Objective To investigate the role of reactive oxygen species(ROS)and the extracellular signal-regulated kinase(ERK)/cAMP response element binding protein(CREB)signaling pathway in arsenic-induced apoptosis in HT-22 cells.Methods HT-22 cells were cultured in vitro and exposed to NaAsO2.The cells were divided into the following groups:control group,4,6,8,and 10 μmol/L NaAsO2 groups,NAC(5 mmol/L)group,and NAC(5 mmol/L)+NaAsO2(10 μmol/L)group.ROS levels were measured using a DCFH-DA assay.The expression of ERK/CREB signaling pathway-related and apoptosis-related proteins were analyzed by Western blotting.Apop-tosis rates were evaluated using flow cytometry.Results Compared with the control group,ROS levels in HT-22 cells significantly increased,while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly decreased in the NaAsO2 only exposed groups(P＜0.05).Additionally,the apoptosis rate significantly increased in the 8 and 10 μmol/L NaAsO2 groups compared with the control group(P＜0.05).In the NAC+NaAsO2 group,ROS levels and the apoptosis rate significantly decreased while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly increased compared with the 10 μmol/L NaAsO2 group(P＜0.05).Conclusion Arsenic exposure induces oxidative stress,inhibits the nuclear translocation of p-ERK,and dis-rupts the CREB signaling pathway,leading to apoptosis.

Purpose To evaluate the differential diagnostic value of 5.0T MRI susceptibility-weighted imaging(SWI)in hepatocellular carcinoma(HCC)and mass-forming intrahepatic cholangiocarcinoma(MICC).Materials and Methods A total of 56 patients with HCC and 36 patients with MICC confirmed by pathology from March 2023 to November 2024 in Anhui Provincial Hospital were retrospectively enrolled.Two radiologists independently analyzed three features of the lesions,including the low-signal rims around the lesion,hemorrhage within the lesion,and the relationship between lesions and adjacent vessels,on the SWI sequence between the two groups,respectively,via inter-rater consistency analysis.These above features between the two groups were compared and contrasted them with those obtained from conventional MR plain and enhanced scans,respectively.For intralesional hemorrhages,the diagnostic value was quantified by calculating the internal tissue susceptibility signal.Results The radiologists showed good consistency in the low-signal rims,intratumoral hemorrhage as well as the relationship between the lesion and the blood vessel on the SWI in the HCC group and the MICC group(Kappa=0.802-0.929,all P<0.001).Compared with conventional MR plain,SWI significantly enhanced the detection rates of perilesional low-signal rims and intratumoral hemorrhage(χ2=89.409,46.210,both P<0.001).These findings were more prevalent in HCC patients.The internal tissue susceptibility signal grading showed that HCC predominantly exhibited grade 3,whereas MICC predominantly exhibited grade 1,with statistically significant differences(Z=-4.059,P<0.05).Additionally,compared with enhanced MRI,SWI demonstrated higher accuracy in diagnosing the relationship between lesions and blood vessels in both groups;however,these differences were not statistically significant(χ2=0.275,0.247,P=0.871,0.619).In the HCC group,the relationship between tumors and blood vessels was primarily characterized by compression and tumor thrombus formation,while in the MICC group,it was predominantly marked by invasive changes,including vessel encasement,stenosis or occlusion,with a statistically significant difference between the two groups(Z=-6.809,P<0.001).Conclusion SWI sequence of 5.0T MRI provides clear visualization of the internal and peripheral structures of HCC and MICC.It can accurately delineate the relationship between lesions and blood vessels without the need for contrast agents,offering significant clinical utility in differentiating these two conditions.

