N6-methyladenosine demethylase FTO related to hyperandrogenism in PCOS via AKT pathway.

BACKGROUND: Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and obesity-associated protein (FTO), a m6A demethylase, is abnormal in the occurrence of ovarian diseases. However, the mechanism of FTO in the pathogenesis of PCOS is still unclear. METHODS: The level of FTO in clinical samples, PCOS rat with hyperandrogenism and granulosa cells (GCs) lines effected by DHT were investigated by ELISA, qRT-PCR, WB, and IHC, while m6A RNA methylation level was studied by m6A Colorimetric and androgen level was tested through ELISA. Changes in steroid hormone synthetase and androgen receptor (AR)/prostate-specific antigen (PSA) levels in vitro were visualized by WB after transient transfection silenced FTO. The effect of DHT combined with FTO inhibitor meclofenamic acid (MA) on FTO, AR/PSA, and AKT phosphorylation were also demonstrated by WB. The co-localization of FTO and AR in KGN cells was analyzed by confocal microscopy, and the physiological interaction between FTO and AR was studied by Co-IP assay. The effect of FTO-specific inhibitor MA, AKT phosphorylation inhibitor LY294002, and the combined them on GCs proliferation and cell cycle were evaluated by drug combination index, EDU assay, and flow cytometry analysis. RESULTS: FTO expression was upregulated in follicular fluid and GCs in PCOS patients clinically. The high FTO expression in patients was negative with the level of m6A, but positive with the level of androgen. The upregulation of FTO was accompanied with a decrease in the level of m6A in PCOS rat with hyperandrogenism. Dihydrotestosterone (DHT) promoted the FTO expression and inhibited m6A content as a dose-dependent way in vitro. In contrast, suppression of FTO with siRNA attenuated the expression of steroid hormone synthetase such as CYP11A1, CYP17A1, HSD11B1, HSD3B2 except CYP19A1 synthetase, ultimately inducing the decrease of androgen level. Suppression of FTO also decreased the biological activity of androgen through downregulation AR/PSA. MA treatment as the specific FTO antagonist decreased cell survival in time- and dose-dependent way in GCs lines. Correspondingly, MA treatment decreased the expression of FTO, AR/PSA expression, and AKT phosphorylation in the presence of DHT stimulation. Additionally, we also speculate there is a potential relation between FTO and AR according to FTO was co-localized and interacted with AR in KGN cells. Compared with AKT phosphorylation inhibitor LY294002 or MA alone, LY294002 combined with MA synergistically inhibited cell survival and increased G2/M phase arrest in GC line. CONCLUSIONS: We first evaluated the correlation of FTO and m6A in PCOS clinically, and further explored the mechanism between FTO and hyperandrogenism in PCOS animal and cell models. These findings contributed the potential therapy by targeting the FTO for hyperandrogenism in PCOS.

Identifying a prognostic model and screening of potential natural compounds for acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is one of the most common hematologic malignancies with a poor prognosis and high recurrence rate. The discovery of new predictive models and therapeutic agents plays a crucial role. Methods: The differentially expressed gene that was explicitly highly expressed in The Cancer Genome Atlas (TCGA) and GSE9476 transcriptome databases were screened and included in the least absolute shrinkage and selection operator (LASSO) regression model to derive risk coefficients and build a risk score model. Functional enrichment analysis was conducted on the screened hub genes to explore the potential mechanisms. Subsequently, critical genes were incorporated into a nomogram model based on risk scores to analyze prognostic value. Finally, this study combined network pharmacology to find potential natural compounds for hub genes and used molecular docking to verify the binding ability of molecular structures to natural compounds to explore drug development for possible efficacy in AML. Results: A total of 33 highly expressed genes may be associated with poor prognosis of AML patients. After LASSO and multivariate Cox regression analysis of 33 critical genes, Rho-related BTB domain containing 2 (RHOBTB2), phospholipase A2 (PLA2G4A), interleukin-2 receptor-α (IL2RA), cysteine and glycine-rich protein 1 (CSRP1), and olfactomedin-like 2A (OLFML2A) were found to played a significant role in the prognosis of AML patients. CSRP1 and OLFML2A were independent prognostic factors of AML. The predictive power of these 5 hub genes in combination with clinical features was better than clinical data alone in predicting AML in the column line graphs and had better predictive value at 1, 3, and 5 years. Finally, through network pharmacology and molecular docking, this study found that diosgenin in Guadi docked well with PLA2G4A, beta-sitosterol in Fangji docked well with IL2RA, and OLFML2A docked well with 3,4-di-O-caffeoylquinic acid in Beiliujinu. Conclusions: The predictive model of RHOBTB2, PLA2G4A, IL2RA, CSRP1, and OLFML2A combined with clinical features can better guide the prognosis of AML. In addition, the stable docking of PLA2G4A, IL2RA, and OLFML2A with natural compounds may provide new options for treating AML.

