Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity.

Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.

Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China.

BACKGROUND: Colorectal juvenile polyps are rare and generally considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We systematically evaluated the characteristics and potential malignancy of colorectal juvenile polyps in adults. METHODS: We retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from September 2007 to May 2020 at our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed. RESULTS: The average age of patients with juvenile polyps was 43.2 years (range, 19 to 78 years). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, and two patients had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia and cancerization did not appear in the two patients with multiple polyps. A 27-year-old female had a 2-cm polyp with well-differentiated adenocarcinoma in the mucosa in the sigmoid colon with erosion on the surface. CSM was observed adjacent to 17 polyps, which were all located in the rectum and sigmoid colon, and one polyp showed low-grade intraepithelial neoplasia. CONCLUSIONS: Colorectal juvenile polyps occur in a wide range of locations and in variable sizes and numbers. These polyps are solitary in most patients and have neoplastic potential. CSM is not a tumorigenic marker in colorectal juvenile polyps and usually occurs in the distant colorectum. Colorectal juvenile polyps in adults may progress from low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and then to carcinoma and should be treated when discovered and regularly followed as colorectal adenomas.

Ileocecal intussusception caused by two different tumors - which is the culprit lesion? A case report.

BACKGROUND: Ileocecal intussusception caused by two different tumors is rare, according to a literature review. We describe a case of a male patient with a cauliflower-like mass in the middle of the transverse colon observed by colonoscopy before surgery. It was considered to be intussusception caused by colon cancer. However, a substantial lipomatous mass was seen in the distal end of the intussusception by computed tomography before surgery, which posed a challenge in the preoperative diagnosis. CASE SUMMARY: We report a 72-year-old male patient with intussusception. The patient underwent right hemicolectomy and cholecystectomy in our hospital on April 29, 2019. During operation, the ileum was inserted into the ascending colon by about 15 cm, and a tumor with a diameter of approximately 3.0 cm was observed in the distal part of the intestine. An atypical liposarcoma/highly differentiated liposarcoma in the adipose tissue was suspected in the postoperative pathology, and a lipoma was diagnosed after MDM2 gene testing. A 4.0 cm × 5.0 cm polypoid mass was seen immediately adjacent to the mass, and the postoperative pathology report suggested a high-level tubular adenoma. The patient was eventually cured and discharged with an uneventful follow-up. CONCLUSION: Intussusception caused by two different types of masses is extremely rare. At present, surgery is the best treatment once intussusception is diagnosed.

Huge primary dedifferentiated pancreatic liposarcoma mimicking carcinosarcoma in a young female: A case report.

BACKGROUND: Pancreatic liposarcoma is a rare tumor. According to a literature review, the patient described in this study is the seventh case of pancreatic liposarcoma reported in the English literature and the third case of dedifferentiated liposarcoma. Furthermore, this case had the largest primary tumor volume, and a primary pancreatic liposarcoma was diagnosed based on sufficient evidence. CASE SUMMARY: We here report a rare case of a 28-year-old female with a huge dedifferentiated liposarcoma in the pancreatic tail. In June 2015, the patient underwent distal pancreatectomy with splenectomy. During the operation, a huge liposarcoma of approximately 28.0 cm × 19.0 cm × 8.0 cm was found, which had a yellow and white fish-like incisal surface. Based on both pathology and MDM2 gene amplification, the tumor was diagnosed as a dedifferentiated liposarcoma. The patient was treated with surgery but declined postoperative chemotherapy. She was well at the 26-mo follow-up, and no relapse was observed. CONCLUSION: Pancreatic liposarcoma has a low incidence. Chemotherapy should be included in the treatment regimens. Complete resection is the only effective treatment.

Huge peripheral primitive neuroectodermal tumor of the small bowel mesentery at nonage: A case report and review of the literature.

Extraskeletal Ewing's sarcoma/peripheral primitive neuroectodermal tumor (E-EWS/pPNET) is a rare aggressive malignant small round cell tumor. In this report, we present the case of a 15-year-old boy who suffered from acute abdominal pain accompanied by hematemesis and melena, and was eventually diagnosed with E-EWS/pPNET. To date, there have been only five reported cases of E-EWS/pPNET of the small bowel including the patient in this report. To the best of our knowledge, this is the first documentation of a pPNET of the small bowel mesentery at nonage. All these have made this report rare and significant.

miR-429 functions as a tumor suppressor by targeting FSCN1 in gastric cancer cells.

It has been previously reported that the deregulation of microRNAs in gastric cancer (GC) was correlated with the progression and prognosis. miR-429, a member of the miR-200 family, was previously shown to play an important role in human carcinomas. Our study shows that miR-429 is significantly downregulated in GC tissues compared with matched nontumor tissues. Overexpression of miR-429 in GC cells suppressed cell proliferation. Fascin-1 (FSCN1) was identified as one of the targets of miR-429 and knockdown of FSCN1 mimics the function of miR-429 overexpression. In conclusion, miR-429 acts as a tumor suppressor by targeting FSCN1, suggesting that miR-429 and FSCN1 can both be potential therapeutic targets of GC.

