OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Developmental dyslexia (DD) is a prevalent learning disorder, and the KIAA0319 gene is a DD-associated gene, potentially affecting reading ability by influencing brain development. This review provides an overview of the impact of KIAA0319 gene on brain development in fish, non-primate mammals, primate mammals, and humans. In studies involving fish, the kiaa0319 gene was found to be expressed in the brain, eyes and ears of zebrafish. In mammalian studies, abnormal Kiaa0319 gene expression affected neuronal migration direction and final position, as well as dendritic morphology during embryonic development in rats, leading to abnormal white and gray matter development. Knocking down the Kiaa0319 gene impaired the primary auditory cortex in rats, resulting in phoneme processing impairment similar to DD. In mice, Kiaa0319 overexpression affected the neuronal migration process, causing delayed radial migration of neurons to the cortical plate. Knockout of the Kiaa0319 gene led to abnormal development of the gray matter in mice, resulting in reduced volume of the medial geniculate nucleus and then impacting auditory processing. In primate studies, research on marmosets found that KIAA0319 gene is expressed in the visual, auditory, and motor pathways, while studies on chimpanzees revealed that KIAA0319 gene abnormalities primarily affected the gray matter volume and microstructure of the posterior superior temporal gyrus, morphology of the superior temporal sulcus and gray matter volume of the inferior frontal gyrus. The impact of KIAA0319 gene on human brain development is mainly concentrated in the left temporal lobe, where abnormal KIAA0319 gene expression caused reduced gray matter in the left inferior temporal gyrus, middle temporal gyrus and fusiform gyrus, as well as reduced white matter volume in the left temporoparietal cortex. Abnormalities in KIAA0319 gene also led to decreased hemispheric asymmetry in the superior temporal sulcus. The above-mentioned brain regions are crucial for language and reading processing. It is analyzed that the abnormalities in the DD-associated KIAA0319 gene affect neuronal migration and morphology during brain development, resulting in abnormal development of subcortical structures (such as the medial geniculate nucleus and lateral geniculate nucleus) and cortical structures (including the left temporal cortex, temporoparietal cortex and fusiform gyrus) which are involved in human visual and auditory processing as well as language processing. Impairment of the medial geniculate nucleus affects the information transmission to the auditory cortex, leading to impaired phoneme processing. Abnormalities in the magnocellular layers within the lateral geniculate nucleus hinder the normal transmission of visual information to the visual cortex, affecting the dorsal visual pathway. The left temporal lobe is closely related to language and reading, and abnormalities in its gray matter and connections with other brain areas can affect the language and word processing. In summary, abnormalities in the KIAA0319 gene can partly explain current research findings on the cognitive and neural mechanisms of DD, providing a genetic basis for theoretical models related to DD (such as general sensorimotor theory and the magnocellular theory). However, the mechanism of developmental dyslexia is complex, and there are mutual influences between different DD-associated genes and between genes and the environment, which require further exploration.

