Objective:To explore the predictive factors for extubation in the operating room after single lung transplantation without the assistance of extracorporeal membrane oxygenation (ECMO) in adult patients with end-stage interstitial lung disease (ILD), as well as their short-term (1-year postoperative) prognosis.Methods:A retrospective analysis was conducted on the clinical data of 78 adult ILD recipients who underwent single lung transplantation without ECMO assistance at the First Affiliated Hospital of Guangzhou Medical University from June 2018 to June 2023. Based on whether extubation was completed in the operating room (OR), patients were divided into the OR group (19 cases) and ICU group (59 cases). Baseline characteristics of donors and recipients, as well as intraoperative events, were compared between the two groups. Univariate logistic regression analysis was used to identify potential predictors, and variables with P<0.2 were included in multivariate logistic regression to determine independent predictors for OR extubation. Receiver operating characteristic (ROC) curves were plotted to evaluate predictive performance. The Kaplan-Meier method was used to analyze survival, and short-term prognosis between groups was compared. Results:The rate of OR extubation after single lung transplantation in ILD recipients was 24%(19/78). Compared with the ICU group, the OR group had shorter operation times, lower fluid volumes, reduced transfusions of red blood cells and plasma, less intraoperative bleeding, and lower lactate levels 15 minutes after pulmonary artery reperfusion (all P<0.05). Univariate logistic regression analysis identified the following factors as significantly associated with OR extubation: recipient age ( P=0.100), operative time ( P=0.001), fluid infusion volume ( P=0.005), red blood cell transfusion volume ( P=0.037), plasma transfusion volume ( P=0.039), blood loss ( P=0.004), oxygenation index at 15 minutes after reperfusion ( P=0.174), and blood lactate at 15 minutes after reperfusion ( P=0.041). Multivariate analysis revealed that intraoperative blood loss was an independent predictor of OR extubation ( OR=0.993, 95% CI: 0.986 - 0.999, P=0.026). ROC curve analysis showed that blood loss had an area under the curve (AUC) of 0.822 in predicting OR extubation, with a sensitivity of 64.4% and specificity of 89.5%. Postoperatively, patients in the OR group had significantly shorter durations of mechanical ventilation [0 vs 5 (3,11) days, P<0.001], ICU stay [7(4,8) vs 9(6,20) days, P=0.012], and overall postoperative hospitalization [19 (15,23) vs 25 (19,39) days, P=0.015]. Within one year after surgery, 2 patients (11%) in the OR group and 19 patients (32%) in the ICU group had died, but the difference in 1-year survival rates between the two groups was not statistically significant. Conclusions:Intraoperative blood loss is an independent predictor of extubation in the operating room. Early extubation in non-ECMO-assisted single lung transplantation for ILD patients is associated with improved short-term outcomes.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20％.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Objective:To explore the predictive factors for extubation in the operating room after single lung transplantation without the assistance of extracorporeal membrane oxygenation (ECMO) in adult patients with end-stage interstitial lung disease (ILD), as well as their short-term (1-year postoperative) prognosis.Methods:A retrospective analysis was conducted on the clinical data of 78 adult ILD recipients who underwent single lung transplantation without ECMO assistance at the First Affiliated Hospital of Guangzhou Medical University from June 2018 to June 2023. Based on whether extubation was completed in the operating room (OR), patients were divided into the OR group (19 cases) and ICU group (59 cases). Baseline characteristics of donors and recipients, as well as intraoperative events, were compared between the two groups. Univariate logistic regression analysis was used to identify potential predictors, and variables with P<0.2 were included in multivariate logistic regression to determine independent predictors for OR extubation. Receiver operating characteristic (ROC) curves were plotted to evaluate predictive performance. The Kaplan-Meier method was used to analyze survival, and short-term prognosis between groups was compared. Results:The rate of OR extubation after single lung transplantation in ILD recipients was 24%(19/78). Compared with the ICU group, the OR group had shorter operation times, lower fluid volumes, reduced transfusions of red blood cells and plasma, less intraoperative bleeding, and lower lactate levels 15 minutes after pulmonary artery reperfusion (all P<0.05). Univariate logistic regression analysis identified the following factors as significantly associated with OR extubation: recipient age ( P=0.100), operative time ( P=0.001), fluid infusion volume ( P=0.005), red blood cell transfusion volume ( P=0.037), plasma transfusion volume ( P=0.039), blood loss ( P=0.004), oxygenation index at 15 minutes after reperfusion ( P=0.174), and blood lactate at 15 minutes after reperfusion ( P=0.041). Multivariate analysis revealed that intraoperative blood loss was an independent predictor of OR extubation ( OR=0.993, 95% CI: 0.986 - 0.999, P=0.026). ROC curve analysis showed that blood loss had an area under the curve (AUC) of 0.822 in predicting OR extubation, with a sensitivity of 64.4% and specificity of 89.5%. Postoperatively, patients in the OR group had significantly shorter durations of mechanical ventilation [0 vs 5 (3,11) days, P<0.001], ICU stay [7(4,8) vs 9(6,20) days, P=0.012], and overall postoperative hospitalization [19 (15,23) vs 25 (19,39) days, P=0.015]. Within one year after surgery, 2 patients (11%) in the OR group and 19 patients (32%) in the ICU group had died, but the difference in 1-year survival rates between the two groups was not statistically significant. Conclusions:Intraoperative blood loss is an independent predictor of extubation in the operating room. Early extubation in non-ECMO-assisted single lung transplantation for ILD patients is associated with improved short-term outcomes.