Causal connectivity measures for pulse-output network reconstruction: Analysis and applications.

The causal connectivity of a network is often inferred to understand network function. It is arguably acknowledged that the inferred causal connectivity relies on the causality measure one applies, and it may differ from the network's underlying structural connectivity. However, the interpretation of causal connectivity remains to be fully clarified, in particular, how causal connectivity depends on causality measures and how causal connectivity relates to structural connectivity. Here, we focus on nonlinear networks with pulse signals as measured output, e.g., neural networks with spike output, and address the above issues based on four commonly utilized causality measures, i.e., time-delayed correlation coefficient, time-delayed mutual information, Granger causality, and transfer entropy. We theoretically show how these causality measures are related to one another when applied to pulse signals. Taking a simulated Hodgkin-Huxley network and a real mouse brain network as two illustrative examples, we further verify the quantitative relations among the four causality measures and demonstrate that the causal connectivity inferred by any of the four well coincides with the underlying network structural connectivity, therefore illustrating a direct link between the causal and structural connectivity. We stress that the structural connectivity of pulse-output networks can be reconstructed pairwise without conditioning on the global information of all other nodes in a network, thus circumventing the curse of dimensionality. Our framework provides a practical and effective approach for pulse-output network reconstruction.

[Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA].

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.

[Study on the relationship between indexes of different abnormal weight and dyslipidemia in adults in Beijing City].

Objective: To analyze the relationship and consistency between indexes of different abnormal weight and dyslipidemia in adults in Beijing City. Methods: From August to December of 2017, 4 975 residents aged 18 to 79 years old in 5 districts of Beijing were randomly selected as subjects by using a multi-stage stratified cluster sampling method. Questionnaire, physical examination and laboratory tests were conducted. The prevalence of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was calculated. Partial correlation was used to analyze the correlation of blood lipid with body mass index (BMI), body fat rate, waist circumference and waist-height ratio. Logistic regression analysis for complex sampling was used to analyze the relationship between indexes of different abnormal weight and dyslipidemia after controlling for relevant risk factors, including age, sex, smoking status, drinking, insufficiency intake of vegetable and fruit, physical inactivity. Kappa value was computed to analyze the consistency between indexes of different abnormal weight. Results: The weighted prevalence of dyslipidemia was 30.48%, and it was higher in men than that in women (40.16% vs. 20.52%, P<0.01). The weighted rate of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was 56.65%, 47.52%, 42.48% and 59.45%, respectively. BMI, body fat rate, waist circumference and waist-to-height ratio were positively correlated with the level of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and negatively correlated with high-density lipoprotein cholesterol. Logistic regression analysis for complex sampling showed that the high body fat rate (OR=1.67, 95%CI: 1.35-2.07), overweight/obesity (OR=1.65, 95%CI: 1.26-2.14) and high waist-to-height ratio (OR=1.46, 95%CI: 1.09-1.96) were associated with dyslipidemias. Kappa values of high body fat rate with overweight/obesity, high waist-to-height ratio and central obesity were 0.65, 0.53 and 0.58, respectively (P<0.05). Conclusion: In 2017, the prevalence of dyslipidemia in adults in Beijing City is high, especially in men. Overweight/obesity, high body fat rate and high waist-to-height ratio are associated with dyslipidemia. The high body fat rate is most associated with dyslipidemia.

[Investigation on knowledge, attitude and behavior of salt reduction in adults of Beijing in 2017].