Objective To investigate the changes of sex hormones,anti-Müllerian hormone(AMH)level and ovarian ultrasound imaging parameters in women of childbearing age,so as to analyze their predictive value for premature ovarian insufficiency(POI)and establish the predictive model.Methods A total of 1 968 women of childbearing age in The First Affiliated Hospital of Xi'an Jiaotong University from 2018 to June 2022 were selected as research subjects.Their sex hormones and AMH levels were detected,and ultrasonographic features of the ovary were detected,including antral follicle count(AFC),ovarian volume,ovarian cortical volume,ovarian medulla volume,the total area,ovarian cortical area,and ovarian medulla area.The changes in ovarian function status at different age were analyzed,and their predictive value for POI was explored.AMH combined with ovarian ultrasound imaging parameters was used to establish a model for predicting POI.Results Among the 1 968 subjects,the prevalence rate of POI was 3.10％.The prevalence rate of POI was significantly higher in 30-39 years old group than in 20-29 years old group(P＜0.05).The serum AMH level in 30-34 years old group was significantly lower than that in 20-24 years old group and 25-29 years old group(P＜0.05),and the serum follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels were significantly higher in 35-39 years old group than in 30-34 years old group(P＜0.05).The serum estradiol(E2)and AMH levels,AFC,ovarian volume,ovarian cortical volume,ovarian area,and ovarian cortical area were significantly lower than those in the 30-34 years old group(P＜0.05).The serum FSH and LH levels in POI group were significantly higher than women of the same age with normal ovarian function(P＜0.05),while the serum E2 and AMH levels were significantly lower than women of the same age with normal ovarian function(P＜0.05).The AFC,ovarian volume,ovarian cortical volume,ovarian medullary volume,ovarian area,ovarian cortical area,and ovarian medullary area in POI group were significantly lower than women of the same age with normal ovarian function(P＜0.05).The analysis results of the predictive value of hormone indicators for POI showed that AMH had the highest predictive value(AUC=0.957),followed by E2(AUC=0.840).Among the ultrasound imaging indicators,AFC had the largest predictive value(AUC=0.867),followed by ovarian cortical volume(AUC=0.835).The model established by AMH combined with ovarian ultrasound imaging parameters had a good predictive value for POI,and its sensitivity was 94.86％,specificity was 91.23％,AUC was 0.960,and the cutoff value was 12 points.Conclusion The prevalence of POI is high in women aged 30-39 years of reproductive age.The model established by AMH combined with ovarian ultrasound imaging parameters has certain predictive value for POI,especially for women in the occult stage,and thus deserves clinical attention.

Objective To investigate the characteristics of menopause-related symptoms and cognition status of menopausal hormone therapy(MHT)among menopausal women.Methods A total of 619 menopausal women with menopause-related symptoms who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University were selected as the study subjects.Data were collected by questionnaire to analyze the characteristics of menopause-related symptoms,and the menopausal women's cognitive status of MHT and therapeutic effects were explored.Results Among 371 perimenopausal women,the menopause-related symptoms with the top three rates were fatigue(69.81％),insomnia(66.85％),and hot flush-sweating(58.22％).Among 248 postmenopausal women,the menopause-related symptoms with the top three rates were hot flashes and sweating(64.11％),bone and joint pain(60.89％),and fatigue(56.85％).The incidence of insomnia and fatigue in postmenopausal women was significantly lower than that in perimenopausal women(P＜0.01),while the incidence of bone and arthralgia,urinary system infection,vaginal dryness and painful intercourse was significantly higher than that in perimenopausal women(P＜0.01).There was no significant difference in Kupperman score between perimenopausal and postmenopausal women(P＞0.05),but score degree distribution differed significantly(P＜0.05).Perimenopausal women had the highest proportion of mild score while postmenopausal women had the highest proportion of moderate score.There were significant differences in Kupperman score among postmenopausal women with different menopause ages,menopause years and menopause mode(P＜0.05).The earlier menopause age and shorter menopause years,the higher Kupperman score was;the Kupperman score was significantly higher in surgical menopause than in natural menopause(P＜0.05).Multivariate Logistic regression analysis showed that age of 45-54 years old,retirement or unemployment,spouse's disease or death,abnormal sexual life,and high education level were the risk factors for the occurrence of menopausal symptoms(P＜0.05);high family income and＞3 times/week exercise were the protective factors for the occurrence of menopausal symptoms(P＜0.05).The Internet was the way that accounted for the highest proportion of menopausal women's understanding of MHT(39.92％),and the tumor accounted for the highest proportion of menopausal women's concern about MHT(33.67％).There were 465 menopausal women without MHT contraindications(89.77％)who used MHT under the guidance of professional doctors,and their symptoms improved significantly after treatment(P＜0.05).Conclusion Menopausal women have obvious menopause-related symptoms,and the earlier the age,the shorter the menopause years and the more severe symptoms in the surgical menopause.Therefore,it is necessary to pay attention to the impact of menopause on the health of menopausal women and increase the use rate of MHT to improve the quality of life of menopausal women.

