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.

[Impact of autologous hematopoietic stem cell transplantation on the efficacy of CAR-T treatment of relapsed/refractory multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG (χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG (χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

[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.

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.

[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.

[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.

[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 porcine glucagon-like peptides-2 on tight junction in GLP-2R + IPEC-J2 cell through the PI3 k/Akt/mTOR/p70S6K signalling pathway.

Because of rare glucagon-like peptide-2 (GLP-2) receptor (+) cells within the gut mucosa, the molecular mechanisms transducing the diverse actions of GLP-2 remain largely obscure. This research identified the naturally occurring intestinal cell lines that endogenously express GLP-2R and determined the molecular mechanisms of the protective effects of GLP-2-mediated tight junctions (TJ) in GLP-2R (+) cell line. (i) Immunohistochemistry results showed that GLP-2R is localised to the epithelia, laminae propriae and muscle layers of the small and large bowels of newborn piglets. (ii) GLP-2R expression was apparent in the cytoplasm of endocrine cells in IPEC-J2 cell lines. (iii) The protein expressions of ZO-1, claudin-1, occludin, p-PI3 K, p-Akt, p-mTOR and p-p70S6K significantly (p < 0.05) increased in GLP-2-treated IPEC-J2 cells, and all of them significantly (p < 0.05) decreased when LY-294002 or rapamycin was added. GLP-2 improves intestinal TJ expression of GLP-2R (+) cells through the PI3 k/Akt/mTOR/p70S6K signalling pathway.

[Comparison of efficacy and safety between the anterior and the posterior approaches to total hip arthroplasty].

OBJECTIVE: To compare the efficacy and safety between direct anterior approach (DAA) and posterior approach (PA) in total hip arthroplasty. METHODS: This study evaluated postoperative results of 92 consecutive total hip arthroplasties performed by a single surgeon; 44 from the DAA, and 48 from PA. The age, body mass index, operation time, blood loss, hospital stay, positioning of the artificial hip, postoperative Harris score and postoperative complications were recorded and analyzed. RESULTS: Both the average age of the patients separately (58.0±11.9) years in DAA group and (61.0±10.4) years in PA group and the body mass index (25.1±3.7) in DAA group and (24.7±3.3) in PA group, showed no significant difference between the two groups. The DAA group had significantly reduced the hospital stay (3.8±1.7) days vs.(4.9±2.3) days for the PA group (P<0.05) and operation time was (76.0±17.4) min in DAA group, and (71.0±14.3) min in PA group (P>0.05). The amount of blood loss: in group DAA (238.0±55.3) mL, and in group PA (387.0±61.2) mL (P<0.05). There was no statistical difference in the positioning of the artificial hip: the cup anteversion in DAA group and PA group was 17.3°±5.3° vs. 18.6°± 5.1°, the cup inclination was 38.5°±5.7° vs. 37.7°±5.2°. In DAA group, there was significantly less use of assistive devices [(24.6±7.8) d vs. (31.7±10.2) d, P<0.05], and the pain was significantly lower. Harris score at the end of 6 weeks of the follow-up: in DAA group 85.7±5.4, and in PA group 81.3±6.1 (P<0.05); at the end of the last follow-up: in DAA group 93.4±4.7, and in PA group 92.3±5.3 (P>0.05). Complications were encountered in the two groups. There were two intraoperative complications (4.4%), 1 great trochanter fracture and 1 lateral cutaneous nerve injury in DAA group. No dislocation was observed in DAA group. One dislocations and 1 groin pain were recorded in PA group. No prosthesis loosening, deep vein thrombosis, sciatic nerve injury and other complications occurred in the two groups. CONCLUSION: Total hip arthroplasty using the anterior approach allows for superior recovery and better stability.

Horizontal transfer and functional evaluation of high pathogenicity islands in Avian Escherichia coli.

High pathogenicity islands (HPIs) in Escherichia coli encode genes that are primarily involved in iron uptake and regulation, and confer virulence and pathogenicity. The aim of this study was to investigate the transfer of HPIs in avian E. coli and identify the function of HPI in the acceptor strain. The HPI transfer strain was obtained under conditions of low temperature and low iron abundance, and the donor and acceptor strains were confirmed. E. coli HPIs are transferred by horizontal gene transfer events, which are likely mediated primarily by homologous recombination in HPI-adjacent sequences. Assays for biological activity and pathogenicity changes in the acceptor strain indicated that HPIs might not be involved in pathogenesis in avian E. coli, and thus the main function of HPIs in this strain of bacteria may be to regulate iron nutrition.