Objective: To explore the knowledge, attitude and behavior of salt reduction in adults of Beijing in 2017. Methods: Based on the monitoring data of chronic diseases and corresponding risk factors in adults of Beijing in 2017, the indicators of salt reduction knowledge, attitude and behavior of 13 240 participants aged 18-79 years old were analyzed. The awareness rate, attitude support rate and behavior rate were calculated by complex weighting method, and compared among different age groups, genders, residential areas, and history of hypertension. The proportion of people taking various salt reduction measures to the total number of people was compared. Results: The awareness rate of recommended daily salt intake, the awareness of hypertension caused or aggravated by more salt intake, the attitude support rate and behavior rate of adults were 31.77%, 88.56%, 90.27% and 53.86%, respectively. After weighted adjustment, the awareness rate of recommended daily salt intake was 31.08%, which increased with age (χ2trend=431.56, P<0.001) and education level (χ2trend=95.44, P<0.001). The awareness rate of women was higher than that of men (χ²=118.89, P<0.001), and the awareness rate of population in urban areas was higher than that of population in suburban areas (χ²=34.09, P=0.001). The awareness rate of hypertension caused or aggravated by eating more salt was 86.73%. The support rate of salt reduction attitude was 90.45%. The rate of salt-reducing behavior was 54.05%. Among different salt reduction measures, reducing salt when cooking was the most common measure (52.41%), while the least common one (35.22%) was using low sodium salt. Logistic regression model analysis showed that the gender, age, education level, self-reported history of hypertension, awareness of salt recommendation, awareness of hypertension caused or aggravated by eating more salt, and salt reduction attitude were significantly associated with salt reduction behavior. Conclusion: In 2017, adults in Beijing have a basic understanding of the impact of high-salt diet on health and support salt reduction, but the rate of salt reduction behavior is still relatively low. There are obvious gender and age differences, and the salt reduction measure is simple. Targeted measures should be taken to promote the formation of salt reduction behavior.

[Analysis of the current status and related factors of oral nutritional supplements intake among 18-79 years old in Beijing in 2017].

Objective: To understand the current status of taking nutrient supplements for residents aged 18 to 79 years old in Beijing and its related factors. Methods: Data were gathered from the 2017 Beijing Non-communicable and Chronic Disease Surveillance Program. Multiple classified cluster sampling method was used, and participants aged 18-79 were sampled from 16 districts. The questionnaire included chronic diseases and related risk factors, health knowledge, and oral nutritional supplements within 12 months. Multivariate logistic regression models were established to analyze associated factors that affect the intake of nutrient supplements. Results: The weighted prevalence of supplements use was 13.1% among 12 696 subjects within the past 12 months. The proportions of multivitamins (4.7%), B vitamins (4.5%), and folic acid (3.2%) were higher. The prevalence of supplement use of young people (18-39 years old) and the elderly (60-79 years old) was higher than middle-aged people (40-59 years old) (χ2=54.09, P<0.001). Except for the age group of 70-79 years old, the consumption rate of women was significantly higher than that of men (P<0.05). After adjusting age and sex, among patients with hypertension, diabetes, or dyslipidemia, the control rates of blood pressure, glucose and lipids of patients who take nutrient supplements were higher than those who do not (P<0.05). And participants who took nutrient supplements had a more heightened awareness rate of health knowledge, such as the hazards of smoking and second-hand smoke, and recommended amount of salt per day (P<0.001). The multi-factor logistic analysis found that nutrient supplement-related factors include women, old age, higher education level, living in urban, insufficient physical activity, sleeping problems, active physical examination, blood pressure control among patients, and health knowledge (P<0.05). Conclusions: The factors of nutrient supplements use were related to sex, age, education level, health status, and health literacy. We should pay attention to key populations and guide them to establish the correct concept of taking nutrient supplements.

[Long-term safety and activity of humanized CD19 chimeric antigen receptor T cells for children and young adults with relapsed/refractory acute lymphoblastic leukemia].

Objective: To investigate the efficacy and safety of humanized CD19-specific chimeric antigen receptor T cells (hCART19s) in treating children and young adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and to analyze relevant factors affecting its curative effect and prognosis. Methods: We conducted a single-center clinical trial involving 31 children and young adult patients with R/R B-ALL who were treated with humanized CD19-specific CAR-T cells (hCART19s) from May 2016 to September 2021. Results: Results showed that 27 (87.1%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) one month after CAR-T cell infusion. During treatment, 20 (64.5%) patients developed grade 1-2 cytokine release syndrome (CRS) , and 4 (12.9%) developed grade 3 CRS. Additionally, two patients had grade 1 neurological events. During the follow-up with a median time of 19.3 months, the median event-free survival (EFS) was 15.7 months (95% CI 8.7-22.5) , and the median overall survival (OS) was 32.2 months (95% CI 10.6-53.9) . EFS and OS rates were higher in patients who have undergone hemopoietic stem cell transplantation (HSCT) than in those without [EFS: (75.0 ± 12.5) % vs (21.1 ± 9.4) %, P=0.012; OS: (75.0 ± 12.5) % vs (24.6 ± 10.2) %, P=0.035]. The EFS and OS rates were significantly lower in patients with >3 treatment lines than in those with <3 treatment lines [EFS: 0 vs (49.5±10.4) %, P<0.001; OS: 0 vs (52.0±10.8) %, P<0.001]. To the cutoff date, 12 patients presented with CD19(+) relapse, and 1 had CD19(-) relapse. Conclusion: hCART19s are effective in treating pediatric and young adult R/R ALL patients, with a low incidence of severe adverse events and reversible symptoms. Following HSCT, the number of treatment lines can affect the long-term efficacy and prognosis of pediatric and young adult R/R ALL patients.

