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Background: Hydroxychloroquine (HCQ) has been used as a supportive therapy for IgA nephropathy (IgAN). We aimed to determine the long-term efficacy and safety of HCQ therapy in patients with IgAN. Methods: A total of 180 patients with IgAN who had received HCQ therapy for at least 1 year were enrolled in this study. The changes in proteinuria and the estimated glomerular filtration rate (eGFR) were analyzed during the follow-up period. Results: The level of proteinuria decreased from 1.69 [1.24, 2.30] to 1.01 [0.59, 1.74] g/day (− 37.58 [− 57.52, 8.24] %, P < 0.001) at 12 months and to 1.00 [0.59, 1.60] g/day (− 55.30 [− 71.09, − 3.44] %, P < 0.001) at 24 months. There was no significant change in the eGFR of these patients at 12 months (65.82 ± 25.22 vs. 63.93 ± 25.96 ml/min/1.73 m2, P = 0.411); however, the eGFR decreased from 65.82 ± 25.22 to 62.15 ± 25.81 ml/min/1.73 m2at 24 months (P = 0.003). The cumulative frequency of all patients with a 50% decrease in proteinuria was 72.78% at 12 months. Sixty (33.3%) patients changed to corticosteroid therapy during the follow-up period. No serious adverse effects were documented during HCQ treatment. Conclusions: HCQ effectively and safely reduces proteinuria in IgAN patients with different levels of eGFR, supporting the maintenance of stable kidney function in the long term. Graphic abstract:

Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.

The tumor microenvironment is a complex system that plays a vital role in proliferation, invasion and metastasis. In this work, an oxygen concentration gradient microfluidic chip was designed to construct an in vitromodel of tumor hypoxic microenvironment. The microfluidic chip was composed of two parts, one was a serpentine-shape channel for hypoxia reagent mix to generate oxygen gradient, the other part contained three parallel channels for the co-culture of cancer cells (Heap1-6 cells) and hepatic stellate cells (JS-1 cells). Using the microfluidic chip, oxygen gradient was created under the culture condition to simulate hypoxic tumor microenvironment in vivo. In the hypoxic gradient environment, the drug resistance of Hepa1-6 cells to paclitaxel and tirapazamine (TPZ) was studied and the potential molecular mechanism was supposed. The results showed that the concentration of oxygen gradient ranged from 2.3% to 16.7%. Under this hypoxic condition, the viability of co-cultured Hepa1-6 cells decreased significantly under TPZ intervention, while the Hepa1-6 cells expressed resistance to paclitaxel. The results of immunofluorescence assay showed that hypoxia and co-culture condition could promote the expression of TIMP-1 and TGF-β, which induced the activation of JS-1 cell and further enhanced the drug resistance of Hepa1-6 cell to paclitaxel.

Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN.

Heavy metals have been found to be endocrine disruptors in invertebrates. Lead is one of the most widespread elements of contamination, but there has been no research about the effects of lead stress on vitellogenin (Vg) gene expression in insects exposed to lead over multiple generations. In this paper, the effects of different concentrations of lead (0, 0.3, 4.8 and 76.8 mg kg–1) on the expression of Vgin the beet armyworm over five successive generations were studied. The results showed that lead stress had significant effects on Vgexpression in a dose-dependent manner. For females at the larval and adult stages, as lead concentration increased, Vgexpression was significantly inhibited; for males at these two developmental stages, Vgexpression was induced and increased as lead concentration increased. In addition, with the increase over stressed generations, inhibited effects for females and induced effects for males at the larval and adult stages became increasingly more obvious. However, at the pupal stage, Vgexpression in the two genders was different from that at the larval and adult stages. The results indicate that lead stress can upregulate Vgexpression in males which should be a useful indicator for environmental risk assessment.

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

An analysis of the neutron activation and shutdown dose rates was performed for the EAST high-power deuterium neutral beam injector test facility (EAST NBITF) by using the multiparticle transport code FLUKA 2011.2. Also, the neutron and neutron-induced gamma spectra of the facility’s vacuum vessel were evaluated. The results identified the major radionuclides 99Mo, 65Ni, 58Co, 56Mn, and 51Cr for the vacuum vessel and the primary nuclide 64Cu for both the ion dump and the calorimeter. The simulated results indicated that, when the EAST NBITF operates within the design parameters of deuterium energy 80 keV, current 50 A, and pulse 100 s, the neutron intensity will achieve 1011n/s with no radiation safety problems after the EAST NBITF shuts down.

Microfluidic chips have been proven to be attractive platforms for cell culture in vitro. Microfluidic chip-based organs-on-chips technology has received more attention because it can mimic the complex structures and functions of human organs. In this review, the recent advances of organs-on-chips technology in different organs are introduced, including the build of human physiological models, drug discovery, and toxicology research. The development trend of this technology is also proposed.

Eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12 (P12), which is earlier than in the dLGN (P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.

