Search

Abstract This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

In this work, we have reported the biogenic supported silver nanoparticles over surface of magnetic Fe3O4 nanoparticles by using Pomegranate peel extract. The extract was used as a green reducing agent and an excellent stabilizer of the synthesized Ag NPs. Physicochemical characterization of the as-synthesized Fe3O4/Ag NPs was carried out through electron microscopy (SEM and TEM), energy dispersive X-ray spectroscopy (EDX), elemental mapping (WDX), vibrating sample magnetometer (VSM), X-ray diffraction (XRD) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). The anti-ovarian cancer effects of biologically synthesized Fe3O4/Ag NPs against ovarian cancer cell lines were assessed. The anti-ovarian cancer properties of the Fe3O4/Ag NPs could significantly remove NIH: OVCAR-3‎, ES-2‎, TOV-21G cancer cell lines in a time and concentration-dependent manner by MTT assay. The antioxidant activity of Fe3O4/Ag NPs was determined by DPPH method. The Fe3O4/Ag NPs showed the high antioxidant activity according to the IC50 value. It seems that the anti-human ovarian cancer effect of recent nanoparticles is due to their antioxidant effects. After clinical study, Fe3O4/Ag NPs bio-composite can be utilized as an efficient drug in the treatment of human ovarian cancer in humans.

IntroductionProper controlling gestational diabetes mellitus (GDM)-related gestational weight gain (GWG) during pregnancy can optimize pregnancy outcomes and improve postpartum glucose homeostasis. This study aimed to explore the existing intervention programs, the effects on pregnancy outcomes, and the experiences of weight management for GDM-related GWG in women with GDM.MethodsThis mixed-methods systematic review was retrieved from nine databases. The retrieval time was from the database construction to September 20, 2023, and all studies were published in English and Chinese. The included records used quantitative, qualitative, or mixed methods and reported original studies of weight-related intervention regimens, effects on pregnancy outcomes, and women’s experiences and perceptions. This review used a convergent segregated approach to synthesize and integrate research findings from Joanna Briggs Institute (JBI) mixed-methods systematic reviews.ResultsThere were 16 articles that met the inclusion criteria, and the articles came from seven different countries and included 23,997 women with GDM. The meta-analysis pooled outcomes for the incidence of weight gain exceeding the Institute of Medicine (IOM) recommendations after GDM diagnosis to delivery was 0.31% (95% CI 0.21-0.42). The effectiveness of GDM-related weight interventions in reducing weight gain after GDM diagnosis was supported by quantitative evidence. The GDM-related GWG below the IOM recommendations is a protective factor (OR=0.68, 95%CI 0.48-0.97) for large for gestational Age (LGA), and above the IOM recommendations is a risk factor (OR=1.62, 95%CI 1.15-2.27) for LGA. In addition, no significant statistical significance was found in the pooled outcomes of small for gestational age (SGA). Avoiding excessive weight gain helps to optimize neonatal birth weight, pregnancy outcomes, and maternal blood glucose levels. According to qualitative survey results, some women with GDM experienced weight stigma, and a positive relationship between healthcare providers and GDM women helped in weight management.ConclusionFollowing a diagnosis of GDM, weight management interventions positively affected GWG and pregnancy outcomes. In order to improve compliance and safety of weight management in women with GDM, criteria and interventions for weight gain associated with GDM need to be further explored and improved.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=404492, identifier CRD42023404492.

Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague–Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of “course simulation” type of oligospermia animal model.

IntroductionWomen with overweight or obesity and gestational diabetes mellitus (GDM) are at a high risk of developing type 2 diabetes mellitus (T2DM) and other metabolic diseases. Healthy postpartum lifestyles in women with GDM are important for effectively preventing early T2DM occurrence; however, few studies and guidelines focus in China on this issue.AimsThis qualitative study aimed to understand the puerperium experience and lifestyle of women with overweight/obesity and GDM.MethodsA face-to-face, in-depth, and semi-structured interview was conducted using a hermeneutical phenomenology method to collect data that were analyzed through thematic analysis.ResultsOut of 61 recruited women with overweight/obesity and history of GDM, 14 women underwent an interview and provided detailed descriptions of their lifestyle experiences during puerperium. The interview data were used to generate four themes—puerperium dietary behavior, weight perception and “confinement” behavior, family support, disease knowledge, and perceived risk—and nine sub-themes.ConclusionUnhealthy lifestyles, misconceptions about food, the conflict between physical activity and confinement behavior, a lack of social and family support, and low awareness of disease risk are all common among overweight/obese women with a history of GDM. Thus, we emphasized that healthcare providers should provide continuous preventive care from pregnancy to postpartum and promote long-term health in high-risk populations with a history of GDM associated with overweight/obesity.

