OBJECTIVE: To assess the feasibility of first polar body transfer (PB1T) combined with preimplantation mitochondrial genetic testing for blocking the transmission of a pathogenic mitochondrial DNA 8993T>G mutation. METHODS: A Chinese family affected with Leigh syndrome which had attended the Reproductive Medicine Centre of the First Affiliated Hospital of Anhui Medical University in September 2021 was selected as the study subject. Controlled ovarian hyperstimulation was carried out for the proband after completing the detection of the mitochondrial DNA 8993T>G mutation load among the pedigree members. Mature MII oocytes were inseminated by intracytoplasmic sperm injection (ICSI), cultured in vitro for 5 to 6 days to the blastocyst stage, and trophoblastocytes were obtained by microbiopsy. Mitochondrial DNA testing (PGT-MT) and chromosomal aneuploidy (PGT-A) analyses were carried out after whole-genome amplification, and the embryos with zero mutation load were selected for transfer. Amniotic fluid and umbilical cord blood samples were collected during middle pregnancy and after birth respectively for mitochondrial DNA testing to verify the reliability of embryo screening. As an attempt, PB1 with good morphology of MII oocytes was selected for transfer into the enucleated oocytoplasm from healthy donors, followed by ICSI fertilization, blastocyst culture and PGT of embryos using the same procedure. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. 2021zhyx-B12). RESULTS: An antagonist protocol was used for ovarian stimulation, and a total of 19 oocytes were obtained, of which 14 MII were fertilized by ICSI, and 2 had developed into blastocysts. PGT-MT was carried out on biopsied trophoblastocytes, in which the mitochondrial DNA 8993T>G mutation load was not detected in one embryo, the other was 100% mutated, and the mutation loads of the remaining unfertilized eggs and developmentally arrested embryos ranged from 0% ~ 100%, presenting a clear biased distribution. With fully informed consent, one PGT-MT zero mutation load blastocyst was transferred and clinical pregnancy was achieved. Mitochondrial DNA and chromosomal testing of amniotic fluid cells during middle pregnancy had revealed no abnormalities. The proband had delivered a healthy boy through Caesarean section at 39⁺⁵ weeks of gestation, and no mutation was detected in the cord blood sample. Five well-formed PBs from 14 eggs were selected for PB1 transfer, followed by ICSI and culture, and two of the reconstituted embryos had formed blastocysts, with none of the above mutations detected in the biopsied samples. CONCLUSION The PGT-MT technology can help families affected with mitochondrial diseases to have healthy offspring. PB1 transfer in combination with ICSI and PGT-MT holds the promise of turning waste into treasure and providing an alternative means of fertility for such families.
Humans ; Preimplantation Diagnosis/methods* ; Female ; DNA, Mitochondrial/genetics* ; Genetic Testing/methods* ; Pregnancy ; Mitochondrial Diseases/genetics* ; Polar Bodies ; Adult ; Feasibility Studies ; Sperm Injections, Intracytoplasmic/methods* ; Embryo Transfer/methods* ; Mutation ; Male ; Blastocyst/metabolism* ; Pedigree

OBJECTIVE: To investigate the characteristics of chromosomal abnormalities in amniotic fluid among pregnant women in Liangshan Prefecture and explore strategies for optimizing prenatal diagnosis. METHODS: A retrospective analysis was conducted on 1 024 amniocentesis samples collected at the Prenatal Diagnosis Center of Liangshan Prefecture Maternal and Child Health Care Hospital between February 2022 and December 2024. Chromosome karyotyping analysis (3 cases had failed culture, 1 021 valid samples) was combined with high-throughput chromosome sequencing analysis (CNV-seq) for the detection. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-07). RESULTS: The overall detection rate of chromosomal karyotype abnormalities in the amniotic fluid cells was 4.02% (41/1 021), with numerical abnormalities accounting for 80.49% (33/41) and structural abnormalities for 19.51% (8/41). Numerical abnormalities were primarily trisomy 21 (16/41, 39.02%) and 47,XXY (6/41, 14.63%). Structural abnormalities included translocations (6 cases) and mosaicism (2 cases). CNV-seq detected 22 pathogenic or likely pathogenic copy number variations, whilst the undetection rate for balanced translocations reached 100% (7/7). The combined application of karyotyping and CNV-seq, leveraging complementary strengths, can enhance the overall detection rate. CONCLUSION The distribution characteristics of chromosomal abnormalities in amniotic fluid from pregnant women in Liangshan exhibit regional specificity. A combined testing strategy significantly optimizes prenatal diagnosis efficacy, providing crucial evidence for enhancing the effectiveness of prenatal diagnosis in ethnic minority regions.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Retrospective Studies ; Adult ; Amniotic Fluid ; Karyotyping ; Amniocentesis ; Chromosome Disorders/genetics* ; China ; High-Throughput Nucleotide Sequencing ; DNA Copy Number Variations/genetics*

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Objective:To exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes.Methods:This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1∶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital′s medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups.Results:After propensity score matching (1∶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group ( t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group ( χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group ( t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups ( t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group ( χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group ( χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group ( χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle ( χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions:PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.