Purpose To evaluate the differential diagnostic value of 5.0T MRI susceptibility-weighted imaging(SWI)in hepatocellular carcinoma(HCC)and mass-forming intrahepatic cholangiocarcinoma(MICC).Materials and Methods A total of 56 patients with HCC and 36 patients with MICC confirmed by pathology from March 2023 to November 2024 in Anhui Provincial Hospital were retrospectively enrolled.Two radiologists independently analyzed three features of the lesions,including the low-signal rims around the lesion,hemorrhage within the lesion,and the relationship between lesions and adjacent vessels,on the SWI sequence between the two groups,respectively,via inter-rater consistency analysis.These above features between the two groups were compared and contrasted them with those obtained from conventional MR plain and enhanced scans,respectively.For intralesional hemorrhages,the diagnostic value was quantified by calculating the internal tissue susceptibility signal.Results The radiologists showed good consistency in the low-signal rims,intratumoral hemorrhage as well as the relationship between the lesion and the blood vessel on the SWI in the HCC group and the MICC group(Kappa=0.802-0.929,all P<0.001).Compared with conventional MR plain,SWI significantly enhanced the detection rates of perilesional low-signal rims and intratumoral hemorrhage(χ2=89.409,46.210,both P<0.001).These findings were more prevalent in HCC patients.The internal tissue susceptibility signal grading showed that HCC predominantly exhibited grade 3,whereas MICC predominantly exhibited grade 1,with statistically significant differences(Z=-4.059,P<0.05).Additionally,compared with enhanced MRI,SWI demonstrated higher accuracy in diagnosing the relationship between lesions and blood vessels in both groups;however,these differences were not statistically significant(χ2=0.275,0.247,P=0.871,0.619).In the HCC group,the relationship between tumors and blood vessels was primarily characterized by compression and tumor thrombus formation,while in the MICC group,it was predominantly marked by invasive changes,including vessel encasement,stenosis or occlusion,with a statistically significant difference between the two groups(Z=-6.809,P<0.001).Conclusion SWI sequence of 5.0T MRI provides clear visualization of the internal and peripheral structures of HCC and MICC.It can accurately delineate the relationship between lesions and blood vessels without the need for contrast agents,offering significant clinical utility in differentiating these two conditions.

Objective To investigate the role of reactive oxygen species(ROS)and the extracellular signal-regulated kinase(ERK)/cAMP response element binding protein(CREB)signaling pathway in arsenic-induced apoptosis in HT-22 cells.Methods HT-22 cells were cultured in vitro and exposed to NaAsO2.The cells were divided into the following groups:control group,4,6,8,and 10 μmol/L NaAsO2 groups,NAC(5 mmol/L)group,and NAC(5 mmol/L)+NaAsO2(10 μmol/L)group.ROS levels were measured using a DCFH-DA assay.The expression of ERK/CREB signaling pathway-related and apoptosis-related proteins were analyzed by Western blotting.Apop-tosis rates were evaluated using flow cytometry.Results Compared with the control group,ROS levels in HT-22 cells significantly increased,while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly decreased in the NaAsO2 only exposed groups(P＜0.05).Additionally,the apoptosis rate significantly increased in the 8 and 10 μmol/L NaAsO2 groups compared with the control group(P＜0.05).In the NAC+NaAsO2 group,ROS levels and the apoptosis rate significantly decreased while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly increased compared with the 10 μmol/L NaAsO2 group(P＜0.05).Conclusion Arsenic exposure induces oxidative stress,inhibits the nuclear translocation of p-ERK,and dis-rupts the CREB signaling pathway,leading to apoptosis.

In order to study the effect of antimicrobial drug reduction on the resistance of E.coli and diversity of antibiotic resistance genes(ARGs)and mobile genetic elements(MGEs)in the intes-tinal microbiota of dairy cows in dairy farms in Hebei Province,and to evaluate the implementation effect of antimicrobial drug reduction actions,anal swab samples and fecal samples were collected from three qualified dairy farms and two non-standard dairy farms in different regions of Hebei Province,and E.coli was isolated from the anal swab samples and tested for their resistance to 16 antimicrobial drugs,and the differences in the drug resistance rate of E.coli in the two types of dairy farms were analyzed.SYBR fluorescent dye method was used to detect ARGs and MGEs in dairy feces,their relative abundance was calculated,the differences and correlation between the two types of dairy farms were analyzed.The results showed that a total of 192 ARGs and 7 MGEs were detected in 15 samples,and the relative abundance of ARGs was the highest in β-lactam resistance genes,followed by tetracycline resistance genes.The detection of ARGs and MGEs in some stand-ard dairy farms was lower than that in non-standard farms,suggesting that the large use of antimi-crobial drugs may be related to the production and transmission of ARGs,and the number of MG-Es detected was correlated with the number of ARGs detected,and ARGs may be transmitted through horizontal gene transfer.The results showed that there was little difference in the drug re-sistance rate of E.coli from the two types of dairy farms,and multi-drug resistant strains were more likely to occur in non-standard farms.The implementation of antimicrobial reduction had a certain effect on the diversity of antibiotic resistance genes,but had no significant effect on the prevalence of E.coli drug resistance and the diversity of ARGs in dairy farms in the short term,and there was little difference between different regions,which also revealed the prevalence of anti-biotic resistance in dairy farms.

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

Objective: To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Methods: Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People′s Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. Results: This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. Conclusions BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.

