Correspondence to Professor Wenjie Zheng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical ...College, Beijing 100730, China; wenjzheng@gmail.com Behçet’s syndrome (BS) is a chronic inflammatory disease characterised by recurrent oral and genital ulcers, frequently complicated with uveitis gastrointestinal, neurological, major vessel and cardiac involvement. AA, aortic aneurysm; ADA, Adalimumab; AR, aortic valve regurgitation; ARD, aortic root dilation; AZA, azathioprine; COL, colchicine; CS, corticosteroids; CSA, ciclosporin; CTX, cyclophosphamide; G, genital ulcer; GOL, golimumab; IFX, infliximab; LEF, leflunomide; MDS, myelodysplastic syndrome; MDS, myelodysplastic syndrome; MMF, mycophenolate mofetil; MTX, methotrexate; O, oral ulcer; PE, pulmonary embolism; PH, pulmonary hypertension; PVL, postoperative paravalvular leakage; S, skin; SASP, salazosulfapyridine; TAC, tacrolimus; TCZ, tocilizumab; THD, thalidomide; V, vascular. Transcriptome analysis in patients with BS demonstrates that Th17-related genes and type I interferon-inducible genes were upregulated, and JAK/STAT signalling was activated through Th1/Th17 cytokines.7 Tofacitinib inhibited STAT1 and T-bet phosphorylation and suppressed Th1 and Th17 cell differentiation.8 As expected, our data showed that tofacitinib was effective for relieving the clinical manifestations and improving laboratory parameters in patients with BS. Funding This work was supported by the National Natural Science Foundation of China (grant number 81871299); CAMS Initiative for Innovative Medicine (grant numbers CIFMS2017-I2M-1-008 and CIFMS2016-I2M-1-013), National Key Research and Development Program: “Precise Medical Research” (grant number 2016YFC0906201).
Objective:
The aim of this study was to evaluate the effectiveness and safety of low-dose interferon alpha-2a (IFNα2a) in Behçet’s syndrome (BS) patients with refractory vascular/cardiac or ...neurological involvement.
Methods:
In this retrospective cohort study, we consecutively included 25 BS patients with refractory vascular/cardiac (n = 16) or neurological involvement (n = 9) who received IFNα2a treatment in our center between June 2018 and September 2021. The low-dose IFNα2a (3 million IU, every other day) was used as an add-on treatment with the continuation of glucocorticoids (GCs) and immunosuppressants.
Results:
In total, 25 patients (20 males, 5 females) with a mean age of 31.92 ± 9.25 years were included. IFNα2a was administered for BS patients with refractory vascular/cardiac involvement (n = 16) and neurological involvement (n = 9). Before the initiation of IFNα2a, patients had insufficient response or intolerance to conventional therapies. After a median follow-up of 23 interquartile range (IQR), 11–30 months, all patients achieved clinical improvement. The Behçet’s disease Current Activity Form (BDCAF) score improved significantly (5 versus 0, median, p < 0.0001). BS Overall Damage Index (BODI) and vasculitis damage index (VDI) remain stable (p > 0.05). Decrease in erythrocyte sedimentation rate ESR; 24 (IQR, 12–43.5) versus 5 (IQR, 2.75–10.5) mm/h, p = 0.0001 and C-reactive protein CRP; 6.64 (IQR, 3.67–19.82) versus 1.24 (IQR, 0.24–3.12) mg/liter, p < 0.005 was achieved effectively. The median GCs dosage tapered from 26.25 (IQR, 11.88–41.25) to 10.00 (IQR, 7.50–10.63) mg/d, p < 0.0001. Immunosuppressants were also reduced in number (p < 0.005). No serious adverse events were observed during follow-up.
Conclusion:
Our study suggests that low-dose IFNα2a, combined with GCs and immunosuppressants, is well-tolerated and effective for BS patients with refractory vascular/cardiac or neurological involvement and has a steroid- and immunosuppressant-sparing effect.
ObjectiveTo develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI).MethodsA draft of index items for assessing organ damages in patients with IgG4-RD was ...generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters.ResultsIgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91).ConclusionThe IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.