Inflammatory bowel disease and risk of Parkinson's disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals.

Background: The relationship between inflammatory bowel disease (IBD) and the risk of Parkinson's Disease (PD) has been investigated in several epidemiological studies. However, the results of these studies were inconclusive and inconsistent. We evaluated the potential relationship between IBD and PD risk by a meta-analysis. Methods: Search the electronic databases PubMed, Embase and Cochrane databases from inception to November 30, 2022, to identify relevant studies that assess the risk of PD in patients with IBD. The cohort, cross-sectional, mendelian randomization and case-control studies that reported risk estimates of PD and IBD were included in our analysis. The random-effect model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). Results: In total, 14 studies (nine cohort studies, two cross-sectional studies, two mendelian randomization studies and one case-control study) involving more than 13.4 million individuals were analyzed in our analysis. Our results suggested that the risk of PD in IBD patients is moderately increased, with the pooled RR was 1.17 (95% CI: 1.03-1.33, P = 0.019). Omit of any single study from this analysis had little effect on the combined risk estimate. No evidence of publication bias was found. In the subgroup analysis, the combined RR was 1.04 (95% CI: 0.96, 1.12, P = 0.311) for Crohn's disease (CD), and 1.18 (95% CI: 1.06, 1.31, P = 0.002) for ulcerative colitis (UC). In addition, a significant association was identified in patients with IBD aged ≥ 60 years (RR = 1.22; 95% CI: 1.06-1.41, P = 0.007), but not in age < 60 years (RR = 1.19; 95% CI: 0.58-2.41, P = 0.639). Meanwhile, the meta-analysis results suggested a protective role for IBD medication use against PD development, with the RR was 0.88 (95% CI: 0.74, 1.04, P = 0.126). Conclusion: Our results indicated that patients with IBD had a moderately higher risk of PD compared to non-IBD individuals. Patients with IBD should be aware of the potential risks for PD, especially who were ≥ 60 years old.

Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking.

OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

A homozygous PRKN-associated juvenile Parkinson's disease with pregnancy in China.

Background: Although Parkinson's disease (PD) is the second most common neurodegenerative disorder, pregnancy in patients with PD is a relatively rare occurrence because the most common age of onset of PD is beyond the childbearing age, except in patients with Young-Onset PD (YOPD) caused by parkin RBR E3 ubiquitin protein ligase (PRKN) mutations. Case: In this study, we report the case of a 30-year-old Chinese woman who was affected by PRKN-associated YOPD and was treated with levodopa/benserazide during pregnancy. She gave birth to a healthy baby boy with an Apgar score of 9 through an uncomplicated vaginal delivery. Conclusion: This case further suggests that levodopa/benserazide during pregnancy is safe in the treatment of PRKN-associated YOPD.

Two new species of the bamboo-feeding planthopper genus Neobelocera Ding & Yang from China (Hemiptera, Fulgoromorpha, Delphacidae).

Two new species of the bamboo-feeding genus Neobelocera Ding & Yang, 1986, N.furcatasp. nov. and N.parvulasp. nov., are described and illustrated from China. A key based on the male genitalia is given to distinguish species of this genus and a map provided to show their geographic distribution. Habitus photos for adults and illustrations of male genitalia are also given.

Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles.

