Case report: A rare case of sintilimab-induced gastric stenosis and literature review

Sintilimab is a fully human IgG4 monoclonal antibody against programmed death-1 (PD-1) used to treat classical Hodgkin’s lymphoma and various solid tumors. With increasing use of sintilimab, some rare adverse reactions have been reported. Here, we report a case of a 50-year-old woman with squamous non-small cell lung cancer (NSCLC) (metastasis to pericardium and pleura) who received two cycles of 200 mg sintilimab immunotherapy combined with albumin-bound paclitaxel and carboplatin chemotherapy and one cycle of sintilimab monotherapy. She was diagnosed with Sjogren’s syndrome (with symptoms of fever, dry mouth, dysphagia, and eating difficulty) after three cycles’ treatment and received standard steroidal therapy. Prior to admission, the patient experienced severe stomach discomfort with vomiting and was hospitalized. Upper gastrointestinal iodine angiography showed significant gastric stenosis as well as lower esophageal stenosis. Subsequent ultrafine gastroscopy revealed ulceration at the stenotic site and an absence of normal peristalsis of the gastric wall. Pathological examination of the lesions showed reactive changes, including ulceration, fibrosis, and inflammatory cell infiltration. After multidisciplinary consultation, it was considered that the patient’s gastric stenosis with inflammatory fibrosis changes was due to a sintilimab-induced immune hyperinflammatory reaction. The patient had been treated with standard steroidal therapy since suffering from Sjogren’s syndrome, but the gastric stenotic changes were not relieved. The patient then received regular bouginage of esophago-cardiac stenosis under gastroscopy to physically reexpand the fibrous hyperplasia and stenotic site, enabling normal eating function. To our knowledge, this is the first case of gastric stenosis in a patient with squamous NSCLC after using sintilimab and may help clinicians better understand potential immune-related adverse events due to sintilimab and improve assessment and management

Molecular evolution of the H6 subtype influenza a viruses from poultry in eastern China from 2002 to 2010

<p>Abstract</p> <p>Background</p> <p>Although extensive data demonstrates that the majority of H6 duck isolates belonged to a single H6N2 virus lineage with a single gene constellation in southern China from 2000 to 2005, the prevalence of H6N2 virus in poultry in Eastern China is largely unknown.</p> <p>Results</p> <p>Epidemiology revealed that H6N2 viruses were the most frequently detected influenza subtypes in live bird markets from 2002 to 2008 in Eastern China, but from 2009 onwards, they were replaced with novel H6N6 viruses. We phylogenetically and antigenically analyzed 42 H6 viruses isolated mainly in domestic ducks from 2002 to 2010 in Eastern China. Surprisingly, none of these isolates grouped with the previously described H6N2 viruses which belonged to a single H6N2 virus lineage with a single gene constellation in domestic ducks in southern China from 2000 to 2005. Two distinct hemagglutinin lineages were identified and they all underwent frequent reassortment with multiple virus subtypes from the natural gene pool, but few reassortants were persistent or prevalent.</p> <p>Conclusions</p> <p>Five subtypes of H6 influenza viruses (H6N1, H6N2, H6N5, H6N6 and H6N8) cocirculated in Eastern China, which form a significant part of the natural influenza virus reservoir in domestic ducks, and significant viral reassortment is still ongoing in this species.</p

Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota

Polycystic ovary syndrome (PCOS) is a common disease, affecting 8%–13% of the females of reproductive age, thereby compromising their fertility and long-term health. However, the pathogenesis of PCOS is still unclear. It is not only a reproductive endocrine disease, dominated by hyperandrogenemia, but also is accompanied by different degrees of metabolic abnormalities and insulin resistance. With a deeper understanding of its pathogenesis, more small metabolic molecules, such as bile acids, amino acids, and short-chain fatty acids, have been reported to be involved in the pathological process of PCOS. Recently, the critical role of gut microbiota in metabolism has been focused on. The gut microbiota-related metabolic pathways can significantly affect inflammation levels, insulin signaling, glucose metabolism, lipid metabolism, and hormonal secretions. Although the abnormalities in gut microbiota and metabolites might not be the initial factors of PCOS, they may have a significant role in the pathological process of PCOS. The dysbiosis of gut microbiota and disturbance of gut metabolites can affect the progression of PCOS. Meanwhile, PCOS itself can adversely affect the function of gut, thereby contributing to the aggravation of the disease. Inhibiting this vicious cycle might alleviate the symptoms of PCOS. However, the role of gut microbiota in PCOS has not been fully explored yet. This review aims to summarize the potential effects and modulative mechanisms of the gut metabolites on PCOS and suggests its potential intervention targets, thus providing more possible treatment options for PCOS in the future

Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects

Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can’t restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF

Toxicity of microplastics and nanoplastics: invisible killers of female fertility and offspring health

