Bacterial therapy has attracted increasing attention due to its special mechanism and abundant applications. With the flourishing development of synthetic biology, therapeutic genes have been introduced into engineering bacteria to improve their antitumor efficacy. However, it is difficult to spatiotemporally control the expression of these therapeutic genes at the tumor site in vivo, thereby considerably limiting the application of engineered bacteria in tumor treatment. To resolve this problem, we constructed a temperature-responsive bacterial strain capable of triggering the expression of exogenous genes in a laser-controllable way. Noxa, a pro-apoptotic protein, is chosen to test the expression of exogenous protein and its anti-tumor effect in engineered bacteria upon laser irradiation. Firstly, Noxa was fused to the C-terminus of the bacterial outer membrane protein cytolysin A (ClyA), and then the recombinant gene fragment ClyA-Noxa was inserted into the temperature-sensitive plasmid pBV220 and the recombinant plasmid was transformed into non-pathogenic Escherichia coli MG1655. Thus, we constructed the engineering strain (TRB@Noxa) that could express Noxa on the bacterial surface. TRB@Noxa could target and colonize the tumor tissue without causing notable host toxicity. The bacterial infection triggered thrombosis in the tumor tissue, resulting in the darkness of tumor sites. In a xenograft mouse tumor model, our strategy demonstrated precise tumor targeting and strong tumor inhibition. In conclusion, we successfully constructed a new engineering bacterial strain TRB@Noxa. TRB@Noxa combined with photothermal therapy could arrest tumor growth in the absence of photosensitizers, which represents an appealing method for antitumor therapy in the future.
Escherichia coli/radiation effects* ; Animals ; Humans ; Lasers ; Mice ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Neoplasms/therapy* ; Genetic Engineering ; Cell Line, Tumor ; Escherichia coli Proteins/genetics*

Objective:To analyze the clinical characteristics of dissociative symptoms induced by esketamine hydrochloride nasal spray in patients with treatment-resistant depression (TRD).Methods:The medical records of patients in phase Ⅲ clinical trials for the treatment of TRD who received esketamine hydrochloride nasal spray in Beijing Anding Hospital, Capital Medical University from June 2018 to February 2021 were collected. The general situation of patients (age, gender, comorbid diseases, etc.), the medication of esketamine hydrochloride nasal spray, the combined use of antidepressants, the time from medication to the occurrence of dissociative symptoms each time, duration, severity, evaluation results of causal relationship with esketamine application, intervention and prognosis were recorded, and a retrospective descriptive statistical analysis was performed.Results:A total of 21 patients with TRD were enrolled in the study, including 17 (81.0%) with dissociative symptoms, 10 males and 7 females; the age ranged from 20 to 53 years, with a median age of 36 years. All patients were treated with esketamine hydrochloride by nasal spray. The first dose was 56 mg, and the other seven doses were 56 mg or 84 mg, twice a week, lasting for 4 weeks. The 17 patients were all given combination treatment with oral antidepressants. A total of 88 times of dissociative symptoms occurred in the 17 patients. The time from medication to the onset of dissociative symptoms ranged from 4 to 128 min, with a median time of 15 min. The duration of dissociative symptoms ranged from 12 to 326 minutes, with a median time of 70 minutes. The dissociative symptoms were mostly mild. The causal relationship analysis between the esketamine hydrochloride nasal spray and the dissociative symptoms showed that it was definitely related in 6 cases, probably in 1 case, and possibly in 10 cases. The dissociative symptoms in all patients were subsided without intervention.Conclusions:Esketamine hydrochloride nasal spray can cause dissociative symptoms in patients with TRD, most of which occur within 30 minutes after the treatment. The duration of symptoms in most patients is less than 120 minutes, most of which are mild and can subside on their own, and the prognosis is good.

Objective:To analyze the clinical characteristics of dissociative symptoms induced by esketamine hydrochloride nasal spray in patients with treatment-resistant depression (TRD).Methods:The medical records of patients in phase Ⅲ clinical trials for the treatment of TRD who received esketamine hydrochloride nasal spray in Beijing Anding Hospital, Capital Medical University from June 2018 to February 2021 were collected. The general situation of patients (age, gender, comorbid diseases, etc.), the medication of esketamine hydrochloride nasal spray, the combined use of antidepressants, the time from medication to the occurrence of dissociative symptoms each time, duration, severity, evaluation results of causal relationship with esketamine application, intervention and prognosis were recorded, and a retrospective descriptive statistical analysis was performed.Results:A total of 21 patients with TRD were enrolled in the study, including 17 (81.0%) with dissociative symptoms, 10 males and 7 females; the age ranged from 20 to 53 years, with a median age of 36 years. All patients were treated with esketamine hydrochloride by nasal spray. The first dose was 56 mg, and the other seven doses were 56 mg or 84 mg, twice a week, lasting for 4 weeks. The 17 patients were all given combination treatment with oral antidepressants. A total of 88 times of dissociative symptoms occurred in the 17 patients. The time from medication to the onset of dissociative symptoms ranged from 4 to 128 min, with a median time of 15 min. The duration of dissociative symptoms ranged from 12 to 326 minutes, with a median time of 70 minutes. The dissociative symptoms were mostly mild. The causal relationship analysis between the esketamine hydrochloride nasal spray and the dissociative symptoms showed that it was definitely related in 6 cases, probably in 1 case, and possibly in 10 cases. The dissociative symptoms in all patients were subsided without intervention.Conclusions:Esketamine hydrochloride nasal spray can cause dissociative symptoms in patients with TRD, most of which occur within 30 minutes after the treatment. The duration of symptoms in most patients is less than 120 minutes, most of which are mild and can subside on their own, and the prognosis is good.