[Influence of prognostic nutritional index and controlling nutritional status on the prognosis of patients with multiple myeloma].

Objective: To explore the influence of prognostic nutritional index (PNI) and controlling nutritional status (CONUT) on the prognosis of patients with multiple myeloma. Methods: Data of 157 patients with multiple myeloma (MM) at the affiliated hospital of Xuzhou medical university from January 2014 to December 2018 were retrospectively evaluated. The operating characteristic (ROC) curve analysis was adopted as the optimal cut-off point. PNI and CONUT were grouped based on the cut-off points of 44.45 and 3.5, respectively, and the differences between age, gender, serum calcium, ß(2)-microglobulin, serum creatinine, lactate dehydrogenase, and hemoglobin were analyzed. The prognostic factors were analyzed via univariate and Cox multivariate regression analyses. Results: The level of PNI and CONUT is the influencing factor of OS time. The univariate analysis revealed that age, LDH, plasma cell ratio, ß(2)-microglobulin, ISS stage, PNI, and CONUT were the risk factors for the prognosis of patients with MM. The multivariate analysis revealed that age (HR=1.636, 95%CI 1.014-2.640) , plasma cell ratio (HR=1.953, 95%CI 1.232-3.096) , and PNI (HR=0.513, 95%CI 0.287-0.917) were the independent prognostic risk factors of patients with MM. Conclusion: Low PNI in patients with MM indicates a poor prognosis, which is an independent prognosis risk factor.

Evaluation of the probiotic and functional potential of Lactobacillus agilis 32 isolated from pig manure.

Escherichia coli is a symbiotic bacterium in humans and animals and an important pathogen of humans and animals. Prevention and suppression of E. coli infection is of great concern. In this study, we isolated a strain of Lactobacillus agilis 32 from pig manure and evaluated its biological characteristics, and found that its bacterial survival rate was 25% after 4 h of treatment at pH 2, and under the condition of 0·5% bile concentration, its survival rate exceeds 30%. In addition, L. agilis 32 has a cell surface hydrophobicity of 77·8%, and exhibits 67·1% auto-aggregation and 63·2% aggregation with Enterotoxigenic E. coli 10 (ETEC 10). FITC fluorescence labelling showed that the fluorescence intensity of cecum was significantly higher than that of duodenum, jejunum or colon (P < 0·05), but no significant difference from ileum. Lactobacillus agilis 32 bacterial culture and CFS showed average inhibition zone diameters of 14·2 and 15·4 mm respectively. Lactobacillus agilis 32 CFS treatment can significantly reduce the pathogenicity of ETEC 10. These results show that L. agilis 32 is an active and potential probiotic, and it has a good antibacterial effect on ETEC10, which provides basic research for probiotics to prevent and treat intestinal diarrhoea pathogen infection.

[Association between sleep and serum hemoglobin A1c in nondiabetic population in Beijing].

