OBJECTIVE To observe the efficacy of cetrorelix combined with aspirin in preventing early-onset ovarian hyperstimulation syndrome （OHSS）. METHODS A retrospective analysis was conducted on clinical data from 38 early-onset OHSS patients， who received treatment in our hospital from January 1st to July 1st， 2022. These patients were divided into intervention group （19 cases） and control group （19 cases） according to the therapy regimen. On the first day after oocyte retrieval surgery， the control group was given aspirin enteric-coated tablets 100 mg orally until menstruation began. The intervention group was given cetrorelix for injection 0.25 mg subcutaneously， for consecutive 3 days+aspirin enteric-coated tablets （same usage and dosage as the control group）. The first luteal phase， the degree of OHSS， and the ovarian volume， ascites volume， serum estradiol （E2）， white blood cell count （WBC）， hematocrit （HCT）， neutrophil ratio （NEUT%）， D-dimer （DD）， prothrombin time （PT）， fibrinogen （Fib） after oocyte retrieval surgery were observed and measured in 2 groups. RESULTS The first luteal phase was significantly shorter， and the proportions of median and severe OHSS cases were significantly lower in the intervention group compared to the control group （P＜0.05 or P＜0.01）. After oocyte retrieval surgery， the intervention group showed significantly lower ovarian volume， ascites volume， serum E2， WBC， NEUT%， HCT， DD and Fib compared to the control group， but PT of intervention group was signiticantly higher than that of control group （P＜0.05）. CONCLUSIONS Cetrorelix combined with aspirin is more effective in preventing early-onset OHSS than aspirin alone.

MELAS syndrome is a genetic disease caused by mutations in mitochondrial DNA(mtDNA)or nuclear DNA.Eighty percent of the cases are caused by m.3243A>G mutation.Heteroplasmy,defined as the presence of both normal and mutant mtDNA in cells,is related with the severity of MELAS syndrome.This article reviews the research in mtDNA heterogeneity related to MELAS syndrome,aiming to provide an insight into new therapies for the syndrome.

OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction （MBD/ BDD） applied in post-stroke depression （PSD）. METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress， and then were randomly divided into PSD model group， MBD/BDD group （12.6 g/kg， by raw drug）， and fluoxetine hydrochloride （FLX） group （positive control， 2.3 mg/kg）； a blank control group was also set up， with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained （such as IL1B and AKT1， etc.）， which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats， and significantly shorten the cumulative immobility time （P＜0.05）. After treatment with MBD/BDD， the number of genes that changed in rat brain tissue was much higher than that in the FLX group， and there were significant differences in gene profiles among the PSD model group， MBD/BDD group， and FLX group. There were 1 351 differentially expressed genes （DEGs） between the MBD/BDD group and the PSD model group， of which 178 were significantly down-regulated and 1 173 were significantly up-regulated （P＜0.05）. Above 1 351 DEGs were involved in neuronal differentiation， chemical synaptic transmission regulation. They were significantly enriched in axonal guidance， cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation， development， differentiation， and migration. After MBD/BDD intervention， the expressions of Fezf2， Arx， Ostn， Nrgn genes， brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased （P＜0.05）. CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation， development， differentiation and migration， as well as the promotion of neural structural and functional repair.

Objective:To explore the mediating effect between anxiety, depression and quality of life in adult patients with epilepsy.Methods:A total of 118 adult patients with epilepsy from Affiliated Hospital of Jining Medical University were investigated with the ruminative responses scale (RRS), neurological disorders depression inventory for epilepsy (NDDI-E), generalized anxiety disorder (GAD-7), quality of life scale for adult epilepsy patients (QOLIE-31 Chinese Version) and the self-made general situation questionnaire. Statistical analysis was performed by SPSS 20.0 software.Pearson correlation analysis was employed to assess the relationships between rumination, quality of life, anxiety, and depression scores. Hierarchical regression analysis was employed to examine the mediating effect.Results:Among the 118 participants, 5 (4.24%), 58 (49.15%), and 55 (46.61%) patients exhibited high (RRS=66-88), middle (RRS=44-65), and low (RRS=22-43) level of rumination, respectively. Pearson correlation analysis revealed significantly negative correlations between the scores of rumination and its dimensions and quality of life in patients with epilepsy ( r=-0.411--0.318, all P<0.05). Additionally, there were significantly positive correlations between the scores of rumination and its dimensions and anxiety scores ( r=0.524-0.676, all P<0.05) and depression scores ( r=0.566-0.767, all P<0.05). Hierarchical regression analysis demonstrated that rumination played partially mediating role in the relationship between anxiety and quality of life, as well as the relationship between depression and quality of life, with mediation effect values of -0.201 and -0.215, respectively. Conclusion:Anxiety and depression can affect the quality of life of adult patients with epilepsy through rumination.

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.

Objective:To explore the effects and possible mechanisms of Tyrobp gene on neuroinflammation in Tourette's syndrome mice.Methods:Twenty C57BL/ 6J and Tyrobp knock-out male mice aged 6 weeks were randomly divided into 4 groups according to random number table method: WT+ NS group, Tyrobp -/-+ NS group, WT+ IDPN group and Tyrobp -/-+ IDPN group. Mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were injected with IDPN intraperitoneally at a dose of 150 mg/kg·d, while mice in WT+ NS group and Tyrobp -/-+ NS group were injected with equal volume of normal saline, once a day for 7 days. Then stereotypical behavior of mice were evaluated. Western blot was used to detect the levels of Tyrobp, TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα in the striatum of mice. Immunofluorescence staining was used to observe the activation of microglia. Statistical analysis was performed using GraphPad Prism 8.0 software, and t-test was used for comparison between two groups. One-way ANOVA was used to compare the means of multiple samples, and LSD test was used for further pairwise comparison. Results:The results of behavior assessment showed that there were significant differences in the motor stereotypic behavior and categorical stereotypic behavior score( F=270.9, 379.7, P<0.01), and the scores in WT+ IDPN group were higher than those in Tyrobp -/-+ IDPN group (motor stereotypic behavior: (3.23±0.26), (2.13±0.21), t=9.02, P<0.05; categorical stereotypic behavior: (45.80±4.29), (26.60±3.48), t=12.00, P<0.05). Western blot results showed that there were significant differences in the protein expression level of TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα ( F=29.07, 23.09, 39.36, 57.6, 52.55, 15.50, 40.48, all P<0.05), the level of those in WT + IDPN group was higher than those in WT+ NS group( t=8.31, 7.37, 8.13, 11.43, 10.47, 6.05, 9.96, all P<0.05), Tyrobp -/-+ IDPN group was higher than Tyrobp -/-+ NS group ( t=3.60, 3.00, 5.84, 4.81, 3.59, 2.26, 4.68, all P<0.05), and WT + IDPN group was higher than Tyrobp -/-+ IDPN group ( t=3.97, 3.93, 4.14, 6.40, 7.63, 3.45, 3.03, all P<0.05). Immunofluorescence showed that microglial cells in the striatum region of mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were enlarged and microglial cells were activated, and the activation pattern of microglial cells in WT+ IDPN group was more obvious than that in Tyrobp -/-+ IDPN group. Conclusion:Tyrobp may be involved in the pathogenesis of Tourette's syndrome by promoting neuroinflammation mediated by TLR4/Myd88/NF-κB signaling pathway.

Objective:To explore the changes of mRNA N6-methyladenosine methylation level and methyltransferase-like 3 (METTL3) and demethylase fat mass and obesity-associated (FTO) in the blood of patients with Alzheimer's disease (AD) compared with normal controls.Methods:From January 2020 to June 2021, totally 40 AD patients treated in the outpatient and inpatient department of Neurology of the Affiliated Hospital of Jining Medical University were selected as the patient group, and 40 healthy volunteers as the control group. The blood samples were collected to extract plasma and peripheral blood mononuclear cells for enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real-time PCR (qPCR) and m6A methylation quantification experiments respectively to detect the methylation levels of METTL3, FTO and m6A. The data were analyzed by SPSS 23.0 statistical software for t-test. Results:The plasma concentrations of METTL3 and FTO protein in AD group were lower than those in control group (METTL3: (22.33±3.01)ng/mL, (25.63±1.70)ng/mL, t=6.055, P<0.01; FTO: (63.51±4.95)pg/mL, (69.60±4.60)pg/mL, ( t=5.704, P<0.01). The band gray values of METTL3 and FTO protein in blood cells in AD group were lower than those in control group (METTL3: 0.399 5±0.028 7, 0.676 6±0.053 3, t=7.935, P=0.001; FTO: 0.439 4±0.017 8, 0.782 6±0.087 6, t=6.652, P=0.003). The expression levels of METTL3 and FTO in blood cell RNA in AD group were lower than those in control group (METTL3: 0.387 8±0.020 3, 1.010 0±0.177 0, t=6.041, P=0.004; FTO: 0.442 8±0.037 1, 1.003 0±0.090 4, t=9.931, P=0.001). The levels of m6A in blood cell RNA in AD group were lower than those in control group((0.000 571±0.000 167)%, (0.002 514±0.001 284)%, t=6.041, P=0.004). Conclusion:The levels of METL3, FTO and m6A methylation are down-regulated in the plasma and peripheral blood mononuclear cells of patients with AD, indicating that there is a certain association between mRNA N6-methyladenosine methylation and AD.

At present, many drugs were developed based on the main pathological feature of Alzheimer′s disease (AD): "β-amyloid cascade hypothesis and abnormal tau protein aggregation" as targets, but the efficacy is unsatisfactory. With the progress on the study of pathological mechanism of AD, the role of microglia and their related expression genes, such as TREM2, CD 33, ABCA7 gene and their related signal transduction pathways in the pathological mechanism of AD has been paid more and more attention. The study on AD biomarkers and therapeutic targets based on microglia and their related expression genes has also increased significantly. This review will mainly focus on the pathophysiology of microglia, the mechanism of microglia in AD, the biomarkers related to microglia and the drug treatment of AD.

Objective:To analyze the efficacy and safety of enzyme therapy in late-onset Pompe disease (LOPD) patients, so as to provide reference for the treatment and prognosis of LOPD.Methods:The effect of α-glucosidase (GAA) on a patient diagnosed with LOPD in the Affiliated Hospital of Jining Medical University was observed and analyzed. Besides, literature related to enzyme therapy in LOPD patients were searched in PubMed, Web of Science, Medline databases. Twenty-one studies containing clinical data from 910 LOPD patients related to enzyme therapy were finally included for analysis.Results:The patient developed muscle weakness since he was 16 years old. The GAA activity in peripheral blood was 0. Electromyography suggested myogenic lesions in both lower extremities. Compound heterozygous mutations of GAA gene were found by next- generation sequencing. Muscle biopsy revealed characteristic vacuolar changes. After eight years of diagnosis, the patient was given enzyme therapy for 18.5 months, 20 times in total. The symptoms of muscle weakness were slightly improved in the early stages of treatment without obvious adverse reactions. Most of the 910 LOPD patients were stabilized or had improved muscular and (or) respiratory function following treatment with GAA.Conclusion:GAA treatment is effective and well tolerated. In patients with advanced severe LOPD, enzyme replacement therapy remains effective even years after onset.

Objective:To compare the expression of myeloid cell trigger receptor expressed on myoid cell 2 (TREM2) in different brain regions of tyrosine kinase binding protein(TYROBP) knockout mice and wild-type mice at different months of age, and to explore the relationship between TREM2, TYROBP and early onset Alzheimer's disease(EOAD).Methods:Healthy TYROBP gene knockout mice were divided into three groups according to the results of gene sequencing: the homozygous (TYROBP -/-) group, the heterozygous (TYROBP -/+ ) group, and the wild type (WT) group.Western blot and RT-qPCR were used to detect the expression of TREM2 in prefrontal cortex and hippocampus of 2, 4 and 6 month old mice in the three groups and with 10 in each group at each time point. Results:(1) In the prefrontal cortex: Western blot and RT-qPCR results showed that compared with WT mice (2-month-old: (0.993±0.048), (1.654±0.033); 4-month-old: (0.503±0.019), (2.169±0.023); 6-month-old: (0.600±0.036), (1.468±0.057)), the levels of TREM2 protein and mRNA in 2-month-old TYROBP -/+ group ((0.746±0.062), (1.137±0.067)) and TYROBP -/- group ((0.661±0.028), (0.644±0.012)) were decreased.While in 4-month-old and 6-month-old TYROBP -/+ group (4-month-old: (1.140±0.006), (5.483±0.088); 6-month-old: (0.827±0.043), (3.020±0.082)) and TYROBP -/- group (4-month-old: (1.071±0.010), (3.012±0.150); 6-month-old: (0.627±0.026), (1.633±0.027)) were increased, especially in 4-month-old mice and the differences were statistically significant ( F=12.946, 134.445; 725.318, 289.202; 12.172, 202.791; all P<0.05). (2) In the hippocampus: Western blot results showed that compared with WT mice (2-month-old: (1.268±0.036); 4-month-old: (0.813±0.010); 6-month-old: (0.312±0.021)), the level of TREM2 protein in 2-month-old TYROBP -/+ group ((0.804±0.034)) and TYROBP -/- group ((0.534±0.020)) were decreased.While in 4-month-old and 6-month-old TYROBP -/+ group ((0.932±0.011); (0.769±0.031)) and TYROBP -/- group ((0.910±0.014); (0.609±0.018)) were increased, especially in 4-month-old mice and the differences were statistically significant ( F=142.807; 27.884; 94.067; all P<0.05). Conclusion:The expression level of TREM2 decreases in 2-month-old TYROBP gene knockout mice while increases in 4-month-old and 6-month-old TYROBP gene knockout mice.It is presumed that TREM2/TYROBP signal pathway participates in the pathological process of EOAD and plays different roles in different pathological stages of EOAD.