With the continuous development of China's economy,the people expect for higher quality medical services,and medical humanistic care is increasingly emphasized.Under this background,the"Duplex Linkage Mode",which integrates medical social workers and volunteers,has emerged.This paper reviews the current state of applying the mode in China,ex-pounds its benefits,and details its application within hospital services.This application covers guidance for outpatient and emer-gency department,inpatient ward services,hospice care,and community residents volunteer services.In addition,this paper proposes suggestions on furth for optimizing recruitment and training programs,improving management systems,establishing intel-ligent management systems,and improving volunteer support mechanisms.These measures aim to promote the sustainable and healthy development of medical humanistic services and to support the implementation of the Healthy China Initiative.

Objective To investigate the current status of compassion fatigue among nurses in the geriatrics department of a tertiary hospital in Chongqing,analyze its influencing factors,and construct a predictive model.Methods A total of 39 nurses from the geriatrics department were enrolled as study participants.General demographic data were collected,and the Chi-nese versions of the Compassion Fatigue Scale,Big Five Personality Scale,and Social Support Rating Scale were used to assess the nurses'compassion fatigue,Big Five personality traits,and social support.A logistic regression model was constructed to ana-lyze the data.Results Among the 39 nurses,31 experienced compassion fatigue,with an incidence rate of 79.49％.Univariate analysis revealed that average daily working hours,income satisfaction,job satisfaction,and sleep quality had significant impacts on the occurrence of compassion fatigue(P＜0.05).Correlation analysis showed that compassion satisfaction scores were posi-tively correlated with conscientiousness and negatively correlated with neuroticism.Multiple regression analysis confirmed the sig-nificant relationship between neuroticism and compassion satisfaction.The regression equation was established as follows:Com-passion Satisfaction Score=28.104-4.111 x Average Daily Working Hours-2.171 x Income Satisfaction-2.83 x Job Satis-faction-0.226 x Sleep Quality-0.452 x Neuroticism Score+0.721 x Conscientiousness Score+0.176 x Subjective Support Score+0.684 x Support Utilization.Conclusion Neuroticism is an independent influencing factor of compassion fatigue among nurses in the geriatrics department.The constructed logistic regression model provides valuable reference for the management of compassion fatigue and offers new scientific evidence for the early clinical identification of nurses at risk of compassion fatigue.

Objective To investigate the current status of compassion fatigue among nurses in the geriatrics department of a tertiary hospital in Chongqing,analyze its influencing factors,and construct a predictive model.Methods A total of 39 nurses from the geriatrics department were enrolled as study participants.General demographic data were collected,and the Chi-nese versions of the Compassion Fatigue Scale,Big Five Personality Scale,and Social Support Rating Scale were used to assess the nurses'compassion fatigue,Big Five personality traits,and social support.A logistic regression model was constructed to ana-lyze the data.Results Among the 39 nurses,31 experienced compassion fatigue,with an incidence rate of 79.49％.Univariate analysis revealed that average daily working hours,income satisfaction,job satisfaction,and sleep quality had significant impacts on the occurrence of compassion fatigue(P＜0.05).Correlation analysis showed that compassion satisfaction scores were posi-tively correlated with conscientiousness and negatively correlated with neuroticism.Multiple regression analysis confirmed the sig-nificant relationship between neuroticism and compassion satisfaction.The regression equation was established as follows:Com-passion Satisfaction Score=28.104-4.111 x Average Daily Working Hours-2.171 x Income Satisfaction-2.83 x Job Satis-faction-0.226 x Sleep Quality-0.452 x Neuroticism Score+0.721 x Conscientiousness Score+0.176 x Subjective Support Score+0.684 x Support Utilization.Conclusion Neuroticism is an independent influencing factor of compassion fatigue among nurses in the geriatrics department.The constructed logistic regression model provides valuable reference for the management of compassion fatigue and offers new scientific evidence for the early clinical identification of nurses at risk of compassion fatigue.

