Objective To study the expressions of apoptotic protease activating factor-1(Apaf-1)and astrocyte elevated gene-1(AEG-1)in colonic carcinoma,and to explore their correlations with the clinical path-ological features. Methods The expressions of Apaf-1 and AEG-1 were detected in 63 colonic carcinoma sam-ples and 30 normal colonic mucosa adjacent to tumor nest by immunohistochemical method,and their correla-tions with clinical features of colonic carcinoma were analyzed. Results The positive expressions of Apaf-1 and AEG-1 in colonic carcinoma were 23. 81%(15 / 63)and 68. 25%(43 / 63),respectively. The positive expre-ssions of Apaf-1 and AEG-1 in normal colonic mucosa were 76. 67%(23 / 30)and 26. 67%(8 / 30),respec-tively. The positive expression rate of AEG-1 was significantly higher in colonic carcinoma than that in normal tissue(χ2 = 14. 192,P = 0. 000). However,the expression of Apaf-1 was signi-ficantly lower in colonic carci-noma than that in normal tissue(χ2 = 23. 497,P = 0. 000). The expression of Apaf-1 was negatively correlated to the expression of AEG-1(r = - 0. 339,P = 0. 007). The expressions of AEG-1 and Apaf-1 were associated with differentiation degree(χ2 = 4. 643,P = 0. 031;χ2 = 12. 034,P = 0. 001)and clinical stage(χ2 = 6. 628, P = 0. 010;χ2 = 8. 246,P = 0. 004),but they were not correlated with age(χ2 = 1. 462,P = 0. 227;χ2 =2. 401,P = 0. 121)and tumor size(χ2 = 0. 333,P = 0. 564;χ2 = 0. 590,P = 0. 442). Conclusion The expression of AEG-1 is up-regulated in colonic carcinoma,but the expression of Apaf-1 is down-regulated,with a significant negative correlation. Apaf-1 and AEG-1 may be closely related to the occurrence and development of colon carcinoma. Therefore,combination detection of Apaf-1 and AEG-1 may be more valuable for the prog-nosis evaluation of colonic carcinoma.

Objective To investigate the expressions and significances of Bcl-2 and Bax in basal-like breast carcinoma (BLBC).Methods The expressions of Bcl-2 and Bax were detected in 43 cases of BLBC, 57 cases of non-BLBC and 60 cases of normal breast tissues by immunohistochemistry,and their relationships with physiological and pathological characteristics of patients were analysized.Results The positive rate of Bcl-2 in BLBC was 69.77%,higher than 43.86% in non-BLBC (χ2 =6.647,P =0.01 0)and 21 .67% in normal breast tissues (χ2 =23.831 ,P =0.001 ).The positive rate of Bax in BLBC was 20.93%,lower than 45.61 % in non-BLBC (χ2 =6.564,P =0.01 0)and 76.67% in normal breast tissues (χ2 =31 .270,P =0.001 ).The expressions of Bcl-2 and Bax were correlated with lymphnode metastasis (χ2 =6.927,P =0.008;χ2 =6.203,P =0.01 3)and pTNMstaging of BLBC (χ2 =6.331 ,P =0.01 2;χ2 =5.972,P =0.01 5).There was negative correlation between the expression of Bcl-2 and Bax in BLBC (r = -0.408,P <0.01 0). Conclusion High expression of Bcl-2 and low expression of Bax interact with each other leading to unbalance of cell deferation and apoptosis,resulting in promoting genesis and progress of BLBC.

