Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

[Untargeted metabolomics study of dexamethasone-induced congenital cleft palate in New Zealand rabbits].

Objective: To investigate the metabolic disorders in placental tissues of dexamethasone induced cleft palate mode. Methods: Twelve pregnant rabbits were randomly divided into dexamethasone group (experimental group, 8) and saline control group (4), and a certain amount of dexamethasone and saline were administered intramuscularly to the experimental and control groups respectively from embryonic days (ED) 13 to 16, and placental tissue samples were collected on day 21 of gestation. The corresponding profiles of the embryonic placental tissue samples were obtained by liquid chromatography-triple tandem quadrupole(LC-MS), and the metabolites of the embryonic placental tissues were characterized by principal component analysis among the dexamethasone-treated group with cleft palate (D-CP group), the dexamethasone-treated group without cleft palate (D-NCP group) and the control group. Results: There were significant metabolic differences among the D-CP group, D-NCP group and control group, with a total of 133 differential metabolites (VIP>1, P<0.05) involving in important metabolic pathways including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism, and galactose metabolism. The four metabolites, vitamin B6, galactose, lysine and urea, differed among the three groups (P<0.05). There were significant differences in vitamin B6 (0.960±0.249, 0.856±0.368, 1.319±0.322), galactose (0.888±0.171, 1.033±0.182, 1.127±0.127), lysine (1.551±0.924, 1.789±1.435, 0.541±0.424) and urea (0.743±0.142, 1.137±0.301, 1.171±0.457, respectively) levels among control group, D-NCP group and D-CP group (F=5.90, P=0.008; F=5.59, P=0.009; F=4.26, P=0.025; F=5.29, P=0.012). Conclusions: The results indicated that dexamethasone induced cleft palate may be highly correlated with metabolic disorders including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism and galactose metabolism.

[The study of mitochondrial disorder pedigree associated with FASTKD2 variants and uniparental disomy].

Objective: To analyse the genetic cause of a proband with mitochondrial disease caused by FASTKD2 gene variation and uniparental disomy. Methods: Detailed medical history of a child suspected "mitochondrial disease" were inquired in Peking University First Hospital on November 23, 2017. c.810_820dup homozygous variation in FASTKD2 gene was found by high-throughput sequencing, and her mother had heterozygous variation, but her father didn't have such variation, which didn't conform to the genetic law of variation. Further clinical examinations and molecular genetic tests were carried out. The venous blood of the child and her parents was drawn, and genomic DNA was extracted. Sanger sequencing, polymerase chain reaction (PCR) testing, short tandem repeat (STR) analysis, chromosome microarray analysis and loss of heterozygosity (LOH) genetic relationship analysis were performed on the proband and the parents to determine the variation. Results: The clinical manifestations, physical examination and laboratory examination of the child supported the diagnosis of mitochondrial disease. c.810_820dup(p.Ser274Phefs*8) homozygous variant in FASTKD2 gene was identified. Sanger sequencing indicated that the mother was a heterozygote of the variant, while the father had no such variation, which did not conform to the genetic law. PCR testing and Sanger sequencing review to eliminate sampling errors, PCR amplification and sequencing errors. Non-biological father was excluded by STR analysis. Three large segmental LOH of FASTKD2 gene were found by chromosome microarray analysis, then the LOH relative analysis verified the child was a mixed maternal uniparental disomy of chromosome 2. The child was diagnosed as mitochondrial disease caused by oxidative phosphorylation coupling defect of type 44. Conclusions: In this study, an autosomal recessive mitochondrial disease which does not conform to the genetic law was found, and it was confirmed that this mitochondrial disease family had both pathogenic variation and uniparental disomy phenomenon. It was diagnosed as mitochondrial disease caused by type 44 oxidative phosphorylation coupling defect.

Impact of Treatment Modality on Quality of Life Among Uterine Cancer Survivors.