In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no ...standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib. .
Purposes
In patients with advanced lung cancer, immune checkpoint inhibitors (ICIs) dramatically extended survival. We aimed to investigate the experiences of patients with advanced lung cancer who ...are receiving ICIs, with a focus on perceptions and sentiments on ICIs, to inform future research and clinical care.
Methods
Patients were recruited from January to July 2022 at Tianjin Medical University Hospital Cancer Institute & Hospital. The method of purposive sampling was used. Patients with stage IV lung cancer who were taking ICIs as a single therapy were recruited. Data were gathered using semi-structured and face-to-face interview. An inductive approach to analysis was used.
Results
Of the 42 eligible patients, 27 were invited, 20 agreed to participate, and ultimately 17 patients completed the interview. A total of 5 themes were extracted: suffered from adverse effects but generally tolerable; focus on survival, hope, and expectation; uncertainty about durability of response and the future; poor knowledge and attitude of ICIs; and financial stress and guilt over family.
Conclusion
These findings make an important contribution to healthcare professionals’ understanding of what it is like to be a patient with advanced lung cancer who is receiving ICIs. In general, the experience of immunotherapy is different from that of chemotherapy; financial and family pressures and uncertainty issues are likely to be heavier in this population. Oncology specialist nurses should provide tailored education to improve the patient’s knowledge of immunotherapy, especially to improve risk awareness of immune-related adverse events and objective prognosis expectations.
•A novel photoelectrochemical aptamer sensor was successfully constructed.•The work conditions of sensor based on rare-earth doped Bi2WO6 and Ag2S were optimized.•The aptamer sensor exhibited good ...detection specificity, stability and reproducibility.•This study provides a rapid detection method of Vibrio parahaemolyticus.
In this work, layer-by-layer self-assembly method was used to construct the working electrode of the photoelectrochemical (PEC) aptamer sensor. Rare-earth doped Bi2WO6 (BWO-1) and Ag2S are combined as highly efficient photoactive material to reduce the recombination rate of electron-hole pairs and enhance the photocurrent responsiveness under visible light. The PEC aptamer sensor, with BWO-1 concentration of 12 mg/mL, AgNO3 concentration of 0.14 mol/L, ascorbicacid (AA) concentration of 0.13 mol/L, pH value of 7.4, aptamer concentration of 2 μmol/L, and incubation time of 50 min, had an optimal photocurrent responsiveness. The developed method showed a wide linear range from 3.2 × 102 CFU/mL to 3.2 × 108 CFU/mL. The detection limit was 40 CFU/mL. The constructed PEC aptamer sensor exhibited good detection specificity, stability and reproducibility for Vibrio parahaemolyticus and provided a simple, low-cost and rapid detection strategy for prevention and control of foodborne diseases. This method could be promising for the rapid detection of other food-bornepathogenicbacteria in the food.
Blockchain technology resolves the bottleneck of traditional centralized data storage technology. It can better facilitate the seamless operation and supervision of port cold chain logistics and can ...meet the massive business demand for cold chain imports and the surging demand for pandemic prevention and control. However, it is a challenging task to incentivize cold chain enterprises in the maritime industry to adopt blockchain technology and actively participate in information sharing platform. Using evolutionary game theory, through an analysis of evolutionary stability strategies, this paper explores the evolutionary path of port cold chain logistics enterprises that participate in information sharing. An incentive mechanism based on blockchain smart contract is designed to encourage cold chain logistics enterprises to actively participate in information sharing within chains. Smart contracts can continuously encourage enterprises to participate in information sharing by timely adjusting the incentive participation costs of participating enterprises.
•A novel photoelectrochemical immunosensor for the detection of VP was assembled.•Ho3+ and Yb3+ doping TiO2 improved the photocurrent responsiveness of PEC sensors.•The working electrode based on ...CdSe QDs sensitized Ho3+/Yb3+-TiO2 was constructed.•PEC sensors had a detection limit of 25 CFU/mL, a detection range of 102–108 CFU/mL.•This study provides a promising rapid and ultrasensitive detection method for VP.