Objective To analyze and summarize the sonographic features of immunoglobulin G4(IgG4)-related submandibular gland disease.Methods The retrospective analysis on the sonographic results of 22 lesions in 19 patients with IgG4-related submandibular gland disease were conducted,including submandibular gland size,shape,lesion range,internal echo,blood flow,and peripheral lymph nodes.Results The sonographic features of 22 lesions of IgG4-related submandibular gland disease were classified into localized nodule changes,diffuse nodule changes,and tumor-forming changes.The localized nodule appearance,includes 2 lesions in 2 patients,shows a hypo-echoic area with a coarse echotexture in the superficial site of the gland and rich blood flow.In the diffuse nodule appearance,includes 12 lesions in 11 patients,the gland shows an irregular net or honeycomb structure.Further,the gland shows echo enhancement,thickening,uneven,and rich blood flow with the features of multiple,variously sized hypoechoic foci and surrounding parallel echogenic foci.The tumor-forming appearance,includes 8 lesions in 7 patients,shows the decrease of echogenic heterogeneity,coarse gland texture,multiple parallel echogenicity,and rich blood flow.Conclusions Ultrasonography can be used as the preferred diagnostic method for IgG4-related submandibular gland disease.When a patient is suspected of having IgG4-related submandibular gland disease,the tissues and organs often involved in IgG4 related diseases should be further examined,meanwhile conducting ultrasound-guided biopsy.

Purpose To study the clinicopathological characteristics in 22 cases of ovarian mature teratoma with malignant transforma-tion. Methods Clinical and pathologic features were collected and analyzed in 22 out of 1 826 cases of ovarian mature teratoma by retrospective studies, together with immunohistochemical staining. Results In our study, 22 cases (1. 2%) of ovarian mature terato-ma with malignant transformation were identified. The median age was 56. 5 (range, 31~79) years. The main clinical manifestations were pelvic masses, including 13 cases in the left ovary, 8 cases in the right, 1 case was bilateral. Gross cystic teratoma were saw in 19 cases, 3 cases of cystic and solid, the bilateral one was solid in the left which the right was cystic. The teratomas size were 5. 0~30 cm with average 12. 4 cm in diameter. The malignant components’ maximum diameter was about 1. 0~10. 0 cm with average 3. 7 cm. Microscopicically, there were poorly differentiated squamous cell carcinoma in 14 cases, carcinoid carcinoma in 4 cases, adeno-carcinoma in 2 cases, papillary thyroid carcinoma in 2 cases, and the last one was sarcomatoid carcinoma. The FIGO stage distribution was as follows:16 were stage IA, 1 was stage IB, 1 was stage IIA, 4 were stage IIB. Follow up showed 6 cases recurrened, 2 patients died, the rest are survival. Conclusions A low incidence of ovarian mature teratoma in somatic cells with malignant transformation, which are common in postmenopausal women and present with pelvic mass. The main malignant components is squamous cell carcino-ma, patients of stage I have better prognosis. Both clinic and pathology should take more attention to the comprehensive examination and diagnosis of teratoma for prevent misdiagnosis.

BACKGROUNDSuppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR). However, few studies link MSTN suppression by ladder-climbing training (LCT) and IR. Therefore, we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.

METHODSThe rats were randomly assigned to two types of diet: normal pellet diet (NPD, n = 8) and high-fat diet (HFD, n = 16). After 8 weeks, the HFD rats were randomly re-assigned to two groups (n = 8 for each group): HFD sedentary (HFD-S) and high-fat diet ladder-climbing training (HFD-LCT). HFD-LCT rats were assigned to LCT for 8 weeks. Western blotting, immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt-activated targets (mTOR, FoxO1 and GSK-3β).

RESULTSThe LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats. MSTN protein levels decreased in matching serum (42%, P = 0.007) and muscle samples (25%, P = 0.035) and its receptor mRNA expression also decreased (16%, P = 0.041) from obese rats after LCT. But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups (P = 0.074). The ladder-climbing training significantly enhanced PI3K activity (1.7-fold, P = 0.024) and Akt phosphorylation (83.3%, P = 0.022) in HFD-fed rats, significantly increased GLUT4 protein expression (84.5%, P = 0.036), enhanced phosphorylation of mTOR (4.8-fold, P < 0.001) and inhibited phosphorylation of FoxO1 (57.7%, P = 0.020), but did not affect the phosphorylation of GSK-3β.

CONCLUSIONSThe LCT significantly reduced IR in diet-induced obese rats. MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

Animals ; Blotting, Western ; Diet, High-Fat ; adverse effects ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; metabolism ; Immunohistochemistry ; Insulin Resistance ; physiology ; Male ; Myostatin ; metabolism ; Obesity ; etiology ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quadriceps Muscle ; metabolism ; Rats ; Rats, Sprague-Dawley