The design uses silicon-AlN thin films as the piezoelectric substrate, Use apo- dization weighting methods to optimize the design of IDT. The improved δ function model was Modeling Tools of Apodization weighted ellipse IDT structure, According to the result of simulation, we designed a layout of SAW band-pass filter and fabricated a sample of it which center frequency is 300MHz and insertion loss is 7dB, The research shows the consistency of simulation results with the experimental results.

Based on typical parts CNC machining technology solutions, using the inverted spindle, high-capacity storage automatic loading and unloading of the workpiece conveyor systems, temperature tracking control system, ladder-shaped bed base and other new technologies. A milling-turning flexible machining cell was researched and developed, which means once the piece was fixed, all the procedures, including turning, milling, drilling, reaming, tapping and other processes integrated processing, can be completed. As an advanced manufacturing mode, it was suitable for the efficient processing of short-sleeve-type parts, panel parts, etc.

.In this paper, a video tracking approach based on particle filter is proposed. Texture information is used instead of color. In the proposed approach, gray cooccurrence matrices are used as the texture metric. Experimental results show that the proposed algorithm lead to better result than color feature-based particle filter-based video tracking algorithm and is an effective tool for complicated video tracking application.

Vitamin D has shown efficacy in the reduction of proteinuria in patients with chronic kidney disease. This study aimed to determine the effect of calcitriol on urinary protein excretion in patients with immunoglobulin A (IgA) nephropathy.

This paper investigates the hand-eye calibration and points registration methods based on Cartesian coordinate’s transformation in armed robot inspection system. Different from traditional imaged based approach, the sphere radius of the inspection probe is considered; the hand-eye calibration and 3D points’ registration are both derived as constrained optimization problem. Matrix transformation of parameter separation is presented to get the approximate resolution. Finally, iterative cycles are provided to calculate the nearest points on designed surface corresponding to the inspection points. Experiment results illustrated the application of these ideas and demonstrated the validity of the proposed framework for inspection robots.

In this article, we introduce what we call twisted Kronecker products of cocycles of finite groups and show that the twisted Kronecker product of two cocycles is a Hadamard cocycle if and only if the two cocycles themselves are Hadamard cocycles. This enables us to generalize some known results concerning products and factorizations of central semiregular relative difference sets. © 2008 Wiley Periodicals, Inc. J Combin Designs 16: 431–441, 2008

In this paper,Eis a real Banach space,A:E**×E**→E* is a semi-monotone operator. We first study the variational inequality problem: Findu∈K, such that (A(u,u),v−u)≥0, whereK⊂E** is a closed convex subset; then the operator equationA(u,u)=p*, and we also construct a degree theory for demi-continuous semi-monotone operators in reflexive Banach spaces.

We present a construction of Hadamard difference sets in abelian groups of order 4p4n, whose Sylowp-subgroups are elementary. By a standard composition procedure, we can now conclude that (4h2, 2h2−h,h2−h)-Hadamard difference sets exist forh= 2ϵ13ϵ2u2, where ϵ1, ϵ2= 0 or 1 anduis a positive integer. We then generalize the construction of Hadamard difference sets to construct a family of (4q2n(q2n− 1)/(q2−1),q2n−1[2(q2n− 1)/(q+ 1) + 1], (q2n−q2n−1)(q2n−1 + 1)/(q+ 1)-difference sets, whereqis an even power of an odd prime or any power of 3.

The purpose of this paper is to study the existence problem of solutions and perturbation problem for some kind of variational inequalities with monotone operators in nonreflexive Banach spaces, and to obtain some results.

A difference setD in a groupG is called a skew Hadamard difference set (or an antisymmetric difference set) if and only ifG is the disjoint union ofD, D(-1), and {1}, whereD(-1)={d-1|d?D}. In this note, we obtain an exponent bound for non-elementary abelian groupG which admits a skew Hadamard difference set. This improves the bound obtained previously by Johnsen, Camion and Mann.

LetPbe a cone in a Banach spaceE. In this paper, we show the existence of solutions of the operator equationy∈−Ax+Txfory∈P, whereTis a 1-set-contraction operator inPandAis an accretive operator inPsatisfyingR(I+λA)=Pfor all λ>0. Further, a sufficient condition forR(I+λA)=Pis also given.

In this paper, we present a new way of viewing Xia's construction of Hadamard difference sets. Based on this new point of view, we give a character theoretic proof for Xia's construction. Also we point out a connection between the construction and projective three-weight codes.

The main result of this paper is that vertex-transitive graphs and digraphs of orderp4are Hamiltonian, wherepis a prime number.

Pulmonary atypical carcinoid (PAC) is a rare subtype of pulmonary neuroendocrine neoplasm. Although EML4-ALK fusionhas been detected in PAC, EGFRmutations have not been reported before.

The purpose of this paper is to introduce the concept of semi-inner products in locally convex spaces and to give some basic properties.

Let P be cone Banach space E, A, K are two mappings in P, A accretive, K is K—set contraction, then fixed point index defined for mapping −A+K, some fixed point theorems are also deduced.