Analysis of risk factors and severity prediction of acute pancreatitis induced by pegaspargase in children / 中华实用儿科临床杂志

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

Effect of LncRNA p21 regulating Hippo-YAP signaling pathway on formation of abdominal aortic aneurysm in mice and its mechanism / 中国药理学通报

Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE

Cerebral venous sinus thrombosis caused by pegasparaginase: a clinical analysis of 8 cases / 中华神经医学杂志

Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.

Effect of laser artificial shrinkage on pregnancy outcome in vitrification of human expanded blastocysts / 西安交通大学学报(医学版)

Objective To investigate the effect of laser artificial shrinkage(LAS)on pregnancy outcome in vitrification of human expanded blastocysts.Methods We selected 3859 frozen-thawed blastocyst-stage embryo transfers from January 2014 to December 2015.The transfers were divided into LAS group(n=3 176)and non-LAS group(n=683),which were then subdivided into ＜36 y subgroup and ≥36 y subgroup according to their age.Main outcomes measures were thawing rate,implantation rate and clinical pregnancy rate.Results Thawing rate, clinical pregnancy rate and implantation rate were 97.32%(5 453/5 603),66.81%(2 118/3 170),and 53.55%(2 912/5 438)in LAS group.In non-shrink group,they were 95.13%(1 173/1 233),62.70%(427/681),and 49.74%(582/1 170),which did not significantly differ from those in the former group(P＜0.05).Further analysis of the subgroups showed that thawing rate was significantly higher in LAS group than in non-shrink group of patients＜36 y(97.27% vs.95.33%;P＜0.05).Thawing rate and biochemical pregnancy rate were significantly higher in LAS group than in non-shrink group in patients ≥36 y(97.75% vs.93.66%;65.45% vs.50.65%,P＜0.05). Cancellation rate was not significantly different between the two groups(0.19% vs.0.29%, P ＞ 0.05). Conclusion LAS technique can increase thawing rate,clinical pregnancy rate and implantation rate before cryopreservation of blastocysts.

Paeoniflorin alleviates TNF-α induced intestinal barrier dysfunction by inhibition of MLCK / 中国药理学通报

Aim To investigate the protective effect of paeoniflorin on TNF-α induced intestinal epithelial barrier dysfunction and its mechanisms.Methods The Caco-2 cells were cultured and the MTF assay was used to determine the effects of the paeoniflorin on Caco-2 cell activity.The Caco-2 cell intestinal epithelial barrier dysfunciton model was established through incubation of cells with TNF-α.The effects of paeoniflorin on intestinal epithelial barrier dysfunciton were studied.Results The transmembrane resistance in Caco-2 epithelial barrier was significantly reduced by TNF-α incubation;MLCK significantly increased,while tight junction protein occludin and ZO-1 significantly decreased by TNF-α.These changes were significantly reversed by paeoniflorin,which reduced MLCK expression and enhanced expression of occludin and ZO-1.The protective effects against epithelial barrier dysfunction could be abrogated by small interfering RNA(siRNA) of MLCK.Conclusions Paeoniflorin alleviates the epithelial barrier dysfunction induced by TNF-αthrough down-regulation of MLCK and enhancement of tight junction protein occludin and ZO-1.This study supplies a potential candidate drug for the clinical treatment of inflammatory bowel diseases.

The rate of morphologically normal sperm does not affect the clinical outcomes of conventional IVF in patients with one retrieved oocyte / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the influence of the rate of morphologically normal sperm (MNS) on the clinical outcomes of conventional in vitro fertilization (IVF) in patients with one retrieved oocyte.</p><p><b>METHODS</b>From January 2013 to January 2015, a total of 256 couples with one retrieved oocyte underwent conventional IVF in our center. According to the rate of MNS, the patients were divided into two groups: MNS < 4% (134 cycles) and MNS ≥ 4% (122 cycles). We compared the rates of no transferrable embryo cycles, fertilization, cleavage, normal fertilization, abnormal fertilization, high-quality embryo and transferrable embryo between the two groups. A total of 75 fresh embryo transfer cycles were performed, 43 in the MNS < 4% group and the other 32 in the MNS ≥ 4% group. We also compared the rates of implantation, clinical pregnancy and abortion between the two groups.</p><p><b>RESULTS</b>There were no statistically significant differences between the two groups in the rates of no transferrable embryo cycles, fertilization, cleavage, normal fertilization, abnormal fertilization, high-quality embryo and transferrable embryo (P > 0.05). The rates of implantation, clinical pregnancy and abortion exhibited no remarkable differences either in the fresh embryo transfer cycles between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>The rate of MNS does not affect the clinical outcomes of conventional IVF in patients with one retrieved oocyte.</p>

