brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Maximizing US nitrate removal through wetland protection and restoration.

Growing populations and agricultural intensification have led to raised riverine nitrogen (N) loads, widespread oxygen depletion in coastal zones (coastal hypoxia)1 and increases in the incidence of algal blooms.Although recent work has suggested that individual wetlands have the potential to improve water quality2-9, little is known about the current magnitude of wetland N removal at the landscape scale. Here we use National Wetland Inventory data and 5-kilometre grid-scale estimates of N inputs and outputs to demonstrate that current N removal by US wetlands (about 860 ± 160 kilotonnes of nitrogen per year) is limited by a spatial disconnect between high-density wetland areas and N hotspots. Our model simulations suggest that a spatially targeted increase in US wetland area by 10 per cent (5.1 million hectares) would double wetland N removal. This increase would provide an estimated 54 per cent decrease in N loading in nitrate-affected watersheds such as the Mississippi River Basin. The costs of this increase in area would be approximately 3.3 billion US dollars annually across the USA-nearly twice the cost of wetland restoration on non-agricultural, undeveloped land-but would provide approximately 40 times more N removal. These results suggest that water quality improvements, as well as other types of ecosystem services such as flood control and fish and wildlife habitat, should be considered when creating policy regarding wetland restoration and protection.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

Early life supplementation with mannan-rich fraction to regulate rumen microbiota, gut health, immunity and growth performance in dairy goat kids.

Enhancing gastrointestinal health, immunity, and digestion are key factors to support dairy goat kid performance. Several additives have been studied in relation to these actions. This study investigated the impact of mannan-rich fraction (MRF) inclusion in goat milk on the growth performance, gut health, rumen fermentation and microbial profiles of Xinong Saanen dairy goat kids. Eighty kids aged 14 d and 4.72 ± 0.33 kg body weight (BW) were randomly assigned into 2 groups: Control and MRF (1g/d MRF mixed into milk), each group consisted of 40 kids with 10 kids per pen. All kids were given milk individually and fed starter diet by pen, with the trial lasting 10 weeks. BW and blood samples were collected on the 7th day at 2, 6, 10 and 12 weeks of age, and feed intake was determined daily. From the 1st to 7th day at 12 weeks of age, fecal samples were collected on 4 kids from each group to analyze nutrient digestibility. On the 7th day of 12 weeks of age, 4 kids from each group were slaughtered for evaluation of rumen fermentation, rumen microbiota and gut morphology. The results indicated that MRF supplementation led to greater overall BW (P < 0.01), overall starter dry matter intake (DMI) (P < 0.01) and overall average daily gain (ADG) (P = 0.021), while showing lower overall diarrhea rate (P < 0.01). However, no difference in overall feed efficiency (FE) (P = 0.063) and apparent digestibility of nutrients was observed (P > 0.05). Furthermore, MRF supplementation resulted in increased ileal villus height (P = 0.05), and higher RNA expression of Claudin-1 and Occuldin in the duodenum (P < 0.05), ZO-1, JAM-2, and Occuldin in the jejunum (P < 0.05), and Claudin-1, JAM-2, and Occuldin in the ileum (P < 0.05). Additionally, the concentrations of overall IgA, overall IgM and overall IgG were higher in the MRF group (P < 0.01). The concentrations of ruminal acetate and total volatile fatty acid (TVFA) were higher with MRF supplementation (P < 0.05). Meanwhile, supplementation with MRF resulted in higher abundance of Bacteroidetes and Succinivibrio, but lower abundance of Firmicutes and Succiniclasticum in the rumen. In conclusion, growth performance, gut health, immunity, and ruminal microbial structure of dairy goat kids benefited from MRF supplementation.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Evidence for Band Renormalizations in Strong-Coupling Superconducting Alkali-Fulleride Films.

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

Comparative Analysis of Rhizosphere and Endophytic Microbial Communities Between Root Rot and Healthy Root of Psammosilene tunicoides.

