ( P < 0.001). There were no differences in the saturation of peripheral oxygen, paO 2 , and paCO 2 between the groups before anesthesia and before extubation ( P > 0.05). There were statistically significant differences in paO 2 between the two groups before anesthesia and 1 h after extubation and immediately after extubation and 1 h after extubation ( P < 0.001). However, there were no significant differences in the oxygen tolerance score before leaving the room, airway humidification, and pulmonary complications 3 d after surgery between the two groups ( P > 0.05)., Conclusion: HFNCO can improve oxygen partial pressure and respiratory function in elderly patients undergoing orthopedic surgery under general endotracheal anesthesia. Thus, HFNCO can be used to prevent postoperative hypoxemia., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aβ) generation in the brain. However, the potential effect of lead exposure on Aβ transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aβ clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1β in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aβ transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aβ 1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aβ endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aβ deposition in BCSFB and BBB and impairs Aβ clearance in the liver, which would ultimately disturb Aβ transportation via choroid plexus/brain microvessels and facilitate Aβ deposition in the brain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence-associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated., Methods: The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy., Results: 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high-senescent score group had significantly reduced overall survival compared with those in the low-senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune-associated pathways were increased in the low-senescent score group significantly. High-senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect., Conclusion: A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective: To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals., Design: Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort., Results: In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93)., Conclusion: Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection., Competing Interests: Competing interests: X-DD is the cofounder of Precogify Pharmaceutical. All other authors declare no conflicts of interest or competing financial interests with respect to this manuscript., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abdominal aortic aneurysm is defined as a dilated aorta with a diameter at least 1.5 times of the normal aorta.There is no effective drug for AAA.We summarized the high-risk factors,pathologic features,current therapies,and animal models in the pre-clinical study to gain comprehensive understanding of AAA.With this review,we aim to provide scientific support for the mining of therapeutic targets for AAA.

Microcystis aeruginosa, as a typical alga, produces microcystin with strong liver toxicity, seriously endangering the liver health of human and animals. Inhibiting the bloom of the Microcystis aeruginosa in lakes becomes a significant and meaningful work. Ultrasonic cavitation is currently considered to be the most environmentally friendly and effective method for the removal of Microcystis aeruginosa. However, the commercialized ultrasonic algae removal systems require multi-Langevin transducers to achieve omnidirectional ultrasonic irradiation due to the single irradiation direction of the Langevin transducer, resulting in the complex design and high energy consumption. To achieve a low-cost, simple structure, and high-efficiency algae removal system, a novel omnidirectional ultrasonic cavitation removal system for Microcystis aeruginosa is proposed. The proposed system is major composed of a novel omnidirectional ultrasonic transducer, which generates the omnidirectional ultrasonic irradiation by its shaking-head motion coupled by two orthogonal bending vibration modes. Modal simulation, sound field simulation, and cavitation bubble radius simulation are first carried out to optimize the geometric sizes of the proposed transducer and verify the correctness of the omnidirectional ultrasonic irradiation principle. Then the vibration characteristics of the transducer prototype are measured by vibration tests and impedance tests. Finally, the feasibility and effectiveness of the proposed omnidirectional ultrasonic removal system for Microcystis aeruginosa are evaluated through the algae removal experiments. The experimental results exhibit that the algal cells damaged by ultrasonic irradiation from the proposed system do not have the ability to self-repair. In addition, the algal removal rates reached 55.41% and 72.97% after 30 min of ultrasonic treatment when the corresponding ultrasonic densities are 0.014 W/mL and 0.021 W/mL, respectively. The proposed omnidirectional ultrasonic algae removal system significantly simplifies the configuration and reduces energy consumption, presenting the potential promise of algae removal and environmental protection., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

