Objective:To explore the correlation between functional constipation （FC）and its related factors with acute appendicitis（AA）in children，so as to provide a reference for the prevention and clinical diagnosis and treatment of children with AA. Methods:A case-control study was conducted on 170 children diagnosed with AA in the Department of Pediatrics，the Second Affiliated Hospital of Air Force Military Medical University，from August 2022 to March 2023，and 170 non-AA children during the same period were selected as control objects.The clinical data，incidence of FC，symptoms related to FC，Bristol stool classification，past constipation history and other information were compared between two groups.Results:The incidence of FC in 170 children with AA was 22.9%（39/170），which was significantly higher than 10.6%（18/170）in the non-AA group（ P<0.01）；For children under four years old，the proportion of faecal retention in AA group was higher than that in non-AA group（25.6% vs. 9.3%, P<0.05）；For children ≥ 4 years old，the proportion of faecal retention and dyschezia in AA group were higher than those in non-AA group（28.2% vs. 6.9%，29.0% vs. 16.4%，respectively,all P<0.05）.The proportion of past constipation history in AA group was higher than that in non-AA group（29.4% vs.14.1%）.The duration of constipation in AA group was longer than that in non-AA group [0.00（0.00，1.25）month vs. 0.00（0.00，0.00）month,all P<0.01].The proportion of children with low Bristol stool classification in AA group was higher than that in non-AA group（ P<0.01）.Multivariate Logistic regression analysis showed that faecal retention[ OR=6.186（95% CI 2.336~16.380）] and long constipation time [ OR=1.310（95% CI 1.095~1.567）]were independent risk factors for AA in children（all P<0.05）. Conclusion:The incidence of faecal retention in children with AA is higher than that in children without AA，and the median duration of constipation is longer than that in children without AA.Fecal retention and long-term constipation are independent risk factors for AA in children.

Objective:To analyze the mutation spectrum and hematological phenotype of hemoglobin subunit delta(HBD) gene among prenatal population in Xiangtan City, and to provide scientific basis for screening and diagnosis of rare and complex hemoglobinopathia.Methods:Prenatal population underwent screening and genetic testing for thalassemia at Xiangtan Maternal and Child Health Hospital from October 2022 to December 2023 were selected as the study subjects, combined with capillary electrophoresis results, further HBD gene sequencing was performed to identify specific genotypes.Results:A total of 5 371 subjects were enrolled, 22 cases of HBD gene mutations were detected, with a mutation carrier rate of 0.41% (22/5 371). Among them, 14 cases were diagnosed with δ thalassemia, 7 cases were δ abnormal hemoglobin, and 1 case was δ thalassemia combined with δ abnormal hemoglobin. There were 7 HBD mutant genotypes were included, with -77(T>C) being the most common, followed by hemoglobin (Hb) A 2-Huadu and CD34(+GGT); accounting for 68.2% (15/22), 9.1% (2/22), 9.1% (2/22). CD34(+GGT) was a newly discovered genotype, and CD7(GAG>TAG) was the first reported genotype in Chinese population. The Hb content, mean corpuscular volume, and mean corpuscular hemoglobin content were normal or nearly normal in 22 carriers of the HBD gene mutation; capillary electrophoresis demonstrated reduced Hb A 2 content in all cases. Conclusions:HBD gene mutations have been detected in the prenatal population in Xiangtan City, with -77(T>C) being the most common mutation genotype. None of the mutation carriers showed anemia.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].

Background:The musk glands of adult male Chinese forest musk deer(Moschus berezovskii Flerov,1929)(FMD),which are considered as special skin glands,secrete a mixture of sebum,lipids,and proteins into the musk pod.Together,these components form musk,which plays an important role in attracting females during the breeding season.However,the relationship between the musk glands and skin of Chinese FMD remains undiscovered.Here,the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing(RNA-seq),and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin.Methods:A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted.Then,based on the anatomical structure of the musk gland,skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD.These tissues were used for RNA-seq,hematoxylin-eosin(HE)staining,immunohistochemistry(IHC),western blot(WB),and quantitative real-time polymerase chain reaction(qRT-PCR)experiments.Results:Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod,while juvenile FMD did not have any well-developed musk pods.Transcriptomic data revealed that 88.24%of genes were co-expressed in the skin and musk gland tissues.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis found that the genes co-expressed in the abdomen skin,back skin,and musk gland were enriched in biological development,endocrine system,lipid metabolism,and other pathways.Gene Ontology(GO)enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division.Moreover,the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific.qRT-PCR and WB revealed that sex-determining region Y-box protein 9(Sox9),Caveolin-1(Cav-1),and androgen receptor(AR)were expressed in all three tissues,although the expression levels differed among the tissues.According to the IHC results,Sox9 and AR were expressed in the nuclei of sebaceous gland,hair follicle,and musk gland cells,whereas Cav-1 was expressed in the cell membrane.Conclusions:The musk gland of Chinese FMD may be a derivative of skin tissue,and Sox9,Cav-1,and AR may play significant roles in musk gland development.