The wild resources of Psammosilene tunicoides have decreased sharply because of the long-term mining and excavation, which has led to the increased demand for its artificial cultivation. However, root rot represents a significant obstacle leading to a poor quality and product of P. tunicoides. Previous reports have not focused on root rot in P. tunicoides. Therefore, this study explores the rhizospheric and root endophytic microbial community structure and composition of healthy and root rot P. tunicoides to understand the mechanism underlying root rot. The properties of the rhizosphere soil were assessed using physiochemical methods, and the bacterial and fungal populations were studied through amplicon sequencing of the 16S rRNA genes and ITS regions in the root and soil. Compared to healthy samples, the pH, hydrolysis N, available P, and available K were significantly decreased in the diseased samples while the organic matter and total organic carbon were significantly increased in the diseased samples. Redundancy analysis (RDA) showed that soil environmental factors are related to changes in the root and rhizosphere soil microbial community of P. tunicoides indicating that the physiochemical properties of soil affect plant health. Alpha diversity analysis showed that the microbial communities of healthy and diseased samples were similar. Some bacterial and fungal genera were significantly increased or decreased (P < 0.05) in diseased P. tunicoides, and certain microbial factors that antagonized root rot were further explored. This study provides an abundant microbial resource for future studies and contributes to improving soil quality and P. tunicoides agricultural production.

Cost-minimisation analysis of intravenous versus subcutaneous trastuzumab regimen for breast cancer management in Hong Kong.

INTRODUCTION: In 2017, breast cancer was the most common cancer and third leading cause of cancer death among women in Hong Kong. Approximately 20% of patients were human epidermal growth factor receptor-2 (HER2)-positive. This study was conducted to investigate cost differences between intravenous and subcutaneous trastuzumab regimens in Hong Kong using medical resources utilisation data from other countries. METHODS: A cost-minimisation model was developed to compare the cost of total care, including direct medical cost and full-time equivalent (FTE) hours. The drug acquisition cost was obtained from the manufacturer, whereas the costs for hospitalisation and clinic visits were acquired from the Hong Kong Gazette. Time (in FTE hours) was determined by literature review. All costs were expressed in US dollars (US$1 = HK$7.8). Costs were not discounted because of the short time horizon. One-way deterministic sensitivity analysis was performed to identify the effects of changes in drug acquisition cost, changes in FTE hours (based on confidence intervals reported), and changes in body weight (±20%). RESULTS: Literature review indicated that 0.18 FTE hour of nursing time (7.9 hours) and 0.14 FTE hour of pharmacist time (6.2 hours) could be saved each week if the subcutaneous formulation was used. Using data in 2017, after 18 cycles of treatment with subcutaneous trastuzumab, the drug acquisition and healthcare professional time costs were reduced by US$9451.28 and US$566.16, respectively, yielding an annual savings of over US$8 million. CONCLUSION: The subcutaneous formulation of trastuzumab is a potential cost-saving therapy for HER2-positive breast cancer patients in Hong Kong. The drug acquisition cost was the parameter with the greatest effect on the total cost of treatment.

[Genetic mutation profiles for children with congenital hypothyroidism in Fujian province].

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.

[Factors affecting BK polyomavirus infection after kidney transplantation in post-school children and a predictive infection model].