AIMS: Our understanding of the impact of adjuvant therapy on longitudinal quality of life (QoL) following surgery for patients with uterine cancer is limited. The purpose of this study was to compare QoL in patients who have undergone surgery with or without radiation therapy for uterine cancer. MATERIALS AND METHODS: This was a cross-sectional cohort study that examined women treated for uterine cancer at MD Anderson Cancer Center from 2006 to 2017. Participants included those who underwent hysterectomy/bilateral salphingo-oophorectomy alone, with brachytherapy or external beam radiation therapy (EBRT). A non-cancer cohort of women who underwent a hysterectomy/bilateral salphingo-oophorectomy for benign indications was also identified (non-CA). To compare QoL we used the Functional Assessment of Cancer Therapy - Endometrial survey (FACT-En), a validated survey used to assess QoL. The survey has five subscales: physical, social, emotional, functional and an endometrial cancer-specific subscale. Cohorts were compared using ANOVA tests. RESULTS: In total, 309 women responded to the questionnaire (hysterectomy/bilateral salphingo-oophorectomy 64, brachytherapy 77, EBRT 96, non-CA 72). The median time from surgery to survey completion was 6.7 years. The mean total FACT-En score for the entire cohort was 144 [standard deviation 22]. Overall QoL was different between cohorts, with the EBRT cohort reporting the lowest QoL (mean 139.4 [21.6]) and the brachytherapy cohort the highest (150.6 [18.2], P = 0.006). Among patients who had undergone cancer treatment, the EBRT cohort reported the worst endometrial-specific QoL (53.5 [8.6]), while again the brachytherapy group reported the highest score (57.5 [6.1], P = 0.007). CONCLUSIONS: QoL differences in women who have undergone different treatments for uterine cancer may persist years after treatment. In women with endometrial cancer who require adjuvant therapy, brachytherapy does not appear to have any long-term detriments on QoL.

[Occurrence of live-born twins with birth weight-discordance and its relationship to the adverse birth outcomes].

Objective: To investigate the occurrence of live-born twins with birth weight-discordance and its relationship to adverse birth outcomes. Methods: A retrospective analysis was performed on 4 011 pairs of live-born twins in the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020. Based on the birth-weight discordance (∆BW, ∆BW=(birth-weightbig-birth-weightsmall)/birth-weightbig×100%)), twins were divided into 4 groups, including ∆BW≤15%,>15%-20%,>20%-25%, and>25%. The differences in maternal and neonatal outcomes among 4 groups were explored. Then the correlation between ∆BW and neonatal adverse outcomes were explored. Results: The ΔBW was 9 (4, 16)% and males were accounted for 53.8% (4 315 cases) of 4 011 pairs of twins. The gestational age was (35.3±2.7) weeks at birth. There were 2 908 pairs (72.5%) of twins with ΔBW≤15%, 481 pairs (12.0%) with ΔBW>15%-20%, 281 pairs (7.0%) with ΔBW 20%-≤25%, and 341 twin pairs (8.5%) with ΔBW>25%. With ∆BW of 20% as the diagnostic cutoff, the incidence of birth weight discordance was 15.5% (622/4 011). The proportion of natural births in the ∆BW≤15% group was higher than that in the ∆BW>15%-20% group (10.5% (288/2 740) vs. 6.3% (29/463), P<0.008 3). The ∆BW>25% group had a significantly higher prevalence of maternal hypertensive disorders during pregnancy than that of the other 3 groups (25.5% (87/341) vs. 16.7% (47/281) vs.17.3% (83/480) vs. 13.8% (400/2 899), all P<0.008 3). Univariate analysis found that the ΔBW>25% group had a lower gestational age and a higher rate of preterm birth than the other groups. The rate of extremely low birth weight (ELBW) or very low birth weight (VLBW), small for gestational age (SGA), and transferring to the department of neonatology in the smaller twins were significantly different among the 4 groups (all P<0.05). Multivariate analysis showed that higher degree of birth weight discordance was all positively associated with the rate of ELBW, SGA, and transferring to the department of neonatology in smaller twin, even after adjusting maternal age and gestational hypertension, year of birth, mode of delivery, gender, and gestational age (all P<0.05). Moreover, the Mantel-Haenszel test also indicated that there were significantly low to moderate correlations between ΔBW and the unfavorable outcomes (r=0.22, 0.53, 0.21, all P<0.001, respectively). The receiver operating characteristic (ROC) curve found that adverse birth outcomes would be well predicted by birth weight-discordant when the diagnostic cut-off of ΔBW was 12%-17%, with an acceptable sensitivity (0.53-0.78) and a high specificity (0.72-0.79). Conclusions: Birth weight discordant is not uncommon in live-born twins, and is associated with adverse outcomes including ELBW, SGA, and transferring to the department of neonatology in the small twins. Besides, the risk is linearly related to the increase of ΔBW. In the future, more researches are needed to explore the underline mechanism and long-term impact of birth weight discordance, to guide the prevention and management.