Objective:To explore the relationship between red meat intake level and the incidence of stroke in Chinese adults.Methods:The baseline data were from China Chronic Disease Surveillance Project conducted in 60 surveillance sites in 11 provinces in China in 2010. A total of 27 762 subjects with complete data in baseline survey were included in the cohort follow-up from 2016 to 2017. Multivariate nutrient-density cox proportional hazards regression model was used to analyze the association between red meat intake level and the incidence of stroke. Subgroup analysis were performed based on baseline characteristics. Sensitivity analysis was performed by using standard multivariate model, energy partition model and nutrient residual model.Results:In the 26 187 subjects, 1 259 stroke cases, including 1 074 ischemic stroke cases, occurred during an average of 6.0 years of follow-up, the incidence density was 815.0/100 000 person-years for stroke and 692.0/100 000 person-years for ischemic stroke. In models using the multivariate nutrient-density model of energy adjustment, compared with quintile group, red meat intake in quintile 2 group showed no significant association with stroke [hazard ratio ( HR)=1.07, 95% CI: 0.87-1.32] and ischemic stroke ( HR=1.03, 95% CI: 0.80-1.32) and in group of quintile 3-5, the red meat intake related risk for stroke increased by 23% ( HR=1.23, 95% CI: 1.00-1.51), 27% ( HR=1.27, 95% CI: 1.03-1.58) and 32% ( HR=1.32, 95% CI: 1.06-1.64), respectively, while the risk for ischemic stroke increased by 32% ( HR=1.32, 95% CI: 1.04-1.68), 35% ( HR=1.35, 95% CI: 1.05-1.73) and 38% ( HR=1.38, 95% CI: 1.07-1.79), respectively. Subgroup analysis revealed that blood pressure had modification effect on the association between red meat intake and incidence of stroke (interaction P=0.037). The sensitivity analysis showed no changes. Conclusions:These findings suggest that higher intake of red meat is significantly associated with an increased risk for stroke and ischemic stroke. It is necessary to take red meat intake level as one of the important indicators of stroke prevention and control.

Objective To investigate the expression and prognostic value of FOXO1 gene in liver cancer tissues based on TCGA and HPA databases. Methods The RNA-seq data of FOXO1 gene in liver cancer were downloaded from TCGA. The difference of FOXO1 gene expression between tumor and adjacent tissues was obtained via R software. The correlation between FOXO1 and clinicopathological features of liver cancer patients was analyzed. Survival analysis was carried out to evaluate the prognostic significance of FOXO1 gene expression in liver cancer patients. Univariate and multivariate Cox analyses were performed to explore prognostic factors. The correlation between FOXO1 expression and TIICs in tumor microenvironment was performed by CIBERSORT. KEGG pathways enrichment analysis was performed for the potential function of FOXO1 gene in liver cancer. Results FOXO1 was downregulated in liver cancer tissues compared with normal tissues (P=1.321E-15). Survival analysis showed that high expression of FOXO1 was positively associated with favorable OS of liver cancer patients (P < 0.05). Clinical stage, T and M stages could be prognostic indicators while FOXO1 wasn't an independent prognostic factor in patients with liver cancer. In TME of liver cancer, the expression of FOXO1 was positively correlated with resting memory CD4 T cells and naive B cells while negatively related to activated memory CD4 T cells and macrophages M2. GSEA identified that FOXO1 participated in multiple cancer-related pathways. Conclusion FOXO1 is down-regulated in liver cancer tissues, and its expression level is associated with OS of patients. FOXO1 might be a biomarker related to the prognosis of liver cancer patients and is expected to be a target for diagnosis and treatment of liver cancer.

China still has more than 30,000 patients of advanced schistosomiasis while new cases being reported consistently. D-dimer is a fibrin degradation product. As ascites being the dominating symptom in advanced schistosomiasis, the present study aimed to explore a prediction model of ascites with D-dimer and other clinical easy-achievable indicators. A case-control study nested in a prospective cohort was conducted in schistosomiasis-endemic area of southern China. A total of 291 patients of advanced schistosomiasis were first investigated in 2013 and further followed in 2014. Information on clinical history, physical examination, and abdominal ultrasonography, including the symptom of ascites was repeatedly collected. Result showed 44 patients having ascites. Most of the patients' ascites were confined in the kidney area with median area of 20 mm². The level of plasma D-dimer and pertinent liver function indicators were measured at the initial investigation in 2013. Compared with those without ascites, cases with ascites had significantly higher levels of D-dimer (0.71±2.44 μg/L vs 0.48±2.12 μg/L, P=0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04 vs 44.50 μg/L). Receiver operating characteristic curve analyses indicated a moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64 (95% CI: 0.54–0.73) and the cutoff value as 0.81 μg/L. Dichotomized by the cutoff level, D-dimer along with other categorical variables generated a prediction model with AUC of 0.76 (95% CI: 0.68–0.89). Risks of patients with specific characteristics in the prediction model were summarized. Our study suggests that the plasma D-dimer level is a reliable predictor for incident ascites in advanced schistosomiasis japonica patients.
Area Under Curve ; Ascites* ; Case-Control Studies ; China ; Cohort Studies ; Collagen Type IV ; Fibrin ; Humans ; Kidney ; Liver ; Physical Examination ; Plasma* ; Prospective Studies* ; ROC Curve ; Schistosoma japonicum ; Schistosomiasis japonica* ; Schistosomiasis* ; Ultrasonography