Abstract Background Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed during adolescence and adulthood. Assessment of the long-term risks of the current drugs for ADHD treatment has been insufficient, and little is known concerning the long-term therapeutic effects of psychostimulants. Commercially available traditional Chinese medicine compound oral preparations [e.g., Dimu Ningshen (DMNS)] have been widely used in the clinical treatment of ADHD, but their influence on the interaction between gut microbes and potential metabolomes remains inconclusive. Methods We used a series of behavioral experiments to evaluate the behavioral effects of DMNS on adolescent and adult ADHD rats and used 16S rDNA sequencing of gut microbes and nontarget metabolomics to evaluate the potential pathogenesis of ADHD and explore the biological mechanism of DMNS in ADHD treatment. Results For the first time, DMNS was shown to reduce the excessive activity of adult and adolescent ADHD rats and improve the attention deficit of adult ADHD rats. DMNS improved the structural composition of the ADHD gut microbiota and reduced the abundance of Ruminococcaceae_NK4A214_group, Ruminococcus_2, and Eubacterium_nodatum_group. Simultaneously, DMNS increased the circulating levels of peripheral monoamine neurotransmitter precursors (e.g., phenylalanine) and reduced the circulating levels of peripheral fatty acid amides (e.g., oleamide). Finally, the changes in the ADHD serum metabolites were strongly correlated with the gut microbiota. Conclusion DMNS has a good effect in treating ADHD, and it may exert this effect by regulating the gut microbiota and affecting metabolites in the peripheral circulation.

Total gestational weight gain (GWG) is identified as a strong and potentially controllable predictor of long-term health outcomes in women with gestational diabetes mellitus (GDM) and infants. When the total GWG of women with excess weight/obesity and GDM does not exceed the Institute of Medicine (IOM) suggested range, neonatal birthweight outcomes may be favorable, but the evidence is limited. Therefore, the objective of this study was to evaluate the dose-response relationship between increased total GWG and the risk of neonatal birthweight in Chinese women with excess weight/obesity and GDM. This study obtained electronic medical records (EMR) from the hospital information system (HIS) of the Chongqing Health Center for Women and Children between July 2017, and June 2020. A retrospective study analyzed the effect of the total GWG of women with excess weight/obesity and GDM on neonatal birthweight. The dose-response relationship between total GWG and neonatal birthweight was studied using a generalized linear model and embedded restricted cubic splines (RCS). The average age of all women with GDM was 31.99 ± 4.47 years, and 27.61% were advanced maternal age (≥35 years). The total GWG among women with excess weight and obesity and GDM greater than the IOM recommendations were found in 42.96% and 58.62% of cases, respectively. Total GWG in women with excess weight and excessing the IOM recommended range is a risk factor for large gestational age (LGA) [adjusted odds ratio (aOR) 0.1.47, 1.08–2.01] and macrosomia (aOR 1.55, 1.04–2.31). In the obesity above group, excessive weight gain increased the risk of LGA (aOR 2.92, 1.33–6.41) and macrosomia (aOR 2.83, 1.03–7.72). We used an RCS to examine pregnant women with excess weight and GDM and discovered a linear dose-response relationship between total GWG and LGA/macrosomia. In women with excess weight and obesity, increases in total GWG above the lowest end of the IOM recommendations range (7 kg and 5 kg) were associated with an increased risk of LGA and macrosomia. Therefore, research is urgently needed to support maternal and newborn health to provide recommendations for the ideal weight increase in women with excess weight/obesity and GDM.