Objective: To analyze high-risk factors affecting BK polyomavirus (BKPyV) infection and to construct a prediction model for BKPyV infection in children after renal transplantation. Methods: The clinical data of 332 children who received allogeneic kidney transplantation in the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2022 were retrospectively collected. According to the BKPyV load level, the dynamic change process of lymphocytes at different time points were analyzed. The factors that have potential influence on BKPyV infection were screened by Cox regression analysis, and the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of the predictive model of infection. Results: Among the 332 children, there were 215 males and 117 females; the age of transplantation was (12.2±3.9) years old; 37 cases were preschool (1-5 years old), and 295 cases were post-school age (6-18 years old). BKPyV load in 224 urine samples and 30 blood samples of children were detected. There were 9 cases of BKPyV-associated viruria and 3 cases of BKPyV associated viremia in pre-school children, 76 cases BKPyV associated viruria and 14 cases of BKPyV associated viremia in post-school children. Multivariate Cox regression analysis showed that higher body mass index (BMI) (HR=1.105, 95%CI: 1.020-1.197), antithyroglobulin (ATG) application (HR=2.196, 95%CI: 1.335-3.613), and higher tacrolimus concentration (HR=2.484, 95%CI: 1.298-4.753), higher natural killer (NK) lymphocyte count (HR=1.193, 95%CI: 1.009-1.411), higher CD14++CD16-cell count (HR=1.096, 95%CI: 1.024-1.173) were independent risk factors for BKPyV associated viruria in post-school children. Delayed graft function (DGF) (HR=4.993, 95%CI: 1.555-16.038), Acute rejection (AR) (HR=6.021, 95%CI: 1.930-18.787), higher CD14++CD16-cell count (HR=1.227, 95%CI: 1.081-1.392) were independent risk factors for BKPyV associated viremia in post-school children. The results of ROC curve analysis showed that combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, and CD14++CD16-cell count predicted the occurrence of BKPyV associated viruria in post-school children after kidney transplantation at 0.5, 1, 2, and 5 years with area under curve (AUC) of 0.712 (95%CI: 0.626-0.798), 0.708 (95%CI: 0.612-0.804), 0.754 (95%CI: 0.668-0.840) and 0.767 (95%CI: 0.685-0.849). The sensitivity and specificity of the model were 64.9%, 61.4%, 61.6%, 55.8% and 70.9%, 72.4%, 76.0%, 84.0%, respectively. Combined with DGF, AR, and CD14++CD16-cell counts predicted the occurrence of BKPyV-associated viremia at 0.5, 1, 2, and 5 years after renal transplantation in post-school children with AUC of 0.791 (95%CI: 0.631-0.951), 0.744 (95%CI: 0.547-0.936), 0.786 (95%CI: 0.629-0.946) and 0.812 (95%CI: 0.672-0.948). The sensitivity and specificity of the model were 76.1%, 67.1%, 75.0%, 77.9% and 88.9%, 89.0%, 89.9%, 88.0%, respectively. Conclusions: The postoperative CD14++CD16-cell level can be used as an independent predictor of BKPyV infection in post-school children after renal transplantation. Combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, CD14++CD16-cell count and combined DGF, AR, CD14++CD16-cell count show good fitting effect in predicting the occurrence of BKPyV-associated viruria and viremia after transplantation in post-school children respectively.

[Molecular epidemiology and antibiotic resistance of Pseudomonas aeruginosa isolated from blood in a hospital in Shandong Province from 2014 to 2021].

Objective: To identify the antibiotic resistance, virulence genes, and sequence types of Pseudomonas aeruginosa (P. aeruginosa) strains isolated from blood. Methods: From November 2014 to December 2021, a total of 94 nonrepetitive P. aeruginosa isolates were obtained from blood samples of patients at the First Affiliated Hospital of Shandong First Medical University in Shandong Province, China. The bacteria were identified using matrix-assisted laser desorption ionization time of flight mass spectrometry. Antibiotic resistance of the P. aeruginosa isolates was detected using Vitek 2 Compact system. Polymerase chain reaction (PCR) was conducted for the 18 virulence genes, and multi locus sequence typing (MLST) was performed to identify the sequence types of the P. aeruginosa strains. The resistance rates and distributions of virulence genes between carbapenem resistant pseudomonas aeruginosa (CRPA) and carbapenem susceptible pseudomonas aeruginosa (CSPA) isolates were compared using the Chi-square test. Results: Among 94 P. aeruginosa isolates, 19 (20.2%) isolates were found to be multidrug resistant (MDR) bacteria, of which 17 were CRPA isolates and 2 were CSPA isolates. All strains contained more than 10 virulence genes. Except for exoU gene, the detection rate of other genes was above 83%. MLST analysis revealed a total of 66 different STs, including 59 existing STs and 7 novel STs. Among them, ST244 (n=11, 11.7%) and ST270 (n=7, 7.4%) were the dominant STs. Although these two types of isolates harbored the same virulence genes, the resistance rates to carbapenem were different. 54.5% (6/11) ST244 isolates were CRPA but all 7 ST270 isolates were CSPA. Conclusion: Although the resistance rates of P. aeruginosa strains isolated from blood were at a low level, some MDR and CRPA isolates were detected. As the high virulence gene detection rates and genetic diversity were found for P. aeruginosa strains isolated from blood, close attention should be paid to avoid transmission and outbreaks.