Isolation and characterization of a goose parvovirus from Yan goose.

NO ABSTRACT Keywords: goose parvovirus; Yan goose; isolation; characterization.

Association Analysis of Myosin Heavy-chain Genes mRNA Transcription with the Corresponding Proteins Expression of Longissimus Muscle in Growing Pigs.

The goal of this work was to investigate the correlations between MyHC mRNA transcription and their corresponding protein expressions in porcine longissimus muscle (LM) during postnatal growth of pigs. Five DLY (Duroc×Landrace×Yorkshire) crossbred pigs were selected, slaughtered and sampled at postnatal 7, 30, 60, 120, and 180 days, respectively. Each muscle was subjected to quantity MyHCs protein contents through an indirect enzyme-linked immunosorbent assay (ELISA), to quantity myosin heavy-chains (MyHCs) mRNA abundances using real-time polymerase chain reaction. We calculated the proportion (%) of each MyHC to total of four MyHC for two levels, respectively. Moreover, the activities of several key energy metabolism enzymes were determined in LM. The result showed that mRNA transcription and protein expression of MyHC I, IIa, IIx and IIb in LM all presented some obvious changes with postnatal aging of pigs, especially at the early stage after birth, and their mRNA transcriptions were easy to be influenced than their protein expressions. The relative proportion of each MyHC mRNA was significantly positively related to that of its corresponding protein (p<0.01), and MyHC I mRNA proportion was positively correlated with creatine kinase (CK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) activities (p<0.05). These data suggested that MyHC mRNA transcription can be used to reflect MyHC expression, metabolism property and adaptive plasticity of porcine skeletal muscles, and MyHC mRNA composition could be a molecular index reflecting muscle fiber type characteristics.

Tissue distribution, expression, and antimicrobial activity of Anas platyrhynchos avian ß-defensin 6.

In this study, a novel avian ß-defensin (AvBD) was isolated from the Chaohu duck. The complete nucleotide sequence of the gene contained a 204-bp open reading frame that encoded 67 amino acids (aa), including a signal peptide of 20 aa, a propiece of 5 aa, and a mature peptide of 42 aa. The homology, characterization, and comparison of this gene with AvBD from other avian species confirmed that it was duck AvBD6. Also, the preproprotein of AvBD6 from chicken, goose, and duck was highly conserved with 100% aa homology. The AvBD6 mRNA was widely expressed in the investigated tissues of healthy 5-mo-old ducks, with the exception of the skin, kidney, and bursa. The AvBD6 mRNA was highly expressed in the spleen, lung, stomach, tongue, and egg yolk, successively; moderately expressed in the bone marrow and liver; and expressed to lower degrees in the trachea, heart, intestine, muscle, esophagus, and testis. We produced recombinant AvBD6 by expressing the gene in Escherichia coli. The yield of soluble glutathione S-transferees (GST)-AvBD6 in the inclusion bodies increased significantly as the incubation temperature was decreased from 37 to 30°C. As expected, the GST-AvBD6 exhibited strong bactericidal properties [minimum inhibitory concentration (MIC) = 0.5 to 2 µM] against the Aeromonas veronii biovar sobria strain BJCP-5, E. coli, and Enterococcus faecalis [ATCC 29212); it possessed medium bactericidal properties (MIC = 4 to 8 µM) against Staphylococcus aureus, Salmonella enteritidis, Pseudomonas aeruginosa (ATCC 27853), and Bacillus subtilis (CMCC 63501;; and it possessed low bactericidal properties (MIC = 16 µM) against Candida albicans (ATCC 10231). Additionally, the antimicrobial activity of GST-AvBD6 proved to be the same as that of synthetic AvBD6. The A. veronii biovar sobria strain BJCP-5 cells that were treated with GST-AvBD6 showed lysis and shrinkage under scanning electron microscopy. The mechanisms of AvBD6-mediated killing of A. veronii biovar sobria involved both cell lysis and nonlysis. Our results indicate that AvBD6 plays an important role in the innate immunity of the Chaohu duck.

[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.

[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.

Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).

BACKGROUND: Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA. OBJECTIVE: To determine the impact of T-cell costimulation modulation in patients with UA or very early RA. METHODS: In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years. RESULTS: At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group. CONCLUSION: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.