Abstract Natron-based glass was a vital part of material culture in the Mediterranean and Europe for nearly two millennia, but natron glass found elsewhere on the Eurasian Continent has not received adequate discussion, despite its influence on ancient Asian glass. Here we present a new interpretation of natron glass finds from both the West and the East. After establishing the compositional types and technological sequence of Mediterranean natron glass (eighth-second century BCE) using trace elements, we report the analysis of a mid-1st millennium BCE glass bead from Xinjiang, China, which was likely made with Levantine raw glass, and identify common types of stratified eye beads in Eurasia based on a compositional and typological comparison. Combining these findings, we propose that a considerable number of Mediterranean natron glass products had arrived in East Asia at least by the fifth century BCE, which may have been a contributing factor in the development of native Chinese glass-making. The swift diffusion of natron glass across Eurasia in the 1st millennium BCE was likely facilitated by a three-stage process involving maritime and overland networks and multiple forms of trade and exchange, indicating a highly adaptable and increasingly efficient transcontinental connection along the ‘Proto-Silk Road’.

The microwave scatterometer onboard the China-France Oceanography Satellite (CFOSAT Scatterometer, CSCAT) is the first rotating fan-beam scatterometer (RFSCAT) in operation. It is used to obtain the ocean surface wind field by measuring the backscattering coefficient over a large observation swath. To estimate the backscattering coefficient, the scatterometer needs to measure the scattered signal accurately. The process of removing noise from the echo signal (scattered signal plus noise) is called noise subtraction. Noise subtraction has a great influence on the measurement of the backscattering coefficient and subsequent wind field retrieval. Therefore, accurate noise subtraction is necessary and important. In this article, an improved noise subtraction method for CSCAT is proposed. According to the distribution characteristics of backscattering coefficients, noise correction factors are introduced to improve the noise subtraction of CSCAT. The ocean surface wind fields are obtained using the improved backscattering coefficient data, and the deviation of wind speed and direction are calculated by comparison with the European Centre for Medium Range Weather Forecasts wind fields. The results show that the improved noise subtraction method can lead to improvement of the quality of wind field effectively. In addition, based on the improved method of noise subtraction, a method of estimating the noise correction factor is proposed at a large incidence angle, furtherly improving the noise subtraction method. The results show that the proposed method is effective.

Objective: To introduce the emergency management of nursing human resources and supplies of a large general hospital when facing the outbreak of coronavirus disease 2019(COVID-19). Method: The Nursing Department of the hospital fully executed its functional authority to establish a three-level echelon of sustainable support, allocate human recourses dynamically, organize pre-service training, supervise the key working steps, formulate positive incentive methods, and deploy medical supplies scientifically. Result: By taking these strategies, the hospital effectively improved the coping capacity of the nursing team and played a positive role in the prevention and treatment of COVID-19. Conclusion: The emergency management of nursing human resources and material resources for COVID-19 of the hospital is successful. But several deficiencies were identified as well, which indicated that the hospital needs to establish an efficient emergency management system, and pay attention to the practice of nursing emergency plans to enhance coping capacities in public health emergencies.

Sleep disturbance is common in patients with cancer and is associated with poor prognosis. However, the effects of sleep deprivation (SD) on immune surveillance during the development of hepatocellular carcinoma (HC) and the underlying mechanisms are not known. This was investigated in the present study using mouse models of SD and tumorigenesis. We determined that acute and chronic sleep deprivation (CSD) altered the relative proportions of various immune cell types in blood and peripheral organs. CSD increased tumor volume and weight, an effect that was enhanced with increasing CSD time. Expression of the cell proliferation marker Ki-67 was elevated in tumor tissues, and tumor cell infiltration into adjacent muscles was enhanced by CSD. Multicolor flow cytometry analysis revealed that CSD significantly reduced the numbers of antitumor CD3+ T cells and natural killer (NK) cells and increased that of immunosuppressive CD11b+ cells infiltrating into the tumor microenvironment from the spleen via the peripheral blood. These results indicate that CSD impairs immune surveillance mechanisms and promotes immunosuppression in the tumor microenvironment to accelerate tumor growth, underscoring the importance of alleviating sleep disturbance in HC patients in order to prevent HC progression.

