Objective:To investigate the clinicopathological and molecular genetic features of high-grade astrocytomas with piloid features (HGAP).Methods:Clinical, histopathological and imaging data of 7 cases of HGAP diagnosed at the Neuropathology Center of Beijing Tiantan Hospital, Beijing, China from August 2023 to October 2024 were collected. The histopathological and molecular features for each case were analyzed.Results:Among the seven patients there were 4 males and 3 females, with the median age of 37 (34, 51) years. Patients exhibited various clinical symptoms and signs depending on the tumor′s location. Four tumors were located in the cerebellum, 2 in the supratentorial region, and 1 in the spinal cord. Magnetic resonance imaging showed that 6 of the 7 patients had cystic and solid lesions, with focal or nodular enhancement and relatively unclear boundaries. Histopathological features had a diverse morphological spectrum and extensive grading. Five cases displayed a pilocytic astrocytoma-like appearance with infiltrative growth patterns, while two cases presented glioblastoma-like morphology, containing locally anaplastic pleomorphic xanthoastrocytoma with minor pilocytic components. All tumors were diffusely positive for GFAP and Olig2, while 4 tumors exhibited partial or complete loss of ATRX. The Ki-67 proliferation index ranged from 2% to 40%. Next-generation sequencing showed that tumor cells most commonly harbored MAPK pathway gene mutations, and/or homozygous deletions of CDKN2A/B, and/or ATRX mutations. Among the 7 HGAP models, 3 cases showed the three types of molecular genetic variations, 1 case showed MAPK mutations and homozygous deletions of CDKN2A/B, 1 case had MAPK mutations and ATRX mutations, 1 case had only MAPK mutations, and 1 case showed no detectable molecular changes. DNA methylation clustering analyses showed that the median model prediction score was 0.94 (range, 0.85-0.99) for the 7 HGAP models. Five cases showed the MGMT promoter hypermethylation. Four patients received radiotherapy and concomitant temozolomide treatment after surgery, while three patients received no known treatments. At the last follow-up, seven patients were alive without any tumor, two patients had recurrence, and one patient was alive with the tumor.Conclusions:HGAP is relatively rare and predominantly occurs in adults. It has a wide histopathological spectrum and various histological grades, characterized by piloid astrocytoma-like and glioblastoma-like histological features. Its diagnosis relies on methylation clustering analysis. Most tumors harbor gene alterations in the MAPK signaling pathway, along with homozygous deletions of CDKN2A/B or ATRX mutations. The biological behavior is typically aggressive, while imaging and histological findings can be misleading. Therefore, clinicians need to increase their diagnostic awareness of this tumor and prevent missed diagnoses.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To investigate the clinicopathological and molecular genetic features of high-grade astrocytomas with piloid features (HGAP).Methods:Clinical, histopathological and imaging data of 7 cases of HGAP diagnosed at the Neuropathology Center of Beijing Tiantan Hospital, Beijing, China from August 2023 to October 2024 were collected. The histopathological and molecular features for each case were analyzed.Results:Among the seven patients there were 4 males and 3 females, with the median age of 37 (34, 51) years. Patients exhibited various clinical symptoms and signs depending on the tumor′s location. Four tumors were located in the cerebellum, 2 in the supratentorial region, and 1 in the spinal cord. Magnetic resonance imaging showed that 6 of the 7 patients had cystic and solid lesions, with focal or nodular enhancement and relatively unclear boundaries. Histopathological features had a diverse morphological spectrum and extensive grading. Five cases displayed a pilocytic astrocytoma-like appearance with infiltrative growth patterns, while two cases presented glioblastoma-like morphology, containing locally anaplastic pleomorphic xanthoastrocytoma with minor pilocytic components. All tumors were diffusely positive for GFAP and Olig2, while 4 tumors exhibited partial or complete loss of ATRX. The Ki-67 proliferation index ranged from 2% to 40%. Next-generation sequencing showed that tumor cells most commonly harbored MAPK pathway gene mutations, and/or homozygous deletions of CDKN2A/B, and/or ATRX mutations. Among the 7 HGAP models, 3 cases showed the three types of molecular genetic variations, 1 case showed MAPK mutations and homozygous deletions of CDKN2A/B, 1 case had MAPK mutations and ATRX mutations, 1 case had only MAPK mutations, and 1 case showed no detectable molecular changes. DNA methylation clustering analyses showed that the median model prediction score was 0.94 (range, 0.85-0.99) for the 7 HGAP models. Five cases showed the MGMT promoter hypermethylation. Four patients received radiotherapy and concomitant temozolomide treatment after surgery, while three patients received no known treatments. At the last follow-up, seven patients were alive without any tumor, two patients had recurrence, and one patient was alive with the tumor.Conclusions:HGAP is relatively rare and predominantly occurs in adults. It has a wide histopathological spectrum and various histological grades, characterized by piloid astrocytoma-like and glioblastoma-like histological features. Its diagnosis relies on methylation clustering analysis. Most tumors harbor gene alterations in the MAPK signaling pathway, along with homozygous deletions of CDKN2A/B or ATRX mutations. The biological behavior is typically aggressive, while imaging and histological findings can be misleading. Therefore, clinicians need to increase their diagnostic awareness of this tumor and prevent missed diagnoses.

