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Background Inflammatory bowel disease (IBD) patients living in regional or remote Queensland are often disadvantaged by limited access to IBD specialist care. Telehealth clinics could potentially address this disparity and improve patient outcomes. Aim We report the impact of the Royal Brisbane and Women's Hospital (RBWH) IBD telehealth clinics from March 2011 to December 2017 including patient satisfaction and healthcare activity. Methods Patient satisfaction surveys were collected prospectively between March 2011 and March 2012. Healthcare activity was assessed through occasions of service (OOS), number of enrolled patients on biologics and IBD related admissions to RBWH. Results Overall, 3764 OOS were completed including 576 new patient and 3188 follow up visits. Mean age at first telehealth visit was 44 years (range:16-87). The IBD telehealth clinics were well accepted with 99% of the first 153 patients surveyed choosing to continue with telehealth and 94% rated the telehealth experience as very good or excellent. The net number of patients under active review increased from 125 patients in 2011 to 345 patients in 2017. Enrolled patients on biologics also increased from 9 patients in 2011 to 63 patients in 2017. There was an initial dip in annual IBD related admissions to RBWH in 2011 but these have progressively increased over time although the average length of inpatient stay annually has remained stable. Conclusion The RBWH IBD telehealth clinics have shown that telemedicine is well received and can be used successfully to deliver IBD specialist care to patients living in regional or remote areas. This article is protected by copyright. All rights reserved.

In the current study, a one‐pot method to prepare small lipid‐indocyanine green (ICG) nanoparticles (L‐ICG NPs) is proposed for the treatment of colorectal cancer. The L‐ICG NPs showed size distribution at around 20 nm with high stability and biocompatibility. In addition, they can respond to light irradiations to exert oxidative/thermal stress damage, which showed effective anticancer benefits in vitro and in vivo using HT‐29 cells as the model.

Objective Inflammatory bowel disease (IBD) is a chronic intestinal disease. This study was attempted to investigate the effects of long noncoding RNA KIF9-AS1 (KIF9-AS1) on the development of IBD and its underlying mechanism of action. Methods Quantitative real time PCR (qRT-PCR) was implemented to examine the expression of KIF9-AS1 and microRNA-148a-3p (miR-148a-3p). The IBD mouse model was induced by dextran sulfate sodium (DSS). The body weight, disease activity index (DAI) score, colon length and histological injury were used to evaluate the colon injury. The levels of proinflammatory cytokines were measured by ELISA. In vitro, IBD was simulated by DSS treatment in colonic cells. Then the apoptosis of colonic cells was detected by flow cytometry assay. Furthermore, a dual-luciferase reporter assay was used to demonstrate the interactions among KIF9-AS1, miR-148a-3p and suppressor of cytokine signaling (SOCS3). Results KIF9-AS1 expression was upregulated in IBD patients, DSS-induced IBD mice and DSS-induced colonic cells, whereas miR-148a-3p expression was downregulated. KIF9-AS1 silencing attenuated the apoptosis of DSS-induced colonic cells in vitro and alleviated colon injury and inflammation in DSS-induced IBD mice in vivo. Additionally, the mechanical experiment confirmed that KIF9-AS1 and SOCS3 were both targeted by miR-148a-3p with the complementary binding sites at 3'UTR. Moreover, miR-148a-3p inhibition or SOCS3 overexpression reversed the suppressive effect of KIF9-AS1 silencing on the apoptosis of DSS-induced colonic cells. Conclusion KIF9-AS1 silencing hampered the colon injury and inflammation in DSS-induced IBD mice in vivo, and restrained the apoptosis of DSS-induced colonic cells by regulating the miR-148a-3p/SOCS3 axis in vitro, providing a new therapeutic target for IBD.

Purpose: We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who had restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at an Australian institution over 26 years.Methods: Data including clinical characteristics, preoperative medical therapy, and surgical outcomes were collected. We divided eligible patients into 3 period arms (period 1, 1990 to 1999; period 2, 2000 to 2009; period 3, 2010 to 2016). Outcomes of interest were IPAA leak and pouch failure.Results: A total of 212 patients were included. Median follow-up was 50 (interquartile range, 17 to 120) months. Rates of early and late complications were 34.9% and 52.0%, respectively. Early complications included wound infection (9.4%), pelvic sepsis (8.0%), and small bowel obstruction (6.6%) while late complications included small bowel obstruction (18.9%), anal stenosis (16.8%), and pouch fistula (13.3%). Overall, IPAA leak rate was 6.1% and pouch failure rate was 4.8%. Eighty-three patients (42.3%) experienced pouchitis. Over time, we observed an increase in patient exposure to thiopurine (P=0.0025), cyclosporin (P=0.0002), and anti-tumor necrosis factor (P

Background: Serum-derived exosomes are correlated with disease severity of human systemic lupus erythematosus (SLE). The proteins in the T-cell-derived exosomes from SLE patients could contribute to inflammation. Methods: We characterized proteins of T cell-derived exosomes from SLE patients and healthy controls by proteomics. To study the potential pathogenic role of the identified exosomal protein, we generated and characterized T-cell-specific transgenic mice that overexpressed the identified protein in T cells using immunohistochemistry, immunoblotting, and single-cell RNA sequencing. Results: We identified an overexpressed protein, bactericidal/permeability-increasing protein (BPI), in SLE T cells and T-cell-derived exosomes. T-cell-specific BPI transgenic (Lck-BPI Tg) mice showed multi-tissue inflammation with early induction of serum IL-1β levels, as well as serum triglyceride and creatinine levels. Interestingly, exosomes of Lck-BPI Tg T cells stimulated IL-1β expression of wild-type recipient macrophages. Remarkably, adoptive transfer of BPI-containing exosomes increased serum IL-1β and autoantibody levels in recipient mice. The transferred exosomes infiltrated into multiple tissues of recipient mice, resulting in hepatitis, nephritis, and arthritis. ScRNA-seq showed that Lck-BPI Tg T cells displayed a decrease of Treg population, which was concomitant with ZFP36L2 upregulation and Helios downregulation. Furthermore, in vitro Treg differentiation was reduced by BPI transgene and enhanced by BPI knockout. Conclusions: BPI is a negative regulator of Treg differentiation. BPI overexpression in T-cell-derived exosomes or peripheral blood T cells may be a biomarker and pathogenic factor for human SLE nephritis, hepatitis, and arthritis.

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, which is widespread in warm-blooded animals and humans. Currently, many studies regarding T. gondii infection in sheep have been published worldwide. However, there is no meta-analysis of sheep infection in China. In this study, five databases were used to retrieve articles related to T. gondii in China. A total of 59 studies from 1987 to June 30, 2020, have been included. We estimated that the combined prevalence of T. gondii in the selected period was 8.5% (3197/28,099). In the analysis of publication year, the lowest positive rate after 2010 was 7.4% (1883/17,313). Geographically, the highest prevalence of T. gondii in sheep was recorded in Southwest China 19.2% (490/2080). Analysis according to age showed that the prevalence of infection in sheep older than 12 months was significantly (P 0.05) higher than that in younger animals. The prevalence of T. gondii in sheep farmed by farmers was 7.2% (566/6336), which was higher than 5.3% (660/3121) of large-scale farming, suggesting a role for the feeding and husbandry. We also analyzed the impact of different geographic and climatic factors on the prevalence of T. gondii infection in sheep. The results showed that the prevalence was higher in low altitude, warm, humid, and high rainfall areas. We suggest that appropriate control programs should be formulated according to the differences in reproduction patterns and geographical conditions in different regions to reduce the prevalence of T. gondii among sheep in China.

The proportion of allergic diseases attributable to atopy remains a subject of controversy. This study aimed to estimate the population risk of physician-diagnosed asthma, rhinitis and eczema attributed to atopy among a population sample of Asian school-age children. Asian children aged 5–18 years (n = 1321) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were tested for serum allergen-specific immunoglobulin E. Physician-diagnosed asthma, rhinitis and eczema were assessed by a modified International Study of Asthma and Allergies in Childhood questionnaire. Atopy was defined as the presence of serum allergen-specific immunoglobulin E. In this population-based study, 50.4% of the subjects with asthma, 46.3% with rhinitis, and 46.7% with eczema were attributable to atopy. The population attributable risk (PAR) of atopy for three allergic diseases was higher in adolescents (asthma, 54.4%; rhinitis, 59.6%; eczema, 49.5%) than younger children aged less than 10 years (asthma, 46.9%; rhinitis, 39.5%; eczema, 41.9%). Among the seven allergen categories, sensitization to mites had the highest PARs for all three allergic diseases (51.3 to 64.1%), followed by sensitization to foods (asthma, 7.1%; rhinitis, 10.4%; eczema 27.7%). In conclusion, approximately half (46.3 to 50.4%) of Asian children in Taiwan with allergic diseases are attributable to atopy.

BACKGROUND Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B4 (LTB4 ), characterizes childhood asthma. While fractional exhaled nitric oxide (FeNO) has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. METHODS Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. RESULTS In addition to those previously reported, including LTB4 , the levels of exhaled 15-hydroxyeicosatetraenoic acid (15-HETE), but not thromboxane B2 (TXB2 ), showed significant difference between asthmatics (N = 318) and healthy controls (N = 97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver operating characteristic (ROC) curve analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 (forced expiratory volume in the first second), and FeNO, while the 15-HETE/LTB4 ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p

Summary In order to safely carry out organ donation transplants during the outbreak of coronavirus disease 2019 (COVID‐19), we have formulated strict procedures in place for organ donation and transplantation. We retrospectively analyzed our transplantation work from January 20 to May 5, 2020, to discuss whether organ transplantation can be carried out safely during the epidemic period. From January 20 to May 5, 43 cases of donation were carried out in our hospital, and the utilization rate of liver, kidney, heart, lung, and pancreas donations was more than 90%. Forty‐one cases of liver transplantation and 84 cases of kidney transplantation were performed. No graft loss or recipient death occurred within one month after kidney transplantation, and one patient (2.4%) died after liver transplantation. There was no significant difference in the length of hospital stay compared with that during the same period in the previous three years. More importantly, COVID‐19 infection did not occur among healthcare providers, donors, patients, or their accompanying families in our center. Under the premise of correct protection, it is safe and feasible to carry out organ transplantation during the epidemic period. Our experience during the outbreak might provide a clinical reference for countries facing COVID‐19 worldwide., The global epidemic caused by the rapid spread of coronavirus disease‐ 2019 (COVID‐19) to a global epidemic has posed a huge challenge to organ donation and transplantation. From potential donor management, to organ donation and transplantation, we have formulated detailed rules to strictly control all aspects of clinical work. The practice of our center has confirmed that transplantation activities can be carried out normally under the right protection. Our experience might provide a clinical reference for the countries facing COVID‐19 worldwide.

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Moreover, EGFR, MET, PIK3CA, PKHD1 and RB1 mutant groups were found to have high CAA burden, while those with BRAF, ERBB2 and KRAS mutations belonged to the low CAA burden group. Comparing EGFR L858R and EGFR 19del mutants, distinct CAA co-occurrences were observed. Network-based stratification with population based genomic evolution analysis revealed two distinct subtypes of LUAD with different CAA signatures and unique CAA order of acquisition. In summary, our study presented a comprehensive characterization of arm aneuploidy landscape and evolutionary trajectories in lung adenocarcinoma, which could provide basis for both biological and clinical investigations in the future.

Background Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Materials and Methods Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. Results In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5 s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Conclusion Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

BackgroundHepatitis B surface antigen (HBsAg) reverse seroconversion (RS) can happen in patients with rheumatoid arthritis (RA) with resolved hepatitis B (RHB) undergoing biological disease-modifying antirheumatic drugs (bDMARDs). But the incidence and risk factors need to be delineated.MethodsFrom 2003 to 2019, 1937 patients with RA with available HBsAg and antibody to hepatitis B virus (HBV) core antigen data were retrospectively reviewed, and 489 patients with RHB undergoing bDMARDs treatment were identified. Factors associated with HBsAg RS were analysed.ResultsDuring 67 828 person-months of follow-up, 27 (5.5%) patients developed HBsAg RS after bDMARD treatment. As compared with those without HBsAg RS, patients with HBsAg RS were older, had lower frequency of antibody to HBsAg (anti-HBs), and lower baseline anti-HBs levels. In multivariate analysis, rituximab, abatacept and baseline negative for anti-HBs were the independent risk factors for HBsAg RS (adjusted HR: 87.76, 95% CI: 11.50 to 669.73, pConclusionsNot only rituximab, but also abatacept has a high risk of HBV reactivation in patient with RA with RHB. Anti-HBs positivity cannot confer HBV reactivation-free status if the anti-HBs levels are not high enough for patients with RHB on rituximab and abatacept treatment.

Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, is recognized as a potential target for cancer immunotherapy as well as for the induction of transplantation tolerance. However, how the crosstalk between stem cell programming and cytokine signaling regulates PD-L1 expression during stem cell differentiation and cancer cell plasticity remains unclear. Herein, we reported that PD-L1 expression was regulated by SOX2 during embryonic stem cell (ESC) differentiation and lung cancer cell plasticity. PD-L1 was induced during ESC differentiation to fibroblasts and was downregulated during SOX2-mediated reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs). Furthermore, SOX2 activation affected cancer cell plasticity and inhibited PD-L1 expression in lung cancer cells. We discovered that the H3K27ac signal at the PD-L1 locus was enhanced during ESC differentiation to fibroblasts as well as during cancer plasticity of SOX2-positive lung cancer cells to SOX2-negative counterparts. Romidepsin, an epigenetic modifier, induced PD-L1 expression in lung cancer cells, whereas TGF-β stimulation downregulated SOX2 but upregulated PD-L1 expression in lung cancer cells. Furthermore, in addition to PD-L1, the expressions of EGFR and its ligand HBEGF were downregulated by activation of endogenous SOX2 expression during lung cancer cell plasticity and iPSC reprogramming, and the activation of EGFR signaling by HBEGF upregulated PD-L1 expression in lung cancer cells. Together, our results reveal the crosstalk between SOX2 programming and cytokine stimulation influences PD-L1 expression, and these findings may provide insights into PD-L1-mediated therapeutics.

Background: The association between oxidative stress and atopic diseases is uncertain. Several risk factors for atopic diseases have been identified, however, a comprehensive investigation of the relationship between oxidative stress markers and atopic indices related to atopic diseases is currently lacking. Methods: We investigated 132 children who completed a 7-years follow-up in a birth cohort. Oxidative stress markers including plasma glutathione peroxidase (GPx), myeloperoxidase (MPO), total anti-oxidant capacity (TAC), and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured. Allergen-specific IgE levels, FeNO levels, and pulmonary function tests were also obtained. Results: The activity of GPx and levels of MPO were inversely correlated to food (shrimp and crab) and house dust mite sensitization respectively. The 8-OHdG levels were strongly negatively correlated with FeNO levels (p

The aim of this study is to compare the long-term functional outcome and quality of life between total knee arthroplasty (TKA) and fixed-bearing unicompartmental knee arthroplasty (UKA) for the treatment of isolated medial compartment osteoarthritis.Between 2000 and 2008, a total of 218 patients underwent primary UKA at our tertiary hospital. A TKA group was matched through 1:1 propensity score matching and adjusted for age, gender, body mass index, preoperative knee flexion, and function scores. All patients had medial compartment osteoarthritis. The patients were assessed with the range of motion, Knee Society Knee Score and Knee Society Function Score, Oxford Knee Score, Short Form-36 physical component score (PCS) and mental component score preoperatively, at 6 months, 2 years, and 10 years. Patients' satisfaction, expectation fulfillment, and minimal clinically important difference were analyzed.There were no differences in baseline characteristics between groups after propensity score matching (P.05). UKA had greater knee flexion at all time points. Although the Knee Society Function Score was superior in UKA by 5.5, 3, and 4.3 points at 6 months, 2 years, and 10 years, respectively (P.001), these differences did not exceed the minimal clinically important difference (Knee Society Knee Score 6.1). There were no significant differences in the Oxford Knee Score and Short Form-36 physical component score/mental component score. At 10 years, similar proportions of UKA and TKA were satisfied (90.8% vs 89.9%, P = .44) and had expectation fulfillment (89.4% vs 88.5%, P = .46). Between 2 and 10 years, all function scores deteriorated significantly for both groups (P.01).UKA and TKA are excellent treatment modalities for isolated medial compartment osteoarthritis, with similar functional outcomes, quality of life, and satisfaction at 10 years.

BACKGROUND Lung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries. AIM To evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review. METHODS We searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger’s linear regression test. Data analysis was performed using R software. RESULTS The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events. CONCLUSION COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.

Background: Atopic eczema and food allergy most commonly occur in the early childhood. However, the relationships between eczema onset and their relevance to the occurrence of atopic diseases relating to allergen sensitization remain unclear. Methods: We investigated 186 children who were followed up regularly at the clinic for 4 years in a birth cohort study. The children were classified into three groups: early-onset eczema (

Background A sizeable proportion of knee osteoarthritis is limited to the medial and patellofemoral compartments. Whilst short- and medium-term studies comparing bicompartmental knee arthroplasty (BCA) and total knee arthroplasty (TKA) have shown similar outcome scores, there are no studies comparing long-term outcomes. This study aims to determine which procedure resulted in superior long-term outcome scores. Methods Forty-eight patients with medial and patellofemoral compartment knee osteoarthritis were randomised to receive treatment in two groups: unlinked, modular BCA and TKA. The main outcome measures compared were the range of motion, Knee Society Function Score, Knee Society Knee Score, Oxford Knee Score, Physical Component Score and Mental Component Score of SF-36 pre-operatively and post-operatively up to 10 years. Radiographs of the operated knees were taken pre-operatively, post-operatively and at 10-year follow-up. Results Twenty-six underwent BCA and 22 underwent TKA. Overall improvement was seen in both groups compared to pre-operatively, however there were no significant differences detected between the groups at 10 years. The median Hip–Knee–Ankle (HKA) angle was 183.38 (175.17–187.94) in the BCA group and 180.73 (174.96–185.65) in the TKA group. One patient from the BCA group had a peri-prosthetic fracture necessitating revision surgery to a TKA. Conclusions Outcome scores for BCA results were comparable to TKA at long-term follow-up. BCA is an alternative arthroplasty option in selected patients.

Background Angiotensin receptor blockers (ARBs) have been reported to ameliorate anxiety and mood disorders in animal models. Cohort links between ARB use and suicide risk in humans require clarification. Methods Data were obtained from the National Health Insurance Research Database. Patients diagnosed as having hypertension according to the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification (401-405) from January 1, 2000 to December 31, 2012 were enrolled as the target population. We defined enrollees who had received ARB prescriptions for at least 28 days as ARB users. Those who had never taken ARB prior or during the study period were defined as ARB nonusers and were propensity score–matched with ARB users. The end outcome was confirmation of a suicide attempt. Results After propensity score matching was conducted, 40,976 ARB users and 40,976 nonusers were selected as the matched cohorts. The overall incidence rate of suicide attempt was significantly lower in ARB users than in nonusers (0.51 vs. 1.07 per 10,000 person-years; adjusted hazard ratio = 0.48, 95% confidence interval = 0.26–0.87). A Kaplan–Meier survival analysis with a log-rank test revealed a lower cumulative incidence of suicide attempt in ARB users than in nonusers (p Conclusions ARB use was not associated with an increased risk for suicide compared with non-ARB use.

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by

Background Parkinson's disease (PD) adversely affects physical function after joint replacement. The biomechanical advantages of unicompartmental knee arthroplasty (UKA) may be particularly beneficial for these patients who suffer from gait and kinetic abnormalities. We aimed to describe the functional outcomes, complications and survivorship after UKA in patients with PD. Methods Ten patients (11 knees) undergoing primary fixed-bearing UKA for medial osteoarthritis were studied. Knee Society Knee (KSKS) and Function Scores (KSFS), as well as the Short-Form-36 (SF-36) Mental (MCS) and Physical Component Scores (PCS) were assessed preoperatively, at six months and at two years postoperatively. Complications, survivorship and all-cause mortality were analyzed. Results No perioperative complications occurred. Length of stay was 5 ± 2 days and no patients were discharged to rehabilitation or readmitted. Nine of 11 knees had a flexion contracture preoperatively and this remained unchanged at two years. KSKS and SF-36 PCS improved significantly. However, there was no improvement in KSFS or SF-36 MCS. All patients achieved minimal clinically important difference for KSKS, six of 11 for KSFS and nine of 11 for SF-36 PCS. At mean 10 ± 5 years, there was one revision for progression of osteoarthritis. Seven of 10 patients progressed in Hoehn and Yahr stage and only three were able to ambulate independently at last follow-up. Conclusions Patients suffering from osteoarthritis and PD can experience a substantial improvement in knee pain with low morbidity after UKA. However, the improved kinematics of UKA did not translate to an improved range of motion or knee function postoperatively.

Cryptosporidium is an important zoonotic parasite that can infect a variety of hosts, including pigs and humans, through water and food. Many studies on Cryptosporidium infection in pigs have been reported worldwide. However, the meta-analysis of Cryptosporidium infection in pigs in China has not been published. This study retrieved articles related to Cryptosporidium in pigs in China by using four databases: Chinese National Knowledge Infrastructure (CNKI), PubMed, VIP Chinese journal database and Wanfang Data. We retrieved 40 studies related to Cryptosporidium infection in China, and those articles were harvested from the inception to 1 January 2020. We estimated that the overall prevalence of pigs with Cryptosporidium in the selected period was 12.2% (4,349/30,404). In the sampling year subgroup, the prevalence rate after 2010 was the lowest at 8.7% (2,087/18,100). In Northern China, the Cryptosporidium prevalence was 47.9% (34/71). By contrast, the prevalence of Cryptosporidium in Southwestern China was only 6.9% (778/6,445). The infection rate of Cryptosporidium in diarrhoea pigs of 15.6% (74/384) was higher than that in non-diarrhoea pigs at 10.8% (378/2,840). Among the four age groups, the prevalence of weaning pigs of 16.2% (530/3,243) was the highest, and the difference was significant (p < .05). The prevalence of Cryptosporidium in extensive farming was 25.7% (660/3,121), which was significantly higher than in intensive farming 8.7% (566/6,336), and the prevalence of infection was related to the farming modes (p < .05). We also analysed the impact of different geographic factor subgroups (longitude, latitude, precipitation, temperature, humidity, climate and altitude) on the prevalence of pigs. The results showed that cryptosporidiosis was widespread in pigs in China. We suggest that appropriate control schemes should be developed according to the differences in breeding patterns and geographic conditions in different regions, and effective management measures should be developed to reduce the spread between pigs.

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges to healthcare systems worldwide. Orthopaedic departments have adopted business continuity models and guidelines for essential and non-essential surgeries to preserve hospital resources as well as protect patients and staff. These guidelines broadly encompass reduction of ambulatory care with a move towards telemedicine, redeployment of orthopaedic surgeons/residents to the frontline battle against COVID-19, continuation of education and research through web-based means, and cancellation of non-essential elective procedures. However, if containment of COVID-19 community spread is achieved, resumption of elective orthopaedic procedures and transition plans to return to normalcy must be considered for orthopaedic departments. The COVID-19 pandemic also presents a moral dilemma to the orthopaedic surgeon considering elective procedures. What is the best treatment for our patients and how does the fear of COVID-19 influence the risk-benefit discussion during a pandemic? Surgeons must deliberate the fine balance between elective surgery for a patient’s wellbeing versus risks to the operating team and utilization of precious hospital resources. Attrition of healthcare workers or Orthopaedic surgeons from restarting elective procedures prematurely or in an unsafe manner may render us ill-equipped to handle the second wave of infections. This highlights the need to develop effective screening protocols or preoperative COVID-19 testing before elective procedures in high-risk, elderly individuals with comorbidities. Alternatively, high-risk individuals should be postponed until the risk of nosocomial COVID-19 infection is minimal. In addition, given the higher mortality and perioperative morbidity of patients with COVID-19 undergoing surgery, the decision to operate must be carefully deliberated. As we ramp-up elective services and get “back to business” as orthopaedic surgeons, we have to be constantly mindful to proceed in a cautious and calibrated fashion, delivering the best care, while maintaining utmost vigilance to prevent the resurgence of COVID-19 during this critical transition period. Cite this article: Bone Joint Open 2020;1-6:222–228.

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P

BACKGROUND AND AIM Therapeutic drug monitoring of infliximab (IFX) using the established laboratory-based enzyme-linked immunosorbent assay (ELISA) cannot produce results fast enough to allow IFX dose adjustments prior to each IFX infusion. We investigate the validity of IFX trough levels obtained through the Quantum Blue IFX (QB-IFX) rapid assay compared with the established ELISA. METHODS Adult inflammatory bowel disease patients receiving maintenance IFX infusions at Middlemore Hospital and Dunedin Public Hospital were prospectively recruited from July to October 2016. Serum samples were stored at -40 °C until processed using QB-IFX by a clinician at Middlemore Hospital and a research staff at Dunedin Public Hospital strictly following the manufacturers' instructions in an open label fashion. RESULTS Forty four inflammatory bowel disease patients were recruited. Median duration of IFX therapy was 21 months (interquartile range: 12-44). Overall, the correlation between ELISA and QB-IFX trough levels was 0.73 (95% confidence interval [CI]: 0.53-0.85). The sensitivity and specificity of a QB-IFX level

Background: The regulatory network of ulcerative colitis (UC)-associated miRNAs is not fully understood. In this study, we aim to investigate the global profile and regulatory network of UC associated miRNAs in the context of dextran sulfate sodium (DSS). Methods: UC was induced in C57BL mice using DSS. Differentially expressed miRNAs were screened by RNA sequencing and subjected to the Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis. RT-qPCR was used to verify the differential expression of miRNAs and candidate target mRNA. Luciferase reporter vector bearing a miRNA binding site was constructed to verify the binding site of the miRNA on mRNA. Results:A total of 95 miRNAs (31 were up-regulated and 64 were down regulated) differentially expressed in the colonic tissues of the UC mice. Among the differentially expressed miRNAs, IL-25 pathway genes were enriched. Subsequent RT-qPCR confirmed a decreased expression of IL-25 and a significant up regulation of IL-25 target miRNAs including mmu-miR-135b-5p, mmu-miR-7239-5p and mmu-miR-691 in UC mice. Conclusion: Using the luciferase assay, we verified the biding sites of mmu-miR-135b-5p and mmu-miR-691 to the IL-25 3ʹUTR. In conclusion, mmu-miR-135b-5p:IL-25 and mmu-miR-691:IL-25 interactions are important pathways that may exert a protective role in UC., Graphical abstract

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P Atopobium (P Fusobacterium (P

Goblet cell adenocarcinoma (GCA) is a rare amphicrine tumor and difficult to diagnose. GCA is traditionally found in the appendix, but extra-appendiceal GCA may be underestimated. Intestinal adenocarcinoma with signet ring cell component is also very rare, and some signet ring cell carcinomas are well cohesive, having some similar morphological features to GCAs. It is necessary to differentiate GCA from intestinal adenocarcinomas with cohesive signet ring cell component (IACSRCC). The goal of this study is to find occurrence of extra-appendiceal GCA and characterize the histological, immunohistochemical, transcriptional, and immune landscape of GCA. We collected 12 cases of GCAs and 10 IACSRCCs and reviewed the clinicopathologic characters of these cases. Immunohistochemical stains were performed with synaptophysin, chromogranin A, CD56, somatostatin receptor (SSTR) 2, and Ki-67. Whole transcriptome RNA-sequencing was performed, and data were used to analyze differential gene expression and predict immune cell infiltration levels in GCA and IACSRCC. RNA-sequencing data for colorectal adenocarcinoma were gathered from TCGA data portal. Of the 12 patients with GCA, there were 4 women and 8 men. There were three appendiceal cases and nine extra-appendiceal cases. GCAs were immunohistochemically different from IACSRCC. GCA also had different levels of B-cell and CD8+ T-cell infiltration compared to both colorectal adenocarcinoma and cohesive IACSRCCs. Differential gene expression analysis showed distinct gene expression patterns in GCA compared to colorectal adenocarcinoma, with a number of cancer-related differentially expressed genes, including upregulation of TMEM14A, GOLT1A, DSCC1, and HSD17B8, and downregulation of KCNQ1OT1 and MXRA5. GCA also had several differentially expressed genes compared to IACSRCCs, including upregulation of PRSS21, EPPIN, RPRM, TNFRSF12A, and BZRAP1, and downregulation of HIST1H2BE, TCN1, AC069363.1, RP11-538I12.2, and REG4. In summary, the number of extra-appendiceal GCA was underestimated in Chinese patients. GCA can be seen as a distinct morphological, immunohistochemical, transcriptomic, and immunological entity. The classic low-grade component of GCA and the immunoreactivity for neuroendocrine markers are the key points to diagnosing GCA.

BACKGROUND The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis (SUP) for patients with sepsis who have gastrointestinal (GI) bleeding risks, however, the effect of SUP has not been specially studied in these patients. AIMS The purpose of this study is to determine the effects of SUP versus no prophylaxis on patient-important outcomes in critically ill adult patients with sepsis who have risk factors for GI bleeding. METHODS This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care III database. We compared those who received SUP with proton pump inhibitors or histamine-2 receptor antagonists for ≥3 days with those who received no prophylaxis. Propensity score matching (PSM) was conducted to make comparisons between groups with similar distributions of study variables. The primary outcome was in-hospital mortality. RESULTS A total of 7,744 patients were included in the analysis, with 1,088 (14.0%) in the non-SUP group and 6,656 (86.0%) in the SUP group. A 1:1 PSM created 866 patients in each cohort. No significant differences were noted between the two groups with regard to in-hospital mortality (22.3%vs.20.4%, p=0.379), GI bleeding (4.7%vs.6.4%, p=0.172), pneumonia(38.9%vs.36.6%,p=0.346), Clostridium difficile infection(6.4% vs. 8.9%, p=0.0.057), or ICU length of stay (LOS) (4.2 d vs. 4.6 d, p=0.394). CONCLUSIONS Among critically ill, septic, adult patients at risk for gastrointestinal bleeding, stress ulcer prophylaxis showed no effect on hospital mortality, the rate of GI bleeding, pneumonia, CDI, and ICU LOS. This article is protected by copyright. All rights reserved.

Background The purpose of this study was to determine risk factors of postoperative complications in tuberculosis-destroyed lung (TDL) patients. Methods We retrospectively analyzed the data from all consecutive TDL patients undergoing surgical treatment at the Beijing Chest Hospital from January 2001 to September 2019. Results Of 113 TDL cases experiencing surgery, 33 (29.2%) experienced postoperative complications. The patients with low BMI were more likely to have postoperative complications compared to those with normal BMI, whereas a significant lower rate of postoperative complications was noted in patients with BMI ≥ 25 kg/m2. In addition, significant increased risk was observed in patients with smoking history. We found that the patients with underlying infection, including aspergillus and nontuberculous mycobacteria (NTM), had significantly higher odds of having postoperative complications compared with those without underlying infection. The anaemia was another important independent factor associated with postoperative complication. Patients with blood transfusion above 1000 mL had a strongly increased frequency of postoperative complications than patients with blood transfusion below 1000 mL. Conclusion In conclusion, our data demonstrate that approximate one third of TDL patients experience postoperative complications in our cohort. Patients with low BMI, anaemia, tobacco smoking, and coinfected aspergillus or NTM are at markedly higher risk to experience postoperative complications after pneumonectomy.

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p &lt, 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.

IntroductionThe associated mortality and morbidity in hip fracture patients pose a major healthcare burden for ageing populations worldwide. We aim to analyse how an individual’s comorbidity profile based on age-adjusted Charlson Comorbidity Index (CCI) may impact on functional outcomes and 90-day readmission rates after hip fracture surgery.Materials and MethodsSurgically treated hip fracture patients between 2013 and 2016 were followed up for 1-year and assessed using Parker Mobility Score (PMS), EuroQol-5D (EQ-5D) and Physical and Mental Component Scores (PCS and MCS, respectively) of Short Form-36 (SF-36). Statistical analysis was done by categorising 444 patients into three groups based on their CCI: (1) CCI 0–3, (2) CCI 4–5 and (3) CCI ≥ 6.ResultsPMS, EQ-5D and SF-36 PCS were significantly different amongst the CCI groups pre-operatively and post-operatively at 3, 6 and 12 months (all P < 0.05), with CCI ≥ 6 predicting for poorer outcomes. In terms of 90-day readmission rates, patients who have been readmitted have poorer outcome scores. Multivariate analysis showed that high CCI scores and 90-day readmission rate both remained independent predictors of worse outcomes for SF-36 PCS, PMS and EQ-5D.DiscussionCCI scores ≥6 predict for higher 90-day readmission rates, poorer quality of life and show poor potential for functional recovery 1-year post-operation in hip fracture patients. 90-day readmission rates are also independently associated with poorer functional outcomes. Peri-operatively, surgical teams should liaise with medical specialists to optimise patients’ comorbidities and ensure their comorbidities remain well managed beyond hospital discharge to reduce readmission rates. With earlier identification of patient groups at risk of poorer functional outcomes, more planning can be directed towards appropriate management and subsequent rehabilitation.ConclusionFurther research should focus on development of a stratified, peri-operative multidisciplinary, hip-fracture care pathway treatment regime based on CCI scores to determine its effectiveness in improving functional outcomes.

The importance of miRNA prognostic signature in cancer, particular cancer metastasis is increasingly being realized. Bone metastasis from several primary human cancers can be managed in clinics by surgical intervention but the prognostic impact of miRNA signature on post-surgery outcome of patients is unknown. This study evaluated a miRNA signature for post-operative outcome of patients with bone metastatic disease. First, the miRNAs, miR-135, miR-203, miR-10b, miR-194, miR-886, and miR-124 were evaluated in bone metastatic tissues, relative to adjacent control tissue. The cohorts of samples (n = 44) consisted of bone metastatic cancer patients with primary lung (n = 18) or breast cancer (n = 26). miR-203 was significantly down-regulated while miR-10b was significantly up-regulated in bone metastasis. Additionally, miR-135 was significantly differentially expressed in the primary lung cancer patients while miR-194 in primary breast cancer patients. The low miR-203- high miR-10b expression was designated high risk group and, compared to the low risk group (high miR-203-low miR-10b expression). Patients with the signature high risk fared significantly better with surgical intervention, in terms of survival at 12 months time point (40% survival with surgery vs. 10% survival without surgery), as revealed by retrospective analysis of patient data. This work reveals potential utilization of miRNA expression levels in not only the general prognosis of cancer metastasis but also the prognosis of surgical intervention with implication for better stratification of patients.

Objectives T cells play critical roles in the pathogenesis of systemic lupus erythematosus (SLE). Serum-derived exosomes are increased in SLE patients and are correlated with disease severity. The proteins in the T-cell-derived exosomes from SLE patients could play important roles in SLE pathogenesis. Methods We characterized proteins of SLE T cell-derived exosomes by exosome MACSPlex analysis and proteomics using T-cell supernatants from SLE patients and healthy controls. To study the potential pathogenic functions of the identified exosomal protein, we generated and characterized T-cell-specific transgenic mice that overexpressed the identified protein in T cells. Results We identified eosinophil cationic protein (ECP, also named human RNase 3) that was overexpressed in SLE T cell-derived exosomes. T-cell-specific ECP transgenic mice displayed early induction of serum IFN-γ levels and multi-tissue inflammation. The aged T-cell-specific ECP transgenic mice also displayed an increase of follicular helper T cells, plasma B cell, and autoantibodies. Single-cell RNA sequencing (scRNA-seq) also showed the induction of IFN-γ mRNA and inflammatory pathways in ECP transgenic T cells. Remarkably, adoptively transferred ECP-containing exosomes stimulated serum levels of IFN-γ and autoantibodies in the recipient mice. The transferred exosomes infiltrated into multiple tissues of the recipient mice, resulting in hepatitis, nephritis, and arthritis. Conclusions ECP overexpression in T cells or T-cell-derived exosomes may be a biomarker and pathogenic factor for human SLE nephritis, hepatitis, and arthritis.

Objective We aimed to compare the efficacy and risks of proton pump inhibitor (PPI) versus histamine-2 receptor blocker (H2B) use for stress ulcer prophylaxis (SUP) in critically ill patients with sepsis and risk factors for gastrointestinal bleeding (GIB). Methods In this retrospective cohort study, we used the Medical Information Mart for Intensive Care III Clinical Database to identify critically ill adult patients with sepsis who had at least one risk factor for GIB and received either an H2B or PPI for ≥48 hours. Propensity score matching (PSM) was conducted to balance baseline characteristics. The primary outcome was in-hospital mortality. Results After 1:1 PSM, 1056 patients were included in the H2B and PPI groups. The PPI group had higher in-hospital mortality (23.8% vs. 17.5%), GIB (8.9% vs. 1.6%), and pneumonia (49.6% vs. 41.6%) rates than the H2B group. After adjusting for risk factors of GIB and pneumonia, PPI use was associated with a 1.28-times increased risk of in-hospital mortality, 5.89-times increased risk of GIB, and 1.32-times increased risk of pneumonia. Conclusions Among critically ill adult patients with sepsis at risk for GIB, SUP with PPIs was associated with higher in-hospital mortality and higher risk of GIB and pneumonia than H2Bs.

BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB. RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

The cytokine IL-17A plays critical roles in the pathogenesis of autoimmune diseases. The frequencies of MAP kinase kinase kinase kinase 3 [also named germinal center kinase–like kinase (GLK)]-overexpressing T cells are correlated with disease severity of systemic lupus erythematosus (SLE). T-cell–specific GLK-transgenic mice develop spontaneous autoimmune responses through IL-17A. GLK signaling selectively stimulates IL-17A production in murine T cells through inducing aryl hydrocarbon receptor (AhR)–retinoic acid receptor–related orphan nuclear receptor-γt (ROR-γt) complex formation. Here, we investigated whether GLK-induced AhR–ROR-γt complex in T cells is a therapeutic target for human SLE. The population of GLK+IL-17A+ T cells was enhanced in the peripheral blood from patients with SLE compared with that of healthy controls using flow cytometry. The receiver operating characteristic curve analysis showed that increased GLK+IL-17A+ T-cell population in peripheral blood reflected an active stage of SLE. In addition, peripheral blood T cells from patients with SLE displayed induction of ROR-γt phosphorylation and the AhR–ROR-γt (and AhR–phosphorylated ROR-γt) complex. Moreover, we identified a small-molecule inhibitor, verteporfin, that inhibited GLK kinase activity and AhR–ROR-γt interaction. The small-molecule inhibitor verteporfin suppressed the disease severity in autoimmune mouse models and IL-17A production in T cells from patients with SLE. Collectively, the GLK-induced AhR–ROR-γt (and AhR–phosphorylated ROR-γt) complex is a therapeutic target for the GLKhighIL-17Ahigh subpopulation of human patients with SLE.—Chuang, H.-C., Chen, Y.-M., Chen, M.-H., Hung, W.-T., Yang, H.-Y., Tseng, Y.-H., Tan, T.-H. AhR–ROR-γt complex is a therapeutic target for MAP4K3/GLKhighIL-17Ahigh subpopulation of systemic lupus erythematosus.

Retrospective study using prospectively collected registry data.The authors examine the influence of preoperative mental health on outcomes after anterior cervical discectomy and fusion (ACDF) and determine the impact of ACDF on postoperative mental health.While studies have reported a negative correlation between preoperative mental health and outcomes following lumbar spine surgery, the influence on outcomes following cervical spine surgery remains relatively understudied.Prospectively collected registry data of 104 patients who underwent single-level ACDF for cervical spondylotic myelopathy were reviewed. Patients were dichotomized into top and bottom halves based on preoperative SF-36 MCS (Mental Component Summary) using a cutoff of 48. Outcomes assessed were visual analogue scale for neck pain, arm pain, AAOS Neck Pain and Disability, Neurogenic Symptoms, Neck Disability Index, Short-Form 36, Japanese Orthopaedic Association myelopathy score, return to work, return to function, satisfaction and expectation fulfilment up to 2 years postoperatively.The preoperative MCS was 37.5 ± 8.1 and 57.4 ± 6.3 in the Low and High MCS groups respectively (P 0.001). The Low MCS group had poorer preoperative scores (P 0.05). There was no significant difference in length of stay or comorbidities (P 0.05). The High MCS group had less neck pain (P = 0.002) and showed a trend towards lower Neck Disability Index (P = 0.062) at 2 years. The Low MCS group demonstrated greater improvement in Japanese Orthopaedic Association (P = 0.007) and similar improvement in other scores (P 0.05). There was no significant difference in proportion that achieved minimal clinically important difference for each score (P 0.05). Both groups had similar rates of return to work, return to function, expectation fulfilment, and satisfaction (P 0.05). Lower preoperative MCS was predictive of greater improvement in MCS (r = -0.477, P 0.001).Despite relatively greater pain and disability at 2 years, patients with poor baseline mental health experienced similar improvement in clinical outcomes, return to work, and satisfaction rates.3.

Background Over the past years, only few cases of follicular lymphoma diagnosed by laparoscopy have been reported in the world. Since follicular lymphoma related ascites often causes occult disease and lacks specific clinical manifestations, it is often difficult to identify the cause by routine laboratory tests and imaging methods. Diagnostic experience is not sufficient and more cases need to be accumulated for further analysis. Case summary Ascites due to unknown reasons often causes problems for clinical diagnosis and treatment. In this paper, we report one case with ascites in whom the reason causing ascites was not identified through routine examination. Laparoscopic examination of the celiac lesions and histological examination of the lesions were performed and the final diagnosis was peritoneal follicular lymphoma. Conclusion Laparoscopic abdominal examination is of great significance for the definite diagnosis of ascites due to an unknown reason.

The Warburg effect plays an important role in the proliferation and invasion of malignant tumors. Glucose transporter 1 and hexokinase II are two key energy transporters involved in mediating the Warburg effect. This review will analyze the mechanisms of these two markers in their effects on the biological behavior of head and neck cancer.

Aim To assess the real-world effectiveness and safety of rituximab (RTX) at 24 months in patients with established rheumatoid arthritis (RA) and to identify predictors of low disease activity/remission and a good European League Against Rheumatism (EULAR) response. Methods Seventy RTX-treated RA patients were enrolled. Predictors for low disease activity/remission and a good EULAR response at 24 months were identified by multivariate analyses. Results At 24 months, the mean Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) decreased from 6.88 ± 0.85 at baseline to 3.47 ± 0.85. Twenty-nine patients (41.4%) reached low disease activity/remission, while all patients had a moderate/good EULAR response. After adjustment by multivariate analyses, we found concomitant methotrexate at a dosage >10 mg/week (odds ratio [OR] 5.17; 95% CI 1.34-19.93; P = 0.017) predicted low disease activity/remission, and baseline DAS28 ≤6.5 (OR 4.97; 95% CI 1.22-20.30; P = 0.026) predicted good EULAR response at 24 months. The most common adverse events were infusion-related (5.7%), and there was no incidence of malignancy or mortality during the treatment. Conclusions RTX was effective and safe in real-life management of RA patients with high disease activity. Patients taking concomitant methotrexate and with lower baseline DAS28-ESR were more likely to benefit from RTX.

Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2–EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-β stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.

