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

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.

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

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 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.

Sickle cell disease (SCD) is an imported disease, and patients with SCD have obviously higher incidence of cardiovascular and cerebrovascular diseases. Stroke in SCD patients is quite different from those caused by atherosclerosis, and treatments and secondary prevention methods are also unique. This article reviews the pathogenesis, treatment and prevention of stroke in SCD patients briefly, aiming to increase the domestic understanding of SCD combined with stroke.

Objective To investigate the effect of postoperative analgesia by using loxoprofen sodium on dental implant patients at different time points. Methods A total of 400 patients with dental implant treatment were divided into two groups by random number table method. The experimental group was firstly given loxoprofen sodium tablets (60 mg) in 30 minutes preoperatively, and the control group was firstly given on three hours after surgery (60 mg). Local anesthesia was used to all dental implant surgery. Using the Wong-Baker Smile Assessment method in operation and Numerical Rating Scale (NRS) in postoperative respectively to assess pain level in surgery and 3 h, 6 h, 12 h and 24 h after surgery. Results The percentages of painless patients of the experimental group and the control group in operation were 99%(198/200) and 97%(194/200), and there was no significant difference between them (χ2=2.041, P>0.05); the percentages of painless patients of the experimental group at 3 h, 6 h, 12 h after surgery were 60.5%(121/200), 79.0%(158/200), 83.5%(167/200), and the control group were 47.0%(94/200), 64.5%(129/200), 71.5%(143/200), and there was significant difference between the control group and the experimental group (χ2=14.255,15.447, 11.165, P=0.007, 0.004, 0.011); however, in the two groups, there was no significant difference at 24 h after surgery, the experimental group was 93.0% (186/200), the control group was 89.5% (179/200) (χ2=2.468, P>0.05). Conclusions Preoperative administration with loxoprofen sodium tablets can significantly reduce the risk of postoperative pain, and could be used as a conventional implant surgery analgesic program.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.