Objective:To investigate the clinic value of ultrasound 3-dimensional shear wave elastography (3D-SWE) in therapeutic effect evaluation of neoadjuvant chemotherapy (NAC) for HER-2 positive breast cancer patients.Methods:A total of 43 lesions from 43 HER-2 positive breast cancer patients were selected and all of the lesions were confirmed by biopsy. Ultrasound examination was performed routinely before each chemotherapy cycle. The interested regions were selected under the 3-dimensional (3D) elasticity and gray-scale mode, the relevant data such as shear waves in the transverse, longitudinal and coronal sections of the mass were generated automatically. According to the histopathological results, the patients were divided into the pathological complete remission (pCR) group and the incomplete remission (non-pCR) group. The maximum elastic hardness value (Emax) and the reduction degree (ΔEmax) of the lesions in the two groups were measured and compared in each cycle of NAC. The accuracy of 3D-SWE technique for predicting the efficacy of NAC was evaluated using indicators such as sensitivity, specificity and area under the receiver operating characteristic (ROC) curve.Results:The clinicopathologic features between pCR group (18 cases) and non-pCR Group (25 cases) were not significantly different ( P>0.05). Compared with pre-chemotherapy, the Emax values of pCR group and non-pCR Group during chemotherapy were declined ( P<0.05). Moreover, the Emax values of pCR group before and after chemotherapy were lower than those of non-pCR group ( P<0.05). At the end of the first cycle of chemotherapy, the predictive specificity, sensitivity and area under the curve (AUC) of pCR group were 72.0%, 83.3% and 0.838 (95% CI=0.680~0.930) respectively when the cutoff value of Emax was 118 kPa. At the end of the second cycle, the predictive specificity, sensitivity and AUC of pCR group were 76.0%, 83.3% and 0.863 (95% CI=0.720~0.940) respectively when the cutoff value of Emax was 87 kPa. At the end of the third cycle, the predictive specificity and sensitivity and the AUC of the pCR group were 88.0%, 77.8% and 0.893 (95% CI=0.760~0.970) when the cutoff value of Emax was 57 kPa. At the end of the fourth cycle of chemotherapy, the predictive specificity, sensitivity and AUC of pCR group were 92.5%, 88.9% and 0.960 (95% CI=0.850~0.990) respectively when the cutoff value of Emax was 30 kPa. After one cycle of NAC, the predictive sensitivity and specificity and AUC of pCR group were 88.0%, 60.0%, and 0.719 (95% CI=0.620~0.890) when the cutoff value of ΔEmax was 16.8%. After two cycles, the predictive sensitivity, specificity and AUC of pCR group were 55.5%, 80.0% and 0.712 (95% CI=0.550~0.840) when the cutoff value of ΔEmax was 34.9%. After three cycles, the predictive sensitivity, specificity and AUC of pCR group were 67.4%, 81.2% and 0.779 (95% CI=0.680~0.930) when the cutoff value of ΔEmax was 55.2%. After four cycles, the predictive sensitivity, specificity and AUC of pCR group was 72.3%, 92.0% and 0.831 (95% CI=0.690~0.930) when the cutoff value of ΔEmax was 75.1%. Conclusion:The Emax and ΔEmax values measured by 3D-SWE technology can predict the curative effect of NAC for breast cancer.

Objective:To investigate the clinic value of ultrasound 3-dimensional shear wave elastography (3D-SWE) in therapeutic effect evaluation of neoadjuvant chemotherapy (NAC) for HER-2 positive breast cancer patients.Methods:A total of 43 lesions from 43 HER-2 positive breast cancer patients were selected and all of the lesions were confirmed by biopsy. Ultrasound examination was performed routinely before each chemotherapy cycle. The interested regions were selected under the 3-dimensional (3D) elasticity and gray-scale mode, the relevant data such as shear waves in the transverse, longitudinal and coronal sections of the mass were generated automatically. According to the histopathological results, the patients were divided into the pathological complete remission (pCR) group and the incomplete remission (non-pCR) group. The maximum elastic hardness value (Emax) and the reduction degree (ΔEmax) of the lesions in the two groups were measured and compared in each cycle of NAC. The accuracy of 3D-SWE technique for predicting the efficacy of NAC was evaluated using indicators such as sensitivity, specificity and area under the receiver operating characteristic (ROC) curve.Results:The clinicopathologic features between pCR group (18 cases) and non-pCR Group (25 cases) were not significantly different ( P>0.05). Compared with pre-chemotherapy, the Emax values of pCR group and non-pCR Group during chemotherapy were declined ( P<0.05). Moreover, the Emax values of pCR group before and after chemotherapy were lower than those of non-pCR group ( P<0.05). At the end of the first cycle of chemotherapy, the predictive specificity, sensitivity and area under the curve (AUC) of pCR group were 72.0%, 83.3% and 0.838 (95% CI=0.680~0.930) respectively when the cutoff value of Emax was 118 kPa. At the end of the second cycle, the predictive specificity, sensitivity and AUC of pCR group were 76.0%, 83.3% and 0.863 (95% CI=0.720~0.940) respectively when the cutoff value of Emax was 87 kPa. At the end of the third cycle, the predictive specificity and sensitivity and the AUC of the pCR group were 88.0%, 77.8% and 0.893 (95% CI=0.760~0.970) when the cutoff value of Emax was 57 kPa. At the end of the fourth cycle of chemotherapy, the predictive specificity, sensitivity and AUC of pCR group were 92.5%, 88.9% and 0.960 (95% CI=0.850~0.990) respectively when the cutoff value of Emax was 30 kPa. After one cycle of NAC, the predictive sensitivity and specificity and AUC of pCR group were 88.0%, 60.0%, and 0.719 (95% CI=0.620~0.890) when the cutoff value of ΔEmax was 16.8%. After two cycles, the predictive sensitivity, specificity and AUC of pCR group were 55.5%, 80.0% and 0.712 (95% CI=0.550~0.840) when the cutoff value of ΔEmax was 34.9%. After three cycles, the predictive sensitivity, specificity and AUC of pCR group were 67.4%, 81.2% and 0.779 (95% CI=0.680~0.930) when the cutoff value of ΔEmax was 55.2%. After four cycles, the predictive sensitivity, specificity and AUC of pCR group was 72.3%, 92.0% and 0.831 (95% CI=0.690~0.930) when the cutoff value of ΔEmax was 75.1%. Conclusion:The Emax and ΔEmax values measured by 3D-SWE technology can predict the curative effect of NAC for breast cancer.