Infertility is a major health concern worldwide. This retrospective study aimed to assess the predictive value of the morphokinetic parameters of temporary-arrest embryos for the pregnancy outcomes of women undergoing frozen embryo transfer (FET) cycles. In this study, we evaluated 244 FET cycles with 431 day-4 temporary-arrest embryos. They were categorized into two groups (pregnancy and non-pregnancy) according to the pregnancy outcomes of the women after embryo transfer on day 5, and their fundamental characteristics were compared. The morphokinetic parameters from the time-lapse monitoring system were assessed according to different pregnancy outcomes. The mean number of embryo blastomeres thawed on day 3 in the pregnancy group was 7.47, which was significantly higher than the number in the non-pregnancy group (p < 0.01). Besides, embryos in the non-pregnancy group contained more embryo fragments and lower grades than those in the pregnancy group (p < 0.001). Furthermore, morphokinetic parameters: tPNa, t2, t5, and t5_tPNf showed a statistical difference between the pregnancy and non-pregnancy groups (p < 0.05). Receiver-operating characteristic analysis revealed that the time from pronuclear fading to the 5-cell stage (t5_PNF) predicted the clinical prognosis outcomes (area under the curve = 0.64; 95% confidence interval [CI], 0.58-0.70; p < 0.001). The morphokinetic parameter t5_PNF could be regarded as a potential implantation predictor in our study.

An additional medium renewal of D4 embryo culture improves the concordance of noninvasive chromosome screening with trophectoderm biopsy.

Our research question was to evaluate the chromosome concordance of trophectoderm (TE) biopsy with noninvasive chromosome screening (NICS) using embryo culture medium renewed twice on Day 3 (D3) and Day 4 (D4). In this study, we evaluated 64 cycles with 223 biopsied blastocysts. These were categorized into two groups based on replacing embryo culture medium on D3 (control group) or on D3 and D4 (experimental group). The fundamental characteristics and main outcomes were compared. The concordance rates of NICS results with TE biopsy were determined according to next generation sequencing results. In total, 103 experimental and 120 control embryo cultures were collected, and the euploid status was analyzed using NICS technology. The overall concordance rates with TE biopsy of the experimental and control groups were 0.86 and 0.75, respectively. Statistically significant difference was found between the two groups. An additional medium renewal of the D4 embryo culture can improve the concordance of NICS with TE biopsy.

Medical Arrangement Strategies for Infertility Female Patients during COVID-19 Mini-Outbreak.

Over the past two years, COVID-19 pandemic is an unprecedented health emergency. All countries have taken their
own measures to mitigate the spread of the virus in the first and subsequent mini-outbreaks of infection. In view of the
current situation of small outbreaks of COVID-19, guidelines on epidemic prevention should be developed specifically
for reproductive medical centers. It is necessary to establish a dynamic patient assessment and management system
to identify patients who need priority fertility treatment during epidemic control. Female Patients were assigned
as grade A and required hospitalization in the inpatient ward after egg retrieval. Patients who underwent controlled
ovarian stimulation were classified as grade B, and they can choose to be hospitalizedat home according to their own
convenience. Patients undergoing frozen embryo transfer (FET) cycle or planned downregulation with gonadotropinreleasing
hormone agonists were defined as grade C, who could continue the assisted reproductive technology (ART)
treatment cycle with negative COVID-19 nucleic acid test and there was no fever or respiratory symptoms. This brief
comment summarizes the working procedure of the reproductive medical center in the first hospital of Lanzhou University
in China to minimize the probability of hospital infection and ensure the safe conduct of assisted reproductive
technology therapy.

[Research progress on bidirectional effect of microRNA on Alzheimer's disease and intervention with traditional Chinese medicine].

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.

A New Day 4 Grading System to Assess Embryo Quality in Frozen Embryo Transfer Cycles.

