OBJECTIVES: To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells. METHODS: The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both. RESULTS: LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown. CONCLUSIONS LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Cell Proliferation ; Cell Movement ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung ; Neoplasm Invasiveness ; A549 Cells ; Adenocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.

Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.

This paper proposed to understand the pathogenesis and provide syndrome differentiated treatment for anxiety and depression-related dry eyes from the perspective of the liver and the lung， in order to provide ideas for treatment of this disease with traditional Chinese medicine. It is believed that the occurrence and development of anxiety and depression-related dry eyes is related to the ethereal qi and blood damage and blocked circulation of qi and blood. The liver and the lung are the main located zang-fu （脏腑） organs of the disease， and the qi movement， sweat pores， meridians and collaterals abnormalities of the liver and the lung are the pathological basis. The basic pathogenesis is disharmony of the liver and the lung， loss nourishment of eyes， and loss calm of the mind. In clinical practice， the root treatment is to restore the functions of the liver governing ascent and the lung governing descent， and to open up the sweat pores， meridians and collaterals， while the branch treatment is to promote the production of body fluids， nourish yin and calm the mind. Both the root and the branch causes are treated to restore the physiological functions， and Danzhi Xiaoyao Powder （丹栀逍遥散） combined with Shengmai Powder （生脉散） with modification is often used as the basic prescription.

Objective:To investigate the iodine nutritional status, prevalence and distribution characteristics of thyroid nodules among children and adolescents in Jurong City, Jiangsu Province, and study the risk factors for thyroid nodules in children and adolescents.Methods:In 2021, a cluster sampling method was used to select one primary and one secondary school in the urban and rural areas of Jurong City, ≥150 children and adolescents were selected as survey respondents from each school on a class-by-class basis, including third-grade children in primary schools and seventh-grade adolescents in secondary schools. The basic information and mental health status of survey respondents were collected by basic information questionnaires and Children's Anxiety Related Emotional Disorders Screening Form (SCARED). Water samples were collected from schools where survey respondents were enrolled and from townships where schools were located, and the iodine content in the water were tested. At the same time, household salt and urine samples from survey respondents were collected to test the salt iodine and urine iodine. Thyroid volume and thyroid nodules were measured using B-ultrasound method to analyze goiter (swelling of the thyroid gland) and thyroid nodules. The Cochran-Armitage trend test method was applied for trend analysis, and a multivariate logistic regression model was used to analyze the risk factors for thyroid nodules.Results:A total of 710 children and adolescents (370 males and 340 females) were surveyed, including 347 children (169 males and 178 females) and 363 adolescents (201 males and 162 females). A total of 14 water samples were collected, with an iodine content range of 8.98 to 10.82 μg/L and a median iodine content of 9.98 μg/L. A total of 710 edible salt samples were tested, with a salt iodine content of (20.94 ± 1.94) mg/kg, an iodine salt coverage rate of 100.00%, and a qualified iodine salt consumption rate of 97.46% (692/710). A total of 710 urine samples were tested, with a median urine iodine of 288.13 μg/L, median urinary iodine for boys and girls was 310.29 and 245.12 μg/L, respectively, and the difference between the two was statistically significant ( Z = - 5.91, P < 0.001). A total of 710 children and adolescents were tested by B-ultrasound, and the detection rate of goiter and thyroid nodules was 2.25% (16/710) and 25.07% (178/710). There was no significant upward trend in the detection rate of thyroid nodules with age (χ 2trend = 0.45, P = 0.651). The detection rates of thyroid nodules in boys and girls were 20.00% (74/370) and 30.59% (104/340), respectively, and the difference between the two was statistically significant (χ 2 = 10.57, P < 0.001). Multivariate logistic regression analysis indicated that female students who participated in extracurricular tutoring/interest classes in the past month were two influencing factors for thyroid nodules in children and adolescents ( OR = 1.76, 1.54, 95% CI: 1.25 - 2.49, 1.09 - 2.17, P < 0.05). Conclusions:The iodized salt coverage rate, qualified iodized salt consumption rate, and goiter rate in children and adolescents in Jurong City have all reached the elimination standard for iodine deficiency disorders, and their iodine nutrition is at a super-appropriate level. However, the external environment of Jurong City is still iodine-deficient. The detection rate of thyroid nodules in children and adolescents is at a high level. Female students and those who have participated in extracurricular tutoring/interest classes in the past month are risk factors for thyroid nodules in children and adolescents.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