Objective To study the mechanism of Yangjing Zhongyu Decoction in regulating the initiation of primordial follicles in model rats with diminished ovarian reserve(DOR)based on lncRNA.Methods Three-day-old female rats were selected and their ovaries were cultured in vitro.The blank group,model group,DHEA group and Yangjing Zhongyu Decoction high-,medium-and low-dosage groups were set.The DOR model was induced by triptolide,corresponding drug containing serum was given to culture respectively.HE staining was used to observe germ cells and follicles,Western blot was used for determining the expressions of AMH,BMP15,PTEN,MST,TGF-β1,p-Smad1 protein,RT-PCR was used to detected AMH,BMP15,PTEN,MST,LTCONS-00011173,TGF-β1,Smad1 mRNA expression.Results Compared with the blank group,the number of primordial and growing follicles in the model group rats decreased(P<0.05),the expression of AMH,BMP15,TGF-β1,p-Smad1 protein in ovarian tissue decreased(P<0.05),expressions of PTEN and MST proteins increased(P<0.05),AMH,BMP15,TGF-β1,Smad1 mRNA expression decreased(P<0.05),while the expressions of PTEN,MST,and LTCONS-00011173 mRNA increased(P<0.05).Compared with the model group,the DHEA group and Yangjing Zhongyu Decoction high-and medium-dosage groups showed an increase in the number of primordial and growing follicles(P<0.05),the expressions of AMH,BMP15,TGF-β1 and p-Smad1 protein in ovarian tissue increased(P<0.05),PTEN and MST protein expressions decreased(P<0.05),AMH,BMP15,TGF-β1,Smad1 mRNA expressions increased(P<0.05),while PTEN,MST,and LTCONS-00011173 mRNA expressions decreased(P<0.05).Conclusion Yangjing Zhongyu Decoction may mediate TGF-β1/Smad1 signaling pathway through LTCONS-00011173,regulating primordial follicle initiation in DOR model rats.

Wolfiporia cocos (F. A. Wolf) has been praised as a food delicacy and medicine for cen-turies in China. Here, we present the genome and transcriptome of the Chinese strain CGMCC5.78 of W. cocos. High-confidence functional prediction was made for 9277 genes among the 10,908 total predicted gene models in the W. cocos genome. Up to 2838 differentially expressed genes (DEGs) were identified to be related to sclerotial development by comparing the transcriptomes of mycelial and sclerotial tissues. These DEGs are involved in mating processes, differentiation of fruiting body tissues, and metabolic pathways. A number of genes encoding enzymes and regulatory factors related to polysaccharide and triterpenoid production were strikingly regulated. A potential triter-penoid gene cluster including the signature lanosterol synthase (LSS) gene and its modified compo-nents were annotated. In addition, five nonribosomal peptide synthase (NRPS)-like gene clusters, eight polyketide synthase (PKS) gene clusters, and 15 terpene gene clusters were discovered in the genome. The differential expression of the velevt family proteins, transcription factors,carbohydrate-active enzymes, and signaling components indicated their essential roles in the regu-lation of fungal development and secondary metabolism in W. cocos. These genomic and transcrip-tomic resources will be valuable for further investigations of the molecular mechanisms controlling sclerotial formation and for its improved medicinal applications.

Objective To investigate the relationship of TNF-αgene promoter 308 locus(TNF-α-308)polymorphism with the susceptibility and severity of central venous catheter-related sepsis(CRS). Methods One hundred and five CRS patients admitted in Kaihua People's Hospital from January 2015 to May 2017 were enrolled in the study.According to whether complicated with multiple organ dysfunction syndrome(MODS), they were divided into CRS complicated MODS group(n=34)and CRS non-MODS group(n=71).Meanwhile,210 patients with no catheter-related infection(case control group)and 105 healthy subjects(healthy control group)were also enrolled in the study.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to genotype TNF-α-308, and the relationship of TNF-α-308 polymorphism with the susceptibility and severity of CRS was investigated.SPSS 16.0 was used to analyze the data.Results There were no significant differences in frequencies of GG, GA,AA genotypes and G,A allele of TNF-α-308 among CRS group,case control group and healthy control group(χ2=2.262 and 0.907,both P>0.05).Compared with CRS non-MODS group,case control group and healthy control group, the frequency of GG genotype was significantly lower and the frequencies of genotype GA and AA of TNF-α-308 were significantly higher in CRS MODS group(χ2=8.809,7.700 and 9.220,all P<0.05).Compared with CRS non-MODS group,case control group and healthy control group, the allele frequencies of G were significantly lower and allele frequency of A allele of TNF-α-308 was significantly higher in CRS MODS group(χ2=9.823, 8.624 and 7.654, all P<0.05).There were no significant differences in genotype frequency and allele frequencies of TNF-α-308(χ2=0.852 and 0.975, both P>0.05)among CRS non-MODS group and case control group,healthy control group(χ2=1.022 and 0.535,both P>0.05).The odds ratio of GA +AA genotype and A allele of TNF-α-308 in CRS MODS group were 2.664(95%CI 1.259-5.639)and 2.440(95%CI 1.326-4.490).Conclusion TNF-αgene promoter 308 locus polymorphism is not a predisposing factor for CRS, but may be associated with complication of MODS in CRS patients.