Effect of ontological insecurity on vaccination behavior against COVID-19: a hospital-based cross-sectional study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has brought great uncertainty to our society and it may have disrupted people's ontological security. Consequently, this hospital-based study concerns the impact of ontological insecurity on vaccination behavior against COVID-19. STUDY DESIGN: This cross-sectional study was conducted among hospital inpatients. METHODS: A questionnaire survey addressing inpatient ontological insecurity and vaccination behavior against COVID-19 was administered in Taizhou, China. A total of 1223 questionnaires were collected; specifically, 1185 of them were credible, for a validity rate of 96.9%. RESULTS: The score of ontological insecurity was 13.27 ± 7.84, which was higher in participants who did not recommend vaccination for others than those who did (12.95 ± 8.25 vs 14.00 ± 6.78, P = 0.022). There was no difference between the vaccinated and unvaccinated groups (13.22 ± 7.96 vs 13.35 ± 7.67, P = 0.779). Lower ontological insecurity (odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.08-1.81) and being inoculated with COVID-19 vaccines (OR = 2.17, 95% CI: 1.67-2.82) were significantly associated with recommendation of COVID-19 vaccines to others after adjusting for sex, age, education, and occupation. Associations between low ontological insecurity and recommendations for COVID-19 vaccines were observed in men, adults aged 18-59 years, non-farmers, and vaccine recipients. CONCLUSIONS: This study suggests that the ontological insecurity of participants affects their behavior of recommending the COVID-19 vaccination to others rather than getting vaccinated themselves. This promotion of vaccination can be considered from the perspective of improving ontological security in China.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

[Role of the CCL28-CCR10 pathway in monocyte migration in rheumatoid arthritis].

OBJECTIVE: To examine the expression of chemokine receptor CCR10 on monocytes/macrophages in the joints of patients with rheumatoid arthritis (RA), and to investigate the role of chemokine CCL28 and its receptor CCR10 in the migration of RA monocytes and its mechanism. METHODS: The expression of CCR10 in synovial tissues from 8 RA patients, 4 osteoarthritis (OA) patients, and 4 normal controls was analyzed by immunohistochemistry, and cell staining was scored on a 0-5 scales. Flow cytometry was used to measure the percentage of CCR10 positive cells in CD14+ monocytes from peripheral blood of 26 RA patients and 20 healthy controls, as well as from synovial fluid of 15 RA patients. The chemotactic migration of monocytes from RA patients and healthy controls in response to CCL28 was evaluated using an in vitro Transwell system. Western blotting was conducted to assess phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways in RA monocytes upon CCL28 treatment. RESULTS: CCR10 was predominantly expressed in RA synovial lining cells and sublining macrophages, endothelial cells, and lymphocytes. CCR10 expression was significantly increased on lining cells and sublining macrophages in RA synovial tissue compared with OA and normal synovial tissue (both P < 0.01). The patients with RA had markedly elevated expression of CCR10 on peripheral blood CD14+ monocytes compared with the healthy controls [(15.6±3.0)% vs. (7.7±3.8)%, P < 0.01]. CCR10 expression on synovial fluid monocytes from the RA patients was (32.0±15.0)%, which was significantly higher than that on RA peripheral blood monocytes (P < 0.01). In vitro, CCL28 caused significant migration of CD14+ monocytes from peripheral blood of the RA patients and the healthy controls at concentrations ranging from 10-100 µg/L (all P < 0.01). The presence of neutralizing antibody to CCR10 greatly suppressed CCL28-driven chemotaxis of RA monocytes (P < 0.01). Stimulation of RA monocytes with CCL28 induced a remarkable increase in phosphorylation of ERK and Akt (both P < 0.05). ERK inhibitor (U0126) and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) strongly reduced the migration of RA monocytes in response to CCL28 (both P < 0.01). CONCLUSION: RA patients had increased CCR10 expression on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages. CCL28 ligation to CCR10 promoted RA monocyte migration through activation of the ERK and PI3K/Akt signaling pathways. The CCL28-CCR10 pathway could participate in monocyte recruitment into RA joints, thereby contributing to synovial inflammation and bone destruction.

[Diagnostic performances of salivary gland ultrasonography for Sjögren's syndrome].

OBJECTIVE: To evaluate the diagnostic performances of salivary gland ultrasonography(SGUS)in Sjögren's syndrome(SS). METHODS: A total of 246 patients with dry mouth and/or eyes who were treated in the outpatient department and inpatient department of Rheumatology and Immunology Department of the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to January 2022 were collected. All patients received SGUS examination and scored by 2019 outcome measures in rheumatology clinical trial (OMERACT)ultrasonic scoring system.Their general information, unstimulated saliva flow rate(USFR), Schirmer test and serological test results were recorded. In the study, 193 cases had lip gland biopsy. The 2016 American College of Rheumatology(ACR)/ European League Against Rheumatism(EULAR)classification criteria were adopted as the diagnostic standard of SS. χ2 test was used to compare the difference of salivary gland ultrasonic scores between the two groups. The receiver operating characteristic(ROC) curve was used to evaluate the accuracy of SGUS in diagnosing SS, and the disease characteristics of SGUS positive group and negative group in the SS patients were compared. RESULTS: A total of 175 patients were SS group according to the ACR/EULAR classification, and the remaining 71 patients were non-SS group.There was no significant difference in age [(54.2±11.8) years vs. (53.4±14.9) years, P=0.705] and female (94.4% vs.93.1%, P=1.000) between SS and non-pSS groups. A total of 109 patients were SGUS positive (≥ 2 points), of whom 104 patients met the SS diagnosis and 5 patients did not meet the SS diagnosis. The positive rate of SGUS in SS group was significantly higher than that in non-SS group (59.4% vs. 7.0%, P < 0.001). The accuracy of 2019 OMERACT ultrasonic scoring system to predict ACR/EULAR classification was good, with an area under the curve of 0.762 (95%CI 0.701-0.823). The absolute agreement between the SGUS outcome and ACR-EULAR classification was 69.1%(170/246), with a sensiti-vity of 59.4%(104/175), specificity of 93%(66/71), positive predictive value of 95.4%(104/109) and negative predictive value of 48.2% (66/137). A total of 81 patients were positive SGUS combined with anti-SSA antibody, 100% (81/81) fulfilled the ACR-EULAR criteria, 85 patients were negative SGUS and anti SSA antibody, and 60 patients(70.6%, 60/85) did not fulfil the ACR-EULAR criteria. SGUS positive group had higher antinuclear antibody(ANA) positive rate(83.1% vs. 98.1%, P < 0.001) in the patients with SS. CONCLUSION: The OMERACT ultrasonic scoring system has high diagnostic value in SS. The combination of SGUS and anti-SSA antibody can improve the diagnostic value.

[Efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma].

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

Amsp3 may act upstream of Amdnmt3 in female caste differentiation in the honeybee (Apis mellifera).

In honey bees, the process of producing two female castes, including queens and workers, is nutritionally controlled by differential feeding royal jelly to newly emerged larvae. Although they have almost identical genetic blueprints, these castes show striking differences in their morphologies, longevities and reproductive capabilities. DNA methyltransferase 3 (Amdnmt3) gene is involved in the regulatory network for honeybee caste differentiation. Due to the role of two zinc fingers containing transcription factors, SP1 and SP3 in controlling mammalian Dnmts, this study aimed to determine a similar interaction of SPs with Amdnmt3 in the honeybee. We confirmed that the promoter region of Amdnmt3 contained multiple predicted SP1/SP3 binding sites and then investigated the role of AmSP3 in queen-worker differentiation network. We observed that the expression level of Amsp3 was significantly higher in worker larvae than that in queen larvae at 48 h, 84 h and 120 h. Knockdown of Amsp3 expression by RNAi in worker larvae significantly reduced the expression level of Amdnmt3 and caused morphological changes in adult bees towards a queen-like phenotype. However, the expression levels of Amsp3 and Amdnmt3 were repressed by juvenile hormone (JH). Our results suggest that AmSP3 is an important part of the queen-worker differentiation network and supports the role of Amdnmt3 in determining the phenotypic outcome of developing larvae.

Fecal microbiota transplantation for Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbiota transplantation (FMT) is an emerging treatment approach for CD. But its efficacy and safety remain controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD patients. METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT for CD. Clinical remission was established as the primary outcome. Secondary outcome was clinical response. Odds ratios with 95% confidence intervals (CIs) were reported. RESULTS: In all, 12 trials were included in our study. Pooled analysis showed that 0.62 (95% CI 0.48, 0.81) of CD patients achieved clinical remission and 0.79 (95% CI 0.71, 0.89) of CD patients achieved clinical response post-FMT. Sub-analyses suggested the rate of clinical remission with fresh stool FMT was higher than with frozen stool FMT (73% vs 43%; p < 0.05). Most adverse events were minor and self-resolving and no major FMT-related adverse event has been reported so far. CONCLUSIONS: The evidence showed that FMT is an effective and safe therapy for CD. FMT may be successful because it increases the overall diversity of enteric microbiome. Additional randomized controlled studies are needed.

PDLCs and EPCs Co-Cultured on Ta Discs: A Golden Fleece for "Compromised" Osseointegration.

Material research in tissue engineering forms a vital link between basic cell research and animal research. Periodontal ligament cells (PDLCs, P) from the tooth have an osteogenic effect, whereas endothelial progenitor cells (EPCs, E) assist in neovascularization. In the present study, the interaction of PDLCs and EPCs with Tantalum (Ta, I) discs, either alone (IP or IE group) or in 1:1 (IPE) ratio was explored. Additionally, surface analysis of Ta discs with respect to different types and cycles of sterilization and disinfection procedures was evaluated. It was observed that Ta discs could be used for a maximum of three times, after which the changes in properties of Ta discs were detrimental to cell growth, irrespective of the type of the protocol. Cell-Disc's analysis revealed that cell proliferation in the IE group at day 6 and day 10 was significantly higher (p < 0.05) than other groups. A cell viability assay revealed increased live cells in the IPE group than in the IP or IE group. Similarly, adhesion and penetration of cells in the IPE group were not only higher, but also had an increased thickness of cellular extensions. RT-PCR analysis revealed that on day 8, both osteogenic (ALP, RUNX-2, and BSP) and angiogenic genes (VEGFR-2, CD31) increased significantly in the IPE group as compared to the IP or IE groups (p < 0.05). In conclusion, Ta discs promoted cellular proliferation and increased osteogenic and angiogenic activity by augmenting RUNX-2 and VEGFR-2 activity.