Association of fertilization strategy and embryo transfer time with the incidence of ectopic pregnancy / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the fertilization strategy and embryo transfer (ET) time with the incidence of ectopic pregnancy.</p><p><b>METHODS</b>We selected 3,331 fresh and 2,706 frozen-thawed ET cycles for the patients undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The fresh transfers included 2 546 IVF-ET and 785 ICSI-ET cycles and 2,220 day-3 embryo and 1,111 day-5 blastocyst transfers, while the frozen-thawed transfers included 2,080 IVF-ET and 626 ICSI-ET cycles and 741 day-3 embryo and 1 965 day-5 or -6 blastocyst transfers. We compared the incidence rate of ectopic pregnancy associated with different fertilization strategies and ET time.</p><p><b>RESULTS</b>The incidence rate of ectopic pregnancy was 1. 41% (36/2 546) in the IVF-ET cycles and 3.44% (27/785) in the ICSI-ET cycles of the fresh transfers, significantly lower in the IVF-ET than in the ICSI-ET cycles (P < 0.01), and it was 1.01% (21/2,080) in the IVF-ET cycles and 0.80% (5/626) in the ICSI-ET cycles of the frozen-thawed transfers, with no remarkable difference between the two groups (P > 0.05). The IVF-ET and ICSI-ET cycles included 2,220 fresh day-3 (F-D3) embryos, 1,111 F-D5 blastocysts, 741 frozen-thawed day-3 (T-D3) embryos, and 1,965 T-D5/6 blastocysts. The incidence rate of ectopic pregnancy was 1.71% (n = 38) in the F-D3, 2.25% (n = 25) in the F-D5, 1.35% (n = 10) in the T-D3, and 0.81% (n = 16) in the T-D5/6 group, respectively, significantly lower in the T-D5/6 than in the other three groups (P < 0.05).</p><p><b>CONCLUSION</b>The incidence rate of ectopic pregnancy is associated with fertilization strategies, which is significantly lower in frozen-thawed than in fresh embryo transfers.</p>

Intracytoplasmic sperm injection does not improve the clinical outcomes of the males with 100% teratozoospermia / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate whether intracytoplasmic sperm injection (ICSI) can improve the clinical outcomes of the male patients with 100% teratozoospermia.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 152 couples undergoing in vitro fertilization-embryo transfer (IVF-ET), including 75 cycles of IVF and 77 cycles of ICSI. We compared the rates of normal fertilization, high-quality embryos, transferrable embryos, implantation, clinical pregnancy, and abortion between the two groups.</p><p><b>RESULTS</b>In the 100% teratozoospermia patients the number of transferrable embryos was significantly lower in the IVF than in the ICSI group (78.91% vs 84.92%, P < 0.05), while the rates of normal fertilization and implantation were higher in the former than in the latter (60.26% vs 57.87% and 48.00% vs 39.55%, both P > 0.05). There were no statistically significant differences between the two groups in the female age, Gn days, Gn dose, BMI, infertility duration, endometrial thickness, and basal serum FSH and E2.</p><p><b>CONCLUSION</b>ICSI cannot improve the clinical outcomes of the male patients with 100% teratozoospermia.</p>

Influence factors on the cryosurvival rate of post-thaw spermatozoa from sperm donors / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the influence of seasons, blood types and semen parameters on the cryosurvival rate of frozen-thawed spermatozoa from sperm donors.</p><p><b>METHODS</b>We retrospectively analyzed the influence of seasons, blood types, abstinence period, semen volume, sperm morphology, and pre-freeze sperm motility and concentration on the cryosurvival rate of frozen-thawed sperm in 4 088 semen samples from Shaanxi Human Sperm Bank.</p><p><b>RESULTS</b>The cryosurvival rate of the post-thaw sperm was correlated negatively with the progressive motility of the pre-freeze sperm (r = -0.262, P < 0.01), but positively with pre-freeze sperm concentration (r = 0.247, P < 0.01), and it was significantly higher in the 6-day abstinence group ([70.2 +/- 5.4]%) than in the other abstinence groups (P < 0.01), so was it in the normal sperm morphology rate > 20% group ([71.4 +/- 5.1]%) than in the others (P < 0.01). The survival rate of the post-thaw sperm was not correlated with seasons, blood types, and semen volume (P > 0.05).</p><p><b>CONCLUSION</b>Sperm motility, concentration and morphology and the abstinence period of sperm donors may be valuable predictors of the cryosurvival rate of post-thaw sperm, but no correlation was found between the survival rate and seasons, blood types and semen volume.</p>