[Analysis of risk factors for gestational diabetes mellitus in elderly multipara women in the next pregnancy].

Objective: To investigate the risk factors for gestational diabetes mellitus (GDM) in elderly multipara women in the next pregnancy. Methods: A total of 219 elderly multipara women with 2 consecutive delivery records in Tianjin Binhai New Area Tanggu Obstetrics and Gynecology Hospital from January 2018 to May 2019 were included. Among them, 141 had normal glucose tolerance (NGT) and 78 of them had GDM. The clinical data of the previous and current pregnancy were collected to analyze the risk factors of GDM in elderly multipara women. Results: The average ages of 219 elderly women in previous pregnancy and this pregnancy were (31.9±2.2) and (36.7±1.5) years old, and the prevalence of GDM was 35.62% (78 cases). Compared to NGT group, GDM patients had higher fasting blood glucose(previous (5.51±1.43) vs (4.63±0.62) mmol/L; current (5.26±0.63) vs (4.59±0.30) mmol/L, 1 h blood glucose(previous (11.74±2.36) vs (9.50±1.82) mmol/L; current (11.03±2.03) vs (9.51±1.14) mmol/L) in 75 g oral glucose tolerance test (OGTT) in both previous and current pregnancy. The rates of cesarean section, in both previous and current pregnancy were higher in GDM group (previous 34.6% vs 4.3%; current 52.6% vs 22.0%). Furthermore, prenatal weight and body mass index (BMI) of the previous pregnancy, pre-pregnancy weight and BMI, and prenatal BMI of this pregnancy were also higher in GDM group, and the differences were all statistically significant (all P<0.05). Logistic multivariate regression analysis indicated cesarean section history (OR=10.80, 95%CI: (4.09-28.54)), GDM history of previous pregnancy (OR=10.64, 95%CI: (4.02-28.20)), 75 g OGTT fasting blood glucose≥ 4.86 mmol/L (OR=2.70, 95%CI: (1.27-5.70)), 1 h blood glucose after glucose administration ≥ 8.45 mmol/L (OR=1.78, 95%CI: (1.37-2.31)) were risk factors for GDM in elderly multipara women of this pregnancy. Conclusion: The risk of GDM in elderly multipara women with a history of cesarean section and GDM increases significantly. Results of OGTT in previous pregnancy also has predictive value.

Jak3 deficiency blocks innate lymphoid cell development.

Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1tm1Ven/LazJ mouse line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3, generating a SCID phenotype and an inability to generate antigen-independent professional cytokine-producing innate lymphoid cells (ILCs). Mechanistically, Jak3 deficiency blocks ILC differentiation in the bone marrow at the ILC precursor and the pre-NK cell progenitor. We further demonstrate that the pan-JAK inhibitor tofacitinib and the specific JAK3 inhibitor PF-06651600 impair the ability of human intraepithelial ILC1 (iILC1) to produce IFN-γ, without affecting ILC3 production of IL-22. Both inhibitors impaired the proliferation of iILC1 and ILC3 and differentiation of human ILC in vitro. Tofacitinib is currently approved for the treatment of moderate-to-severely active rheumatoid arthritis. Both tofacitinib and PF-06651600 are currently in clinical trials for several other immune-mediated conditions. Our data suggest that therapeutic inhibition of JAK may also impact ILCs and, to some extent, underlie clinical efficacy.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

[Distributions and associations between duration of sleep, daytime naps and insomnia symptoms among Chinese adults].

