Abstract Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological ...features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p = 0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p < 0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Wharton’s duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p < 0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary.
Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients ...remain largely unknown.
In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death.
A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010).
Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.
•We retrospectively studied clinical features of 28 severe Coronavirus Disease 2019 (COVID-19)-infected cancer patients from three hospitals in Wuhan, China.•We analysed risk factors associated with occurrence of admission to an intensive care unit, usage of mechanical ventilation, or death.•COVID-19-infected cancer patients presented poor outcomes with high occurrence of clinically severe event and mortality.•Antitumour treatment within 14 days of COVID-19 diagnosis increased the risk of developing severe events.
Objectives
The aim of this study was to investigate the predictive factors for relapse of IgG4‐related disease (IgG4‐RD) and observe the long‐term clinical outcomes in patients with IgG4‐RD.
Methods
...We included in the present analysis 122 patients who were newly diagnosed with IgG4‐RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded.
Results
The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re‐elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow‐up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day−1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re‐elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long‐term follow‐up.
Conclusions
The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re‐elevation of serum IgG4 levels and lower GC maintenance dosage at follow‐up might be predictive of relapse.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
Background
Thymic stromal lymphopoietin (TSLP), IL‐25, and IL‐33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP, IL‐25, ...IL‐33, and their receptors in type 2 T‐helper (Th) responses in chronic rhinosinusitis with nasal polyps (CRSwNPs) and their cross‐regulation in human nasal epithelial cells (HNECs).
Methods
Immunohistochemistry, quantitative RT‐PCR, ELISA, Bio‐Plex assay, and flow cytometry were used to detect the expression of TSLP/common γ‐like TSLP receptor (TSLPR)/IL‐7 receptor α (IL‐7Rα), IL‐25/IL‐17B receptor (IL‐17RB), and IL‐33/membrane‐bound ST2 (ST2L)/soluble ST2 (sST2) in sinonasal mucosa and HNECs. HNECs cultured at an air–liquid interface were used to explore the expression in regulation of these cytokine systems.
Results
Compared with controls and noneosinophilic CRSwNP, the expression of TSLP/TSLPR/IL‐7Rα and ST2L/sST2 was significantly increased in eosinophilic CRSwNP, predominantly in epithelial cells. In contrast, the expression of IL‐33 and IL‐25/IL‐17RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRSwNP compared to controls. The expression of TSLP, TSLPR, and ST2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRSwNP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST2L was correlated with TSLP and its receptor expression. TSLP could induce ST2L expression that promoted IL‐33‐induced TSLP expression in HNECs. In addition, TSLP/TSLPR/IL‐7Rα and ST2L could be induced by Th2 cytokines, while IL‐25/IL‐17RB and IL‐33 could be upregulated by Th1/Th17 cytokines, in HNECs.
Conclusions
The positive feedback loop between TSLP, IL‐33 and their receptors, and Th2 cytokines may facilitate Th2‐skewed inflammation in eosinophilic CRSwNP.
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 ...promises to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its 'undruggable' nature and potentially limited selectivity. In a previous study, we reported an improved in silico approach targeting the DBD of STAT3 that resulted in a small-molecule STAT3 inhibitor (inS3-54). Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1. In this study, we describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound (inS3-54A18) with increased specificity and pharmacological properties. InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Thus inS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics targeting the DBD of human STAT3 and DBD of transcription factors may not be 'undruggable' as previously thought.
Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected ...patients.
We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
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