Objective: To understand the status quo of sleep and its associations with serum hemoglobin A1c (HbA1c) among nondiabetic people of 18-79 years old in Beijing. Methods: Data was gathered from the 2017 Beijing Non-communicable and Chronic Disease Surveillance Program. Multiple classified clusters sampling method was used while the 18-79 years old were sampled from the 16 districts of Beijing. Questionnaires would include information on demographic characteristics, chronic diseases and related risk factors, sleep duration and related problems (snore/asphyxia, difficult to get to sleep, waking often during the night, waking up early or taking sleeping pills) within the last 30 days. Complex sampling logistic regression models were established to analyze the association between sleep-related problems and serum HbA1c. Results: A total of 11 608 non-diabetic participants were involved in this study, with average age, reported sleep duration and median of serum HbA1c level as (43.36±15.27) years old, (7.49±1.29) h/d and 5.30%, respectively. 47.38% of them reported having sleep problems within the last 30 days. With the increasing time of sleep, serum HbA1c level was fluctuating significantly (F=413.06, P<0.01). Significant differences appeared in serum HbA1c levels among different age groups (t=358.3, P<0.01). Among participants with several kinds of sleep problems, the serum HbA1c levels were significantly higher than those without, through the single factor analysis (U=15.11, P<0.01). After adjusting for potential confounding factors, the combination of one sleep-related problem (OR=1.21, 95%CI: 1.03-1.41) and snore/asphyxia were associated with higher serum HbA1c levels (HbA1c≥5.7%) (OR=1.37, 95%CI: 1.16-1.61). People under 60 years of age were with higher risk of having higher serum HbA1c levels. Conclusion: Duration and sleep-related problems might affect the serum HbA1c levels, especially among those younger than 60 years of age.

Quantitative ultrasound of the tongue: Echo intensity is a potential biomarker of bulbar dysfunction in amyotrophic lateral sclerosis.

OBJECTIVES: To learn if quantitative ultrasound (QUS) distinguishes the tongues of healthy participants and amyotrophic lateral sclerosis (ALS) patients by echo intensity (EI) and to evaluate if EI correlates with measures of bulbar function. METHODS: Ultrasound was performed along the midline of the anterior tongue surface in 16 ALS patients and 16 age-matched controls using a linear hockey stick 16-7 MHz transducer. A region of interest was manually drawn and then EI was determined for the upper 1/3 of the muscle. For patients, the ALS functional rating scale - revised (ALSFRS-R) was used to calculate bulbar sub-scores and the Iowa Oral Performance Instrument (IOPI) was used to measure tongue strength. RESULTS: EI was significantly higher in ALS patients than in healthy participants (49.8 versus 37.8 arbitrary units, p < 0.01). In the patient group, EI was negatively correlated with ALSFRS-R bulbar sub-score (RS = -0.65, p < 0.01). An inverse correlation between EI and tongue strength did not reach significance (RS = -0.34, p = 0.28). CONCLUSIONS: This study suggests that EI can differentiate healthy from diseased tongue muscle, and correlates with a standard functional measure in ALS patients. SIGNIFICANCE: Tongue EI may represent a novel biomarker for bulbar dysfunction in ALS.

[Study on intention of smoking concession, awareness of smoking hazards and impact on smoking status in residents aged 18-65 years in Beijing].

Objective: To understand the awareness of smoking hazards and intention of smoking concession in residents aged 18-65 years in Beijing, and provide scientific evidence for the development and improvement of tobacco control policies and measures. Methods: Data were collected from the 2017 Beijing Non-communicable and Chronic Disease surveillance. A multi-stage stratified cluster sampling method was used to take samples from 165 communities in 16 districts of Beijing. Logistic regression was used to analyze the influencing factors. Results: Among 11 594 participants, 49.93% had no intention of smoking concession. The percentage of refusing smoking concession was higher in men (50.39%) than in women (43.01%), the difference was significant ( χ(2)=14.211, P=0.002), and higher in suburban residents (56.78%) than in urban residents (45.30%), the difference was significant ( χ(2)=51.977, P<0.001). For the smoking cessation motivation, "illness" was the reason for more former smokers (29.88%) compared with current smokers (11.50%), the difference was significant ( χ(2)=85.865, P<0.001). The awareness rates of smoking hazards was higher in women (34.97%) than in men (32.63%), the difference was significant (Z=5.612, P<0.001), higher in suburban residents (35.44%) than in urban residents (33.03%), the difference was significant (Z=-3.734, P<0.001), and higher in never smokers (35.15%) than in smokers (30.06%), the difference was significant ( χ(2)=62.277, P=0.005). Multiple logistic regression analysis results showed people with general awareness (OR=0.61, 95%CI: 0.39-0.94) and poor awareness (OR=0.67, 95%CI: 0.50-0.90) of smoking hazards were less likely to quit smoking and people with general awareness (OR=0.64, 95%CI: 0.53-0.76) and poor awareness (OR=0.87, 95%CI: 0.78-0.98) of smoking hazards were more likely to smoke. Conclusions: Smokers aged 18-65 in Beijing had low willingness for smoking cessation. Health problem was main consideration for smoking cessation. Never-smokers had better awareness of smoking hazards than smokers, and the awareness of smoking hazards was an influencing factor of smoking status.