Protein post-translational modification (PTM) is an important mechanism that is involved in the regulation of protein function. Considering the high-cost and labor-intensive of experimental identification, many computational prediction methods are currently available for the prediction of PTM sites by using protein local sequence information in the context of conserved motif. Here we proposed a novel computational method by using the combination of multiple kernel support vector machines (SVM) for predicting PTM sites including phosphorylation, O-linked glycosylation, acetylation, sulfation and nitration. To largely make use of local sequence information and site-modification relationships, we developed a local sequence kernel and Gaussian interaction profile kernel, respectively. Multiple kernels were further combined to train SVM for efficiently leveraging kernel information to boost predictive performance. We compared the proposed method with existing PTM prediction methods. The experimental results revealed that the proposed method performed comparable or better performance than the existing prediction methods, suggesting the feasibility of the developed kernels and the usefulness of the proposed method in PTM sites prediction.

Background: Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change. Aim: To find out direct correlations between cold stress and ED, through which to further investigate the functional roles of B1R in erectile tissue and to elucidate the therapeutic roles of the B1R antagonist in a cold stress-induced ED rat model. Methods: Cold stress rat models are established through long-term intermittent exposure to low temperature. After their erectile function was assessed, ED rats were treated with the B1R antagonist through intraperitoneal injection. Penile tissues were obtained at the end of the experiment after measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP); the location and distribution of cytokine expression were determined by immunohistochemistry; cytokine levels and NOS and CD31 expression were detected by Western blotting; and collagen fibers and smooth muscles were observed through Masson staining. Outcomes: Cold stress impairs erectile function, and the B1R antagonist protects against it. Results: We observed decreased erection frequency, prolonged erection latency time, decreased ICP/MAP, overexpression of B1R, increased expression of cytokines on cavernous sinus endothelium, and increased levels of collagen fibers/smooth muscles on erectile tissue in response to cold stress. Also, NOS and CD31 expression was downregulated. B1R antagonist treatment shows enhanced erectile function through increased erection frequency, shortened erection latency time, and increased ICP/MAP. Also, it reduces collagen fibers/smooth muscles, TNF-a, TGF-ß1, and IL-6 and upregulates the expression of nNOS and CD31. Clinical Translation: Our findings cast new light on the correlations between cold stress and erectile function and potential new applications of existing B1R antagonist drugs in the field of ED. Strengths and Limitations: Our data support that cold stress impairs erectile function. B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it, and B1R inhibition protects against fibrosis and endothelial damage. Other ways of B1R antagonist blocking methods in different types of ED still need to be investigated. Conclusion: Long-term intermittent cold stress impairs erectile function, and B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it. B1R inhibition also protects against fibrosis and endothelial damage. Our data support the hypothesis that cold stress impairs erectile function and that B1R blockade ameliorates the symptoms of ED, possibly by reversing fibrosis and endothelial damage in erectile tissue. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of h(1) calponin mRNA expression on the biliary tract dynamics, and investigate the molecular mechanisms of gallstone formation in pregnancy., Methods: This study was carried out in Renmin Hospital of Wuhan University, and in the Department of Molecular Biology and Biochemistry, Wuhan University School of Medicine, Wuhan, China from July to December 2004. Thirty female guinea pigs were divided randomly into 3 groups, the nonpregnant group (n=10) (group A), the 30 days of pregnancy group (n=10) (group B), and the 60 days of pregnancy group (n=10) (group C). Animal models of pregnancy were established on pregnant group guinea pigs through feeding animals with one cage according to female versus male as 4:1. The total cholesterol (TC), total bilirubin (TBiL), total bile acid (TBA) in the bile and the serum estradiol (E(2)), progesterone (Pg) levels were determined respectively. Expression levels of h(1) calponin mRNA in gallbladder smooth muscles and Oddi's Sphincter (OS) were evaluated using semiquantitative reverse transcription polymerase chain reaction (RT-PCR)., Results: The concentration of TC, TBiL and the serum E(2) and Pg were more significantly increasing in group C than that in the other 2 groups. However, the concentration of TBA decreased gradually from group A to group C. Up-regulation of h(1) calponin gene expression was observed in the gallbladder smooth muscles in group C, but converse in OS., Conclusion: The h(1) calponin might play an important role in inducing dysfunction of extrahepatic biliary tract, bile stasis in gallbladder and gallstone formation in pregnancy.