Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Objective:To explore the application value of plasma brain natriuretic peptide(BNP) level in cardiac function rating of children with left-to-right shunt congenital heart disease.Methods:Sixty children with left-to-right shunt congenital heart disease(30 cases of right heart type and 30 cases of left heart type) admitted to Zhongshan Boai Hospital and Dayong Hospital from April 2017 to August 2019 were selected in this research.Children with right heart type congenital heart disease were selected as study group 1, children with left heart type congenital heart disease were selected as study group 2, and 30 healthy children undergoing routine physical examination at the same time period were selected as control group.Plasma BNP concentration and echocardiogram were measured in all three groups.The plasma BNP level, left ventricular ejection fraction(LVEF), left ventricular end diastolic inner diameter(LVEDD), right ventricular end diastolic inner diameter(RVEDD), pulmonary circulation blood flow/systemic circulation blood flow ratio(Qp/Qs) and left ventricular Tei index were observed and compared among the three groups.Results:The LVEF and RVEDD in the study group 1 were not significantly different from those in the control group(all P>0.05). The LVEDD[(45.40±7.48)mm], Qp/Qs (1.80±0.25), left ventricular Tei index(0.35±0.14), BNP[(64.33±22.18)ng/L] in the study group 1 were significantly higher than those in the control group[(34.33±4.93)mm, (0.95±0.11), (0.28±0.05), (33.66±10.80)ng/L], the differences were statistically significant ( t=6.77, 17.05, 2.56, 6.81, all P<0.05). The LVEF and RVEDD in the study group 2 were not significantly different from those in the control group(all P>0.05). The LVEDD[(45.39±7.52)mm], Qp/Qs (1.78±0.25), left ventricular Tei index(0.35±0.14) and BNP[(64.30±22.21)ng/L] in the study group 2 were significantly higher than those in the control group[(34.33±4.93)mm, (0.95±0.11), (0.28±0.05), (33.66±10.80)ng/L], the differences were statistically significant( t=6.74, 16.64, 2.58, 6.80, all P<0.05). The BNP level in study group 1 was positively correlated with RVEDD, Qp/Qs and left ventricular Tei index( r=0.629, 0.719, 0.651, all P<0.05). The BNP level in the study group 2 was positively correlated with RVEDD, Qp/Qs and left ventricular Tei index( r=0.539, 0.792, 0.748, all P<0.05). There were no correlations between BNP level and LVEF in the study group 1 and study group 2(all P>0.05). After operation, the BNP[(44.05±12.41)ng/L], LVEDD[(43.48±4.45)mm], Qp/Qs(1.03±0.06) and left ventricular Tei index(0.31±0.10) in the study group 1 were lower than those before operation, and the differences were statistically significant ( t=5.23, 2.94, 18.20, 3.34, all P<0.05). After operation, the BNP[(40.96±14.30)ng/L], LVEDD[(22.23±3.65)mm], Qp/Qs(1.05±0.11) and left ventricular Tei index(0.31±0.05) in the study group 2 were lower than those before operation, and the differences were statistically significant( t=3.86, 3.08, 14.73, 4.26, all P<0.05). Conclusion:The application of plasma BNP level detection in left-to-right shunt congenital heart disease has definite effect and certain application value.

Objective:To investigate the human cytomegalovirus(HCMV)infection and hearing impairment in infants with congenital and perinatal diseases of the Bo′ai Hospital in Zhongshan City, and to explore the risk factors of hearing impairment and clinical outcomes.Methods:A total of 243 cases of infants with congenital and perinatal HCMV infection were collected from Bo′ai Hospital from January 2016 to December 2018.Clinical data and brainstem auditory evoked potential(BAEP)results were analyzed retrospectively.Logistic regression analysis was performed to identify the risk factors of hearing impairment.The children with hearing loss were followed up in out-patient.Results:Positive rates of congenital and perinatal HCMV infection in infants were 4.56%(121/2654), 2.76%(74/2686)and 3.15%(85/2701)from 2016 to 2018 in our hospital respectively.In 243 cases, there were 107 cases with normal hearing(44%), 33 cases with suspicious hearing impairment(14%)and 103 cases with hearing impairment(42%). Multivariate logistic regression analysis showed that the age less than 1 month( P=0.034)and CMV-DNA positive( P=0.003)were independent risk factors for hearing impairment.The manifestations of hearing impairment were various.Twenty cases with suspected hearing impairment were not treated with ganciclovir, in which 19 cases BAEP became normal.Sixty-seven cases with hearing impairment were followed up, of whom 47 cases received standardized ganciclovir antiviral therapy: 30 cases returned to normal, and 12 cases improved, and 3 cases showed no significant changes, and 2 cases aggravated.Twenty cases did not received the antiviral therapy: 5 cases returned to normal, and 8 cases improved, and 3 cases showed no significant changes, and 4 cases aggravated. Conclusion:There was a high rate of HCMV infection of congenital and perinatal infants in our hospital.Infected infants have a higher proportion of hearing impairment.Infants less than 1 month and CMV-DNA positive are more likely to suffer from hearing impairment.It can be considered for clinical observation for the cases with slightly elevated hearing threshold.Standardized ganciclovir antiviral therapy has obvious effect on hearing improvement.