[Diagnosis and treatment of seven primary mediastinal yolk sac tumors].

OBJECTIVE: Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment for this tumor is controversial, and chemotherapy combined with resection of residual lesions is adopted sometimes. We summarized the experience of seven primary mediastinal yolk sac tumors treated with platinum-based chemotherapy and extended resection in Peking University First Hospital. METHODS: Clinicopathological data of the patients with primary mediastinal yolk sac tumor who received operation in Peking University First Hospital between August 2014 and August 2018 were collected and analyzed retrospectively. RESULTS: We experienced seven primary mediastinal yolk sac tumors during this period. Computed tomography scan revealed an anterior mediastinal tumor in all the patients and all of them had markedly raised alphafetoprotein (AFP) and normal ß-human chorion gonadotropin (ß-HCG). Five patients underwent needle core biopsy before treatment, which showed a mediastinal yolk sac tumor. All of these patients received preoperative platinum-based chemotherapy and they all presented partial response according to computed tomography. Two other patients did not receive preoperative biopsy, so they directly underwent extended resection. All of the seven patients underwent operation successfully and two of them experienced postoperative complications, including one with pneumonia and the other with atelectasis. R0 resection was achieved in six patients and R1 resection was achieved in the other patient. According to postoperative pathology, there were one microcyst subtype, one adenoid subtye, one giant capsule subtype and two hybrid subtypes. Surprisingly, there were no yolk sac tumor tissue in the other two patients after preoperative chemotherapy. All the patients received postoperative chemotherapy, excluded one patient who was unable to tolerate chemotherapy after operation. Three patients experienced postoperative pulmonary metastases within one year and two of them died soon. The other patient received chemotherapy and immunotherapy after recurrence and he was alive at the time of writing. Four other patients were alive without recurrence and metastasis. CONCLUSION: Primary mediastinal yolk sac tumor is rare and its prognosis is poor. A multimodality approach including adjuvant chemotherapy and resection of residual lesions is the optimal treatment and it may lead to long-term survival.

[Expression of dishevelled-2 in cartilage of rheumatoid arthritis and its effect on cartilage destruction].

Objective: To study the expression of dishevelled-2 (DVL2) in rheumatoid arthritis cartilage and its effect on cartilage destruction. Methods: Cartilage DVL2 expression in rat models of rheumatoid arthritis (RA), osteoarthritis(OA) and collagen-induced arthritis(CIA) were tested by Western blotting. DVL2 overexpressed lentivirus was transfected into the knee of CIA rats. Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus. Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction (PCR) . Results: Compared with knee articular cartilage in OA patients and normal rats, DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats (P values 0.041 and 0.032, respectively). DVL2 did not significantly affect the destruction of knee cartilage in CIA rats (P=0.885). DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (NOS), matrix metalloproteinase (MMP) 2, MMP-3, and MMP-9, which could be more pronounced when tumor necrosis factor alpha was added. Conclusions: DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/ß-catenin pathway, which involves in the destruction of articular cartilage in RA.

The Dynamics of Balanced Spiking Neuronal Networks Under Poisson Drive Is Not Chaotic.

Some previous studies have shown that chaotic dynamics in the balanced state, i.e., one with balanced excitatory and inhibitory inputs into cortical neurons, is the underlying mechanism for the irregularity of neural activity. In this work, we focus on networks of current-based integrate-and-fire neurons with delta-pulse coupling. While we show that the balanced state robustly persists in this system within a broad range of parameters, we mathematically prove that the largest Lyapunov exponent of this type of neuronal networks is negative. Therefore, the irregular firing activity can exist in the system without the chaotic dynamics. That is the irregularity of balanced neuronal networks need not arise from chaos.

[Construction and in vitro verification of a new humanized anti-CD19 CAR-T cells with high affinity].

Objective: To construct humanized anti-CD19 chimeric antigen receptor T cells and investigate its ability to kill leukemia cells in vitro and in vivo. Methods: Humanized anti-human CD19 antibody with a high affinity was obtained based on mouse anti-human CD19 antibody (FMC63). Humanized CD19 CAR-T cells (hCART19) were constructed through transfection of lentivirus carrying a CAR sequence of humanized anti-CD19 scFv into human peripheral CD3(+) T cells. The ability of hCART19 to kill leukemia cells and secrete cytokines was detected by LDH release assay and ELISA. The in vivo tumor-killing effect of hCART19 was evaluated in a leukemia mouse model. Results: Several different humanized CD19 single-chain antibodies which were constructed by IMGT database were expressed in the eukaryotic expression vector and purified followed by acquiring humanized CD19 antibody (Clone H3L2) with similar binding ability to FMC63. Humanized CD19 CAR lentivirus vector was constructed and transfected into T cells to obtain hCART19 cells. The LDH release experiment confirmed that the killing rate of target cells was increased gradually along with the increased E/T ratio. When the ratio of E/T was 10∶1, the killing rate of target cells by hCART19 reached a maximum. When Raji cells were used as target cells, the hCART19 cells group had a significantly higher kill rate [(87.56±1.99)%] than the untransduced T cells group [(19.31±1.16)%] and the control virus transduced T cells group [(21.35±1.19)%](P<0.001). ELISA analysis showed that the secretion of IL-2 [ (10.56±0.88) pg/ml] and IFN-γ [ (199.02±12.66) pg/ml] in the hCART19 cells group were significantly higher than those in the untransduced T cells group [IL-2: (3.55±0.26) pg/ml; IFN-γ: (37.63±0.85) pg/ml] and the control virus transduced T cells group [IL-2: (2.92±0.32) pg/ml; IFN-γ: (52.07±3.33) pg/ml](P<0.001). The above experiments also showed similar results when CHO-K1-CD19 cells were used as target cells. Moreover, in a human leukemia xenograft animal model, the results showed that mice in the untransduced T cells group and the control virus transduced T cells group all died within 20 to 30 days, and the hCART19 cell group survived >40 days, which was more than the survival time of the other two groups of mice. The difference was statistically significant (χ(2)=11.73, P=0.008). Conclusion: Humanized CD19 CAR-T cells with anti-leukemic activity have been successfully constructed, which will lay a foundation for clinical studies in the future.

[Effects of calcium supplementation during the pregnancy and early infancy stage on the body mass index and gut microbiota in the infants].

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m(2)), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m(2)) were significantly higher(P<0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m(2)), BMI increment ((5.71±0.54)kg/m(2)) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m(2), (4.17±1.01) kg/m(2) and 12.28%±3.86%) (P<0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) (P<0.05). Conclusion: Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

[Effect of Dishevelled 2 on apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through inhibiting JAK-STAT pathway].

Objective: To investigate if Dishevelled 2 (DVL2) regulates the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) via the JAK-STAT pathway. Methods: DVL2 overexpressed lentivirus was transfected into RA-FLS and the apoptosis rate was detected by flow cytometry. The effect of DVL2 on RA-FLS signaling pathway was detected by RNA-seq, and then the key genes were verified by RT-PCR. Results: Compared with the control group, DVL2 significantly increased the apoptosis rate of MH7A (3.2%±2.2% vs 25.7%±4.5%). RNA-seq results showed that DVL2 down-regulated the JAK-STAT pathway.The results of RT-PCR showed that DVL2 inhibited the gene expression of JAK2, Stat1, and Stat2; DVL2 still inhibited the gene expression of JAK2 and Stat2 but not Stat1 after TNF-α stimulation.DVL2 inhibited the gene expression of Bcl-xL, and the gene expression of Bcl-2 and Bcl-xL after TNF-α stimulation. Conclusion: DVL2 can increase the apoptosis rate of RA-FLS through inhibiting the JAK-STAT pathway and its downstream anti-apoptotic gene.

[Effect of docosahexenoic acid supplementation on infant's growth and body mass index during maternal pregnancy].

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.