To present a new day 4 (D4) embryo grading system to assess embryos in frozen-thawed embryo transfer (FET) cycles. A new grading system (grades A-E) was developed from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. Embryos with complete compaction were classified as grade A; those with partial compaction were assigned as grade B; and those without compaction were classified as grades C, D, and E according to their different blastomere number ratio (BNR; number of embryo blastomeres on D4/number of embryo blastomeres on D3, D4/D3). Embryos with a BNR of ≥ 1.5 were defined as grade C, those with a BNR of ≥ 1.2 and < 1.5 were defined as grade D, and those with a BNR of ≥ 1.0 and < 1.2 were defined as grade E. Using this proposed grading model, 5460 embryos with known implantation data were retrospectively analyzed after D4 transfer in FET cycles. The transferred embryos exhibited a similar declining trend in implantation and live birth rates from the top grade A to the lowest grade E. The in vitro fertilization group showed increased implantation rates of grade B and E embryos compared with the intracytoplasmic sperm injection group (grade B: 41.99%, 34.63%, χ2 = 5.84, p < 0.05 and grade E: 18.98%, 14.08, χ2 = 75.62, p < 0.01). Receiver-operating characteristic analysis revealed that our proposed model predicted the implantation outcomes and live birth rates of all embryos (area under the curve = 0.65; 95% confidence interval [CI],0.63-0.66; p < 0.01 and AUC = 0.73; 95%CI, 0.65-0.84; p < 0.001, respectively). This study demonstrates that the new grading system provided by us can be a useful tool for assisting embryo selection via changes in embryo morphology. D4 embryo transfer provides a simple and applicable method for FET cycles in daily practice.

Testing Seven Hypotheses to Determine What Explains the Current Planthopper (Fulgoridae) Geographical and Species Richness Patterns in China.

Although many hypotheses have been proposed to understand the mechanisms underlying large-scale richness patterns, the environmental determinants are still poorly understood, particularly in insects. Here, we tested the relative contributions of seven hypotheses previously proposed to explain planthopper richness patterns in China. The richness patterns were visualized at a 1° × 1° grid size, using 14,722 distribution records for 1335 planthoppers. We used ordinary least squares and spatial error simultaneous autoregressive models to examine the relationships between richness and single environmental variables and employed model averaging to assess the environmental variable relative roles. Species richness was unevenly distributed, with high species numbers occurring in the central and southern mountainous areas. The mean annual temperature change since the Last Glacial Maximum was the most important factor for richness patterns, followed by mean annual temperature and net primary productivity. Therefore, historical climate stability, ambient energy, and productivity hypotheses were supported strongly, but orogenic processes and geological isolation may also play a vital role.

Immunoglobulin G4-related hypertrophic pachymeningitis with spinal cord compression: A case report.

IgG4-related disease (IgG4-RD) is a recently recognized inflammatory condition that can be found in many organs. However, spinal involvement is rare and has been described only in case reports and series. Here, we report a rare case of spinal IgG4-RD that resulted in hypertrophic pachymeningitis with spinal cord compression. This case expands the phenotypic presentation for the neurological sequelae of IgG4-RD. Our case hints that spinal IgG4-RD may be misdiagnosed, and IgG4-RD in patients should be considered when the patient has a dural mass. Although early surgery, steroids, and/or immunosuppressive therapy may prevent neurological complications, the side effects should receive more attention during treatment.

A hydroxyl-functionalized homochiral porous organic cage for gas chromatographic separations.

A hydroxyl-functionalized homochiral porous organic cage (POC) was synthesized and characterized by FTIR, NMR, thermogravimetric analysis (TGA), MALDI-TOF-MS, and elemental analysis. The synthesized homochiral POC was used as stationary phase to prepare a capillary gas chromatography (GC) column by a static coating method. The fabricated column shows excellent selectivity not only for the separation of positional isomers but also for the resolution of various racemates. Thirty-nine racemates have been resolved on the column, including alcohols, diols, halohydrocarbons, epoxides, esters, lactones, ketones, ethers, and organic acids. Compared to the commercial ß-DEX 120 column and previously reported chiral POCs (CC3-R, CC9, and CC10)-coated columns, there are 11, 10, 24, and 15 tested racemates that cannot be resolved on ß-DEX 120 column, CC3-R column, CC9 column, and CC10 column, respectively. This reveals that the fabricated column has prominent complementarity or superior separation performance to these columns in enantioseparation. Besides, the fabricated column can achieve some enantioseparations which are not possible using all previously reported chiral POC-based columns. Some positional isomers (xylenes, dichlorobenzenes, dibromobenzenes, nitrochlorobenzenes, and nitrobromobenzenes) were also separated with high-resolution values. The column exhibits good repeatability, reproducibility, and stability. The relative standard deviation (RSD) values of retention times were 0.03-0.18%, 0.11-0.92%, and 2.1-6.6% for run-to-run (n = 5), day-to-day (n = 5), and column-to-column (n = 3), respectively. The experimental results demonstrate the great potential of POCs for practical application in GC. Graphical Abstract A hydroxyl-functionalized homochiral porous organic cage was used as stationary phase for gas chromatography separation of racemates and positional isomers. The resolution of racemates mainly depended on hydrogen bonding, π-interaction, host-guest inclusion, steric fit, etc., while separation of positional isomers by shape-selective guest binding.

Taxonomic study of the genus Malaxa Melichar, with descriptions of two new species from China (Hemiptera, Fulgoroidea, Delphacidae).

Two new species of the delphacid genusMalaxa Melichar, 1914, M.hamuliferum sp. nov. and M.tricuspis sp. nov., are described and illustrated from southwest China (Yunnan and Hainan), providing the genus with eleven species in total. A key is provided to distinguish the seven Chinese species in the genus.

Two new species of the bamboo-feeding planthopper genus Purohita Distant from China (Hemiptera, Fulgoromorpha, Delphacidae).

Two new species of the bamboo-feeding genus Purohita Distant, 1906, P.castaneus sp. nov. and P.circumcincta sp. nov., are described and illustrated from southwest China (Yunnan), giving the genus thirteen species in total. A key is provided to distinguish eight Chinese species in the genus.

Redescription of Arcifronsarcifrontalis Ding & Yang, 1986 (Hemiptera, Fulgoromorpha, Delphacidae).

The male of Arcifronsarcifrontalis Ding & Yang, 1986 (Hemiptera, Fulgoroidea, Delphacidae, Tropidocephalini) is redescribed. The female genitalia of the species here, is described and illustrated for the first time. The geographic distribution of the species and images of adult habitus are provided.

Giant Serpentine Middle Cerebral Artery Aneurysm.

Giant serpentine aneurysms are rare entity, which have unique presentations and distinct angiographic features, with poor prognosis if not treated. In this paper, a patient with a giant serpentine aneurysm originated from right middle cerebral artery was reported. A 38-year-old woman suffered from progressively headache and vision declined. The computed tomography and magnetic resonance image revealed a partially calcified, large mass (approximately 80 × 70 × 60 mm sized) in the right frontal-temple lobe. On computed tomography angiography, an unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After treatment by craniotomy, the patient was rehabilitation. Operation is an effective method for the treatment of giant serpentine aneurysms. In addition, cerebral angiography and balloon test occlusion are the crucial way of preoperative assessment.

Risk of Stroke in Patients with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Several observational studies suggest that herpes zoster (HZ) may increase the risk of stroke, but the results are inconsistent. Our study was designed to assess the association between HZ and the risk of stroke through a meta-analysis of cohort studies. METHODS: The electronic databases PubMed and EMBASE were searched from inception to May 31, 2016 to identify relevant cohort studies that assess the risk of stroke in patients with HZ. Reference lists were also reviewed to identify potential studies. The random-effects model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Six cohort studies (251,076 HZ patients and 8462 cases of stroke) were identified in the study. The result showed that HZ was significantly correlated with increased risk of stroke, and the pooled RR was 1.36 (95% confidence interval [CI]: 1.10, 1.67) (P = .004). In the subgroup analysis, the significant association was observed except for stroke type (hemorrhage group). In the sensitivity analysis, excluding 1 study, the pooled RR was 1.45 (95% CI: 1.17, 1.80) (P = .001) for HZ, and 4.42 (95% CI: 2.75, 7.11) (P = .000) for herpes zoster ophthalmicus. Considerable heterogeneity was observed in our study. CONCLUSION: Our study furnishes evidence of a positive association between HZ and the risk of stroke.