Chaihu Jia Longgu Muli Decoction can effectively improve the sleep quality of perimenopausal insomnia patients, reduce negative emotions, regulate the neuroendocrine system, improve the other perimenopausal symptoms, and has higher safety. Chaihu Jia Longgu Muli Decoction can play a role in perimenopausal insomnia by correcting hormone levels, regulating a variety of neurotransmitters and cytokines, regulating intestinal flora and other ways.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Objective:To investigate the safety and efficacy of ultrasound-guided transversus abdominis plane (TAP) combined with paracervical block in percutaneous microwave ablation(PMWA) of uterine fibroids.Methods:Twenty-four patients with uterine fibroids who underwent PMWA after ultrasound-guided TAP combined with paracervical block in Sichuan Cancer Hospital from October 2021 to January 2022 were retrospectively analyzed. The success rate and adverse reactions of TAP combined with paracervical block were recorded, and the types and doses of rescue analgesics used during and after operation were recorded. The pain degree of patients was recorded by NRS(numeric rating scales) during and 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours and 24 hours after operation, and the satisfaction of patients was recorded.Results:The success rate of TAP combined with paracervical block was 100%, and there were no adverse reactions during and after operation. During the operation, 5 patients(20.83%) had mild pain, which was tolerable and did not need intervention, 4 patients(16.67%) presented with moderate pain, and the NRS scores were 4, 4, 5 and 6 respectively, the symptoms were relieved after rescue analgesia. All patients completed one ablation, no ablation failure or secondary ablation. Some patients had mild pain after operation, which could be tolerated without intervention, and all were relieved naturally within 6 hours. All patients returned home on the day of ablation and were 100% satisfied with the analgesic effect.Conclusions:Ultrasound-guided TAP combined with paracervical block in PMWA of uterine fibroids is safe and effective, which is worthy of clinical promotion.

Objective:To investigate the association of thallium exposure during pregnancy with pregnant blood pressure changing and hypertensive disorder complicating pregnancy(HDCP).Methods:A total of 3 240 pregnant women who had establish maternal health care manual in Ma′anshan Maternal and Child Health-Care Hospital and met the inclusion and exclusion criteria were included in this study between May 2013 and September 2014.We collected their general demographic characteristics and blood pressure through questionnaire and medical records. Meanwhile we measured serum thallium concentrations by experimental technology. We use multiple logistic regression to analyze the association between thallium exposure during pregnancy and HDCP. Mixed linear model were used to analyze the association between thallium concentration and maternal systolic blood pressure (SBP) or diastolic blood pressure(DBP) in different trimestersResults:The age of 3 240 pregnant woman was (26.61±3.64) years, and the detection rate of HDCP was 5.9%(191).The median ( P 25, P 75) of thallium concentrations in first trimester, second trimester and third trimester were 62.96 (50.79, 77.04), 62.19 (50.87, 75.26), 48.84 (38.00, 66.00) ng/L, respectively. Multiple logistic regression results suggested after adjusting various confounding factors, the risk of HDCP in pregnant women with high concentrations of thallium (>77.04 ng/L) in the first trimester is 1.75 (95% CI:1.01-3.03) times higher than which with low concentrations(<50.82 ng/L). Mixed linear model results suggested there are positive correlation between thallium concentrations with maternal DBP in first trimester (β=1.12, 95% CI: 0.39-1.85). Conclusion:Exposure to high levels of thallium during first trimester may increase the risk of HDCP, and the exposure of thallium may be effective to DBP of pregnant.

Objective:To investigate the association of thallium exposure during pregnancy with pregnant blood pressure changing and hypertensive disorder complicating pregnancy(HDCP).Methods:A total of 3 240 pregnant women who had establish maternal health care manual in Ma′anshan Maternal and Child Health-Care Hospital and met the inclusion and exclusion criteria were included in this study between May 2013 and September 2014.We collected their general demographic characteristics and blood pressure through questionnaire and medical records. Meanwhile we measured serum thallium concentrations by experimental technology. We use multiple logistic regression to analyze the association between thallium exposure during pregnancy and HDCP. Mixed linear model were used to analyze the association between thallium concentration and maternal systolic blood pressure (SBP) or diastolic blood pressure(DBP) in different trimestersResults:The age of 3 240 pregnant woman was (26.61±3.64) years, and the detection rate of HDCP was 5.9%(191).The median ( P 25, P 75) of thallium concentrations in first trimester, second trimester and third trimester were 62.96 (50.79, 77.04), 62.19 (50.87, 75.26), 48.84 (38.00, 66.00) ng/L, respectively. Multiple logistic regression results suggested after adjusting various confounding factors, the risk of HDCP in pregnant women with high concentrations of thallium (>77.04 ng/L) in the first trimester is 1.75 (95% CI:1.01-3.03) times higher than which with low concentrations(<50.82 ng/L). Mixed linear model results suggested there are positive correlation between thallium concentrations with maternal DBP in first trimester (β=1.12, 95% CI: 0.39-1.85). Conclusion:Exposure to high levels of thallium during first trimester may increase the risk of HDCP, and the exposure of thallium may be effective to DBP of pregnant.

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an glioma model, PCC0208017 showed robust anti-tumor activity, blood-brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma.