Search

Abstract Background Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation. Methods Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included. Results The pooled risk of clinical remission rate of patients with Crohn’s disease and ulcerative colitis who were naïve to biologics at 08–14 weeks were 0.66 (95% CI, 0.58–0.75) and 0.48 (95% CI, 0.43–0.54), respectively, and at 100–104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn’s disease and ulcerative colitis who were transitioned from the original agent at 24–32 weeks were 0.84 (95% CI, 0.77–0.92) and 0.78 (95% CI, 0.63–0.93), respectively, and at 48–54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08–14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48–54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn’s disease or ulcerative colitis. Conclusions CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.

The presence of high-density defects is rarely observed in bulk 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) ceramics obtained through conventional pressureless sintering. In the present work, fine-grained dense 147 nm 3Y-TZP ceramics were prepared by pressureless sintering of commercial 0.25 wt% alumina-doped zirconia powders at 1300 ℃. A novel discovery was reported in which large amounts of defects were present in the grain interiors of the sample. The phenomenon was further examined using three types of powder samples, and the reasons for defect formation were investigated by microstructural characterization using high-resolution transmission electron microscopy (HRTEM) analysis and Rietveld refinement. The results confirmed the essential dependence of the defect formation on the alumina addition. The authors attributed the defect formation to the significant difference in ionic radii of the solvent and solute during the dissolution of alumina into the zirconia lattice. The sintering kinetics were proposed to be enhanced by the presence of substantial defects, which consequently favored the low-temperature sintering of the alumina-doped zirconia ceramics.

Background: Stricture in patients with Crohn's disease (CD) carries a high risk of CD-related surgery in the course of the disease. The aim of this study was to assess the rate of occurrence of CD-related surgery and to determine baseline risk factors predicting subsequent surgery in this patient group. Methods: Patients registered with stricturing CD were included. All baseline and follow-up data were collected retrospectively. Patients attended the clinic for follow-up at week 14 to assess their response to infliximab (IFX). CD-related surgery was the observational endpoint. Univariate and multivariate Cox regression analyses were used. Results: A total of 123 patients with stricturing CD were included in this study. The cumulative risk of CD-related surgery for years 1–5 after diagnosis was 18.0%, 26.7%, 32.6%, 40.7%, and 46.4%, respectively. Prior gastrointestinal (GI) surgery, low body mass index (BMI), and high platelet count might be risk factors for future CD-related surgery. With 97 participants treated by IFX, prior GI surgery and primary non-response (PNR) to IFX correlated with future CD-related surgery. Conclusion: Prior GI surgery, BMI, and platelet counts were related to future CD-related surgery. Patients who were PNR to IFX had a higher risk of CD-related surgery in the future.

Purpose: To evaluate the potential efficacy of Triptolide (TP) on cerebral ischemia/reperfusion injury (CIRI) and to uncover the underlying mechanism through which TP regulates CIRI. Methods: We constructed a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate CIRI, and established a lipopolysaccharide (LPS)-stimulated BV-2 cell model to mimic the inflammatory state during CIRI. The neurological deficits score (NS) of mice were measured for assessment of neurologic functions. Both the severity of cerebral infarction and the apoptosis level in mouse brain tissues or cells were respectively evaluated using corresponding techniques. The expression levels of Ionized calcium binding adapter molecule 1 (IBA-1), Inductible Nitric Oxide Synthase (iNOS), Arginase 1 (Arg-1), Tumor necrosis factor-α (TNF-α), Interleukin 1β (IL-1β), Cysteine histoproteinase S (CTSS), Fractalkine, chemokine C-X3-C motif receptor 1 (CX3CR1), BCL-2-associated X protein (BAX), and antiapoptotic proteins (Bcl-2) were detected using immunofluorescence, qRT-PCR as well as Western blot, respectively. Results: Relative to the Sham group, treatment with TP attenuated the increased NS, infarct area and apoptosis levels observed in MCAO/R mice. Upregulated expression levels of IBA-1, iNOS, Arg-1, TNF-α and IL-1β were found in MCAO/R mice, while TP suppressed iNOS, TNF-α and IL-1β expression, and enhanced Arg-1 expression in both MCAO/R mice and LPS-stimulated BV-2 cells. Besides, TP inhibited the CTSS/Fractalkine/CX3CR1 pathway activation in both MCAO/R mice and LPS-induced BV-2 cells, while overexpression of CTSS reversed such effect. Co-culturing HT-22 cells with TP+LPS-treated BV-2 cells led to enhanced cell viability and decreased apoptosis levels. However, overexpression of CTSS further aggravated HT-22 cell injury. Conclusion: TP inhibits not only microglia polarization towards the M1 phenotype by suppressing the CTSS/Fractalkine/CX3CR1 pathway activation, but also HT-22 apoptosis by crosstalk with BV-2 cells, thereby ameliorating CIRI. These findings reveal a novel mechanism of TP in improving CIRI, and offer potential implications for addressing the preventive and therapeutic strategies of CIRI.

Posterior olecranon fracture dislocations (POFDs) were considered posterior Monteggia lesions, which were less described in the literature. The purpose of this study was to provide a systematic review of the diagnosis, treatment, prognosis, and complications of POFDs in adults. A systematic review was performed to identify all relevant studies on the POFDs in the PubMed, Web of Science, Embase, and MEDLINE databases. The methodological quality of the studies was scored using the Methodological Index for Non‐Randomized Studies (MINORS). A total of 117 patients were identified in the nine studies selected. The high‐energy injuries accounted for 42.7% of the included studies. The rates of concomitant coronoid process, radial head fractures, and lateral collateral ligament injury were 84.6% (99/117), 87.2% (102/117), and 5% (6/117), respectively. The procedure was performed with a dorsal mid longitudinal approach to reconstruct all injury components. The postoperative clinical scores included the Broberg/Morrey rating, with a mean rating of excellent or good at 66%, the mean DASH score was 20.6, and the mean ASES score was 83. The flexion and extension arc and forearm rotation arcs were 100° and 134°, respectively. Complications included arthrosis in 28.2% (33/117) of cases, fracture nonunion or delayed union in 9.4% (11/117) of cases, heterotopic ossification in 7% (8/117) of cases, and the re‐operation rate was 16% (19/117). There was nearly no postoperative ulnohumeral instability. The main characteristics of POFDs were disruptions of the trochlear notch, including the olecranon and coronoid processes, and severe radial head fractures, while the lateral collateral ligament was spared. Although the POFDs had a low frequency of instability, the prognosis was relatively poor. The POFDs should be considered independently.

Objective: To explore the characteristics of high-resolution computed tomography (HRCT) in diabetes complicated with coronavirus disease 2019 (COVID-19)-associated pneumonia. Materials and Methods: This study included 584 patients (359 males and 225 females), aged between 60~99 years old (mean, (76±9) years), with positive chest computed tomography (CT) findings and diagnosed with COVID-19 in our hospital from December 14, 2022, to January 10, 2023. Of these, 225 patients were diabetic and 359 were non-diabetic. The features of the chest HRCT from patients with diabetes mellitus complicated with COVID-19 and those without diabetes mellitus complicated with COVID-19 were compared. Moreover, 363 patients in the acute stage of COVID-19 (defined as the time interval between onset and CT examination

Abstract This study aimed to investigate the effect of a single night of continuous positive airway pressure (CPAP) treatment on spontaneous brain activity and the underlying neuropathological mechanisms in patients with severe obstructive sleep apnea (OSA). The study involved 30 severe OSA patients and 19 healthy controls (HC). Fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) methods were employed to evaluate spontaneous brain activity in all participants. Following a single night of CPAP treatment, ReHo values increased in the bilateral caudate and decreased in the right superior frontal gyrus. The fALFF values increased in the left orbital part of the middle frontal gyrus and the right orbital of the inferior frontal gyrus (Frontal_Inf_Orb_R). However, fALFF values decreased in the medial part of the left superior frontal gyrus and the right supramarginal part of the inferior parietal lobe. Pearson correlation analysis revealed a positive relationship between the change in the fALFF in the Frontal_Inf_Orb_R and the change in REM sleep duration (r = 0.437, p = 0.016) following a single night of CPAP treatment. We concluded that observing changes in abnormal fALFF and ReHo in OSA patients before and after a single night of CPAP treatment may enhance our understanding of the neurological mechanisms in patients with severe OSA.

Abstract Objective In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). Methods By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). Results There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. Conclusion Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.

Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαβR-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77–88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).