ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with tall stature and primary amenorrhea presenting with 47,XYY Disorder of sex development (DSD). METHODS: A female patient presenting with "tall stature and primary amenorrhea" at Nanjing Drum Tower Hospital in July 2024 was selected as the study subject. A retrospective study design was employed to collect the patient's clinical data. Peripheral venous blood sample was collected. Following the extraction of genomic DNA, genetic testing was performed including chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), multiplex PCR for the AZF regions and sex-determining genes Y (SRY), and whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing and classified for pathogenicity based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital (Ethics No.: 2022-451-01). RESULTS: The patient had a height of 188 cm and a body weight of 50 kg, in addition with infantile uterus, absent ovaries, and primary amenorrhea. G-banded karyotyping analysis of peripheral blood sample revealed 47,XYY. CNV-seq indicated Seq[GRCh37]Yp11.32q12×2. No deletion was detected in the AZF regions of Y chromosome, and SRY was positive. WES identified a heterozygous c.86C>A (p.Thr29Lys) variant of the NR5A1 gene, leading to substitution of threonine with lysine at position 29 of the encoded protein. Sanger sequencing confirmed the presence of the variant. According to the ACMG guidelines, this variant was classified as variant of uncertain significance (VUS) with supporting evidence (PS3_Moderate+PM5+PP3+PM2_Supporting+PS4_Supporting). Reviewing the nearly 60 years of previously reported cases, all 7 documented 47,XYY DSD patients were assigned a female social gender and presented with abnormal gonadal and external genitalia development. Among them, 5 cases underwent SRY testing, all of which were positive. Only 1 case underwent whole-exome sequencing (WES), but no pathogenic or likely pathogenic variants were identified. CONCLUSION This DSD patient presented with the clinical features of tall stature and primary amenorrhea. The NR5A1 gene variant c.86C>A (p.Thr29Lys) probably underlay the Disorder of sex development in this patient. Above finding has enriched the spectrum of pathogenic variants of the NR5A1 gene.
Humans ; Female ; Steroidogenic Factor 1/genetics* ; DNA Copy Number Variations/genetics* ; XYY Karyotype/genetics* ; Karyotyping ; Retrospective Studies ; Phenotype ; Sex Chromosome Disorders of Sex Development/genetics* ; Sex Chromosome Disorders

Objective:To investigate the clinical phenotype and genetic etiology of a patient with tall stature and primary amenorrhea presenting with 47, XYY Disorder of sex development (DSD).Methods:A female patient presenting with " tall stature and primary amenorrhea" at Nanjing Drum Tower Hospital in July 2024 was selected as the study subject. A retrospective study design was employed to collect the patient′s clinical data. Peripheral venous blood sample was collected. Following the extraction of genomic DNA, genetic testing was performed including chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), multiplex PCR for the AZF regions and sex-determining genes Y ( SRY), and whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing and classified for pathogenicity based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital (Ethics No.: 2022-451-01). Results:The patient had a height of 188 cm and a body weight of 50 kg, in addition with infantile uterus, absent ovaries, and primary amenorrhea. G-banded karyotyping analysis of peripheral blood sample revealed 47, XYY. CNV-seq indicated Seq[GRCh37]Yp11.32q12×2. No deletion was detected in the AZF regions of Y chromosome, and SRY was positive. WES identified a heterozygous c. 86C>A (p.Thr29Lys) variant of the NR5A1 gene, leading to substitution of threonine with lysine at position 29 of the encoded protein. Sanger sequencing confirmed the presence of the variant. According to the ACMG guidelines, this variant was classified as variant of uncertain significance (VUS) with supporting evidence (PS3_Moderate+ PM5+ PP3+ PM2_Supporting+ PS4_Supporting). Reviewing the nearly 60 years of previously reported cases, all 7 documented 47, XYY DSD patients were assigned a female social gender and presented with abnormal gonadal and external genitalia development. Among them, 5 cases underwent SRY testing, all of which were positive. Only 1 case underwent whole-exome sequencing (WES), but no pathogenic or likely pathogenic variants were identified. Conclusion:This DSD patient presented with the clinical features of tall stature and primary amenorrhea. The NR5A1 gene variant c. 86C>A (p.Thr29Lys) probably underlay the disorder of sex development in this patient. Above finding has enriched the spectrum of pathogenic variants of the NR5A1 gene.

