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 explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

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.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

Objective:To investigate the association of risky drinking and decision-making ability among off-spring of fathers with alcohol dependence(OFAD).Methods:A case-control study was conducted according to the cutoff of the Alcohol Use Disorder Identification Test(AUDIT)(delimited as 7).OFAD were divided into"risky drinking group"(n=29)and"non-risky drinking group"(n=43).The Iowa Gambling Task(IGT)was used to e-valuate the decision-making ability.Covariance analysis was used to compare differences of IGT between the two groups,and multivariate logistic regression was used to explore the association between risky drinking and decision making ability.Results:There was no significant difference in total scores of IGT between the risky drinking group and the non-risky drinking group(P＞0.05).Risky drinking group had less Selection 2 in block 5 of IGT[(3.8± 2.5)v.s.(5.7±3.1),P＜0.05]than non-risky drinking group.Selection 2 in block 5 was still associated with risky drinking after controlling the covariates(OR=0.72,95％CI:0.57～0.90,P＜0.05).Conclusion:This study indicates that risky drinking group in offspring of parents with alcohol dependence may have better decision-making ability.

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

In an effort to generate a desired expression construct for making heart-specific expression transgenic zebrafish, a Tol2 plasmid, which can drive EGFP reporter gene specifically expressed in the heart, was modified using subcloning technology. An IRES fragment bearing multiple cloning site (MCS) was amplified directly from pIRES2-EGFP plasmid and was inserted between the CMLC2 promoter and EGFP fragment of the pDestTol2CG vector. This recombinant expression plasmid pTol2-CMLC2-IRES-EGFP can drive any interested gene specifically expressed in the zebrafish heart along with EGFP reporter gene. To test the effectiveness of this new expression plasmid, we constructed pTol2-CMLC2-RED-IRES-EGFP plasmid by inserting another reporter gene DsRed-Monome into MCS downstream of the CMLC2 promoter and injected this transgenic recombinant plasmid into one-cell stage embryos of zebrafish. Under fluorescence microscope, both the red fluorescence and the green fluorescence produced by pTol2-CMLC2-RED-IRES-EGFP were detected specifically in the heart tissue in the same expression pattern. This novel expression construct pTol2-CMLC2-IRES-EGFP will become an important tool for our research on identifying heart development candidate genes' function using zebrafish as a model.
Animals ; Animals, Genetically Modified ; genetics ; growth & development ; DNA Transposable Elements ; genetics ; Genes, Reporter ; genetics ; Genetic Vectors ; biosynthesis ; genetics ; Green Fluorescent Proteins ; genetics ; Myocardium ; metabolism ; Plasmids ; genetics ; Transfection ; Transgenes ; Transposases ; genetics ; Zebrafish ; genetics ; Zebrafish Proteins ; genetics ; metabolism