In line with the Healthy China strategy, new requirements for medical education have been raised. Medical education against the background of a new model of medicine demands an effective response to its inherent complex elements concerning the rule of law. During the course of the implementation of the new medicine strategy, in face of the widening scope of medical risks, the growing awareness of patient rights, and the conventional logic of medical education, elements concerning the rule of law should be incorporated in medical education in the early stage so as to help medical practitioners develop the appropriate legal literacy and rely on ideas of rules, equality and ethical bottomlines to analyze and solve problems. Thus, medical practitioners would be better equiped to effectively respond to the legal problems they encounter in their medical practice. Legal education is the route of choice in response to the transformation in the mode of medical education and the attempt to solve complicated problems through medicine and the rule of law. Through legal education, the risks of technology embeddedness could be avoided, the relationship between patients and medical practitioners could be regulated in a standardized way, and the medical humanistic environment could be reshaped, thereby improving the quality and level of new medical education., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Introduction: The therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and thereby suppress growth of tumors that rely on this signaling pathway. Herein, we characterize the humoral immune responses elicited by the recombinant EGF-CRM197 vaccine in patients with advanced solid tumors in a phase I clinical trial and assess the safety, tolerability, and immunogenicity of this vaccine (CTR20190473)., Methods: A total of 16 subjects were enrolled in this study. Under 6 + 3 design, patients in each dosing cohort were administrated subcutaneously at a dosage of 0.4 mg, 0.8 mg, and 1.6 mg, respectively. The patients received vaccinations for immune induction (once a week for 4 consecutive weeks) and booster vaccinations (once every 4 weeks). Safety evaluation was performed 1 week after the immune induction. Booster vaccination was given until the occurrence of disease progression, intolerance, withdrawal of informed consent by the patient, or negative result of anti-EGF test after two booster vaccinations., Results: Vaccination with EGF-CRM197 is safe and well-tolerated in patients with advanced solid tumors. Adverse reactions at the injection site were the most common adverse events (AEs) in recipients. No severe adverse reactions post vaccination were observed in the present study. Vaccinated patients developed a robust neutralizing antibody response triggered by EGF-CRM197 that significantly reduced the levels of EGF in serum. For lung cancer patients who were super good antibody responders (sGAR) to EGF-CRM197, the median progress-free survival (PFS) was 4.83 months, significantly longer than that of the good antibody responder (GAR) patients with lung cancer whose median PFS was 2.10 months (P=0.0018). The median overall survival (OS) of GAR lung cancer patients was 10.67 months while the OS) for sGAR lung cancer patients was not reached until analysis was performed. The median follow-up of the sGAR lung cancer patients was 14.6 months., Conclusion: Our study demonstrates that the recombinant EGF-CRM197 therapeutic cancer vaccine can induce a good immune response in patients with advanced solid tumors and is safe and well tolerated, which ensures further clinical development of the vaccine for extending the survival time of EGF-CRM197 sensitive patients with advanced solid tumors., Clinical Trial Registration: http://www.chinadrugtrials.org.cn, identifier CTR20190473, EGF-CRM197., Competing Interests: Author G-YC is employed by Shanghai Humantech Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from Shanghai Humantech Biotechnology Co., Ltd. The funder had the following involvement: study design, data analysis and preparation of the manuscript., (Copyright © 2021 Xiong, Fang, Ren, Li, Wang, Zhao, Chen, Xu and Zhou.)

As a self-protective mechanism for cells to obtain energy by degrading their own structures or substances, autophagy widely occurs in basic physiological process of all kinds of eukaryotic cells. In recent years, studies have shown that autophagy can be induced through a variety of mechanical transduction pathways when various tissues and cells are exposed to different types of mechanical stress, and cells and tissues involved can thus regulate cell metabolic functions and participate in the pathological process of a variety of diseases. The stress receptors on the cell membrane and the multiple signaling pathways and cytoskeletons have been shown to play an important role in this process. At present, due to the difficulties in the establishment of the stress loading model and the limitations in the research methods concerned, the specific mechanical transduction mechanisms of autophagy induced by mechanical stress is not clear. Therefore, more reliable in vitro and in vivo models and more advanced research methodology are needed to investigate the mechanical transduction process of autophagy induced by mechanical stress, and to promote ultimately progress in the understanding of autophagy-related diseases and their treatments. This article reviewed the regulatory role of mechanical stress on autophagy in physiological and disease processes and the signal transduction process related to autophagy induced by mechanical stress., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro . Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Zhou, Deng, Wang and Chen.)