Objective To investigate the association between multi-drug resistant 1 (MDR1) gene C3435T and T129C polymorphism with refractory epilepsy in children. Methods A total of 260 children including 60 refractory epilepsy, 100 drug-responsive epilepsy, and 100 healthy children were enrolled. The genotypes for MDR1 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis.The distribution of genotypes and allele frequencies of the three groups were compared. Results The distribution of TT/TC/CC genotypes and T/C allele frequencies of C3435T showed no signiifcant difference between drug-resistant patients and drug-responsive patients or normal control group (P>0.05). Drug-resistant patients were more likely to have the TC genotype and the C allele at T129C when compared with the drug-responsive patients and the normal control group (P<0.05). Conclusions T129C polymorphism of the MDR1 gene was associated with refractory epilepsy in children.

Objective To investigate the relationship between serum progesterone level at the day with human chorionic gonadotrophin (hCG) administration and pregnant outcome from in in-vitro fertilization-embryo transfer(IVF-ET). Methods From Mar. 2002 to Apr. 2007, 786 cycles with serum progesterone measurement on the day of hCG administration for final oocyte maturation in IVF were analyzed retrospectively in Reproductive Medicine Center in First Affiliated Hospital of Nanjing Medical University.All stimulations were down-regulated with gronadotrophin release hormone agonist (GnRH-a) in both long protocols and short protocols before gonadotrophin stimulation. When the thresholds of serum progesterone were set at 5.5, 6.0,6.5,7.0,7.5,8.0,8.5 and 9.0 nmol/L, respectively. If the level of progesterone was less than the thresholds, those patients were in lower progesterone group, on the contrary, more than the threshold value, those patients were in higher progesterone group. The laboratory results and the clinical outcomes between all patients at lower and higher progesterone group at different thresholds value were analyzed. Results The rate of normal fertilization, quality embryos, successful implantation, chemical pregnancy, clinical pregnancy and live birth did not exhibit remarkable difference between patients with higher and lower serum progesterone level at multiple thresholds on the day of hCG administration in the 786 cycles (P >0.05). However, when the thresholds of serum progesterone were at 8.5 and 9.0 nmol/L, early abortion rates of 27.3% (3/11) and 3/7 in higher progesterone group were significantly higher than 8.8% (26/297) and 8.6% (26/301) in lower progesterone group (P<0.05). And the total abortion rates of 3/7 in higher progesterone group were significantly higher than 11.0% (34/301) in lower progesterone group when the thresholds of serum progesterone were 9.0 nmol/L (P<0.05). Conclusions This study did not prove the correlationship between progesterone level at the clay with hCG administration and the probability of clinical pregnancy or live birth. However, early abortion rates or the total abortion rates were associated with higher progesterone level when the thresholds of serum progesterone were at 8.5 nmol/L or 9.0 nmoL/L.

Objective:To investigate the impact of body mass index (BMI) on clinical effect and fresh cycle embryo transfer pregnancy outcome of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) in patients with early follicular phase prolonged protocol.Methods:From January 1st, 2018 to July 1st, 2020, 2 257 cases of early follicular long-term protocol in IVF/ICSI and embryo transfer were collected using the clinical assisted reproductive technologies management system software database of the First Affiliated Hospital of Nanjing Medical University. Patients were divided into three groups according to the recommended Asian BMI cut-off points: low body mass group (BMI<18.5 kg/m 2), normal body mass group (18.5≤BMI<24.0 kg/m 2), and high body mass group (BMI≥24.0 kg/m 2). The ovarian stimulation characteristics among the groups were investigated. Then 1 741 fresh embryo transfer cycles were selected and divided into three groups as above, and then the ovulation induction and clinical outcomes were analyzed among the groups. Results:There were significant differences in the starting dosage of gonadotrophin (Gn), total dosage of Gn and days of Gn used among the low body mass group, normal body mass group, and high body mass group in the 2 257 IVF/ICSI cycles (all P<0.01). The high body mass group needed the most amount of Gn [(2 159±668) U] and longest Gn days [(12.3±2.5) days]. The estradiol and progesterone levels [(7 474±4 852) pmol/L, (3.4±1.9) nmol/L] on hCG trigger day in the high body mass group were lower than those in the low body mass group and normal body mass group (all P<0.01). The oocytes retrieved in high body mass group (8.4±4.1) were significantly lower than normal body mass group ( P<0.05). The normal fertilization number, the available embryo number and high quality embryo number were all lower in the high body mass group than other two groups, while no significant difference showed (all P>0.05). In 1 741 cycles of fresh embryo transfer, the average number of transplanted embryos in the low body mass group (1.2±0.4) was decreased compared with the other two groups ( P<0.05), while the biochemical pregnancy rate, clinical pregnancy rate and live birth rate in the normal body mass group were higher compared with the other two groups, but the differences showed no statistically significance (all P>0.05). Conclusions:Increased BMI might affect ovulation induction response in early follicular phase prolonged protocol IVF/ICSI patients, leading to the increase of Gn dosage and the extension of Gn induction days. Although there is no significant difference in pregnancy outcome among different BMI groups, considering the increased risk of adverse perinatal outcomes during subsequent pregnancy in overweight or obese patients, certain attention should still be paid to the control of BMI in patients receiving assisted reproduction treatment with early follicular phase prolonged protocol.

