Search

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm during early development that are characterized by high self-renewal ability and multidirectional differentiation potential. These cells are present various tissues in the human body and can be cultured in vitro. Under specific conditions, MSCs can differentiate into osteoblasts, neuron-like cells, adipocytes and muscle cells and so on, therefore, have a great application value in cell replacement therapy and tissue repair. In recent years, the application of MSCs in rheumatic diseases has received increasing attention. On the one hand, MSCs have the ability to differentiate into bone and cartilage cells; on the other hand, these stem cells are also involved in immune regulation, resulting in the alleviation of inflammation and anti-fibrotic properties and the promotion of vascular repair, thus bringing new hope for the treatment of rheumatic diseases. This article reviews the clinical progress in MSC application for the treatment of rheumatic diseases. [ABSTRACT FROM AUTHOR]

Background: Membrane lipid composition associates closely with membrane stability and fluidity under water stress. In this study, lipidomic analyses based on electrospray ionization mass spectrometry (ESI-MS/MS) were carried out to explore dynamic changes of membrane lipids in term of molecular species caused by PEG (Polyethylene glycol-6000)-induced water stress in wheat seedlings. Results: Among the main phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) are primary degradation targets, and PC was degraded in the largest degree. Membrane ion leakage dramatically increased later than the significant reduction of these phospholipids, indicating that the loss of membrane integrity lagged behind severe phospholipid degradation. Monogalactosyldiacylglycerol (MGDG) increased firstly and decreased later, while digalactosyldiacylglycerol (DGDG) ratcheted up with stress. DGDG/MGDG increased after stress for 3 days, and unsaturation of DGDG was promoted with stress. Variation trends of galactolipids differed among molecular species. The time when MGDG (34:3), DGDG (34:3) began to decline approached to the time when non-stomatal limitation impaired photosynthesis. While the two predominant molecular species MGDG (36:6) and DGDG (36:6) began to decline later. So we speculated that MGDG (34:3), DGDG (34:3) might be key components in photosynthesis apparatus and participate in photosynthesis directly. While the two predominant molecular species, MGDG (36:6) and DGDG (36:6) might locate in thylakoid lipid bilayer matrix and play roles in stabilizing the membrane. The research provides new insights into the dynamic response of lipid metabolism to PEG-induced water stress. Conclusion: In wheat plants under water stress, the major molecular species of PC, PE and PG were degraded, MGDG and DGDG molecular species had differing degradation time courses. [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental health problem among veterans, with high mortality. Despite the numerous conducted investigations, the prediction and identification of risk factors for depression are still severely limited. This study used a deep learning algorithm to identify depression in veterans and its factors associated with clinical manifestations. Methods: Our data originated from the National Health and Nutrition Examination Survey (2005–2018). A dataset of 2,546 veterans was identified using deep learning and five traditional machine learning algorithms with 10-fold cross-validation. Model performance was assessed by examining the area under the subject operating characteristic curve (AUC), accuracy, recall, specificity, precision, and F1 score. Results: Deep learning had the highest AUC (0.891, 95%CI 0.869–0.914) and specificity (0.906) in identifying depression in veterans. Further study on depression among veterans of different ages showed that the AUC values for deep learning were 0.929 (95%CI 0.904–0.955) in the middle-aged group and 0.924(95%CI 0.900-0.948) in the older age group. In addition to general health conditions, sleep difficulties, memory impairment, work incapacity, income, BMI, and chronic diseases, factors such as vitamins E and C, and palmitic acid were also identified as important influencing factors. Conclusions: Compared with traditional machine learning methods, deep learning algorithms achieved optimal performance, making it conducive for identifying depression and its risk factors among veterans. [ABSTRACT FROM AUTHOR]

Background: Previous investigations into the effect of dietary forage on calf performance have been inconsistent, and there is a paucity of information exploring the effect of age on the growth performance and rumination of calves. Eighty-four female Holstein calves (41.5 ± 4.2 kg) were enrolled at birth, a subset of the calves were fed calf starter only (CON, n = 21) while the rest (n = 63) were classified into three treatment groups: the early (EHAY, n = 26, 5.1 ± 0.8 d), the middle (MHAY, n = 21, 7.9 ± 0.8 d) and the late (LHAY, n = 16, 12.1 ± 1.4 d) hay consumers. The short-term effect of the age at first forage consumption (AFF) on calves' feed intake was monitored until d 84. In addition, the long-term effects of AFF on body weight, structural growth and rumination behavior were recorded until d 196. Rumen samples were collected on d 1, 7, 35, 84 and 196 to analyze the rumen fermentation, while fecal samples were collected from d 78 to 84 to estimate digestibility parameters. Results: Treatment had no effect on feed intake. While, the EHAY calves tended to have lower BW and ADG compared to LHAY and CON calves. Several total-tract apparent digestibility parameters and digestible nutrients intake were significantly lower in EHAY calves compared with CON and LHAY calves. Calves in the EHAY group tended to begin ruminating ealier, while CON calves were the latest (12.3 vs. 15.5 days of age). A treatment and time interaction was present for rumination time due to greater rumination in calves consuming hay compared to CON calves in week 10 to 12, the differences in rumination disappeared afterwards, no long-lasting significant differences in the rumination and rumen fermentation parameters were found between treatments. Conclusions: In conclusion, this study showed that hay consumption earlier in life (in the first week, around 5 days of life) could negatively affect the growth of the calf in the short and long term. Compared to consuming hay from the second week (around 12 days of life) or feeding concentrate only without hay, starting to consume hay from the first week could compromise nutrient digestibility and digestible nutrient intake independent of developing rumination behaviour and rumen fermentation. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

Background: The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation: Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion: Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium. [ABSTRACT FROM AUTHOR]

Background: The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation.Methods: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group.Results: The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872).Conclusion: As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms.Methods: 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed.Results: Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid.Conclusions: Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC.Methods: QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis.Results: ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009).Conclusion: After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients. [ABSTRACT FROM AUTHOR]

Background: The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival is not fully understood. This retrospective cohort study aims to explore the association between early informed diagnosis and survival time in breast cancer patients.Methods: A total of 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors, including knowing the cancer diagnosis status, sex, age, clinical stage, surgery history, grade of reporting hospital and diagnostic year were, analyzed. We followed up all participants every 6 months until June 2017. Propensity score matching (PSM) was used to balance the clinicopathologic characteristics between patients who knew their diagnosis and those who did not.Results: By June 2017, 18.04% of the participants died of breast cancer. Before PSM, both the 3-year and 5-year survival rates of patients who knew their cancer diagnosis were longer (P < 0.001). After PSM, the above conclusion was still established. By stratified analysis, except for the subgroups of male patients and stage III patients, patients who knew their diagnosis showed a better prognosis in all the other subgroups (P < 0.05). Cox regression analysis showed that knowing a cancer diagnosis was an independent risk factor for survival in breast cancer patients (P < 0.001).Conclusions: Being aware of their cancer diagnosis plays a protective role in extending the survival time of breast cancer patients, which suggests that medical staff and patients' families should disclose the cancer diagnosis to patients in a timely manner. Further prospective studies need to be made to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Heat stress (HS) is a major stress event in the life of an animal, with detrimental upshots in production and health. Long-non-coding RNAs (lncRNAs) play an important role in many biological processes by transcriptional regulation. However, no research has been reported on the characterization and functionality of lncRNAs in heat-stressed rats. Results: We studied expression levels of lncRNAs in rats during HS, using strand-specific RNA sequencing. Six rats, three in each of Control (22 ± 1 °C) and H120 (42 °C for 120 min) experimental groups, were used to screen for lncRNAs in their liver and adrenal glands. Totally, 4498 and 7627 putative lncRNAs were identified in liver and adrenal glands of the Control and H120 groups, respectively. The majority of lncRNAs were relatively shorter and contained fewer exons than protein-coding transcripts. In total, 482 (174 up-regulated and 308 down-regulated) and 271 (126 up-regulated and 145 down-regulated) differentially-expressed lncRNAs (DElncRNAs, P < 0.05) were identified in the liver and adrenal glands of the Control and H120 groups, respectively. Furthermore, 1274, 121, and 73 target differentially-expressed genes (DEGs) in the liver were predicted to interact with DElncRNAs based on trans−/cis- and sequence similarity regulatory modes. Functional annotation analyses indicated that these DEGs were mostly significantly enriched in insulin signalling, myeloid leukaemia, and glucagon signalling pathways. Similarly, 437, 73 and 41 target DEGs in the adrenal glands were mostly significantly enriched in the cell cycle (trans-prediction) and lysosome pathways (cis-prediction). The DElncRNAs interacting with DEGs that encode heat shock proteins (HSPs) may play an important role in HS response, which include Hsf4, Dnaja1, Dnajb4, Hsph1 and Hspb1 in the liver, and Dnajb13 and Hspb8 in the adrenal glands. The strand-specific RNA sequencing findings were also further verified through RT-qPCR. Conclusions: This study is the first to provide a detailed characterization and functional analysis of expression levels of lncRNAs in liver and adrenal glands of heat-stressed rats, which provides basis for further studies on the biological functions of lncRNAs under heat stress in rats and other mammalian species. [ABSTRACT FROM AUTHOR]

The current review is designed with aims to highlight the impact of heat stress (HS) on calves and heifers and to suggest methods for HS alleviation. HS occurs in animals when heat gain from environment and metabolism surpasses heat loss by radiation, convection, evaporation and conduction. Although calves and heifers are comparatively heat resistant due to less production of metabolic heat and more heat dissipation efficiency, they still suffer from HS to some degree. Dry matter intake and growth performance of calves and heifers are reduced during HS because of redistributing energy to heat regulation through a series of physiological and metabolic responses, such as elevated blood insulin and protein catabolism. Enhanced respiration rate and panting during HS accelerate the loss of CO2, resulting in altered blood acid-base chemistry and respiratory alkalosis. HS-induced alteration in rumen motility and microbiota affects the feed digestibility and rumen fermentation. Decreased luteinizing hormone, estradiol and gonadotrophins due to HS disturb the normal estrus cyclicity, depress follicular development, hence the drop in conception rate. Prenatal HS not only suppresses the embryonic development by the impaired placenta, which results in hypoxia and malnutrition, but also retards the growth, immunity and future milk production of newborn calves. Based on the above challenges, we attempted to describe the possible impacts of HS on growth, health, digestibility and reproduction of calves and heifers. Likewise, we also proposed three primary strategies for ameliorating HS consequences. Genetic development and reproductive measures, such as gene selection and embryo transfers, are more likely long-term approaches to enhance heat tolerance. While physical modification of the environment, such as shades and sprinkle systems, is the most common and easily implemented measure to alleviate HS. Additionally, nutritional management is another key approach which could help calves and heifers maintain homeostasis and prevent nutrient deficiencies because of HS. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant organisms (MDROs) have emerged as an important cause of poor prognoses of patients in the intensive care unit (ICU). This study aimed to establish an easy-to-use nomogram for predicting the occurrence of MDRO colonization or infection in ICU patients. Methods: In this study, we developed a nomogram based on predictors in patients admitted to the ICU in the First Affiliated Hospital of Xiamen University from 2016 to 2018 using univariate and multivariate logistic regression analysis. We externally validated this nomogram in patients from another hospital over a similar period, and assessed its performance by calculating the area under the receiver operating characteristic (ROC) curve (AUC) and performing a decision curve analysis. Results: 331 patients in the primary cohort and 181 patients in the validation cohort were included in the statistical analysis. Independent factors derived from the primary cohort to predict MDRO colonization or infection were male sex, higher C-reactive protein (CRP) levels and higher Pitt bacteremia scores (Pitt scores), which were all assembled in the nomogram. The nomogram yielded good discrimination with an AUC of 0.77 (95% CI 0.70–0.84), and the range of threshold probabilities of decision curves was approximately 30–95%. Conclusion: This easy-to-use nomogram is potentially useful for predicting the occurrence of MDRO colonization or infection in ICU patients. [ABSTRACT FROM AUTHOR]

Background: High-altitude pulmonary hypertension (HAPH) is a life-threating condition for animals in high altitude, and disturbance of endothelial nitric oxide (NO) synthesis contributes to its pathogenesis. N-carbamylglutamate (NCG), which enhances arginine synthesis, promotes endogenous synthesis of NO. In this study, we determined the effects of NCG on alleviating HAPH in Holstein heifers that ascended to Tibet (Lhasa, 3,658 m). Methods: Exp. 1, 2,000 Holstein heifers were transported from low elevation (1,027 m) to Lhasa. After being exposed to hypoxia for 1 yr, Holstein heifers were assigned to a healthy group (Control, n = 6) with mean pulmonary hypertension (mPAP) < 41 mmHg, and an HAPH affected group (HAPH, n = 6) with mPAP > 49 mmHg. Lung tissues were collected to evaluate histopathological changes and the expression of endothelial nitric oxide synthase (eNOS). Exp. 2, ten healthy heifers and 10 HAPH affected heifers were supplemented with NCG (20 g/d per heifer) for 4 wk. Physiological parameters were determined and blood samples were collected on d − 1 and d 28 of the feeding trial. Results: Expression of eNOS in small pulmonary arteriole intima was higher in the healthy than HAPH group (P = 0.006), whereas HAPH group had significantly thicker media and adventitia than healthy group (all P < 0.05). The mRNA of eNOS and protein level of eNOS were higher in the lungs of heifers in the healthy group than in the HAPH group (both P < 0.001), whereas endothelin-1 protein levels were higher in HAPH group than in the healthy group (P = 0.025). NCG supplementation decreased mPAP and ammonia (both P = 0.001), whereas it increased the expression of eNOS, arginine, and plasma NO (all P < 0.05). Conclusions: The expression of eNOS was decreased in Holstein heifers with HAPH. NCG supplementation decreased mPAP through the restoration of eNOS and endogenous NO synthesis. [ABSTRACT FROM AUTHOR]

Background: Postoperative radiation (PORT) is an option for non-small cell lung cancer (NSCLC) patients with resectable stage IIIA pathological N2 status (pN2). For patients with PORT, this study aims to investigate the impact of the exact number of positive lymph nodes (LNs) on overall survival (OS) and lung cancer-specific survival (LCSS).Methods: Within the Surveillance, Epidemiology, and End Results database, we identified 3373 patients with stage IIIA pathological N2 status (pN2) NSCLC who underwent a lobectomy or pneumonectomy from 2004 to 2013. OS and LCSS were compared among patients coded as receiving PORT or observation. The proportional hazards model was applied for investigation.Results: OS and LCSS favored PORT for patients with stage IIIA (pN2) NSCLC. Multivariable analyses showed that PORT and the exact number of positive LNs (n ≤ 3) were independently associated with better OS and LCSS. Both better OS and LCSS emerged for positive LNs (n > 3) after the use of PORT in survival analyses, whereas the benefits of OS and LCSS were not observed anymore for positive LNs (n ≤ 3) group. More importantly, multivariable analyses showed that the use of PORT is an independent risk factor of survival for positive LNs (n > 3) but not for positive LNs (n ≤ 3).Conclusions: In Stage IIIA (pN2) NSCLC, the use of PORT demonstrated better survival results than no PORT for patients with positive LNs (n > 3), but not for patients with positive LNs (n ≤ 3). [ABSTRACT FROM AUTHOR]

Background: Improving the efficiency of animal production is a relentless pursuit of ruminant producers. Energy utilization and partition can be affected by dietary composition and nutrient availability. Furthermore, the liver is the central metabolic intersection in cattle. However, the specific metabolic changes in the liver under conditions of limit-feeding remain unclear and require further study. The present study aimed to elucidate the effects of a wide range of dietary forage:concentrate ratios (F:C) on energy utilization, and identify potential changes in molecular metabolism by analyzing hepatic transcriptional profiles. Twenty-four half-sib Holstein heifers were fed four F:C diets (20:80, 40:60, 60:40, and 80:20 on a dry matter basis), with similar intake levels of metabolizable energy (ME) and crude protein. Liver biopsy samples were obtained and RNA sequencing was conducted to identify the hepatic transcriptomic changes. Moreover, the ruminal fermentation profiles, growth characteristics, and levels of metabolites in the liver and plasma of the heifers were monitored. Results: The proportion of acetate showed a linear increase (P < 0.01) with increasing dietary forage levels, whereas the proportion of propionate showed a linear decline (P ≤ 0.01). Lower levels of average daily gain and feed efficiency (P < 0.01) were observed in heifers fed high levels of forage, with a significant linear response. Using the Short Time-series Expression Miner software package, the expression trends of significant differentially expressed genes (DEGs) were generally divided into 20 clusters, according to their dynamic expression patterns. Functional classification analysis showed that lipid metabolism (particularly cholesterol and steroid metabolism which were in line with the cholesterol content in the liver and plasma) was significantly increased with increasing dietary forage levels and slightly reduced by the 80% forage diet. Nine DEGs were enriched in the related pathways, namely HMGCS1, HMGCR, MSMO1, MVK, MVD, IDI1, FDPS, LSS, and DHCR7. Conclusions: The ruminal fermentation and feed efficiency results suggest that different mechanisms of energy utilization might occur in heifers fed different F:C diets with similar levels of ME intake. Increased cholesterol synthesis from acetate might be responsible for the reduced efficiency of energy utilization in heifers fed high-forage diets. [ABSTRACT FROM AUTHOR]