Objective To investigate the epidemiological characteristics and drug sensitivity of non-typhoid salmonella in Zhongshan city.Methods We collected the positive cases of non-typhoid salmonella in children of Zhongshan city from 2013 to 2015.The sex,age,place of residence,onset time and main serum type of these cases were collected.The characteristics of the cases were described by descriptive epidemiologi-cal study.Results From 2013 to 2015,3 040 stool specimens from patients with enteritis were collected and 402 strain of non-typhoid salmonella were separated out. The total detection rate was 13.22%,the annual detection rate were 10.26%,12.21% and 16.76%,respectively.The peak period was from July to August every year.Of the 402 children,240 were male,162 were female,and the ratio was 1.48:1.The minimum age was 1 month,the maximum was 5 years and 8 months,the mean age was 13.62 months.All patients were characterized by diarrhea and fever,including 64 cases of bloody stool and 1 case of sepsis.The most com-mon serotypes were 4,5,12:i:-and 4,12:i:-.The resistant strains were salmonella typhimurium and variety salmonella typhimurium strains.From 2013 to 2015,the resistance rate of ceftriaxone and ceftazidime in non-typhoid salmonella isolates increased linearly (ceftriaxone: 17.35%, 26.23%, 39.01%; ceftazidime:12.24%,17.21%,30.77%).The differences were statistically significant(χ2=30.3,P<0.01;χ2=26.3, P<0.01).Conclusion The positive rate of nontyphoid salmonella increased year by year from 2013 to 2015.The most common serotype was salmonella typhimurium, and the resistant strains were salmonella typhimurium and salmonella typhimurium variety.The resistance rate of non-typhoid salmonella to ceftriaxone and ceftazidime increased year by year,and the highest rate of ceftazidime resistance was in July 2015.Non-typhoid salmonella was more resistant to ceftriaxone than ceftazidime.

Objective To evaluate the efficacy difference of different embolization agents in transcatheter embolization for treating massive hemoptysis caused by systemic pulmonary circulation shunt(SPS). Methods The clinical and imaging data in 98 patients with hemoptysis complicating SPS,including bronchodilator in 72 cases,pulmonary tuberculosis in 18 cases and lung carcinoma in 8 cases. All cases were treated with bronchial arterial embolization (BAE). According to different used embolization agents, the cases were divided into the gelfoam group and polyvinyl alcohol(PVA)grains embolization group. All cases were followed up at postoperative 1 d,1,3,6 months as well as 1,2 years. The data were analyzed by using Ridit test. Results Ninety-eight cases of massive hemoptysis were confirmed by DSA,among them,84 cases were complicating pulmonary artery fistula, 18 cases were pulmonary venous fistula and 2 cases were mixed fistula; 32 cases were simple BPS, 62 cases were pulmonary circulation fistula existed in the bronchial arteries and non-bronchial artery and 4 cases were simple non-BPS. The two groups had no complications such as embolism,paraplegia,esophagus-trachea fistula and skin ischemic necrosis. The follow up on postoperative 1 d, at postoperative 1, 3,6 months and at postoperative 1,2 years indicated that among 48 cases in the gelfoam group, 20 cases were cured, 18 cases were significantly effective,6 cases were effective and 4 cases were ineffective,the effective rate was 91.7 % ;among 50 cases in the PVA grain embolization group, 38 cases were cured, 8 cases were significantly effective,4 cases were effective and O case was ineffective, the effective rate was 100%. Moreove no severe complications such as ectopic embolism, paraplegia, esophagus-trachea fistula and skin ischemic necrosis occurred. The difference between the two groups had statistical significance by Ridit analysis. Conclusion Transcatheter embolization for treating massive hemoptysis caused by SPS is safe and reliable,has small trauma, using PVA grains embolization can reduce the long term recurrence rate of hemoptysis.

