Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Research progress of association between the built environment in community and the obesity of children and adolescents / 中国学校卫生

Abstract@#With the socio economic development and urbanization, obesity increased dramatically worldwide among children and adolescents over the past years. The determinants of obesity are complicated, and its association with built environment in community has received great concern in recent years. To provide theoretical basis for building supportive environment beneficial for obesity prevention, the review summarizes obesity related built environment, including food environment, physical activity environment, road traffic environment, lighting at night.

Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm / 亚洲男科学杂志(英文版)

Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.

Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia / 中国当代儿科杂志

OBJECTIVES@#To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA).@*METHODS@#A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed.@*RESULTS@#The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05).@*CONCLUSIONS@#SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

MBOAT1 homozygous missense variant causes nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis. The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family. A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) gene (c.770C>T, p.Thr257Met) was found by whole-exome sequencing (WES). Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the mRNA level of MBOAT1 in the patient was 22.0% lower than that in his father. Furthermore, we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men. Our data identified homozygous variants of the MBOAT1 gene associated with male infertility. This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.

A novel robotic-assistant flexible ureteroscopy system: initial results from the in vitro study and the in vivo experience / 中华泌尿外科杂志

Objective:Objectives The aim of the study is to evaluate the mechanical performance, safety and efficacy of the novel robotic-assistant flexible ureteroscopy system (Ra-fURS) under in vitro and in vivo environments.Methods:Combing with commercial flexible ureteroscopes, the novel Ra-fURS was used for the in vitro test and animal model operation in October 2020. The study included three sections. ①Basic mechanical performance assessment: including endoscope motion control (dual deflection, axial rotation and forward/backward distance), reaction time and fiber regulation. ②Simulated surgery in ex-vivo 3D-printing renal collecting system model: including completion rate and time of calyxes exploration, directional movement and laser fragmentation [gypsum models (0.5×0.5×0.5 cm) were used to stimulate kidney stones]. ③Intrarenal surgeries in animal models (two 5-month female Yorkshire white pigs). In total, 32 surgeries was performed (8 surgeons × 2 pigs × 2 kidneys/pig). In vivo assessments were carried out including: ①consuming time for Ra-fURS installation and offloading; ②completion rate and time of calyxes exploration; ③comfort score (ranging from 0-10) as compared to the manual f-URS, which was corresponding to each Ra-fURS surgery. In simulated surgery and animal surgery sections, 8 surgeons were enrolled in the study (group A 4 without flexible ureteroscopy experience; group B: 4 highly experienced), and results were compared between two groups.Results:Under the Ra-fURS control, the flexible ureteroscope movement in three degrees of freedom (forward / backward: + 11 to -11 cm, axial rotation + 225°to -225°; active duel-flection: + 270°to -270°, as well as the laser fiber regulation + 2.5 to -2.5 cm). In simulated surgery tests, both groups achieved 100% completion rate of calyxes exploration, and there were no statistical differences in the time of the calyxes exploration between group A and group B (116.0±8.0)s vs.(110.3±15.4)s( P>0.05). Time-consumption for laser fragmentation of group B was shorter than that of group A (525.8±58.5)s vs. (780.5±141.2)s( P<0.01). In animal surgery, the installation time of Ra-fURS gradually shortened within the first 7 cases was(234.0±43.0)s, and became comparable in the later 8-32 cases was(149.3±8.0)s. The average uninstall time was (43.9 ±5.9)s and was relatively stable. There were 51 renal calyxes in two pigs. It was higher for the completion rate of calyxes exploration in group B than in group A [(95.5±9.1)% vs. (59.1±9.1)%, P<0.05], and the exploration time was also statistically variant between the two groups group A and group B[(274.8±34.6)s vs.(127.3±18.2)s, P<0.05]. For all the operators, the comfort scores were favorable to the Ra-fURS as compared to the manual f-URS (8.9±0.3 vs. 5.9±1.1, P<0.05). Conclusions:This preliminary study demonstrated that the novel Ra-fURS was capable of controlling flexible ureteroscope to perform retrograde intrarenal surgery and fragmenting stones with laser. Besides, other features, including easy installation, stable performance and comfortable manipulating environment, made it easy to use in clinical application.