The poor prognosis of triple negative breast cancer (TNBC) results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis, which is associated with high recurrence and short overall survival. Here we developed a strategy by employing tumor-targeted self-assembled nanoparticles to coordinately regulate BACH1 (BTB domain and CNC homology 1) and mitochondrial metabolism. The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative (BD) were used to prepare nanoparticles (BH NPs) followed by the modification of chondroitin sulfate (CS) on the surface of BH NPs to achieve tumor targeting (CS/BH NPs). CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites, glycolysis and metastasis-associated proteins, which were related to the inhibition of BACH1 function. Meanwhile, decreased mitochondrial membrane potential, activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism. In a xenograft mice model of breast cancer, CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs. In sum, the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.

Objective To observe the effect of brain-derived microvesicles (BDMVs) on cytoskeleton in human umbilical vein endothelial cells (HUVECs).Methods BDMVs were prepared in vitro and identified by transmission electron microscopy and particle size identification.HUVECs were co-cultured with PKH26-1abeled BDMVs for 0.5,1,and 2 h;flow cytometry was used to detect the phagocytosis of HUVECs for BDMVs at different time points.HUVECs cultured in vitro were divided into control group,BDMVs treatment group and nimodipine treatment group;cells in the BDMVs treatment group were given 1.5× 107/mL BDMVs;cells in the nimodipine treatment group were pretreated with 2 μg nimodipine (0.2 mg/mL) for 10 min,and then,given 1.5×107/mL BDMVs.After being stained with rhodamine-labeled phalloidin,the fluorescence intensity and number of stress fibers of fibroactin in HUVECs were observed by laser confocal microscopy.Results BDMVs had complete membrane structure with a diameter of 100-1000 nm under transmission electron microscopy.The proportion of cells phagocytizing BDMVs increased significantly with prolonged incubation time,enjoying significant differences (0.5h:22.7％±1.2％;1 h:52.3％±1.3％;2h:71.6％±1.9％,P＜0.05).Laser confocal microscopy showed that,as compared with the control group,the fluorescence intensity ofcytoskeletal protein was obviously increased and the number of stress fibers increased was obviously larger in the BDMVs treatment group.As compared with those in the BDMVs treatment group,the fluorescence intensity of cytoskeletal protein was decreased and the number of stress fibers was obviously smaller in the nimodipine group.Conclusion The role of BDMVs in phagocytosis of HUVECs becomes stronger as time being prolonged,and BDMVs phagocytosis leads to cytoskeletal remodeling,which can be partially blocked by nimodipine.

Objective:To develop a lung cancer risk prediction model for female non-smokers.Methods:Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation.Results:Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] ( P=0.004). Both the simple model ( PHL=0.287) and the metabolic index model ( PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion:By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.

Objective:To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis.Methods:The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared.Results:The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group ( P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different ( P<0.05). Further analysis by multivariate logistic regression showed that the male ( OR=5.742, P=0.010), SN ( OR=41.291, P<0.01) and pleural attachment ( OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN ( P<0.01), showing round lesions with well-defined margin, attaching the pleura ( P<0.05). Conclusions:The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

Objective:To develop a lung cancer risk prediction model for female non-smokers.Methods:Based on the Kailuan prospective dynamic cohort (2006.05-2015.12), a nested case-control study was conducted. Participants diagnosed with primary pathologically confirmed lung cancer during follow-up were identified as the case group, and others were identified as the control group. A total of 24 701 subjects were included in the study, including 86 lung cancer cases and 24 615 control population, respectively. Questionnaires, physical examinations, and laboratory tests were conducted to collect relevant information. Multivariable-adjusted logistic regressions were conducted to develop a lung cancer risk prediction model. Area Under the Curve (AUC) and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration, respectively. Ten-fold cross-validation was used for internal validation.Results:Two sets of models were developed: the simple model (including age and monthly income) and the metabolic index model [including age, monthly income, fasting blood glucose (FBG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C)].The AUC (95%CI) [0.745 (0.719-0.771)] of the metabolic index model was higher than that of the simple prediction model [0.688 (0.660-0.716)] ( P=0.004). Both the simple model ( PHL=0.287) and the metabolic index model ( PHL=0.134) were well-calibrated. The results of ten-fold cross-validation indicated sufficient stability, with an average AUC of 0.699 and a standard error (SD) of 0.010. Conclusion:By incorporating metabolic markers, accurate and reliable lung cancer risk prediction model for female non smokers could be developed.

Objective:To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis.Methods:The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared.Results:The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group ( P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different ( P<0.05). Further analysis by multivariate logistic regression showed that the male ( OR=5.742, P=0.010), SN ( OR=41.291, P<0.01) and pleural attachment ( OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN ( P<0.01), showing round lesions with well-defined margin, attaching the pleura ( P<0.05). Conclusions:The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.