Relationship between the expression of HBV mRNA in embryos and father-to-infant HBV transmission / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate father-to-infant transmission of hepatitis B virus (HBV) by detecting HBV mRNA in the IVF embryos with paternal HBV infection.</p><p><b>METHODS</b>We collected 18 discarded IVF embryos (9 cases) with paternal chronic HBV infection, and detected HBV mRNA in the embryos by single-cell RT-PCR.</p><p><b>RESULTS</b>HBV mRNA positive signals were found in 1 of the 18 embryos with paternal serum HBV positive markers (5.6%), but no specific HBV mRNA signals were observed in the 84 embryos of the negative control group. Follow-up visits revealed no significant difference between the experimental and negative control groups either in the rate of clinical pregnancy (P > 0.05) or in that of early abortion (P > 0.05). The IVF embryo with paternal HBV mRNA positive signals was successfully implanted, but early abortion occurred. HBV infection was not transmitted to progeny in either of the two groups.</p><p><b>CONCLUSION</b>The positive results of HBV mRNA indicate that HBV can get into early-cleavage embryos through sperm and replicate there, which may be the main channel of father-to-infant transmission. HBV may interfere with the development of embryos, and even result in abortion and other adverse outcomes.</p>

Expressions of sperm-specific genes in carnitine-cultured testis sperm of obstructive azoospermia patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of carnitine on human sperm motility and its potential role in the treatment of male infertility diseases.</p><p><b>METHODS</b>We obtained sperm by testis puncture from obstructive azoospermia patients and cultured them in vitro with normal culture solution (the control group) and the solution with L-carnitine at the concentration of 100 and 250 mmol/L, respectively. We observed the changes in sperm motility and morphology before and after the treatment, detected the expressions of the germ-specific genes, Vasa, Dazl, Acr, Prm1 and ATPase 6.0 by RT-PCR, and investigated the relationship between L-carnitine and the genes associated with sperm development and maturation.</p><p><b>RESULTS</b>After 24 -72 hours of treatment, the percentage of motile sperm was significantly higher in the 100 mmol/L L-carnitine group than in the control and 250 mmol/L L-carnitine groups (P < 0.01); the number of forward moving sperm was obviously increased and sperm morphology remained normal in the 100 mmol/L L-carnitine group. RT-PCR showed that L-carnitine increased the expressions of Acr, Prm1, Dazl and ATPase 6. 0 at the concentration of 100 mmol/L, and decreased the expressions of Dazl, Acr and Prm1 at 250 mmol/L.</p><p><b>CONCLUSION</b>L-carnitine at a proper concentration may improve the motility of incubated testicular sperm by upregulating the expressions of some sperm-specific genes, which helps sperm selection for intracytoplasmic sperm injection. However, a higher concentration of L-carnitine may reduce the expressions of these genes, probably due to its increased toxicity.</p>

Teratozoospermia affects in vitro fertilization outcome / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the possible causes of total fertilization failure (TFF) in conventional in vitro fertilization (IVF).</p><p><b>METHODS</b>We included in this study 552 couples who accomplished the first conventional IVF cycle in our center from January 2007 to August 2008. All the males met the Kruger/Tygerberg criteria, with the teratozoospermia rate < 96% in the previous 12 months and the postwash motile sperm > 1 million on the day of egg retrieval. The eggs were fertilized totally by conventional IVF.</p><p><b>RESULTS</b>Of the total number, 515 couples got zygotes by conventional IVF, with a fertilization rate of 78.67%, and 37 suffered TFF. The rates of primary infertility and teratozoospermia were significantly higher in the TFF group than in the fertilized group (P < 0.05). There were no statistically significant differences between the two groups in the number of controlled ovarian hyperstimulation (COH) days, the number of oocytes retrieved, the dose of gonadotropin (Gn) used, the age of the couples, the length of protocols and the rate of oligoasthenozoospermia.</p><p><b>CONCLUSION</b>Intracytoplasmic sperm injection (ICSI) can be considered for at least some of the oocytes to avoid unnecessary fertilization failure in teratozoospermia patients by Kruger/Tygerberg strict criteria.</p>

Effects of Astragalus membranaceus and Panax notoginseng on the transformation of bone marrow stem cells and proliferation of EPC in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect and the possible mechanism underlying the promotional effect of Astragalus membranaceus and Panax notoginseng on the transformation of bone narrow stem cells and proliferation of EPC.</p><p><b>METHOD</b>The marrow blood was collected in the patients with ischemia of lower limbs and BM-MNCs were separated and proliferated under different conditions. A. morphologic observation was performed and the ratio of CD34+ cells was measured.</p><p><b>RESULT</b>The shuttle shaped cells lined up as bunches with several round cells scattered. The ratio of CD34+ cells was significantly increased in groups treated with medium (P < 0.01) and lower (P < 0.05) dosages of A. membranaceus and medium (P < 0.01) and high dosages (P < 0.01) of P. notoginseng respectively as compared with control group.</p><p><b>CONCLUSION</b>A. membranaceus and P. notoginseng can promote the transformation and proliferation of EPC.</p>