Loss of heterozygosity at the calcium regulation gene locus on chromosome 10q in human pancreatic cancer.

BACKGROUND: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. MATERIALS AND METHODS: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). RESULTS: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial Ca2+ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. CONCLUSIONS: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

Activated microglia contribute to neuronal apoptosis in Toxoplasmic encephalitis.

BACKGROUND: A plethora of evidence shows that activated microglia play a critical role in the pathogenesis of the central nervous system (CNS). Toxoplasmic encephalitis (TE) frequently occurs in HIV/AIDS patients. However, knowledge remains limited on the contributions of activated microglia to the pathogenesis of TE. METHODS: A murine model of reactivated encephalitis was generated in a latent infection with Toxoplasma gondii induced by cyclophosphamide. The neuronal apoptosis in the CNS and the profile of pro-inflammatory cytokines were assayed in both in vitro and in vivo experiments. RESULTS: Microglial cells were found to be activated in the cortex and hippocampus in the brain tissues of mice. The in vivo expression of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) were up-regulated in TE mice, and accordingly, the neuronal apoptosis was significantly increased. The results were positively correlated with those of the in vitro experiments. Additionally,apoptosis of the mouse neuroblastoma type Neuro2a (N2a) remarkably increased when the N2a was co-cultured in transwell with microglial cells and Toxoplasma tachyzoites. Both in vivo and in vitro experiments showed that minocycline (a microglia inhibitor) treatment notably reduced microglial activation and neuronal apoptosis. CONCLUSIONS: Activated microglia contribute to neuronal apoptosis in TE and inhibition of microglia activation might represent a novel therapeutic strategy of TE.

Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China.

CONTEXT: There are a few prospective population-based cohort studies evaluating the effects of maternal thyroid dysfunctions on fetal and infant developments, but they are inconsistent. OBJECTIVE: The objective of the study was to investigate the effects of maternal thyroid dysfunction on fetal and infant development. SETTING AND PARTICIPANTS: The study was nested within a prospective population-based China-Anhui Birth Defects and Child Development study. A total of 1017 women with singleton pregnancies participated in this study. Maternal serum samples in the first 20 wk of pregnancy were tested for thyroid hormones (TSH and free T(4)). Pregnant women were classified by hormone status into percentile categories based on laboratory assay and were compared accordingly. MAIN OUTCOMES: Outcomes included fetal loss, malformation, birth weight, preterm delivery, fetal stress, neonatal death, and infant development. RESULTS: Clinical hypothyroidism was associated with increased fetal loss, low birth weight, and congenital circulation system malformations; the adjusted odds ratios [95% confidence interval (CI)] were 13.45 (2.54-71.20), 9.05 (1.01-80.90), and 10.44 (1.15-94.62), respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios (95% CI) were 3.65 (1.44-9.26), 3.32 (1.22-9.05), 5.34 (1.09-26.16), and 10.49 (1.01-119.19), respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios (95% CI) were 2.95 (1.08-8.05), 3.55 (1.01-12.83), and 9.12 (1.67-49.70), respectively. Isolated hyperthyroxinemia was associated with spontaneous abortion; the adjusted odds ratio (95% CI) was 6.02 (1.25-28.96). Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio (95% CI) was 12.14 (1.22-120.70). CONCLUSIONS: Thyroid dysfunction in the first 20 wk of pregnancy may result in fetal loss and dysplasia and some congenital malformations.

[Indications, technique and efficacy of organ preserving pancreatectomy].

OBJECTIVE: To discuss the proper surgical management of pancreatic benign and low-grade malignant potential neoplasm. METHODS: The experience of 72 cases who accepted organ preserving pancreatectomy from January 1990 to May 2010 was analyzed retrospectively. There were 24 male and 48 female, aged from 15 to 68 years with mean age of 46 years. There were 9 cases underwent duodenum-preserving resection of the head of the pancreas, 29 cases underwent spleen-preserving distal pancreatectomy, 11 cases underwent middle segmental pancreatectomy, 23 cases underwent tumor extirpation of huge pancreatic cancer in pancreatic head and body. RESULTS: Pancreatic fistula and biliary fistula in 1 case respectively were cured among who accepted duodenum-preserving resection of the head of the pancreas. Pancreatic fistula was found in 3 cases who accepted spleen-preserving distal pancreatectomy. Pancreaticobiliary anastomotic bleeding in 1 case was cured among who accepted middle segmental pancreatectomy. Pancreatic fistula was found in 5 cases among who accepted tumor extirpation of huge pancreatic cancer in pancreatic head and body, and liver metastasis was found in 3 cases at 6, 12, 16 months after surgery respectively. CONCLUSIONS: Organ preserving pancreatectomy can obviously reduce operative injury to patients, its therapeutic effect is similar to that of classical operation, it is the first option of benign and low-grade malignant potential neoplasm.

