OBJECTIVE: To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene. METHODS: A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords "TSEN2 gene" "PCH2B" and "Pontocerebellar Hypoplasia 2B" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892). RESULTS: The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis. CONCLUSION The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.
Child ; Female ; Humans ; Cerebellar Diseases/genetics* ; Exome Sequencing ; Heterozygote ; Mutation

ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC₅₀） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg^-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC₅₀ of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L^-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Objective To investigate the relationship between serum survivin,adenosine triphosphate bind-ing cassette transporter Al(ABCA1)and poor coronary collateral circulation(CCC)in patients with single coronary artery occlusion in acute myocardial infarction(AMI).Methods A total of 155 patients with single coronary artery occlusion in AMI admitted to Handan Fist Hospital from May 2021 to May 2023 were selected as the study objects,and were divided into poor CCC group(n=80)and good CCC group(n=75)according to their CCC status.Serum survivin and ABCA1 levels were compared between the two groups,univariate and multivariate Logistic regression models were used to analyze the influencing factors of poor CCC,and the effi-cacy of serum survivin and ABCA1 in predicting poor CCC was analyzed by receiver operating characteristic curve.Results Compared with good CCC group,serum survivin and ABCA1 in poor CCC group were signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with good CCC group,Gensini score,creatinine kinase isoenzyme-MB(CK-MB),Killip heart function grade≥Ⅱ and history of hy-pertension in poor CCC group were significantly increased,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression model showed that high Gensini score,high CK-MB,Killip heart function grade≥Ⅱ and history of hypertension were risk factors for poor CCC(P＜0.05),while high sur-vivin and high ABCA1 were protective factors(P＜0.05).The area under the curve,sensitivity and specificity of the two indexes combined to predict poor CCC were 0.949,90.70％and 92.52％,which were significantly better than the single detection.Conclusion Serum survivin and ABCA1 are closely relate to poor CCC in pa-tients with single coronary artery occlusion in AMI,the lower the serum levels of survivin and ABCA1,the greater the risk of poor CCC,the combine detection of the two has a high predictive value for poor CCC in pa-tients with single coronary artery occlusion in AMI.

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Objective: To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods: One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results: Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Objective: To analyze the clinicopathological characteristics of ovarian pseudomyxoma peritonei (PMP). Methods: Clinical and pathological data from a total of 272 PMP patients diagnosed at Beijing Shijitan Hospital from January 2010 to January 2019 were collected from a database and retrospectively analyzed to study the origin of PMP tumors. Pathological slides marked with antigens were further studied using immunohistochemical staining, including CK7, CK20, CEA, Villin, CDX2, SATB2, CA125, ER, PR, MUC1, and MUC2. Results: Among the 272 PMP patients studied, the tumors of 245 (90.1%) originated from the appendix, while the remaining 27 (9.9%) originated from non-appendix tissues, including 5 (1.8%) from the ovaries. Ovarian cases included two ovarian teratomas, two ovarian mucinous cystadenomas, and one borderline ovarian mucinous cystadenoma. Histopathological analysis of peritoneal me-tastases further revealed two acellular mucins, two low-grade mucinous carcinoma peritonei, and one high-grade mucinous carcinoma peritonei, while immunohistochemistry revealed positive staining for CK20, CEA, Villin, and CDX2; SATB2 was also found to be partially positive in teratomas with mucinous tumors: negative in two cases and partially positive in one case. Conclusions: The occurrence of ovarian PMP is rare. Its precise diagnosis demands for a serial section of the whole appendix or suspected tissue to exclude any appen-diceal mucinous neoplasms, as well as the combination of a comprehensive analysis of its clinical signs and symptoms, imaging find-ings, surgical findings, histopathological characteristics, and immunohistochemistry.

Objective To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods One?hundred and fifty?five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki?67, p53, MMR?related protein, MUC2 and MUC5AC were analyzed. Clinical follow?up data were reviewed to correlate with pathological prognostic factors using Kaplan?Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low?grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high?grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high?grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki?67 label index<50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival?related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki?67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Objective To establish the patient derived xenograft ( PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B／c?nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B／c?nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high?throughput whole?genome exon sequencing were detected and recorded. Results The successful rate of established orthotopic PDX model of human PMP was 100%(10／10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity.The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells ( PMCA?S ), obvious tumor cell atypia and parenchymal invasion. Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX?2 and Ki?67 were positive, MUC6, CK7 and p53 were negative. Whole?exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c.1621A＞C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA?S is successfully established, which displays the characters of high?degree malignancy, high proliferation and strong aggressiveness.

Objective To establish the patient derived xenograft ( PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B／c?nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B／c?nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high?throughput whole?genome exon sequencing were detected and recorded. Results The successful rate of established orthotopic PDX model of human PMP was 100%(10／10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity.The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells ( PMCA?S ), obvious tumor cell atypia and parenchymal invasion. Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX?2 and Ki?67 were positive, MUC6, CK7 and p53 were negative. Whole?exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c.1621A＞C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA?S is successfully established, which displays the characters of high?degree malignancy, high proliferation and strong aggressiveness.