Semen parameters in men recovered from COVID-19 / 亚洲男科学杂志(英文版)

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Application of permissive hypercapnia in premature infants with respiratory distress syndrome / 中国小儿急救医学

Objective:To analyze the effect of permissive hypercapnia(PHC) in premature infants with respiratory distress syndrome(RDS).Methods:Seventy preterm infants diagnosed with RDS from July 2019 to September 2020 were enrolled.The preterm infants were divided into PHC group[noninvasive high-frequency ventilation(NHFV)+ PHC, n=34] and non PHC group(NHFV, n=36)after injection of pulmonary surfactant by LISA method.Ventilator parameters, time of ventilation, oxygen therapy, enteral feedingand hospitalization days were compared between the two groups.The incidences of patent ductus arteriosus, intracranial hemorrhage, pneumothorax and ventilator-induced lung injury were recorded. Results:The time of mechanical ventilation, oxygen therapy, age of enteral feeding and hospitalization time in PHC group were less than those in non PHC group( P<0.05). PaO 2 and PaCO 2 of the two groups had no difference before mechanical ventilation treatment( P>0.05), and PaO 2 of the two groups had no difference after 24 hours of treatment( P>0.05). After treatment, PaCO 2 in non PHC group was significantly lower, and there was no significant difference in PHC group( P<0.05). There was no significant difference regarding ventilator parameters MAP and FiO 2 after 24 hours of treatment between the two groups( P>0.05), and the ΔP of PHC group was significantly lower than that of non-PHC group ( P<0.05). The incidence of ventilator-induced lung injury in PHC group was lower than that in non-PHC group( P<0.05). Conclusion:Compared with conventional ventilation therapy, PHC has similar therapeutic effect, but it can shorten the mechanical ventilation time, oxygen therapy time, age of enteral feeding and hospitalization days, and reduce the incidence of ventilator-induced lung injury.

Orthogonal compatibility study on main effective parts of Yangyin Tongnao Granules based on pharmacokinetics and pharmacodynamics / 中草药

Objective: To investigate the pharmacokinetic and pharmacodynamic changes of Yangyin Tongnao Granules (YTG) in cerebral ischemia reperfusion rats after the compatibility of main effective parts (total alkaloids, total flavonoids, total saponins and total phenolic acids). Methods: By using the orthogonal design to research the main effective parts of YTG, nine different dosage ratios combinations were formed, which were used for oral administration in cerebral ischemia reperfusion rats. High performance liquid chromatography-diode array detector (HPLC-DAD) was used to determine the concentration of puerarin, ferulic acid, and ligustrazine in rat plasma at different time points. The non-compartmental model was used to fit the pharmacokinetic parameters by Drug and Statistics (DAS) 3.2.6 software. The total quantum statistical moment analysis method and comprehensive evaluation method were used to evaluate the total pharmacokinetic characteristics. Meanwhile, the content of superoxide dismutase (SOD) and catalase (CAT) were determined by enzyme-linked immunosorbent assay (ELISA) kits. Finally, the PK-PD model and the quantitative equations between drug concentration and efficacy were obtained. Results: The pharmacokinetic characteristics of puerarin, ferulic acid and ligustrazine in cerebral ischemia-reperfusion rats were different. Total statistical moment and comprehensive score study showed that different combinations had different effects on ACUT, mean retention time (MRT), and comprehensive evaluation. The effective parts inhibited the reduction of oxidation indexes such as SOD and CAT. Sigmoid-Emax models were adopted in all PK-PD models, and the fitting results had a good correlation with the measured data. The R values were more than 0.85. Conclusion: Compatibility of YTG activity parts had a certain effect on their pharmacokinetic behaviors and antioxidation in model rats. The total quantum statistical moment analysis and comprehensive evaluation method can be used to study the pharmacokinetics of multi-component traditional Chinese medicine prescriptions. PK-PD model could be used to predict and evaluate the correlation between pharmacokinetics and pharmacodynamics of traditional Chinese medicine prescriptions.

Clinical features and gene mutations of children with Shwachman-Diamond syndrome and malignant myeloid transformation / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation.@*METHODS@#Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed.@*RESULTS@#Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The median age of onset of malignant myeloid transformation was 48 months (ranged 7 months to 14 years). Of the 11 children, 45% had abnormalities in the hematological system alone. Mutations of the SBDS gene were detected in all 11 children, among whom 5 (45%) had c.258+2T>C homozygous mutation and 3 (27%) had c.184A>T+c.258+2T>C compound heterozygous mutation. The new mutations of the SBDS gene, c.634_635insAACATACCTGT+c.637_638delGA and c.8T>C, were rated as "pathogenic" and "possibly pathogenic" respectively. The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100% and 0% respectively (P=0.001).@*CONCLUSIONS@#SDS children may have hematological system symptoms as the only manifestation, which needs to be taken seriously in clinical practice. The type of malignant transformation is associated with prognosis.