Objective To summarize the clinical characteristics and drug sensitivity of Pseudomonas aeruginosa in children. Methods The data of children with diagnosed Pseudomonas aeruginosa from 2006 to 2016 were retrospectively analysis. Results There were 14 patients who had diagnosis of Pseudomonas aeruginosa, most of whom were infants and toddlers ( 78 . 6%). The common complications were disseminated intravascular coagulation (DIC) and pulmonary hemorrhage. In 14 patients, 7 patients were cured, 4 were died, and 3 were given up treatment by their family because of serious illness. The antimicrobial susceptibility test showed that isolated pseudomonas aeruginosa had good sensitivity to aminoglycosides and quinolones. Conclusion Pseudomonas aeruginosa sepsis is more common in infants and toddlers, with high mortality. For suspected patients, the antibiotic that covers the Pseudomonas aeruginosa should be used in early antibiotic therapy.

Objective To investigate the clinical significance of testing serum kisspeptin in central precocious puberty (CPP) girls. Methods Sixty eight CPP girls and 68 healthy girls was studied from December 2012 to December 2014. HEK293 cells were cultured. Luciferase reporter assay was performed to verify the binding of miR-137 to the 3′UTR of KISS1. Serum miR-137 level was levaluated by qRT-PCR. Level of serum luteinizing hormone , prolactin , follicle stimulating hormone , thyrotropin , free thyroxine and estradiol was evaluated by chemi-luminescence immunoassay. The level of serum kisspeptin was detected by ELISA. Results MiR-137 was confirmed to bind to the 3′UTR of KISS1. The level of serum miR-137 was downregulated and kisspeptin was enhanced in CPP girls. The expression of miR-137 and kisspeptin was negatively correlated. Serum miR-137 level was negatively related to bone age and bone age advancement. According to the results of GnRH stimulating test, serum miR-137 was related to peak LH and peak/basal LH ratio. Conclusions MiR-137 could bind to the 3′UTR of KISS1. MiR-137 may be a potential biomarker for CPP assisted diagnosis.

Objective To explore the clinical characteristics, treatment and prognosis of pediatric patients with bronchiec-tasis caused by Mycoplasma pneumonia (MP) and Chlamydia pneumonia (CP). Methods The clinical data from 27 MP and CP pneumonia pediatric patients with bronchiectasis suggested by the high resolution CT were retrospectively analyzed. Results The morbility rate of bronchiectasis caused by MP and CP pneumonia is 0.56%. The mean age of these patients was 75.4 ± 52.7 months. Among them, 27 cases (100%) had cough, 19 cases (70.4%) had fever, 10 cases (37%) had respiratory distress and 20 cases had lung auscultation. Sixteen cases were MP-IgM positive, 5 cases (18.5%) were CP-IgM positive and 6 cases (22.2%) were positive of both. Eight cases were combined with other pathogens infections, in which 6 cases were bacterial infections. The imaging ifndings showed diffuse bronchiectasis in 13 cases (48.1%) and local bronchiectasis in14 cases (51.9%). The bronchoscopy found endothelium in-lfammation, mucosal swelling, partial erosion and follicular hyperplasia in 16 cases (66.7%), the formation of short column sputum bolt in 5 cases (20.8%), in which 1 case had plastic bronchitis. All patients were treated with macrolides antibiotics, 10 cases (37%) combined with methylprednisolone, 3 cases (11.1%) combined with immunoglobulin and 20 cases (74%) combined with other anti-biotics. The average length of hospitalization was 12±4.3 days. The bronchiectasis sign disappeared within 4 months in 23 cases (92%). Two cases (8%) still had bronchiectasis after 9 to 15 months, with the recurrent pneumonia. Conclusions MP and CP pneumonia can lead to acute bronchiectasis. Most of patients are recoverable with effective treatment.