Microplastics (MPs) and nanoplastics (NPs) are emergent pollutants, which have sparked widespread concern. They can infiltrate the body via ingestion, inhalation, and cutaneous contact. As such, there is a general worry that MPs/NPs may have an impact on human health in addition to the environmental issues they engender. The threat of MPs/NPs to the liver, gastrointestinal system, and inflammatory levels have been thoroughly documented in the previous research. With the detection of MPs/NPs in fetal compartment and the prevalence of infertility, an increasing number of studies have put an emphasis on their reproductive toxicity in female. Moreover, MPs/NPs have the potential to interact with other contaminants, thus enhancing or diminishing the combined toxicity. This review summarizes the deleterious effects of MPs/NPs and co-exposure with other pollutants on female throughout the reproduction period of various species, spanning from reproductive failure to cross-generational developmental disorders in progenies. Although these impacts may not be directly extrapolated to humans, they do provide a framework for evaluating the potential mechanisms underlying the reproductive toxicity of MPs/NPs

Quelques contributions à l'analyse multifractale en théorie des fractions continues et à la transformée de Fourier des mesures

In this thesis, we are concerned with the Hausdorff dimension of sets of points with prescribed growth rate of partial quotients in continued fractions, and the decay rate of the Fourier transform of a class of probability measures.In the first part, we consider the real numbers whose partial quotients of the continued fractions are non-decreasing. The convergence exponent of such a number is defined as the convergence exponent of its sequence of partial quotients. We do multifractal analysis of the convergence exponents of these real numbers. The multifractal spectrum, which is a function to each level associated the Hausdorff dimension of the level set of convergence exponents, has been determined. It turns out that the spectrum is not differentiable at the level of exponent DOLLAR1DOLLAR. Thus an unusual phase transition of such spectrum appears. Meanwhile, as a complement of a result of Wang and Wu, we obtain the Hausdorff dimensions of some level sets related to the exceptional sets of Borel-Bernstein Theorem in continued fractions.In the second part, we focus on the infinite convolution on DOLLAR[0,1]DOLLAR defined by[mu=ast_{n=1}^{infty}left(frac{1}{2}(1+phi(n))delta_0+frac{1}{2}(1-phi(n))delta_{2^{-n}}right),]where DOLLARdelta_{x}DOLLAR is Dirac measure and DOLLARphiDOLLAR is a weight function defined on DOLLARmathbb{N}DOLLAR taking values in DOLLAR(0,1)DOLLAR. For any given weight function DOLLARphi(n)DOLLAR, we obtain the explicit pointwise rate of decay of the Fourier transform of the measure DOLLARmuDOLLAR. Our result generalizes a classical result of Hartman and Kershner. Using the methods of Cassels and Schmidt and applying the Davenport-ErdH{o}s-Leveque Theorem, we prove that almost all real numbers are absolutely normal with respect to DOLLARmuDOLLAR. As an application, we provide some new examples of measures whose rates of decay of their Fourier transform could be very slow, yet almost all real numbers are absolutely normal, which complements a result of Lyons on the set of non-normal numbers.Dans cette thèse on s'intéresse à la dimension de Hausdorff des points donc le taux de croissance des quotients partiels en fractions continues est prescrit, et au taux de décroissance pour la transformée de Fourier d'une classe de mesures de probabilité. Dans la première partie, on s'intéresse aux nombres réels dont les quotients partiels des fractions continues sont croissants. L'exposant de convergence d'un tel nombre est défini par l'exposant de convergence de sa suite de quotients partiels. On cherche à réaliser l'analyse multifractale de cet exposant de convergence. Ce spectre multifractal, qui à un certain DOLLARhinmathbb{R}DOLLAR associe la dimension de Hausdorff des points d'exposant de convergence DOLLARhDOLLAR, a été calculé. Il résulte de cette '{e}tude que le spectre multifractal n'est pas différentiable au point DOLLARh=1DOLLAR. En conséquence, on observe une transition de phase dans le spectre. D'autre part, en complément d'un résultat de Wang et Wu, on obtient les dimensions de Hausdorff de certains ensembles de niveaux associés aux ensembles exceptionnels issus du théorème de Borel-Bernstein sur les fractions continues. La seconde partie traite la convolution infinie de mesures sur DOLLAR[0,1]DOLLAR définie par[mu=ast_{n=1}^{infty}left(frac{1}{2}(1+phi(n))delta_0+frac{1}{2}(1-phi(n))delta_{2^{-n}}right),]où DOLLARdelta_{x}DOLLAR désigne la mesure de Dirac au point DOLLARxDOLLAR et DOLLARphiDOLLAR est une fonction de poid définie sur DOLLARmathbb{N}DOLLAR et à valeurs dans DOLLAR(0,1)DOLLAR. Pour toute fonction de poid DOLLARphiDOLLAR, on obtient explicitement le taux de décroissance ponctuel de la transformée de Fourier de la mesure DOLLARmuDOLLAR. Notre résultat généralise un résultat classique de Hartman et Kershner. En utilisant la méthode de Cassels et Schmidt et en appliquant le Théorème de Davenport-ErdH{o}s-Leveque, on prouve que DOLLARmuDOLLAR-presque tout nombre réel est absolument normal. En application, on fournit de nouveaux exemples de mesures dont le taux de décroissance de la transformée de Fourier peut être très lent, et pour laquelle presque tout nombre est absolument normal, ce qui complète un résultat de Lyons concernant l'ensemble des nombres non normaux