Clinical and molecular characteristics of GATA2 related pediatric primary myelodysplastic syndrome / 中华血液学杂志

Objective@#To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) .@*Methods@#Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. 2018. The relationship between genotypes and phenotypes was analyzed.@*Results@#Germline GATA2 mutations accounted for 8.5% (11/129) of all primary MDS cases, and 14.0% (11/50) of MDS with excess blasts (MDS-EB) and acute myeloid leukaemia with myelodysplasia-related changes (AML-MRC) . Compared with GATA2 wild-type patients, GATA2 mutated patients were older at diagnosis[8 (1-16) years old vs 6 years old (range: 1 month old-18 years old) , P=0.035]and higher risk of monosomy 7 (72.7%vs 5.2%, P<0.001) and classified into MDS-EB and AML-MRC compared with refractory cytopenia of childhood (RCC) (63.6%vs 36.4%, P=0.111) . The multivariate analysis showed SETBP1 mutation (P=0.041, OR=9.003, 95%CI 1.098-73.787) and isolated monosomy 7 (P=0.002, OR=24.835, 95%CI 3.305-186.620) were significantly associated with germline mutated GATA2. Overall survival (OS) and outcomes of hematopoietic stem cell transplantation (HSCT) were not influenced by GATA2 mutational status.@*Conclusions@#Our data identify germline GATA2 mutations have a high prevalence in older pediatric patients with monosomy 7, and high risk of progression into advanced MDS subtypes. GATA2 mutation status does not affect OS in pediatric primary MDS.

Effect of inhaled nitric oxide with mechanical ventilation in persistent pulmonary hypertension of newborn / 中国小儿急救医学

Objective@#To study the clinical effect of inhaled nitric oxide(iNO) with mechanical ventilation for the neonates with persistent pulmonary hypertension of newborn(PPHN).@*Methods@#A total of 40 neonates with PPHN poorly responding with routine treatment were treated with iNO therapy.Pulmonary artery pressure, blood gas ion analysis and respiratory function changes were observed at different time points before and after iNO.@*Results@#Treatment with iNO resulted in a rapid decrease in pulmonary artery pressure from(54.95±17.08) mmHg(1 mmHg=0.133 kPa) to(20.40±14.26) mmHg.Oxygenation of 40 cases improved in the first 0.5~1 hour after iNO therapy, the values of mean airway pressure(MAP)declined from(13.98±2.40)cmH2O(1 cmH2O=0.098 kPa) to(12.44±2.69)cmH2O, oxygenation index(OI)decreased from 26.89±18.62 to 13.84±5.52, PaO2/FiO2 increased from(60.34±23.49) mmHg to(144.46±23.49) mmHg, and the value of pH increased from 7.31±0.14 to 7.37±0.07.Furthermore, within 48 hours after treatment, PaO2/FiO2 and pH increased gradually, while MAP and OI decreased gradually, which all had statistical differences(P<0.01).@*Conclusion@#Mechanical ventilation combined with iNO therapy in the treatment of PPHN can rapidly improve the oxygenation status of neonates, reduce pulmonary vascular resistance, and then improve the survival rate and long-term prognosis.

Pharmacokinetics of compatible effective components of Mahuang Decoction in febrile rats / 中国中药杂志

