[Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis].

Objective: To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE3) levels and XLI. Methods: A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results: Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant (Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions: The decrease levels of uE3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies.

A comparison was conducted of 213 patients with haematologic malignancies who underwent HLA-identical sibling (n=108) or HLA-haploidentical (n=105) haematopoietic cell transplantation (haplo-HCT) at our centre. The conditioning regimen included fludarabine, busulphan, cyclophosphamide and antilymphocyte globulin (ATG) (FBCA). The total dose of ATG differed between identical and haploidentical groups (3.75 mg/kg versus 12.5 mg/kg). The cumulative incidences of grade II-IV acute GvHD in the identical and haploidentical groups were 20.4% and 21.9% (P=0.73), and 2-year cumulative incidences of chronic GvHD were 36.4% and 24.1% (P=0.17), respectively. The 3-year probabilities of non-relapse mortality for identical and haploidentical groups were 20.5% and 34.9% (P=0.048), and for relapse were 22.2% and 21.0% (P=0.85), respectively. The 3-year overall survivals in the identical and haploidentical groups were 62.6% and 52.6% (P=0.054), whereas the 3-year disease-free survivals were 54.7% and 43.1% (P=0.14), respectively. In the multivariate analysis, patients in the high-risk group exhibited reduced survival, and the higher dose of mononuclear or CD34+ cells resulted in an increase in the likelihood of survival. In conclusion, haplo-HCT based on an FBCA conditioning regimen could achieve nearly comparable outcomes to HLA-identical sibling HCT.

Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative for patients who need a transplant without having conventional donors. One hundred and five consecutive patients with hematologic malignancies who underwent G-CSF-primed peripheral blood haplo-HSCT without in vitro T-cell depletion in our single center were reported in this study. Patients were categorized into the intermediate-risk group (n=28) or high-risk group (n=77) according to the risk stratification. The conditioning regimen included fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin. The cumulative incidence of grades II-IV acute GvHD (aGvHD) on day +100 was 21.9%, and that of grades III-IV aGvHD was 14.3%. The 2-year cumulative incidence of total chronic GvHD (cGvHD) was 24.1%, and that of extensive cGvHD was 5.6% in 83 eligible patients. The 3-year cumulative incidence rates of relapse and no relapse mortality were 21.9% and 30.5%, respectively. After a median follow-up of 35 months, the 3-year probabilities of overall and disease-free survival for the intermediate-risk and high-risk groups were 63.2% and 39.8% and 61.2% and 32.2%, respectively. In multivariate analysis, the outcome of survival (overall survival and disease-free survival) was associated with the risk stratification, disease status at transplant and dose of infused mononuclear cells. Our results suggest that unmanipulated peripheral blood stem cell allograft performed with fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin conditioning regimen is feasible.

Mechanisms for LEPR-mediated regulation of leptin expression in brown and white adipocytes in rat pups.

To investigate the underlying mechanisms for leptin receptor (LEPR)-mediated regulation of leptin gene (Lep) expression in brown (BAT) and white (WAT) adipose tissue and resultant effects on plasma leptin concentrations (plasma-LEP), we examined effects of sympathetic nervous system (SNS) activity, caloric balance, and body fat content on leptin mRNA levels in BAT and WAT in 10-day-old rat pups segregating for Lepr(fa). In mother-reared pups, Lep mRNA levels were fa/fa > +/fa = +/+ in BAT and was fa/fa > +/fa > +/+ in WAT. The genotype effects on Lep expression in BAT and plasma-LEP were virtually eliminated when the differences in SNS activity between fa/fa and +/fa pups were equalized by artificial rearing of pups under thermoneutral conditions with or without oral norepinephrine (NE) administration. NE administration alone had little effect on the Lepr(fa)-dependent stratification of Lep expression in WAT. BAT-Lep mRNA was the main determinant of plasma-LEP. Metabolic rate, a surrogate indicator of SNS activity, explained 87% of the variation in BAT-Lep mRNA (R(2) = 0.93), whereas caloric balance (40%) and body fat mass (6%) accounted for most of the variation in WAT-Lep mRNA (R(2) = 0.53). We conclude that feedback regulation of Lep expression in BAT is primarily via central nervous system-mediated effects of leptin on SNS activity, whereas the control of leptin expression in WAT is more likely via mechanisms not directly dependent on SNS activity.

Mixed chimera converted into full donor chimera with powerful graft-versus-leukemia effects but no graft-versus-host disease after non T cell-depleted HLA-mismatched peripheral blood stem cell transplantation.

Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organic compound believed to block CD4 binding to MHC II molecule of APC) to block donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We successfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplantation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) were donor derived at day +30 and day +60, respectively. Mixed chimerism converted into full donor chimerism, when 99.7% of the MNC in the recipient were donor derived after three courses of DLI. A powerful GVL effect related to mixed chimerism was observed. No acute GVHD occurred, only grade II chronic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HLA barriers without donor T cell depletion; (2) mixed chimerism can be converted into full donor chimerism by DLI; (3) mixed chimerism induced with this approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.

[Re-discovery of yinzhou chaihu].

This paper deals with the distribution, original plant, course of rise and fall in drug market and quality of Yinzhou Chaihu, which was once regarded as a fine sort of Chinese drug Chaihu (Radix Bupleuri) in ancient times. Further research on this medicinal plant is suggested to facilitate its re-exploitation and utilization.