Objective: To investigate the distribution of sleep duration, daytime naps habits, and insomnia-related symptoms among participants from the China Kadoorie Biobank (CKB) study, and to examine the associations between the sleep-associated factors. Methods: A self-designed computer-based questionnaire was adopted to collect social-demographic information and lifestyle-related factors of the participants. A total of 452 829 Chinese adults aged 30-79 years, without self-reported histories of coronary heart disease, stroke, chronic obstructive pulmonary diseases or cancer, were included in this study. General linear regression and multinomial logistic regression models were used to estimate the distributions on duration of sleep, daytime naps habits, and insomnia-related symptoms in different populations, after adjusted for gender, age, and residential regions. Gender-specific logistic regression model was adopted to examine the associations between the above mentioned sleep-related factors. Results: The average sleep duration of the participants was 7.41 hours per day, with 20.3% of them having daytime naps all year round, but 40.1% only had daytime naps in summer, and 39.6% had no habits of daytime naps. 11.0%, 10.0%, and 2.1% of the participants reported having had symptoms as difficulty in falling asleep, waking up too early or with daytime dysfunction, respectively. There were significant differences on the distributions in sleep-related factors between participants with different gender, age, residential areas, education levels,household income, and marital status (P<0.05). Results from the logistic regression showed that longer sleep duration was associated with lower risks of insomnia-related symptoms trend (P<0.001). Factor as without habits of daytime naps seemed to be associated with higher risks of insomnia-related symptoms (P<0.05). Participants with longer sleep duration were more likely to have the habit of taking daytime naps (P<0.05). Conclusions: The distributions of sleep duration, habits on daytime naps and insomnia-related symptoms varied according to the differences on social-demographic factors. There were associations existed between the sleeping-related factors, which would influence the promotion on optimal sleep duration and better quality of sleep.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

[Present situation and analysis of murine allergic rhinitis model].

There have been 20 years of history in the study of allergic rhinitis(AR) using a mice model. At present, the AR mice model still exists some problems in the selection of mice strains, allergens and adjuvant types, molding cycle, allergen dose, model judgment, and so on, which affects the authenticity and comparability of the research results. By gradually solving the problems existing in the mice AR model, it is of great significance to realize the standardization of AR model, and the depth of the AR research.

[Association between age at menarche and height and leg length in adult women: findings from survey in 10 areas in China].

Objective: To describe the regional differences and secular trend in age at menarche, height and leg length in adult women aged 30-79 years in 10 areas included in China Kadoorie Biobank study (CKB), and evaluate the association between age at menarche and height and leg length in adult women in China. Methods: A total of 285 187 women, who had data on age at menarche and who had their menarche at the age between 9-18 years, were included in the analysis. Multiple linear regression models were used to assess the association between age at menarche and height and leg length. Subgroup analyses were performed for different birth cohorts and living areas (urban area or rural area). Results: The overall means (standard deviation) of age at menarche, height and leg length were 15.2 (±1.7) years, 154.2 (±6.0) cm and 71.0 (±3.7) cm, respectively. A significant increasing trend was observed in the mean height and leg length in different birth cohorts(trend: all P<0.001), while a decreasing trend was observed in the mean age at menarche, except for a slight increase in women born in 1940s (trend: P<0.001). Adjusted for age, study area, educational level and hip circumference (only for models for leg length), the average height and leg length in women increased by 0.17 cm and 0.20 cm, respectively, for each later age at menarche (both P<0.001). The positive associations between age at menarche and both height and leg length were stronger in younger birth cohorts (interaction: both P<0.001). Conclusion: Age at menarche was positively associated with height and leg length in women in 10 areas included in CKB study.

[Effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis].

Objective: To study the effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis(AR).Method:Selected 97 cases diagnosed as moderate to severe persistent AR patients, were treated with specific immunotherapy for one year. All patients received the evaluation with symptom check list 90(SCL-90) and rhinoconjunctivitis quality of life questionnaire(RQLQ) before specific immunotherapy, six, and 12 months after specific immunotherapy.Result:The total scores, scores of somatization, obsessive, anxiety, depression and phobia in SCL-90 of AR patients after 12 months treatment were significantly lower than that before treatment（P < 0.05）. Total score of quality of life and subitem score in RQLQ of AR patients after 12 months treatment were obviously lower than that before treatment (P < 0.05）.Conclusion:Specific immunotherapy can effectively alleviate the clinical symptoms and improve psychological health level and quality of life of AR patients.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

ZNF322A encoding a classical Cys2His2 zinc finger transcription factor was previously revealed as a potential oncogene in lung cancer patients. However, the oncogenic role of ZNF322A and its underlying mechanism in lung tumorigenesis remain elusive. Here we show ZNF322A protein overexpression in 123 Asian and 74 Caucasian lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for a poor outcome in lung cancer, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients. Overexpression of ZNF322A promoted cell proliferation and soft agar growth by prolonging cell cycle in S phase in multiple lung cell lines, including the immortalized lung cell BEAS-2B. In addition, ZNF322A overexpression enhanced cell migration and invasion, whereas knockdown of ZNF322A reduced cell growth, invasion and metastasis abilities in vitro and in vivo. Quantitative proteomic analysis revealed potential ZNF322A-regulated downstream targets, including alpha-adducin (ADD1), cyclin D1 (CCND1), and p53. Using luciferase promoter activity assay combined with site-directed mutagenesis and sequential chromatin immunoprecipitation-PCR assay, we found that ZNF322A could form a complex with c-Jun and cooperatively activate ADD1 and CCND1 but repress p53 gene transcription by recruiting differential chromatin modifiers, such as histone deacetylase 3, in an AP-1 element dependent manner. Reconstitution experiments indicated that CCND1 and p53 were important to ZNF322A-mediated promotion of cell proliferation, whereas ADD1 was necessary for ZNF322A-mediated cell migration and invasion. Our results provide compelling evidence that ZNF322A overexpression transcriptionally dysregulates genes involved in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis.

Taxonomic Study of the Genus Apalacris Walker (Orthoptera: Catantopidae).

The research history of the genus Apalacris is reviewed; a key to all known species of the genus is given, and one new species, Apalacris eminifronta n. sp., and one new combination, Apalacris maculifemura (Lin & Zheng), are described. The new species is very closely related to Apalacris antennata Liang, but differs in the following characters: (1) tegmen longer, reaching apex of hind femur; (2) basal part of inner side of hind femur orange red; (3) frontal ridge more protruded, obviously depressed under median ocellus in lateral view; and (4) epiphallus bridge prominent, ancora shorter than anterior projection.

Two New Species of the Genus Criotettix Bolivar (Orthoptera: Tetrigidae), with a Key to the Species of the Genus from China.

Two new species of the tetrigid genus Criotettix Bolivar from China, namely Criotettix interruptaoides Deng & Zheng n. sp. and Criotettix shiwanshanensis Deng & Zheng n. sp. are described. An updated key to all known species of the genus from China is given.

A Review of the Genus Pielomastax Chang (Orthoptera: Eumastacoidea) from China with Description of a New Species.

The review of the genus Pielomastax is given. The genus consists of 14 species distributed in China. Pielomastax cladopygidium n. sp. is described from Shaanxi Province. An annotated list of species and key to species of Pielomastax is provided.