A novel photoelectrochemical (PEC) immunosensor based on CdSe quantum dots (QDs) sensitized Ho3+/Yb3+-TiO2 for the detection of Vibrio parahaemolyticus (VP) was assembled. The working electrode was constructed via the layer-by-layer (LBL) method with the Ho3+/Yb3+-TiO2, CdSe QDs, NHS/EDC, antibody of VP (anti-VP), bovine serum albumin (BSA) modified on the surface of the FTO in sequence. Ascorbic acid (AA) acts as an electron donor to combine photogenerated holes in order to provide a stable current system. Ho3+ and Yb3+ co-doping TiO2 broadened the spectral response range of TiO2 to the infrared region and improved the photocurrent responsiveness of TiO2. The PEC immunosensor, with Ho3+/Yb3+ ratio of 1:5, Ho3+/Yb3+-TiO2 of 2 mg/mL and PBS solution of pH 7.4, had an optimal photocurrent responsiveness. Immobilization of anti-VP was by classical NHS/EDC coupling reactions between COOH groups of CdSe QDs and NH2 groups of the anti-VP. The results indicated that PEC immunosensors had a low detection limit of 25 CFU/mL, a wide detection range of 102–108 CFU/mL, high stability, low price, and short detection time. This method could be promising for the rapid and ultrasensitive detection of pathogenic microorganisms in the food.
Traditionally, vessel air emissions are monitored onboard vessels or at fixed points at sea. These methods are not cost-effective for implementing emission control laws that address air pollution ...monitoring of vessels travelling over a large body of water. Unmanned aerial vehicles (UAVs) equipped with pollution monitoring sensors are becoming a research focus. However, due to battery capacity constraints, the monitoring scope of UAVs is still not optimal. Thus, using a ship (such as a patrol ship) as a UAV mobile supply base can overcome battery limitations and increase monitoring coverage. This paper investigates the joint routing and scheduling problem of ship-deployed multiple UAVs (SDMUs) for the monitoring of pollution from vessels. The artificial bee colony (ABC) algorithm based on simulated annealing is employed to minimize the total monitoring time. The model and solution algorithm are verified by real-time dynamic vessel data from Tianjin Port.
The spotted knifejaw (Oplegnathus punctatus) is an emerging economical aquaculture species in China in recent years. In the present study, we characterized an iridovirus-like disease outbreak in ...spotted knifejaw aquaculture industry in Shandong Province (SKIV-SD), China. SKIV-SD induced severe cytopathic effect (CPE) in spotted knifejaw brain (SKB) cells as the infection proceeded. Moreover, electron microscopic observation showed the abundant hexagonal virus particles of ~140 nm in diameter in the cytoplasm of infected SKB cells. After challenge with SKIV-SD, the cumulative mortality rate was up to 100% at 9 days post-infection. And the diseased spotted knifejaw displayed pathognomonic microscopic lesions, demonstrated by basophilic cytoplasmic inclusions in spleen and kidney which was a general sign of megalocytivirus infection. Using Illumina NovaSeq system, we assembled the sequence data, and annotated the full genome of SKIV-SD, which was composed of 111,198 bp and contained 116 ORFs. Phylogenetic analyses based on 4 iridovirus core genes, including major capsid protein (MCP), myristylated membrane protein (MMP), DNA polymerase and ribonuclease III genes indicated that SKIV-SD shared the nearest relationship to infectious spleen and kidney necrosis virus (ISKNV). Moreover, the genome co-linearity analysis indicated that the gene orders and gene spacing of 25 iridovirus core genes were conserved between SKIV-SD and ISKNV. Together, our data speculated that SKIV-SD, an ISKNV-type megalocytivirus, was a lethal viral pathogen to cultured spotted knifejaw.
•An ISKNV-type megalocytivirus, SKIV-SD was isolated from diseased spotted knifejaw.•SKIV-SD replicated well in spotted knifejaw brain (SKB) cells.•SKIV-SD genome was composed of 111,198 bp and contained 116 ORFs.•Phylogenetic analyses indicated that SKIV-SD shared the nearest relationship to ISKNV.•SKIV-SD genome shared the conserved co-linearity with ISKNV.