Objective:To investigate the clinical phenotype and genetic etiology of a patient with tall stature and primary amenorrhea presenting with 47, XYY Disorder of sex development (DSD).Methods:A female patient presenting with " tall stature and primary amenorrhea" at Nanjing Drum Tower Hospital in July 2024 was selected as the study subject. A retrospective study design was employed to collect the patient′s clinical data. Peripheral venous blood sample was collected. Following the extraction of genomic DNA, genetic testing was performed including chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), multiplex PCR for the AZF regions and sex-determining genes Y ( SRY), and whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing and classified for pathogenicity based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital (Ethics No.: 2022-451-01). Results:The patient had a height of 188 cm and a body weight of 50 kg, in addition with infantile uterus, absent ovaries, and primary amenorrhea. G-banded karyotyping analysis of peripheral blood sample revealed 47, XYY. CNV-seq indicated Seq[GRCh37]Yp11.32q12×2. No deletion was detected in the AZF regions of Y chromosome, and SRY was positive. WES identified a heterozygous c. 86C>A (p.Thr29Lys) variant of the NR5A1 gene, leading to substitution of threonine with lysine at position 29 of the encoded protein. Sanger sequencing confirmed the presence of the variant. According to the ACMG guidelines, this variant was classified as variant of uncertain significance (VUS) with supporting evidence (PS3_Moderate+ PM5+ PP3+ PM2_Supporting+ PS4_Supporting). Reviewing the nearly 60 years of previously reported cases, all 7 documented 47, XYY DSD patients were assigned a female social gender and presented with abnormal gonadal and external genitalia development. Among them, 5 cases underwent SRY testing, all of which were positive. Only 1 case underwent whole-exome sequencing (WES), but no pathogenic or likely pathogenic variants were identified. Conclusion:This DSD patient presented with the clinical features of tall stature and primary amenorrhea. The NR5A1 gene variant c. 86C>A (p.Thr29Lys) probably underlay the disorder of sex development in this patient. Above finding has enriched the spectrum of pathogenic variants of the NR5A1 gene.

Objective:To evaluate the effect of Kuntai capsules combined with progestin-primed ovarian stimulation (PPOS) protocol on the ovarian response, laboratory parameters and embryo transfer outcomes of expected poor ovarian response (POR) patients undergoing invitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was performed at Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital from June 2020 to July 2023. A total of 1 733 expected POR patients were enrolled and divided into the PPOS only group (control group) and the Kuntai capsules combined with PPOS regimen group (trial group). After a 1∶1 propensity score matching, 423 cases were included in each group. Further analyses and comparisons were made between the two groups, concerning the ovarian stimulation outcomes, embryo laboratory parameters and pregnancy rates after the first frozen-thawed embryo transfer cycles. The primary outcome measure was the number of oocytes retrieved.Results:No statistically significant difference was found in baseline characteristics after matching between the two groups (all P>0.05). Compared with control group, the number of oocytes retrieved did not differ significantly in the trial group ( P=0.295). The level of luteinizing hormone (LH) on the trigger day [3.3 (2.2, 5.0) U/L], the number of available blastocysts formed [1 (0, 1)] and the available blastocyst formation rate [46.2% (85/184)] in the trial group were significantly higher than those in control group [2.9 (1.9, 4.5) U/L, P=0.004; 0 (0, 1), P=0.034; 30.0% (48/160), P=0.002]. However, there were no significant differences in the duration and dosage of gonadotropin used, progesterone and estradiol levels on the trigger day, incidence of premature LH surge, number/rate of fertilized oocytes, number/rate of cleaved embryos, number/rate of high-quality embryos, as well as rate of unavailable embryos (all P>0.05). Compared with control group, the trial group demonstrated comparable implantation rate, clinical pregnancy rate, early miscarriage rate, ongoing pregnancy rate and live birth rate after the first frozen-thawed embryo transfer cycles (all P>0.05). Conclusion:Compared with the PPOS only regimen, the combination of Kuntai capsules and PPOS did not increase the number of oocytes retrieved but could increase the number and rate of available blastocysts formed in expected POR patients.

Objective:To explore the relationship between the clinical outcome of emotional symptoms and cognitive performance and related cerebral oxygenated hemoglobin in adolescents with depression.Methods:Through subject recruitment, 46 adolescent patients with depression (patient group) from the First Hospital of Shanxi Medical University were selected as the subjects for this study from December 2020 to December 2021, including 8 males and 38 females, aged 12-18 (15.7±2.3) years old. All patients received sertraline treatment for 8 weeks and were further followed into responders ( n=24) and non-responders ( n=22) according to the outcome of emotional symptoms. In the meantime, 51 healthy controls (control group) were enrolled, including 7 males and 44 females, aged 12-18 (16.1±1.5) years old. The repeatable battery for the assessment of neuropsychological status (RBANS) was conducted to measure the multi-dimensional neurocognitive performance, and the functional near-infrared spectroscopy (fNIRS) was used to assess changes in the concentration of oxyhemoglobin (HBO) during the verbal fluency test. The differences were compared in multi-dimensional cognitive performance and cerebral HBO level between each patient group and control group and between responders and non-responders. The changes were analyzed in cognitive performance and cerebral HBO level after intervention in responders and non-responders. Results:At baseline, compared to the control group, the patient group performed decreased scores of RBANS, immediate memory, speech function, attention, and delayed memory (88.0 (82.8, 100.0) M ( Q1, Q3) vs. 100.0 (90.0, 110.0) scores; 78.0 (73.0, 87.8) vs.85.0 (78.0, 94.0) scores; (84.4±16.1) vs. (95.7±15.7) scores; 106.0 (99.5, 115.0) vs.118.0 (109.0, 128.0) scores; 94.0 (84.5, 99.0) vs.97.0 (91.0, 101.0) scores), and lower HBO levels in 7 channels (all P<0.05). Compared to responders, non-responders showed more severe impairment of visual-spatial and attention performance (103.9±11.0 vs. 94.4±16.7 scores; 112.5±12.1 vs. 98.0±21.2 scores) ( t=2.30 or 2.87; all P<0.05). After treatment, the scores of RBANS and immediate memory improved significantly in responders (98.8±11.2 vs. 93.0±9.7 scores; 95.2±13.8 vs.83.0±14.6 scores) ( t=-3.00 or-4.97; both P<0.05), but the scores of attention and the HBO level of two channels in the prefrontal cortex were still significantly lower than those of the control group (Z=2.27, 3.02 or 3.04; all P<0.05). Besides, there were no significant differences in the scores of immediate memory and the HBO levels of 3 channels in the temporal lobe between the no-responders and the control group (all P>0.05). Conclusion:Immediate memory injure, attention injure and HBO levels of frontal-temporal lobes may be independent of emotional symptoms among adolescents with depression.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

BACKGROUND:Current studies have shown that electronic moxibustion can improve memory function in amnestic mild cognitive impairment;however,its mechanism of action needs to be further investigated.The atrophy of hippocampal volume and impairment of functional connectivity are important imaging markers of amnestic mild cognitive impairment.Whether electronic moxibustion can regulate the volume of hippocampal subregion of partients with amnestic mild cognitive impairment is worth studying. OBJECTIVE:To observe the effect of electronic moxibustion on the volume of hippocampal subregions in patients with amnestic mild cognitive impairment. METHODS:Forty patients with amnestic mild cognitive impairment were recruited from April 1,2018 to January 31,2019 at the community service centers around the Second Affiliated Hospital of Shenzhen University(Baoan Hospital of Southern Medical University),Shenzhen,China.They were randomly divided into treatment group(n=20)and control group(n=20).The treatment group was treated with electronic moxibustion of regulating the mind and benefiting the intelligence,while the control group was treated with placebo moxibustion.Moxibustion was given at 45 oC,20 minutes each time,once a day,5 times a week,for 8 weeks in total.Memory evaluation using Rivermead behavioral memory test and magnetic resonance imaging scanning for detecting the hippocampal subregion volume were performed for each patient before and after treatment,and cognitive function of each patient was assessed using Montreal cognitive assessment and mini-mental state examination.Correlation of hippocampal subregion volumes with scores on each scale was analyzed. RESULTS AND CONCLUSION:After treatment,the volumes of the left parasubiculum and the left hippocampal-amygdala migrating area increased in the treatment group but decreased in the control group,and there was a significant difference between the two groups(P＜0.05).Compared with the pre-treatment data,the Rivermead behavioral memory test,Montreal cognitive assessment,and mini-mental state examination scores were significantly higher in the treatment group after treatment(P＜0.05),while there was no significant change in the three scale scores in the control group after treatment(P＞0.05).The three scale scores were higher in the treatment group than in the control group after treatment(P＜0.05).Pearson correlation analysis showed that the changes in the volume of the left parasubiculum was significantly and positively correlated with the Rivermead behavioral memory test scale score in the treatment group(r=0.418,P=0.014).To conclude,electronic moxibustion can improve memory in patients with amnestic mild cognitive impairment,and the mechanism may be the regulation of structural plasticity in hippocampal subregions.