Background:Previous studies have proved that neutrophil gelatinase-associated lipocalin(NGAL)plays an important role in the progression of Crohn's disease(CD),and may serve as a potential biomarker for disease activity prediction,severity assessment,treatment response evaluation and prognosis monitoring.However,the diagnostic value of NGAL in perianal fistulizing Crohn's disease(pfCD)is still unclear.Aims:To investigate the serum level of NGAL and its diagnostic value in patients with active pfCD.Methods:A total of 66 patients diagnosed as pfCD from July 2021 to June 2023 at Longhua Hospital,Shanghai University of Traditional Chinese Medicine were enrolled,including 36 active pfCD patients and 30 inactive pfCD patients.The disease activity and perianal fistula activity were assessed by Crohn's disease activity index(CDAI)and perianal disease activity index(PDAI),respectively.Serum NGAL,fecal calprotectin(FC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),as well as CDAI score and PDAI score were compared between the active and inactive pfCD patients,and the correlations of NGAL with the other parameters in active pfCD patients were analyzed.ROC curve was drawn to evaluate the values of serum NGAL,FC,CRP and ESR for diagnosis of active pfCD.Results:The serum NGAL,FC,CRP,ESR,CDAI score and PDAI score in active pfCD patients were significantly higher than those in inactive pfCD patients(all P＜0.001).NGAL was positively correlated with FC(r=0.64,P＜0.001),CRP(r=0.55,P＜0.001),ESR(r=0.53,P＜0.001),CDAI score(r=0.59,P＜0.001)and PDAI score(r=0.54,P＜0.001)in active pfCD patients.The optimal cut-off values of NGAL,FC,CRP and ESR were 220.5 μg/L,146.0 μg/g,7.9 mg/L and 23.5 mm/h,respectively,for the diagnosis of active pfCD,and the area under the curve were 0.922(95％CI:0.850-0.995),0.888(95％CI:0.806-0.970),0.853(95％CI:0.763-0.944)and 0.830(95％CI:0.731-0.930),respectively.Conclusions:Serum NGAL level is associated with the disease activity of pfCD,and can be used as a non-invasive biomarker for the clinical diagnosis of active pfCD.

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly asso-ciated with adverse pregnancy outcomes including recurrent miscarriage (RM).However,an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unex-plained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8+ effector T cells,nature killer(NK),and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand-receptor interac-tions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK) subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto-toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56 + CD16 + dNK subset substantially accumulates in RM decidua.These findings reveal a com-prehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

With the widespread application of genomics and transcriptomics in the genetics and cell biology of different species, synonymous codon usage bias has been gradually accepted and used to study the deep connection between biological evolution and biological phenotypes. It is an important part of the life activities that mRNA is expressed into proteins with normal biological activities. The synonymous codon usage patterns, which were named as 'the second genetic codon', can express genetic information carried by themselves at the levels of transcriptional regulations, translational regulations and metabolic activities through molecular mechanisms such as fine-tune translation selection. Some studies have shown that the length of mRNA half-life has significant impacts on mRNA activity and the process of transcription and translation. This review summarized the roles of synonymous codon usage patterns in transcription, translational regulation and post-translational modification, with the aim to better understand how organisms skillfully utilize the genetic effects caused by codon usage patterns to accurately synthesize different types of proteins, so as to ensure the growth or differentiation of the specific gene expression procedures to carry out smoothly and maintain the normal life cycle.
Codon/genetics* ; Codon Usage ; Half-Life ; Protein Processing, Post-Translational ; RNA, Messenger/genetics*

Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans ; Killer Cells, Natural ; Interferon-gamma ; Apoptosis ; Autoimmune Diseases ; Cytokines