Objective:To observe the safety and efficacy of 0.01% atropine eye drops in the prevention of myopia onset in schoolchildren.Methods:A randomized double-blind controlled study was conducted.Sixty Chinese Han children (60 eyes) with binocular spherical equivalent (SE) between + 0.50 D and -0.75 D (pre-myopia) by cycloplegic autorefraction treated in The First Affiliated Hospital of Zhengzhou University were enrolled from July to October 2020.Aged 6-12 years old, the children were divided into 0.01% atropine group and control group according to a random number table, with 30 cases (30 eyes) in each group.The children were given one drop of 0.01% atropine or placebo eye drops in both eyes once a night.The SE, axial length (AL), accommodative amplitude and pupil diameter were compared before and after 3-month, 6-month of treatment between the two groups.Discomforts were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-286). Written informed consent was obtained from guardian of each subject.Results:After treatment, 26 and 25 subjects completed the 6-month follow-up in 0.01% atropine group and control group, respectively, among which 3 subjects in 0.01% atropine group accounting for 11.5% and 9 in control group accounting for 36.0% developed myopia, showing a statistically significant difference ( χ2=4.238, P=0.040). There were significant differences in the overall comparison of SE and AL at different time points between before and after treatment ( Ftime=10.981, 81.854; both at P<0.001). At 3 and 6 months after treatment, there were significant increases in the SE and AL of control group and AL of 0.01% atropine group compared with respective baseline values (all at P<0.05). There was no significant difference in SE at 3 and 6 months after treatment compared with baseline SE in 0.01% atropine group (both at P>0.05). At 6 months after treatment, the change in SE in 0.01% atropine group was (-0.15±0.26)D, which was significantly less than (-0.34±0.35)D in control group, and the change in AL in 0.01% atropine group was (0.17±0.11)mm, Which was significantly shorter than (0.28±0.14)mm in control group, with significant differences between them ( t=2.207, P=0.032; t=3.127, P=0.003). There were significant differences in pupil diameter at different time points between before and after treatment ( Ftime=2.263, P=0.032). At 3 and 6 months after treatment, the pupil diameter was increased in comparison with baseline in 0.01% atropine group (both at P<0.05). There were significant differences in accommodative amplitude at different time points between before and after treatment in the two groups ( Fgroup=0.882, P=0.042; Ftime=0.337, P=0.033). The accommodative amplitude at 3 and 6 months after treatment were decreased in comparison with baseline in 0.01% atropine group and control group at corresponding time points (all at P<0.05). Within a month after treatment, photophobia in bright sunlight occurred in 5 cases in 0.01% atropine group, accounting for 16.7%(5/30), and 2 cases in control group, accounting for 6.7%(2/30), showing no significant difference ( χ2=0.647, P=0.421). No near-vision blur and other uncomfortable symptoms was found in the two groups. Conclusions:After 6-month application of 0.01% atropine eye drops, the prevalence of myopia in pre-myopia schoolchildren decreases and the changing rate of SE and AL slows down.The accommodative amplitude is slightly reduced and pupil diameter is slightly increased, with no obvious effects on study and life.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

ObjectiveTo explore the potential mechanism of acupuncture with the method of soothing the liver and regulating the mind in improving depressive disorder. MethodsEighteen C57BL/6J mice were randomly divided into blank group， model group， and acupuncture group， with 6 mice in each group. The model group and the acupuncture group were subjected to depression induction by intraperitoneal injection of lipopolysaccharide （LPS）， while the blank group received an equal volume of normal saline once daily for seven consecutive days. Concurrently， the acupuncture group received "soothing the liver and regulating the mind" acupuncture intervention starting from the first day of modeling， once daily for 14 days； whereas the blank group and the model group were only restrained without acupuncture. The sucrose preference test was used to assess sucrose preference rate， the open-field test to measure center stay time and total travel distance， and the forced swim test to evaluate immobility time. Hematoxylin-eosin （HE） staining was performed to observe hippocampal morphological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue. Western blot analysis was conducted to examine the protein expression levels of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the hippocampus. ResultsCompared to the blank group， the model group showed a significant reduction in sucrose preference rate， center stay time， and total travel distance， along with a significant increase in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， as well as TLR4 and NF-κB protein expression （P＜0.01）， and the histological examination revealed blurred hippocampal neuronal boundaries， loose arrangement， and some neurons exhibiting nuclear pyknosis and deep staining. Compared to the model group， the acupuncture group demonstrated a significant increase in sucrose preference rate， center stay time， and total travel distance， along with a significant reduction in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， and TLR4 and NF-κB protein expression （P＜0.01）， and the histological analysis showed that hippocampal neurons in the acupuncture group were more tightly arranged， with reduced nuclear pyknosis and deep staining. ConclusionAcupuncture with the "soothing the liver and regulating the mind" method can significantly improve depression-like behavior， potentially by inhibiting the hippocampal TLR4/NF-κB signaling pathway and alleviating inflammatory responses.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia