Feasibility, reliability and validity of self-measurement of knee range-of-motion using an accelerometer-based smartphone application by patients with total knee arthroplasty.

AIMS: Limited knee range-of-motion (ROM) is common following total knee arthroplasty (TKA). It is associated with functional limitations and patient dissatisfaction. Regular knee ROM assessment is important but accurate testing traditionally requires timely access to trained healthcare professionals. Although accelerometer-based smartphone goniometry has shown to provide reliable and valid joint angles, current evidence of its use still positions healthcare providers as end users instead of patients themselves. Therefore, to maximize the impact of smartphone goniometry on post-TKA care, our study aimed to examine the feasibility, reliability, and validity of patients' self-measurement of knee ROM using an accelerometer-based smartphone goniometry application. METHODS: Patients were given standard instructions with a practice trial before the actual measurements. Passive knee flexion and extension ROM was measured on 2 sessions in 30 patients with TKA using 4 block-randomized methods: (i) smartphone self-assessment, (ii) long-arm goniometry by physiotherapist, (iii) smartphone assessment by physiotherapist, and (iv) extendable-arm goniometry by physiotherapist with placement adjudication. Feasibility was assessed by the number of participants who could independently perform the self-measurement. To assess intra- and inter-session reliability, we computed intraclass correlation coefficients (ICCs) from random-effects models. To assess intra- and inter-session agreement, we computed mean absolute differences (MADs) and minimum detectable change (MDC). To assess concurrent validity, we designated extendable-arm goniometry as the "gold standard" and compared other methods against it using ICCs and MADs. RESULTS: All patients were able to comprehend and execute the assessment. 87% (n = 26) found the application easy to administer. Smartphone goniometry by patients showed excellent intra- and inter-session reliability (ICCs>0.97) and minimum variability (MAD = 0.9°-3.9°; MDC95 = 3.1°-9.0°). Smartphone or long-arm goniometry by physiotherapists did not outperform patients' self-assessment (ICC = 0.96-0.99, MAD = 0.7°-3.1°; MDC95 = 2.2°-8.0°). Compared against extendable-arm goniometry, smartphone goniometry by patients measured knee flexion and extension ROM with a MAD of 4.5° (ICC, 0.97) and 2.2° (ICC = 0.98), respectively. CONCLUSION: Our study demonstrates that smartphone goniometry is feasible, reliable and accurate, and can be used with confidence in the self-assessment of knee ROM post-TKA. Future studies should further explore its utility in telemonitored rehabilitation, and its possible integration into mobile health applications to enhance accessibility to care following TKA.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Rational design of soluble expressed human aldehyde dehydrogenase 2 with high stability and activity in pepsin and trypsin.

Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme in alcohol metabolism, and oral administration of ALDH2 is a promising method for alcohol detoxification. However, recombinant ALDH2 is susceptible to hydrolysis by digestive enzymes in the gastrointestinal tract and is expressed as inactive inclusion bodies in E. coli. In this study, we performed three rounds of rational design to address these issues. Specifically, the surface digestive sites of pepsin and trypsin were replaced with other polar amino acids, while hydrophobic amino acids were incorporated to reshape the catalytic cavity of ALDH2. The resulting mutant DE2-852 exhibited a 45-fold increase in soluble expression levels, while its stability against trypsin and pepsin increased by eightfold and twofold, respectively. Its catalytic efficiency (kcat/Km) at pH 7.2 and 3.2 improved by more than four and five times, respectively, with increased Vmax and decreased Km values. The enhanced properties of DE2-852 were attributed to the D457Y mutation, which created a more compact protein structure and facilitated a faster collision between the substrate and catalytic residues. These results laid the foundation for the oral administration and mass preparation of highly active ALDH2 and offered insights into the oral application of other proteins.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Logistics operation and management of public hospitals based on the"one center,four platforms"model / 现代医院

Objective To evaluate the effectiveness of a hospital logistics operation and management based on the"one center,four platforms"model.Methods In line with the grading evaluation standards for hospital intelligent management,we used technologies such as big data,Internet of Things,Internet Plus,and artificial intelligence to develop a"one center,four platforms"model.This model consisted of a logistics intelligent operation and maintenance management center,an equipment control information platform,a security prevention information platform,an energy consumption monitoring information platform,and an operation management information platform.Results The equipment fault resolution capability,enhanced by the"smart linkage",showed a significant improvement.In 2022,false alarms decreased by 28.63%compared to 2021,with high-level and ordinary-level alarms decreasing by 69.53%and 33.15%,respectively.The"one-stop"logistics service capability was signifi-cantly improved,as indicated by a 2.92%decrease in maintenance frequency in 2022 compared to 2021.This improvement was further reflected in the quality of maintenance and a decrease in the repeated maintenance occurrences.The energy consumption control capability,based on the"data mining",showed a significant improvement,with an 8.71%year-on-year decrease in en-ergy expenditure of ten thousand yuan in 2022 compared to 2021.Conclusion The"one center,four platforms"model can sig-nificantly enhance the efficiency of logistics operation and maintenance management.

Albumin-bilirubin score predicts trastuzumab resistance in HER2-positive breast cancer.

BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Palladium-catalyzed synthesis and acetylcholinesterase inhibitory activity evaluation of 1-arylhuperzine A derivatives.

A series of arylated huperzine A (HPA) derivatives (1-24) were efficiently synthesized in good yields (45-88% yields) through the late-stage modification of structurally complex natural anti-Alzheimer's disease (AD) drug huperzine A (HPA), using the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. The acetylcholinesterase (AChE) inhibitory activity of all synthesized compounds was evaluated to screen the potential anti-AD bioactive molecules. The results showed that introducing the aryl groups to C-1 position of HPA resulted in the unsatisfactory AChE inhibitory activity. The present study demonstrably verifies pyridone carbonyl group could be the necessary and unchangeable pharmacophore for maintaining HPA's anti-AChE potency, and provides the helpful information on the further research for developing anti-AD HPA analogues.

Synthesis and Cytotoxicity Evaluation of Dehydroepiandrosterone Derivatives by Iron-Catalyzed Stereoselective Hydroamination.

The direct modification of structurally complex natural product dehydroepiandrosterone (DHEA) through iron-catalyzed direct hydroamination of DHEA with various nitro(hetero)arenes was carried out to afford 5α-arylamino-DHEAs (1-25) in good yields (53-72%). Though as a radical reaction, it features high stereoselectivity, and only the 5α-substituted derivatives were produced. The in vitro antiproliferative activity of these synthesized compounds against the human breast cancer MCF-7 cell was evaluated, showing that most of DHEA analogues possessed the moderate cytotoxic activity. The preliminary structure-activity relationship analysis revealed that the electron-withdrawing groups installed at the para-position of arylamine ring had a great contribution to the improvement of the DHEA's cytotoxic potency. Among them, (4-trifluoromethylaniline)-DHEA (4) displayed the most potent cytotoxicity, with an IC50 value of 19.3 µM, which was 2.3-fold more active than DHEA.

Involvement of Methoprene-tolerant and Krüppel homolog 1 in juvenile hormone-mediated vitellogenesis of female Liposcelis entomophila (End.) (Psocoptera: Liposcelididae).

Methoprene-tolerant (Met) as an intracellular receptor of juvenile hormone (JH) and the Krüppel-homolog 1 (Kr-h1) as a JH-inducible transcription factor had been proved to contribute to insect reproduction. Their functions vary in different insect orders, however, they are not clear in Psocoptera. In this study, LeMet and LeKr-h1 were identified and their roles in vitellogenesis and ovarian development were investigated in Liposcelis entomophila (Enderlein). Treatment with exogenous JH III significantly induced the expression of LeKr-h1, LeVg, and LeVgR. Furthermore, silencing LeMet and LeKr-h1 remarkably reduced the transcription of LeVg and LeVgR, disrupted the production of Vg in fat body and the uptake of Vg by oocytes, and ultimately led to a decline in fecundity. The results indicated that the JH signaling pathway was essential to the reproductive process of this species. Interestingly, knockdown of LeMet or LeKr-h1 also resulted in fluctuations in the expression of FoxO, indicating the complex regulatory interactions between different hormone factors. Besides, knockdown of both LeMet and LeKr-h1 significantly increased L. entomophila mortality. Our study provides initial insight into the roles of JH signaling in the female reproduction of psocids and provided evidence that RNAi-mediated knockdown of Met or Kr-h1 is a potential pest control strategy.

Preoperative Pectoralis Muscle Index Predicts Distant Metastasis-Free Survival in Breast Cancer Patients.

Background: Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Sarcopenia is related to adverse clinical outcomes in patients with malignancies. Muscle index is a key parameter in evaluating sarcopenia. However, there is no data investigating the association between muscle index and distant metastasis in breast cancer. The aim of this study was to explore whether muscle index can effectively predict distant metastasis and death outcomes in breast cancer patients. Study Design: The clinical data of 493 breast cancer patients at the Harbin Medical University Cancer Hospital between January 2014 and December 2015 were retrospectively analyzed. Quantitative measurements of pectoralis muscle area and skeletal muscle area were performed at the level of the fourth thoracic vertebra (T4) and the eleventh thoracic vertebra (T11) of the chest computed tomography image, respectively. The pectoralis muscle index (PMI) and skeletal muscle index (SMI) were assessed by the normalized muscle area (area/the square of height). Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. Result: The patients with metastases had lower PMI at T4 level (PMI/T4) and SMI at T11 level (SMI/T11) compared with the patients without metastases. Moreover, there were significant correlations between PMI/T4 and lymphovascular invasion, Ki67 expression, multifocal disease, and molecular subtype. In addition, multivariate analysis revealed that PMI/T4, not SMI/T11, was an independent prognostic factor for distant metastasis-free survival (DMFS) and overall survival (OS) in breast cancer patients. Conclusions: Low PMI/T4 is associated with worse DMFS and OS in breast cancer patients. Future prospective studies are needed.

Progress on spermatogonial stem cell microenvironment.

Spermatogonial stem cells (SSCs) are germ cells (GCs) with long-term self-renewal and differentiation potential in testis, namely tissue stem cells located on the basement membrane, whose self-renewal and differentiation are regulated by the surrounding microenvironment. In recent years, the research of SSCs has made a series of important progress, which brings the hope for the clinical treatment of some male infertility patients. Among them, the microenvironment is particularly important in regulating SSCs. The microenvironment is responsible for integrating the effects of different types of cell components, extracellular matrix, extracellular regulatory molecules and hormones on SSCs, thus regulating the fate of SSCs. The research on SSCs microenvironment has gradually become one of the main contents of stem cell research. In this review, we mainly summarize the cell composition, regulatory factors and characteristics of mouse SSCs microenvironment, thereby providing background information for in-depth study on the structure and function of SSCs microenvironment, and opportunity to find more abundant cell phenotypes and microenvironmental factors through multiple research models in the future.

Pd-Catalyzed Direct Modification of an Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues.

Palladium/BuAd2P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer's disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).

Pd-Catalyzed Direct Diversification of Natural Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of N-Aryl Huperzine A Analogues.

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogues (1-32) of the natural anti-Alzheimer's disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogues showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments. Three arylated huperzine A analogues (14, 19, and 30) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analogue (30) displayed the most potent AChE inhibition activity, with an IC50 value of 1.5 µM, which was 7.6-fold more active than HPA. Compound 30 also exhibited better neuroprotective activity for H2O2-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship analysis suggested that the electron density of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound 30 showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer's disease drug development.

Taurine attenuates the damage of lupus nephritis mouse via inactivation of the NF-κB pathway.

BACKGROUND: Taurine is an organic amino acid and a major constituent of bile. With its contribution to various cellular functions, it has demonstrated therapeutic effects in a wide range of diseases. Since there is a lack of literature investigating taurine as a treatment for lupus nephritis (LN), here we examined the potential of taurine as a treatment for LN. METHODS: Experiments were carried out using MRL/lpr mice as a model of LN, and C57BL/6 mice were used as negative controls. At 12 weeks old, MRL/lpr mice were divided into four groups and treated with 0, 50 and 100 mg/kg body weight taurine for 5 days. Enalapril is used as a positive control drug. All animals were sacrificed after treatment. LN-induced damage was assessed by proteinuria, blood urea nitrogen (BUN) and serum creatinine (CRE) levels. The degree of inflammation was assessed by inducible nitric oxide synthase (iNOS), interleukin-4 (IL-4), IL-10, and tumor necrosis factor-α (TNF-α) levels. The degree of oxidative stress was assessed by malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (Gpx) levels. Hematoxylin and eosin (HE) staining and TUNEL staining assessed histopathological damage and apoptosis, respectively. The levels of Bcl-2, Bax, caspase-3, caspase-9, and NF-κB p65 were detected by western blot. RESULTS: The data indicated that taurine administration improved kidney functions, reversed cell death, suppressed oxidative stress, and importantly, adjusted the immune response of LN mice to a more balanced state. CONCLUSIONS: These results provide a novel strategy for LN therapy, which may overcome the disadvantages of traditional immunosuppression and hormone treatments with greater efficacy and fewer side effects.

Diagnostic value of three-dimensional reconstruction technique in new classification criteria of lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Objective    To evaluate the application value of three-dimensional (3D) reconstruction in preoperative surgical diagnosis of new classification criteria for lung adenocarcinoma, which is helpful to develop a deep learning model of artificial intelligence in the auxiliary diagnosis and treatment of lung cancer. Methods    The clinical data of 173 patients with ground-glass lung nodules with a diameter of ≤2 cm, who were admitted from October 2018 to June 2020 in our hospital were retrospectively analyzed. Among them, 55 were males and 118 were females with a median age of 61 (28-82) years. Pulmonary nodules in different parts of the same patient were treated as independent events, and a total of 181 subjects were included. According to the new classification criteria of pathological types, they were divided into pre-invasive lesions (atypical adenomatous hyperplasia and and adenocarcinoma in situ), minimally invasive adenocarcinoma and invasive adenocarcinoma. The relationship between 3D reconstruction parameters and different pathological subtypes of lung adenocarcinoma, and their diagnostic values were analyzed by multiplanar reconstruction and volume reconstruction techniques. Results    In different pathological types of lung adenocarcinoma, the diameter of lung nodules (P<0.001), average CT value (P<0.001), consolidation/tumor ratio (CTR, P<0.001), type of nodules (P<0.001), nodular morphology (P<0.001), pleural indenlation sign (P<0.001), air bronchogram sign (P=0.010), vascular access inside the nodule (P=0.005), TNM staging (P<0.001) were significantly different, while nodule growth sites were not (P=0.054). At the same time, it was also found that with the increased invasiveness of different pathological subtypes of lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. Meanwhile, nodule diameter and the average CT value or CTR were independent risk factors for malignant degree of lung adenocarcinoma. Conclusion    Imaging signs of lung adenocarcinoma in 3D reconstruction, including nodule diameter, the average CT value, CTR, shape, type, vascular access conditions, air bronchogram sign, pleural indenlation sign, play an important role in the diagnosis of lung adenocarcinoma subtype and can provide guidance for personalized therapy to patients in clinics.

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.

BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome. AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity. METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data. RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD. CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

Contrast-enhanced CT imaging for the assessment of lymph node status in patients with colorectal cancer.

The aim of the present study was to identify a novel strategy that predicts the metastatic status of lymph nodes (LNs) in patients diagnosed with colorectal cancer, using detailed characteristics of contrast-enhanced CT scan images. A total of 284 preoperative CT scans derived from patients diagnosed with colorectal cancer at Second Affiliated Hospital, Zhejiang University School of Medicine between January 2013 and July 2018 were retrospectively reviewed. A total of 794 LNs were assessed for size, margins, morphology and subtle internal enhancements in the equilibrium phase. Imaging features were analyzed by two abdominal radiologists (Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine and Departments of Radiology; Shaoxing Second Hospital Departments of Radiology, Shaoxing Second Hospital) in a blind manner. If the conclusions were not concordant, the final score was determined by a senior radiologist who specialized in abdominal radiology for ≥30 years. According to the histopathology results, 27.3% (217/794) of LNs were metastatic (LN+). In addition, LNs >10 mm in size demonstrated sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) of 47.0, 80.9, 48.1 and 80.2%, respectively [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.69-5.28]. LNs in the shape of a kidney bean (middle fat depression like kidney) and/or those with an oblong shape were more likely to be metastasis negative LNs (LN-), while lobulated and irregular LNs were more likely to be LN+. In magnified images, internal enhancement characteristics of LN- were defined as homogeneous, spotted, striped and core enhancing. By contrast, rim and heterogeneity enhancement features for LN+ demonstrated sensitivity, specificity, PPVs and NPVs of 46.5, 89.9, 63.5 and 81.7%, respectively (OR, 7.79; 95% CI, 5.33-11.40). The results demonstrated that the internal enhancement features of LNs may be used as a predictor of metastasis. The detailed benign characteristics, such as homogeneity, spotted, striped and core enhancement of LNs may facilitate the identification of LN- in patients with colorectal cancer.

Lrrc34 Is Highly Expressed in SSCs and Is Necessary for SSC Expansion In Vitro.

Objective To discover critical genes contributing to the stemness and maintenance of spermatogonial stem cells (SSCs) and provide new insights into the function of the leucine-rich repeat (LRR) family member Lrrc34 (leucine-rich repeat-containing 34) in SSCs from mice. Methods Bioinformatic methods, including differentially expressed gene (DEG), gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were used to uncover latent pluripotency-related genes. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels, respectively. RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs. Results Eight DEGs between ID4-EGFP+ (G) and ID4-EGFP+/TSPAN8High (TH), eight DEGs between G and ID4-EGFP+/TSPAN8Low (TL) and eleven DEGs between TH and TL were discovered, and eleven protein-protein interaction (PPI) modules were found to be significant in the PPI network of DEGs. One of the DEGs, Lrrc34, was selected as a potential pluripotency-related gene due to its differential expression among ID4-EGFP+ spermatogonia subsets and its interaction with fibroblast growth factor 2 in the fifth module. Immunofluorescence experiments exhibited specific expression of Lrrc34 in a subpopulation of undifferentiated spermatogonia marked by LIN28A, and RT-PCR experiments confirmed the high expression of Lrrc34 in SSCs from P7 and adult mice. The transient knockdown of Lrrc34 in SSCs resulted in reduced colony sizes and significant changes in the transcriptome and apoptotic pathways. Conclusion Lrrc34 is highly expressed in mouse SSCs and is required for SSC proliferation in vitro through effects on transcriptome and signaling transduction pathways.