[Macrocystic serous adenoma of the pancreas: a report of 5 cases].

OBJECTIVE: To investigate the diagnosis and treatment of macrocystic serous adenoma of the pancreas (MSAP). METHODS: The clinical data of 5 patients with MSAP treated from October 1999 to October 2009 were retrospectively analyzed. There were 5 female and 1 male. RESULTS: Of the 5 patients, 3 patients presented with abdominal pain and fullness, 1 patient with jaundice, 1 patient with asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the pancreas; all the lesion showed a well-defined border, internal septations, enhanced cyst walls, with no intramural (mural) nodule and papillary projections; the wall was smooth and thin in 4 cases; irregular lobulation could be observed in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1 case had biliary duct dilatation. The tumors located in the pancreatic body and tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all accepted surgical intervention. The main postoperative complication was pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis were not found in 5 patient followed up postoperatively from 8 to 35 months. CONCLUSIONS: MSAP has no specific symptoms. The imaging appearance of MSAP is similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow up and produce compression symptoms. MSAP can be cured by complete resection.

Adult intussusception: a retrospective review of 41 cases.

AIM: To optimize the preoperative diagnosis and surgical management of adult intussusception (AI). METHODS: A retrospective review of the clinical features, diagnosis, management and pathology 41 adult patients with postoperative diagnoses of intussusception was conducted. RESULTS: Forty-one patients with 44 intussusceptions were operated on, 24.4% had acute symptoms, 24.4% had subacute symptoms, and 51.2% had chronic symptoms. 70.7% of the patients presented with intestinal obstruction. There were 20 enteric, 15 ileocolic, eight colocolonic and one sigmoidorectal intussusceptions. 65.9% of intussusceptions were diagnosed preoperatively using a computed tomography (CT) scan (90.5% accurate) and ultrasonography (60.0% accurate, rising to 91.7% for patients who had a palpable abdominal mass). Coloscopy located the occupying lesions of the lead point of ileocolic, colocolonic and sigmoidorectal intussusceptions. Four intussusceptions in three patients were simply reduced. Twenty-one patients underwent resection after primary reduction. There was no mortality and anastomosis leakage perioperatively. Except for one patient with multiple small bowel adenomas, which recurred 5 mo after surgery, no patients were recurrent within 6 mo. Pathologically, 54.5% of the intussusceptions had a tumor, of which 27.3% were malignant. 9.1% comprised nontumorous polyps. Four intussusceptions had a gastrojejunostomy with intestinal intubation, and four intussusceptions had no organic lesion. CONCLUSION: CT is the most effective and accurate diagnostic technique. Colonoscopy can detect most lead point lesions of non-enteric intussusceptions. Intestinal intubation should be avoided.

[Diagnosis and surgical treatment of 98 cases with adult primary retroperitoneal malignant tumor].

OBJECTIVE: To investigate the diagnosis and surgical treatment of adult primary retroperitoneal malignant tumor (APRMT). METHODS: The clinical data of 98 cases with APRMT underwent resection from January 1990 to April 2003 were analyzed retrospectively. RESULTS: Among the 98 cases, complete excision were performed in 79 cases (80.6%), palliative excision in 16 cases (16.3%), tumor biopsy only in 3 cases (3.1%). Resection of involved adjacent organs were carried out in 25 cases (25.5%) and the re-operation rate for recurrence was 28.6% (28 cases). The 1, 3, 5 year survival rates for 79 cases with complete resection were 93.7%, 73.4% and 34.2%, respectively. The 1, 3, 5 year survival rate for 16 cases with palliative resection were 75.0%, 6.3% and 6.3%, respectively. CONCLUSIONS: Certain imaging examinations are crucial to the diagnosis and preoperative evaluation of APRMT. Resection of the involved organs could improve resection rate and prognosis. For the recurrent cases, earlier reoperation is strongly recommended.

Surgical management of 143 patients with adult primary retroperitoneal tumor.

AIM: To analyze the surgical management of adult primary retroperitoneal tumors (APRT) and the factors influencing the outcome after operation. METHODS: Data of 143 cases of APRT from 1990 to 2003 in the First Affiliated Hospital of China Medical University were evaluated retrospectively. RESULTS: A total of 143 cases of APRT were treated surgically. Among them, 122 (85.3%) underwent complete resection, 16 (11.2%) incomplete resection, and 3 (3%) surgical biopsies. Twenty-nine (20.2%) underwent tumor resection plus multiple organ resections. Ninety-five malignant cases were followed up for 1 mo to 5 years. The 1-year, 3-year, and 5-year survival rates of the patients subject to complete resection was 94.9%, 76.6% and 34.3% and that of patients with incomplete resection was 80.4%, 6.7%, and 0%, respectively (P < 0.001). The Cox multi-various regression analysis showed the completeness of tumor, sex and histological type were associated closely with local recurrence. CONCLUSION: Sufficient preoperative preparation and complete tumor resection play important roles in reducing recurrence and improving survival.