In the present paper,after the febrile rat model was prepared by injecting yeast,orthogonally compatible effective components from prescription drugs of Mahuang Decoction( Ephedra sinica total alkaloids,Cinnamomum cassia essential oil,amygdalin,Glycyrrhiza uralensis total flavonoids+G. uralensis total saponins) with nine different dosage ratios were given by gavage administration.The plasma concentrations of main active ingredients including ephedrine hydrochloride,pseudoephedrine hydrochloride,methylephedrine hydrochloride,cinnamic acid,amygdalin,liquritin and glycyrrhizin at different time points were analyzed by liquid chromatograph mass spectrometer( LC-MS). Based on the pharmacokinetic parameters of non-compartmental model,the area under curve of total quantum( AUCt) and the mean chromatographic retention time of total quantum( MRTt) were further calculated,in order to evaluate the effect of compatibility on the total statistical moment parameters. The results showed that the pharmacokinetic characteristics of main active components in febrile rats were significantly different after treatment with orthogonally compatibility of E. sinica total alkaloids,C.cassia essential oil,amygdalin,G. uralensis total flavonoids and G. uralensis total saponins. Orthogonal analysis confirmed that different compatibility components had different effects on the total statistical moment parameters. The contribution of effective components of Mahuang Decoction to AUCtwas as follows in a descending order: E. sinica total alkaloids>C. cassia essential oil>amygdalin>G. uralensis total flavonoids+G. uralensis total saponin,while the contribution to MRTtwas: E. sinica total alkaloids >G. uralensis total flavonoids+G. uralensis total saponin>amygdalin>C. cassia essential oil. The E. sinica total alkaloid had the greatest effects on both of the above parameters,and the optimal combination was A_3B_3C_2D_1 for AUCt,and A_1B_1C_1D_1 for MRTt.

Effect of inhaled nitric oxide with mechanical ventilation in persistent pulmonary hypertension of newborn / 中国小儿急救医学

Objective To study the clinical effect of inhaled nitric oxide ( iNO) with mechanical ventilation for the neonates with persistent pulmonary hypertension of newborn(PPHN). Methods A total of 40 neonates with PPHN poorly responding with routine treatment were treated with iNO therapy. Pulmona-ry artery pressure,blood gas ion analysis and respiratory function changes were observed at different time points before and after iNO. Results Treatment with iNO resulted in a rapid decrease in pulmonary artery pressure from(54. 95 ± 17. 08) mmHg(1 mmHg＝0. 133 kPa) to(20. 40 ± 14. 26) mmHg. Oxygenation of 40 cases improved in the first 0. 5 ~1 hour after iNO therapy,the values of mean airway pressure(MAP) de-clined from(13. 98 ± 2. 40) cmH2 O(1 cmH2 O＝0. 098 kPa) to(12. 44 ± 2. 69) cmH2O,oxygenation index (OI)decreased from 26. 89 ± 18. 62 to 13. 84 ± 5. 52,PaO2/FiO2 increased from(60. 34 ± 23. 49) mmHg to (144. 46 ± 23. 49) mmHg,and the value of pH increased from 7. 31 ± 0. 14 to 7. 37 ± 0. 07. Furthermore, within 48 hours after treatment,PaO2/FiO2 and pH increased gradually,while MAP and OI decreased gradu-ally,which all had statistical differences(P<0. 01). Conclusion Mechanical ventilation combined with iNO therapy in the treatment of PPHN can rapidly improve the oxygenation status of neonates,reduce pulmonary vascular resistance,and then improve the survival rate and long-term prognosis.

Clinical features and gene mutation spectrum in children with sideroblastic anemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA.@*METHODS@#Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed.@*RESULTS@#Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89% (17/19) were known mutations and 11% (2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A>T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C>T(p.Q59X) was rated as "pathogenic".@*CONCLUSIONS@#ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.

Infiltration of tumor associated macrophages in multiple myeloma and its clinical significance / 中华血液学杂志

Objective@#To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression.@*Methods@#Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed.@*Results@#①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001).@*Conclusion@#The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.

Correlation between pathological types of parathyroid and clinical manifestations in patients with renal secondary hyperparathyroidism / 中华肾脏病杂志