Historically, the median overall survival of patients with metastatic melanoma was less than one year. The recent advent of immunotherapy has changed the outlook dramatically and made long-term disease control achievable. Nivolumab, a monoclonal antibody to programmed cell death 1 (anti-PD1), has been proved to prolong survival in patients with metastatic melanoma. Vitiligo is a skin disorder characterized by the loss of color, and the postulated mechanism is immune-mediated destruction of melanocytes. Anti-PD1 treatment related to vitiligo has been reported to be associated with a favorable response in patients with melanoma. Here we present the case of a 61-year-old woman who received nivolumab for metastatic melanoma. After 6 months of nivolumab therapy, the patient experienced scattered hypopigmentation on her face, chest, and back. Durable response was noticed according to the follow-up images even after nivolumab was discontinued. Keywords: Immunotherapy, Melanoma, Vitiligo

Pulmonary fibrosis (PF) is a progressive and devastating lung disease of unknown etiology, excessive fibroblast proliferation serves as a key event to promote PF. Transcription factor forkhead box M1 (FOXM1) is not only a well-known proto-oncogene, but also an essential driver of cell proliferation. Recently, 5’-AMP-activated protein kinase (AMPK) is reported to reduce the incidence of PF. However, it remains elusive whether have an underlying relationship between AMPK and FOXM1 in fibroblast proliferation-mediated PF. Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6 J mice. Meanwhile, human fetal lung fibroblast1 (HFL1) cells were respectively treated with AMPK activator metformin or AMPK inhibitor Compound C, or FOXM1 depletion by transfected small interfering RNA (siRNA) to unveil roles of AMPK, FOXM1 and the link between them on platelet-derived growth factor (PDGF)‐induced fibroblast proliferation. Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model. In vitro, activation of AMPK attenuated PDGF‐induced fibroblast proliferation accompanied by the down-regulation of FOXM1. In contrast, inhibition of AMPK enhanced PDGF‐induced fibroblast proliferation along with activating FOXM1. These findings suggest that AMPK can ameliorate the progression of fibroblast proliferation during PF via suppressing the expression of FOXM1 and provide new insight into seek PF treatment approaches.

AimsTo characterize the genetic landscape and mutation spectrum of patients with corneal dystrophies (CDs) in a large Han ethnic Chinese Cohort with inherited eye diseases (IEDs).MethodsRetrospective study. A large IED cohort was recruited in this study, including 69 clinically diagnosed CD patients, as well as other types of eye diseases patients and healthy family members as controls. The 792 genes on the Target_Eye_792_V2 chip were used to screen all common IEDs in our studies, including 22 CD-related genes.ResultsWe identified 2334 distinct high-quality variants on 22 CD-related genes in a large IEDs cohort. A total of 21 distinct pathogenic or likely pathogenic mutations were identified, and the remaining 2313 variants in our IED cohort had no evidence of CD-related pathogenicity. Overall, 81.16% (n = 56/69) of CD patients received definite molecular diagnoses, and transforming growth factor-beta-induced protein (TGFBI), CHTS6, and SLC4A11 genes covered 91.07, 7.14, and 1.79% of the diagnosed cases, respectively. Twelve distinct disease-associated mutations in the TGFBI gene were identified, 11 of which were previously reported and one is novel. Four of these TGFBI mutations (p.D123H, p.M502V, p.P501T, and p.P501A) were redefined as likely benign in our Han ethnic Chinese IED cohort after performing clinical variant interpretation. These four TGFBI mutations were detected in asymptomatic individuals but not in CD patients, especially the previously reported disease-causing mutation p.P501T. Among 56 CD patients with positive detected mutations, the recurrent TGFBI mutations were p.R124H, p.R555W, p.R124C, p.R555Q, and p.R124L, and the proportions were 32.14, 19.64, 14.29, 10.71, and 3.57%, respectively. Twelve distinct pathogenic or likely pathogenic mutations of CHTS6 were detected in 28 individuals. The recurrent mutations were p.Y358H, p.R140X, and p.R205W, and the proportions were 25.00, 21.43, and 14.29%, respectively. All individuals associated with TGFBI were missense mutations; 74.19% associated with CHTS6 mutations were missense mutations, and 25.81% were non-sense mutations. Hot regions were located in exons 4 and 12 of TGFBI individuals and located in exon 3 of CHTS6 individuals. No de novo mutations were identified.ConclusionFor the first time, our large cohort study systematically described the variation spectrum of 22 CD-related genes and evaluated the frequency and pathogenicity of all 2334 distinct high-quality variants in our IED cohort. Our research will provide East Asia and other populations with baseline data from a Han ethnic population-specific level.

Pulmonary fibrosis (PF) could severely disrupt the normal lung architecture and function with fatal consequences. Currently, there is no effective treatment for PF or idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the effects of Sodium Houttuyfonate (SH) on bleomycin (BLM) induced PF mice model. Our results indicated that SH could attenuate BLM induced lung injury by reducing the inflammation, fibrogenesis and lung/body weight ratio. The proposed mechanisms for the protective effects of SH include: 1) improvement of pulmonary function in BLM mice, for instance, it can elevate the vital capacity (VC), increase the forced expiratory flow at 50% of forced vital capacity (FEF50) and improve other pulmonary function indices; 2) inhibition of collagen formation in BLM mice; 3) attenuation of the elevation of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), which are triggered by BLM administration; 4) reduction of the mRNA level and protein production of transforming growth factor-β1 (TGF-β1) in BLM mice. Furthermore, it was found that the protective effects of SH against BLM induced PF in mice was comparable to that of prednisone acetate (PA) tablets, a widely used drug for immunological diseases. Although Houttuynia Cordata Thunb has been widely used in China for lung infection and inflammation, the mechanism has not yet been fully elucidated. Our study provides the evidence that SH is an effective compound against pulmonary injury, irritation and fibrogenesis.

BackgroundGastric cancer (GC) is the fifth most common cancer worldwide. Previous studies have suggested that the tumor microenvironment (TME) plays an important role in the development and prognosis of GC. In this study, we aimed to identify genes in tumor-infiltrating immune cells (TICs) that influence the progression and prognosis of GC. MethodsWe used the ESTIMATE algorithm to calculate the scores of the stromal and immune components of the TME in 407 GC samples collected from The Cancer Genome Atlas (TCGA) database.The differentially expressed genes (DEGs) were intersected by a protein-protein interaction (PPI) network and analyzed by univariate Cox regression.Further analysis showed the correlation between MCEMP1 and the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and survival.Then we used Gene set enrichment analysis (GSEA) and CIBERSORT analysis to examine the relationship between MCEMP1 and the TME.ResultsThe analysis revealed that the expression of MCEMP1 was positively correlated with the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and negatively correlated with survival. Gene set enrichment analysis (GSEA) indicated that gene sets in the MCEMP1 high expression group were concentrated mainly in immune-related pathways. CIBERSORT analysis of the proportion of TICs revealed that neutrophils and M2 macrophages were positively correlated with MCEMP1 expression, suggesting that MCEMP1 is responsible for preservation of the immune-dominant status of the TME. ConclusionHigh MCEMP1 expression might be a biomarker of a poor prognosis in GC patients and provide a clue regarding the different statuses of the TME, offering additional insight into therapy for GC.