BACKGROUND: Acquired and primary resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is still the bottleneck of clinical treatment of advanced non-small cell lung cancer (NSCLC). STE029 is a novel anticancer drug which consists of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) inhibitor and novel cancer cell membrane targeting molecular. This study aimed to investigate the reversal mechanism of EGFR-TKI resistance by STE029 in lung adenocarcinoma. METHODS: CCK8 test was used to test the cell viability and survival rate of EGFR mutated PC9 cell (Gefitinib sensitive), PC9/BB4 cell (acquired Gefitinib resistant), and EGFR wild type A549 cell after treatment of STE029, Gefitinib or combination of both. EdU test was applied to detect changes in cell cycle and Hoechst 33258 was applied to detect apoptosis rate in overcoming the EGFR-TKI resistance. The activity of EGFR/PI3K/Akt, cell cycle and apoptosis signal pathways were examined. In vivo, nude mice were exposed to STE029, Gefitinib and STE029+Gefitinib for 5 wk. And the the tumor volume was measured and tumor weight was obtained on the last day. RESULTS: (1) PC9 cells was highly sensitive to Gefitinib, while PC9/BB4 and A549 cell showed significant resistance to Gefitinib treatment; (2) STE029+Gefitinib treatment could significantly decrease the 50% inhibitory concentrarion (IC₅₀) of Gefitinib in PC9, PC9/BB4 and A549 cells (P<0.05, respectively); (3) In PC9 and PC9/BB4 cells, STE029+Gefitinib can block cell cycle and inhibit cell proliferation (P<0.001), while there was no significant difference in apoptosis rate among three drug intervention groups (P>0.05); However, apoptosis rate was increased in STE029+Gefitinib group in A549 cell (P<0.01), while no significance detected in cell proliferation (P>0.05). (4) In PC9 and PC9/BB4 cells, the combination of STE029 and Gefitinib could downregulate p-EGFR, p-Akt, p-Cyclin D1 and Cyclin D1 (P<0.001), and upregulate the expression of GSK-3β (P<0.001), and the expression of cleaved caspase-8, caspase-8 cleaved caspase-9, caspase-9 showed no difference among groups (P>0.05). In A549 cells, the combination of STE029 and Gefitinib could downregulate p-Akt (P<0.001) and upregulate cleaved caspase-8 and cleaved caspase-9 (P<0.001); (5)In vivo, the combination of STE029 and Gefitinib effectively inhibited tumor development and progression compared to STE029 alone or Gefitinib alone, with significant difference (P<0.05) in PC9 and PC9/BB4 xenografted tumor. CONCLUSIONS STE029 could sensitize Gefitinib by inhibiting EGFR/PI3K/Akt pathway, blocking the tumor cell cycle and proliferation and inducing apoptosis through caspase-8 and caspase-9 dependent pathway. STE029 deserves further investigations in overcoming EGFR-TKI resistance in lung cancer.
Animals ; Mice ; Humans ; Gefitinib/pharmacology* ; Caspase 9 ; Caspase 8 ; Cyclin D1 ; Carcinoma, Non-Small-Cell Lung ; Glycogen Synthase Kinase 3 beta ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/drug therapy* ; Protein Kinase Inhibitors/pharmacology* ; ErbB Receptors/genetics*

OBJECTIVE: To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT). METHODS: Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus. RESULTS: The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus. CONCLUSION Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.
Female ; Genetic Counseling ; Humans ; Karyotyping ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

Objective:To predict the risk of systolic anterior motion (SAM) after mitral valvuloplasty(MVP) by intraoperative transesophageal echocardiography (TEE) and its diagnostic value.Methods:From August 2016 to May 2020, 215 patients with mitral valve degeneration underwent MVP, including 182 patients without SAM (non-SAM group), and 33 patients with SAM (SAM group). TEE examination was performed immediately after operation to determine whether SAM phenomenon was relieved. According to the physiological basis of SAM, before cardiopulmonary bypass (CPB) and immediately after CPB, the parameters of SAM group and non-SAM group were measured and compared, including left atrial dimension(LAD), left ventricular end diastolic diameter(LVEDD), left ventricular end systolic diameter(LVESD), left ventricular ejection fraction(LVEF), basal septal diameter(basal-IVDd), left ventricular posterior wall thickness(LVPW), left ventricular outflow tract diameter(LVOTD), left ventricular outflow tract maximum velocity(LVOT-Vmax), left ventricular outflow tract pressure gradient(LVOTG), mitral valve maximum velocity(MV-Vmax), mitral valve mean pressure gradient(MVG-mean), mitral regurgitation area(MR-area), bulging subaortic septum, anterior leaflet length, posterior leaflet length, ratio between the lengths of the anterior and posterior leaflets, coaptation-septum distance(c-sept), nnular diameter of mitral valve, aorto-mitral angle (AMA) to screen the independent risk factors of SAM after MVP.Results:① Compared with the non-SAM group, LVEDd, LVESD, ratio between the length of the anterior and posterior leaflets, c-sep and AMA decreased in SAM group (all P<0.05), while basal-IVDd, LVEF, posterior leaflet length and bulging subaortic septum increased in SAM group (all P<0.05). ②Compared with that before the "edge to edge" technique, LVOT-Vmax decreased from (4.31±2.26)m/s to (2.55±1.39)m/s, LVOTG decreased from (43.58±10.89)mmHg to (23.36±12.76)mmHg, MVG-mean increased from (0.46±0.33)mmHg to (2.27±0.43)mmHg, and MR-area increased from (3.52±0.79)cm 2 to (0.96±0.57)cm 2 (all P<0.05). ③Multivariate logistic regression analysis showed that independent risk factors of SAM were LVEDd<45.430 mm ( OR=0.267, 95% CI=0.084-0.847), basal-IVDd>14.870 mm ( OR=12.049, 95% CI=1.619-89.661), length ratio of anterior and posterior leaflets of mitral valve>1.371 ( OR=0.159, 95% CI=0.045-0.562), angle of bulging angulated subaortic septum>62.330°( OR=18.246, 95% CI=2.824-117.896), c-sept<23.965 mm( OR=0.177, 95% CI=0.05-0.628), and AMA<123.730°( OR=0.197, 95% CI=0.098-0.396). Conclusions:Intraoperative TEE can evaluate the risk factors of SAM before MVP, and find the SAM phenomenon after MVP in time, which is helpful for surgeons to prevent and correct SAM after MVP and avoid secondary operation.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.