Objective To analyze the correlation between the pathological types of parathyroid and clinical manifestations in patients with renal secondary hyperparathyroidism (SHPT),so as to improve the efficacy and safety of treatment.Methods The pathological and clinical data of 130 patients with renal SHPT and maintenance hemodialysis (MHD) who had undergone total parathyroidectomy with autotransplantation (TPTX + AT) were collected.A total of 545 parathyroid glands were obtained and 998 slices were made and read.According to the pathological types of parathyroid hyperplasia,the patients were divided into diffuse hyperplasia (DH) group,diffuse between hyperplasia and nodular hyperplasia (DH/NH) group as well as nodular hyperplasia (NH) group.The clinical and biochemical characteristics of different groups before and after operation (1-,3-,6-,9-,12-month) were compared and analyzed by statistical tests.Results (1) The preoperative status:the dialysis age,serum calcium as well as incidence of bone pain,skin itching and shorten height in the NH group were significantly higher than those in the DH group (all P ＜ 0.05),and the serum phosphorus and iPTH in the NH group were significantly higher than those in DH and DH/NH group (all P ＜ 0.05).(2) The postoperative status:the serum calcium of the NH group at 1-month was lower than that of the DH group,and the incidence of hypocalcemia of the NH group at 1-month was higher than that of the DH group (P ＜ 0.05);the serum phosphorus at 3-,6-,9-month and iPTH at 1-,3-month of the NH group were significantly lower than that of the DH group (all P ＜ 0.05),and the serum phosphorus at 3-month and iPTH at 1-month of the NH group were lower than that of the DH/NH group (all P ＜ 0.05).Among the 3 groups the serum phosphorus change from 1 to 12 months had difference (F=3.241,P=0.042),while the differences of serum calcium and iPTH changes were statistically insignificant.Conclusions The clinical manifestations,serum calcium,phosphorus and iPTH in patients with renal SHPT before and after TPTX+AT are closely related to the pathological types of parathyroid hyperplasia.Compared with the DH patients,before the operation the NH patients have longer dialysis age,more serious the clinical symptoms such as bone disease,higher calcium,phosphorus and iPTH,while greater reduction of the serum calcium,phosphorus and iPTH in the short term after operation.

Renal developmental retardation and the underlying mechanism induced by prenatal caffeine exposure in female fetal rats / 中国药理学通报

Aim To explore the effects of prenatal caf-feine exposure (PCE) on fetal renal growth retardation and corticosterone on the gene expression of metanephric mesenchyme stem cells.Methods Pregnant Wistar rats were administered with caffeine (30,120 mg ·kg-1) from gestational day 9 to 20.Female fetal kidney samples were collected for morphological observation and gene expression examination.The metanephric mesenchyme stem cells were harvested for cell culture,and renal related genes were detected after the treatment of corticosterone with different concentrations (250,500,1 000 μg · L-1) for 24 hours.Results Compared with the control group,the fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft,accompanied with the repression of the gene expression of glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway.The GDNF/c-Ret signaling pathway and angiotensin Ⅱ receptor type 1 (AT1R)/AT2R expression of metanephric mesenchyme stem cells also decreased in corticosterone groups.Conclusions PCE may induce dysplasia of female fetal kidneys.The potential mechanism is related to the repression of the gene expression of AT1R/AT2R and GDNF/c-Ret signaling pathway by PCE mediated by corticosterone in utero.

Clinicopathological analyses of combined hepatocellular carcinoma and cholangio carcinoma / 临床与实验病理学杂志

Purpose To investigate the clinicopathological characteristics and treatment of combined hepatocellular carcinoma-cholangio carcinoma (cHCC-CC).Methods 24 cases of cHCC-CC were collected.The clinical pathological characteristics,imaging,immunophenotyping and clinical features were retrospectively analyzed and reviewed the literature.Results There were 18 males and 6 females in 24 cases of cHCC-CC.The age ranged from 36 to 68 years (mean age was 54.38).Tumour location:right hepatic lobe in 15 cases,left hepatic lobe in 6 cases,both left lobe and right hepatic lobe in 1 case,hepatic caudate and left lateral lobe in 1 case,diffuse nodular liver tumors in 1 case.Grossly,the texture and color of tumor was related to the composition of tumor.Microscopically,classic cHCC-CC had two areas composed of hepatocellular carcinoma area and cholangiocar cinoma area of mixed distribution or migration distribution.3 cases were cHCC-CC with stem cell properties (cholangiolocellular carcinoma type,CLC type).Immunohistochemical staining revealed that HCC like area mainly expressed CD10,CK8,Hepatocyte and CD10,cHCC-CC area expressed CK7 and EMA.CLC type expressed the immunophenotypic features of intermediate type of HCC.Conclusion The clinical manifestations of cHCC-CC are not specific,the preoperative diagnosis is difficult,and it should be combined with pathological characteristics,imaging features and immunophenotype diagnosis.

Clinical characteristics of clonal evolution after immunosuppressive therapy in children with severe/very severe aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).</p><p><b>METHODS</b>The clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.</p><p><b>RESULTS</b>The 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.</p><p><b>CONCLUSIONS</b>The children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.</p>