Objective:To investigate the possible pathogenesis and possible risk factors of tinnitus related to female menopause.Methods:From April 2016 to October 2016, 59 female patients with menopausal syndrome were diagnosed in the menopause comprehensive management clinic. Tinnitus and menopause questionnaires were conducted, based on whether having tinnitus, those patients were divided into two groups: tinnitus group and no tinnitus group. Age, body mass index (BMI), Kupperman menopausal index (KMI) score, follicle-stimulating hormone (FSH) level of patients in the two groups were analyzed. Menopausal symptoms, related medical history and possible related factors of tinnitus were statistically analyzed.Results:A total of 59 cases were collected, 22 of which were accompanied by tinnitus. The incidence of idiopathic tinnitus was 35.1% (20/57) because 2 cases of thyroid related tinnitus with clear etiology were removed. Complete data were obtained from 17 of 20 patients with idiopathic tinnitus and 26 of 37 patients without tinnitus. Age, BMI, menopause KMI score, hormone level, menopause symptoms and possible factors related to tinnitus were statistically analyzed between the two groups, and the incidence of headache was statistically different between the two groups ( χ2=9.098, P=0.003), but no other factors were statistically significant( P>0.05). The severity of insomnia and tinnitus were further analyzed ( χ2=2.841, P=0.417), and there was no significant difference between the two groups. Conclusion:Headache history may be one of the high risk factors for the occurrence of menopausal tinnitus.

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

OBJECTIVE: To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines. METHODS: Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy. RESULTS: Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G₀/G₁ phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified. CONCLUSION Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Wnt Signaling Pathway ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Apoptosis ; Drug Resistance, Multiple ; Membrane Proteins ; Cell Line, Tumor ; Cell Proliferation

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.
Humans ; RNA, Circular ; MicroRNAs/genetics* ; Neoplasms ; Hematologic Neoplasms/genetics* ; Biomarkers

Objective: To analyze the spatial temporal distribution characteristics of tuberculosis among high school students at county levels in Gansu Province from 2018 to 2022,so as to provide a scientific basis for tuberculosis prevention and control in schools. Methods: Tuberculosis data from high school students in counties (districts) reported in Gansu Province from 2018 to 2022 was collected from the Tuberculosis Information Management System and Infectious Disease Information Reporting System of the Chinese Disease Prevention and Control Information Management System. Demographic data of high school students in counties (districts) came from the General Management System of the Chinese Disease Prevention and Control Information Management System, and the spatial clustering of the reported incidence rate of pulmonary tuberculosis among high school students in Gansu Province in the past five years was analyzed using the methods of global spatial autocorrelation (Moran s I) and local indicators of spatial audocorrelation(LISA). Results: A total of 41 885 pulmonary tuberculosis cases were reported in various counties of Gansu Province From 2018 to 2022, with an average reported incidence rate of 32.81/100 000. During the same period, 1 170 high school students cases were reported, with an average reported incidence rate of 13.72/100 000. With the exception of 2020, the reported incidence rate of pulmonary tuberculosis among high school students was non random distribution in other 4 years, showed a moderate intensity of spatial clustering. From 2018 to 2022, most counties in Gansu Province reported that the incidence rate of pulmonary tuberculosis among high school students was 10.00/100 000 or below, the counties with reported incidence rate >40.00/100 000 were mainly distributed in Luqu County, Maqu County, Diebu County, Hezuo City, Xiahe County of Gannan Prefecture, Gangu County and Wushan County of Tianshui Prefecture, Wenxian County and Kangxian County of Longnan Prefecture, Huachi County of Pingliang Prefecture, Huanxian County of Qingyang Prefecture. The number of counties where the reported incidence rate of tuberculosis among high school students more than 30.00/100 000 gradually decreased from 2018 to 2022. In the past five years, the reported incidence rate of tuberculosis among high school students in all counties of Gannan Prefecture remained above 40.00/ 100 000 . The LISA analysis results showed that the high incidence areas were mainly concentrated in Gannan Prefecture. Conclusions The epidemic situation of pulmonary tuberculosis among high school students in Gansu province from 2018 to 2022 is still a serious condition, showing the characteristics of unbalanced regional distribution. The reported incidence rate shows a strong spatial clustering, and the hot spots are concentrated in the counties (districts) of Gannan prefecture in Gansu Province.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*