Objective To investigate the effect of lower thoracic epidural block on intestinal epithelial cell apoptosis during hemorrhagic shock and resuscitation in rats.Methods Sixty-four male SD rats placed with lower thoracic epidural catheter were randomly divided into four groups (n=1 6 each):group Sham (sham operation),group HSR (hemorrhagic shock and resuscitation),group NS (hemorrhagic shock and resuscitation+epidural saline 100 μl/kg),and group TEA (hemorrhagic shock and resuscitation+epidural 0.075% ropivacaine 100 μl/kg).The hemorrhagic shock was made described by Chaudry.Rats were resuscitated by transfusing shed blood and normal saline 60 min after hemorrhagic shock.Malondialdehyde (MDA)content,superoxide dismutase (SOD)activity, and protein expression of Bax and Bcl-2 in intestinal epithelium were detected,and epithelial apoptosis index was calculated at 2 h after resuscitation.Results Compared with group Sham,intestinal epithe-lial MDA,Bax expression and epithelial apoptosis were significantly increased,while SOD activity were markedly decreased in groups HSR,NS and TEA (P<0.05).Compared with groups HSR and NS,intestinal epithelial MDA,Bax expression and epithelial apoptosis were significantly decreased, while SOD activity and Bcl-2 expression were markedly increased in group TEA (P <0.05 ). Conclusion Lower thoracic epidural block can enhance the antioxidant and anti-apoptotic ability,and inhibit the oxidative stress and cell apoptosis of intestinal epithelium.Therefore,it can promote the survival rate after hemorrhagic shock and resuscitation through protecting intestinal barrier.

This paper elaborated the research progress on transduction mechanisms of obese polycystic ovary syndrome (PCOS) and insulin resistance (IR). The action mechanisms of kidney-tonifying, spleen-invigorating and phlegm-resolving in the treatment of obese PCOS and IR were explored. It provided new ideas for the treatment of obese PCOS patients in the clinical practice of traditional Chinese medicine (TCM) gynecology. Literatures on TCM theories and modern signal pathways were used in the analysis of spleen-kidney deficiency and phlegm-dampness retention, which were the key pathogenesis of obese PCOS and IR. The scientific nature of treating obese PCOS and IR from the method of kidney-tonifying, spleen-invigorating and phlegm-resolving was demonstrated. The results showed that the scientific nature of treating obese PCOS and IR from the method of kidney-tonifying, spleen-invigorating and phlegm-resolving was initially demonstrated by the organic combination of TCM and modern medicine theories. It innovatively proposed that the treatment study strategy of transduction molecular mechanism took the interactive dialogue between PI-3K/Akt signal pathway and TNF-α signal pathway as its target. The regulatory role and action mechanism of this method in the treatment of obese PCOS and IR were discussed.

This study was aimed to establish and evaluate obese polycystic ovary syndrome (PCOS) rat model. Rats were randomly divided into the blank control group, high-fat model group, insulin (INS) combined human chorionic gonadotropin (HCG) model group, and INS combined HCG plus high fat emulsion model group. The obese PCOS rat model was induced by subcutaneous injection of INS and HCG on the nape, respectively. The intragastric administration of high fat emulsion was also used in the PCOS rat model establishment. The estrous cycle of rat was monitored. The detection was also made the weight increasing rate of rats, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), high-density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG), cholesterol (TC), fasting plasma glucose (FPG), fasting insulin (FINS), 2 h blood glucose and 2 h INS. Calculation was made on the HOMA index, related viscera index and bilateral ovaries HE staining. The results showed that when INS combined HCG improved method (INS combined HCG plus high fat emulsion model group) rats were sacrificed, the body weight, weight increasing rate, ovary viscera index, T, LH, and HOMA index were significantly higher than that of the blank control group, high-fat model group and INS combined HCG model group (P < 0.05,P < 0.01); HDL was significantly decreased (P < 0.05,P < 0.01). FPG, FINS, and 2 h INS of the INS combined HCG improved method group were significantly higher than that of the high-fat model group (P <0.01). It was concluded that INS combined HCG improved method was one of the ideal animal model establishment methods in the pathogenesis study of PCOS.

AIM: To establish the qualitative method for determining hirudo in Zhiyu Granule (Scorpio, Scolopendra, Rhizoma Coptidis, Radix Astragali, etc.) METHODS: Hirudo was determined by anti-thrombin bioactivity method after being extracted from Zhiyu Granule using 95% ethanol. RESULTS: The difference between Zhiyu Granule and the control sample without hirude was significant and easy to identify. CONCLUSION: After being extracted by 95% ethanol, hirudo can be identified from other anti-thrombin bioactivity components in prescription.