Objective To compare the early embryonic developmental potential and clinical outcomes of oocytes matured in vivo and those matured by modified in vitro maturation(LVM)technology during the same controlled ovarian hyperstimulation(COH)cycle,and to explore the clinical application of melatonin-supplemented IVM technology.Methods 159 patients were recruited into the study.920 mature oocytes were collected during their COH cycles processed for conventional IVF/ICSI protocols,while 1 283 immature oocytes from the same cycles were matured in a melatonin-supplemented IVM medium before ICSI was performed.A retrospective analysis was conducted to compare the impact of conventional assisted reproductive technology and improved IVM technology on the outcomes of assisted reproductive therapy and pregnancy outcomes.Results Compared with mature oocytes collected from COH cycles treated with conventional IVF/ICSI,oocytes promoted by improved melatonin-supple-mented IVM technology had a lower rate of high-quality blastocyst formation.However,after embryo transfer,there was no significant difference in the clinical outcomes of mature oocytes obtained through two methods,including clinical pregnancy rate,full-term birth rate,neonatal length,and neonatal Apgar score.Conclusion The applica-tion of melatonin-supplemented IVM significantly increases the utilization of immature oocytes collected from COH cycles,improving the pregnancy outcomes of patients assisted by assisted reproductive technology.

Objective To explore the presence and potential interactions of microbes and bacteriophages in the blood of healthy individuals by employing in-depth bioinformatics mining to analyze the structure and function of the blood microbi-ome ecosystem.Methods Blood plasma samples from 1 600 voluntary blood donors collected at Mianyang Central Blood Station from 2012 to 2018 were subjected to DNA extraction and library construction.High-throughput sequencing was con-ducted using the Illumina HiSeq 4500 platform,followed by extensive bioinformatics analysis.Microbial abundance in blood samples was analyzed using metagenomic analysis software such as Bowtie2,Trimmomatic and Kraken.Subsequent phage-ome analysis included sequence quality control,assembly,identification,clustering and functional annotation using software such as Megahit,geNomad,CheckV and eggNOG-mapper.Phylogenetic trees,species annotation and host analysis and pre-diction for the identified blood bacteriophages were constructed using iTOL,BLAST and PhaBOX software.Results Met-agenomic sequencing identified microbes across 36 phyla,151 orders,338 families,338 genera and 3 757 species in the plasma samples.At the species level,the most abundant species included Bacillus cereus,Lactobacillus murinus,L.johnso-nii,Faecalibacterium prausnitzii,B.thuringiensis,L.reuteri,Cutibacterium acnes,Dietzia sp.JS16-p6b,Mycoplasma hyo-rhinis,M.hyopneumoniae and Staphylococcus aureus.Through phageome analysis,202 viral Operational Taxonomic Units(vOTUs)were identified,revealing 24 types of bacteriophages.Host analysis using the viral host database completed mat-ches for 15 potential bacteriophage hosts,including Stenotrophomonas maltophilia,Rhodoferax lacus,Pseudoalteromonas marina,Thalassotalea loyana,Vibrio alginolyticus,V.tasmaniensis,V.vulnificus,Pseudomonas sp.,Agrobacterium sp.ST15.13/040,Enterococcus gallinarum,Flavobacterium sp.,Thermotoga naphthophila,Chryseobacterium sp.RU33C,L.acidipiscis and Neisseria mucosa.Conclusion The study of the healthy human blood microbiome and phageome reveals the presence of microbes and phages in the blood,which may have profound impacts on human health.