Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Clinical presentation and magnetic resonance imaging characteristics of lymphocytic hypophysitis: a systematic review with meta-analysis.

Introduction: This meta-analysis was performed to analyze the clinical presentation, magnetic resonance imaging (MRI) characteristics, and the management of lymphocytic hypophysitis (LYH). Material and methods: Four different databases were searched from January 2010 to December 2020, two researchers independently conducted literature screening, data extraction, and quality evaluation. We used a random effects meta-analysis to calculate summary relative risks with 95% CI. Results: This meta-analysis showed that the percentage of women among LYH patients was 78%. LYH was associated with pregnancy in 15% of female patients, with headache (49%) and symptoms of central diabetes insipidus (CDI) (45%) being the most frequent presentation. In 24% of LYH patients, there was an association with another autoimmune disease. The incidence of secondary hypogonadism, secondary hypoadrenalism, secondary hypothyroidism, and growth hormone deficit was 54%, 49%, 43%, and 22%, respectively. Pituitary contrast enhancement (63%), symmetrical pituitary enlargement (60%), thickening of the pituitary stalk (58%), sella mass or suprasellar extension (58%), and loss of posterior pituitary hyperintensity (50%) were typical MRI findings. Regarding LYH treatment, the percentage of patients who had observation or hormone replacement, steroid therapy, and surgery was 43%, 36%, and 34%, respectively. Conclusions: It is of great significance to fully understand the clinical characteristics of lymphocytic hypophysitis, reduce missed diagnosis and misdiagnosis, avoid unnecessary surgery and maintain normal pituitary function.

[Clinical efficacy of combined therapy in children with stage 4 neuroblastoma]. / 儿童4期神经母细胞瘤联合治疗的临床疗效观察.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis.

Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of patients with sepsis was collected to determine WWP1 and YTHDF1 expression. An in vitro sepsis cell model was induced in RAW264.7 cells using lipopolysaccharide (LPS) and ATP and an in vivo septic mouse model by cecal ligation and perforation (CLP). After gain- and loss-of-function assays in vitro and in vivo, TNF-α and IL-1ß levels and the cleavage of gasdermin-D (GSDMD) were detected by ELISA and Western blot assay, followed by determination of lactate dehydrogenase (LDH) activity. Immunoprecipitation and meRIP assay were performed to detect the ubiquitination of NLRP3 and the m6A modification of WWP1 mRNA. The binding of WWP1 to YTHDF1 was explored using RIP-RT-qPCR and dual luciferase gene reporter assay. It was noted that WWP1 and YTHDF1 were downregulated in clinical sepsis samples, LPS + ATP-treated RAW264.7 cells, and CLP-induced mice. The ubiquitination of NLRP3 was promoted after overexpression of WWP1. WWP1 translation could be promoted by YTHDF1. Then, WWP1 or YTHDF1 overexpression diminished LDH activity, NLRP3 inflammasomes and caspase-1-mediated cleavage of GSDMD in LPS + ATP-induced RAW264.7 cells. Overexpressed YTHDF1 restrained inflammatory response in CLP-induced mice. Collectively, the alleviatory effect of m6A reader protein YTHDF1 may be achieved through promotion of NLRP3 ubiquitination and inhibition of caspase-1-dependent pyroptosis by upregulating WWP1.

Tryptophan Metabolites as Biomarkers for Esophageal Cancer Susceptibility, Metastasis, and Prognosis.

Background: Perturbation of tryptophan (TRP) metabolism contributes to the immune escape of cancer; however, the explored TRP metabolites are limited, and their efficacy in clarifying the susceptibility and progression of esophageal cancer (EC) remains ambiguous. Our study sought to evaluate the effects of the TRP metabolic profile on the clinical outcomes of EC using a Chinese population cohort; and to develop a risk prediction model targeting TRP metabolism. Method: A total of 456 healthy individuals as control subjects and 393 patients with EC who were followed up for one year as case subjects were enrolled. Quantification of the plasma concentrations of TRP and its metabolites was performed using HPLC-MS/MS. The logistic regression model was applied to evaluate the effects of the clinical characteristics and plasma metabolites of the subjects on susceptibility and tumor metastasis events, whereas Cox regression analysis was performed to assess the overall survival (OS) of the patients. Results: Levels of creatinine and liver enzymes were substantially correlated with multiple metabolites/metabolite ratios in TRP metabolism, suggesting that hepatic and renal function would exert effects on TRP metabolism. Age- and sex-matched case-control subjects were selected using propensity score matching. Plasma exposure to 5-HT was found to be elevated 3.94-fold in case subjects (N = 166) compared to control subjects (N = 203), achieving an AUC of 0.811 for predicting susceptibility event. Subsequent correlation analysis indicated that a higher plasma exposure to 5-HIAA significantly increased the risk of lymph node metastasis (OR: 2.16, p = 0.0114). Furthermore, it was figured out that OS was significantly shorter for patients with elevated XA/KYN ratio (HR: 1.99, p = 0.0016), in which medium and high levels of XA/KYN versus low level had a significantly lower OS (HR: 0.48, p = 0.0080 and HR: 0.42, p = 0.0031, respectively). Conclusion: This study provides a pivotal basis for targeting endogenous TRP metabolism as a potential therapeutic intervention.

COVID19db: a comprehensive database platform to discover potential drugs and targets of COVID-19 at whole transcriptomic scale.

Many open access transcriptomic data of coronavirus disease 2019 (COVID-19) were generated, they have great heterogeneity and are difficult to analyze. To utilize these invaluable data for better understanding of COVID-19, additional software should be developed. Especially for researchers without bioinformatic skills, a user-friendly platform is mandatory. We developed the COVID19db platform (http://hpcc.siat.ac.cn/covid19db & http://www.biomedical-web.com/covid19db) that provides 39 930 drug-target-pathway interactions and 95 COVID-19 related datasets, which include transcriptomes of 4127 human samples across 13 body sites associated with the exposure of 33 microbes and 33 drugs/agents. To facilitate data application, each dataset was standardized and annotated with rich clinical information. The platform further provides 14 different analytical applications to analyze various mechanisms underlying COVID-19. Moreover, the 14 applications enable researchers to customize grouping and setting for different analyses and allow them to perform analyses using their own data. Furthermore, a Drug Discovery tool is designed to identify potential drugs and targets at whole transcriptomic scale. For proof of concept, we used COVID19db and identified multiple potential drugs and targets for COVID-19. In summary, COVID19db provides user-friendly web interfaces to freely analyze, download data, and submit new data for further integration, it can accelerate the identification of effective strategies against COVID-19.

circMine: a comprehensive database to integrate, analyze and visualize human disease-related circRNA transcriptome.

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA-miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.

Identification and validation of an immune-associated RNA-binding proteins signature to predict clinical outcomes and therapeutic responses in colon cancer patients.

BACKGROUND: The immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs). However, immune-associated RBPs (IARBPs) in CC remain unexplored. METHODS: The data were downloaded from The Cancer Genome Atlas (TCGA) and the patients were divided into four immune subgroups by single sample gene set enrichment analysis (ssGSEA), in which weighted gene correlation network analysis (WGCNA) identified modules of co-expressed genes correlated with immune infiltration. Univariate (UCR) and multivariate Cox regression (MCR) analyses were applied to screen survival-associated IARBPs. Then, a prognostic signature was performed on TCGA dataset. Risk model was constructed based on the TCGA dataset. Based on the median risk score, CC patients were subdivided into low- and high-risk groups. Furthermore, the accuracy and prognostic value of this signature were validated by using Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC). We further validated the findings in Gene Expression Omnibus (GEO) database. Finally, we evaluated the association between gene expression level and drug sensitivity. RESULTS: Based on the infiltration of immune cells, the TCGA patients were divided into four subgroups. In total, we identified 25 IARBPs, after differential expression and WGCNA analysis. Subsequently, two IARBP signatures (FBXO17 and PPARGC1A) were identified to be significantly associated with the overall survival (OS) of CC patients. K-M survival analysis revealed that the low-risk group correlated with prolonged OS. The prognostic signature was an independent prognostic factor and reflects the immune status of CC patients. Finally, FBXO17 was related with drug sensitivity of bleomycin, gemcitabine, and lenvatinib. PPARGC1A was related to drug sensitivity of dabrafenib, vemurafenib, and trametinib. CONCLUSION: A novel two immune-associated RBPs that was established that may be useful in predicting survival and individualized treatment.

Treatment barriers and clinical outcome of children with medulloblastoma in China: a report from the Chinese Children's Cancer Group (CCCG).

BACKGROUND: Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood. Management requires interdisciplinary care and is associated with unique challenges in developing regions. Here, we report the characteristics, clinical outcome and treatment barriers for Chinese children with MB based on a multi-institutional cohort from the Chinese Children's Cancer Group (CCCG). METHODS: Retrospective cohort study among 12 Chinese pediatric oncology units from the CCCG Brain Tumor Workgroup on patients aged <18 years diagnosed with MB from 2016 to 2019. RESULTS: 221 patients (male:female = 138:83) were included, 175 (79%) were ≥3 years of age, and 46 (21%) <3 years. 177 patients (80%) were completely staged, among which 50 (28%) had metastasis and 70 (40%) were considered to have high-risk (HR) disease. Gross/near-total resection was achieved in 203 patients (92%). In patients where molecular grouping could be assigned, 19 (16%), 35 (29%), and 65 (54%), respectively had WNT-activated, SHH-activated, and Group 3/4 MB. The median duration between resection and initiation of adjuvant therapy was 36 days. Respective 2-year PFS and OS rates were 76.0 ± 3.0% and 88.0 ± 2.3%. PFS was significantly associated with age, metastatic status and clinical risk grouping. Chemotherapy use during CSI or alkylator choice were not significant predictors for patient outcome. CONCLUSIONS: We reported the clinical profiles and outcome from the largest cohort of Chinese children with MB after multi-modal therapy. Strengths and limitations on the local provision of neuro-oncology service are identified.

Otago exercise programme for physical function and mental health among older adults with cognitive frailty during COVID-19: A randomised controlled trial.

AIMS AND OBJECTIVES: Quarantine during the COVID-19 pandemic resulted in longer-term sedentary behaviours and mental health problems. Our study aimed to evaluate the impact of the Otago exercise programme (OEP) on physical function and mental health among elderly with cognitive frailty during COVID-19. BACKGROUND: Lockdowns and restrictions during the COVID-19 pandemic result in longer-term sedentary behaviours related disease and mental problem. Older people with cognitive frailty are more vulnerable to be influenced. Timely intervention may achieve better outcomes, OEP exercise was designed as a balance and muscle-strengthening programme for elderly people. DESIGN: A parallel-group, assessor-blinded randomised controlled trial was performed according to CONSORT guidelines. METHODS: This study was conducted from July 2020 to October 2020 among 62 elderly people with cognitive frailty from a nursing home. Participants were randomly divided into an OEP group (n = 31) or a control group (n = 31). Both groups received sleep- and diet-related health education. The OEP group also received a 12-week group exercise programme. The Five Times Sit to Stand Test (FTSST), Berg Balance Scale (BBS), and Timed Up and Go Test (TUGT) were used to assess physical function. The Geriatric Depression Scale-15 (GDS-15) and the 12-Item Short Form Health Survey Mental Component Summary (SF-12 MCS) were used to assess mental health. Outcomes were measured at 6 and 12 weeks. RESULTS: Physical function and mental health were similar in the two groups at baseline. At 12 weeks, the OEP group (difference in change from baseline: FTSST, -2.78; TUGT, -3.73; BBS, 2.17; GDS-15, -0.72; SF-12 MCS, 2.58; all p < .001) exhibited significantly greater improvements than the control group (difference in change from baseline: FTSST, 1.55; TUGT, 1.66; BBS, -0.10; GDS-15, 1.07; SF-12 MCS, -5.95; all p < .001). CONCLUSION: Our findings showed the OEP group had better physical function and mental health outcomes than the control group. OEP can be used to improve the physical and mental function among elderly people with cognitive frailty during the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: Otago exercise program intervention programmes should be implemented to improve physical function for cognitive frailty elderly to reduce the harm of longer-term sedentary behaviours, and to ruduce depression symptom and improve mental health, particularly during COVID-19 pandemic period.

MiR-140-3p Impedes Gastric Cancer Progression and Metastasis by Regulating BCL2/BECN1-Mediated Autophagy.

INTRODUCTION: MiRNAs have been proven to modulate the progression of gastric cancer (GC). In this field, we evaluated the role and mechanism of miR-140-3p in GC. METHODS: Western blotting and qRT-PCR were used to detect the levels of miR-140-3p and BCL2. The interaction of miR-140-3p and BCL2 was confirmed by dual-luciferase reporter and miRNA pull-down assays. CCK-8, EdU, wound healing, and Transwell invasion assays were performed to evaluate cell proliferation, migration and invasion. Autophagy was analyzed using Western blot analysis of the LC3-II/I ratio and immunofluorescence staining. A xenograft model was established to reveal the role of miR-140-3p in tumorigenesis. RESULTS: In GC cell lines and tissues, miR-140-3p was highly expressed, and BCL2 was expressed at low levels. MiR-140-3p directly inhibited BCL2 expression and indirectly promoted BECN1 expression, and BCL2 inhibited BECN1 expression. MiR-140-3p overexpression or silencing restrained or facilitated migration, invasion and EMT in GC cells. Moreover, we noticed that overexpression or downregulation of miR-140-3p promoted or suppressed BECN1-dependent autophagy in GC cells. BCL2 introduction or BECN1 silencing in GC cells partially blocked the effects of miR-140-3p. In conclusion, miR-140-3p directly downregulated the expression of BCL2, BCL2 downregulation further activated BECN1-dependent autophagy, and autophagy activation further inhibited EMT. CONCLUSION: miR-140-3p may act as a tumor suppressor by targeting BCL2 and regulating downstream BECN1-induced autophagy and metastasis in GC progression.

Maternal Fucosyltransferase 2 Status Associates with the Profiles of Human Milk Oligosaccharides and the Fecal Microbiota Composition of Breastfed Infants.

Human milk oligosaccharides (HMOs) play key roles in shaping infant fecal microbiota, and HMOs profiles have been reported to vary according to the mother's glycosyltransferase phenotype. In this study, the profiles of HMOs in human milk from secretor or non-secretor mothers collected at 2 months postpartum were analyzed by liquid chromatography quadrupole time-of-flight tandem mass spectrometry. 16S rRNA sequencing was used to characterize the fecal microbiota of breastfed infants. The amount of total and fucosylated HMOs were higher in secretor than non-secretor mothers, while Bifidobacterium genus were highly enriched in infants fed by non-secretor mothers. Associations between HMOs and infant fecal microbiota showed that the relative abundance of Bifidobacterium-OTU158 was positively associated with 2'-fucosyllactose and 3-fucosyllactose, and Bifidobacterium-OTU90 was negatively associated with lacto-N-difucohexaose. The present study provides the HMO profiles from Chinese mothers and their associations with infant fecal microbiota composition, suggesting that HMO compositions are associated with different Bifidobacterium strains in species-specific manner.

Meta-analysis on the effect of pituitary adenoma resection on pituitary function.

OBJECTIVE: A meta-analysis was conducted on the effect of pituitary adenoma resection on pituitary function. METHODS: The Cochrane Library, Ovid, PubMed, the Excerpta Medica Database (EMBASE), and the Chinese Biomedical Literature Databases (CBM) were searched to find trials about the evaluation of pituitary target glands before and after pituitary adenoma resection. The databases were searched from the earliest available trials until the end of September 2019. Based on the inclusion and exclusion criteria, two researchers independently selected literature, extracted data, and evaluated the quality of the studies, and then used Revman 5.2 software to conduct a meta-analysis. RESULTS: Eleven clinical trials were included, with a total of 3,237 subjects. Meta-analysis showed that the number of patients with hypofunction of the thyroid and gonadal axes substantially decreased after pituitary tumour resection, and that the difference was statistically significant: odds ratio (OR) = 1.72 [95% confidence interval (CI), 1.18-2.52; P = 0.005] and OR = 2.06 (95% CI, 1.42-3.00; P = 0.0002). The number of patients with a poor total suprarenal gland axis after pituitary tumour resection did not change significantly compared to the number found before the operation; the difference was not statistically significant: OR = 1.04 (95% CI, 0.72-1.48; P = 0.85). However, the number of patients who had adrenal axis dysfunction both before and after the operation was significantly reduced, and the difference was statistically significant: OR = 1.46 (95% CI, 1.21-1.78; P = 0.0001). CONCLUSION: The function of the thyroid and gonadal axes of pituitary gland tumour patients can be improved, to some extent, after pituitary tumour resection. Patients with pituitary tumours who have hypofunction of the adrenal axis can recover effectively after tumour resection.

[Evaluation of short-term clinical effect of minimally invasive total hip arthroplasty with direct anterior approach in lateral position].

OBJECTIVE: To investigate the short-term clinical effect of direct anterior approach (DAA) in total hip arthroplasty(THA). METHODS: From January 2018 to September 2018, the data of 30 patients(33 hips) who underwent the first THA using the side lying DAA completed by the same operation team were followed up and evaluated. There were 19 males and 11 females;the age was 58 to 80 (69.0±5.4) years old;the visual analogue scale (VAS) of pain was used, Harris scoring system, operation time, intraoperative blood loss, related complications and hip radiographs were evaluated in clinical and imaging aspects. RESULTS: Thirty patients (33 hips) were followed up for 12 to 20(14.3±3.7) months, operation time (66.0±7.2) min and intraoperativehemorrhage (156±32) ml. The position of acetabulum prosthesis was examined by imaging:anteversion angle (18.6±3.6)° and abduction angle (41.2±4.8)° respectively. The VAS score was improved from 7 to 9(8.1±1.4) before operation to 1 to 3(1.9±0.7) at 1 month after operation. Harris score of hip joint improved significantly, from 28 to 46(35.4±5.2) before operation to 76 to 92 (88.6±4.5) at 1 month after operation, 74 to 93 (85.6±6.9) at 6 months after operation, and 79 to 95 (90.7±8.1) at 12 months after operation, the difference was statistically significant(P<0.05). Complications occurred in 3 cases of fracture of the proximal femur, including 1 case of hip sprain fracture due to careless walking one month after operation. Considering that incomplete fracture may have occurred during the operation, 1 case of avulsion fracture of anterior inferior iliac spine, no deep infection, no dislocation. There were 1 case of injury of lateral femoral cutaneous nerve and 2 cases of injury of tensor fascia lata, among which 1 case was complete incision of the edge of the hook. CONCLUSION: The primary THA with DAA in lateral position has a good short;term clinical effect, can meet the needs of patients' rapid recovery, and is a safe and effective surgical approach.

Clinical significance of CD133 and Nestin in astrocytic tumor: The correlation with pathological grade and survival.

BACKGROUND: We aimed to investigate the interaction between CD133 and Nestin and further assessed the correlation of CD133 and Nestin with clinicopathological characteristics and survival in patients with astrocytic tumor. METHODS: Totally 127 patients with astrocytic tumor underwent surgical resection were enrolled. Patients' age, gender, and World Health Organization (WHO) grade were recorded, and the survival data were extracted from the follow-up records. The expressions of CD133 and Nestin in astrocytic tumor tissues were analyzed by immunohistochemistry assay. The WHO grade I and II astrocytic tumors were defined as low-grade astrocytic tumors (LGA), the WHO grade III and IV astrocytic tumors were defined as high-grade astrocytic tumors (HGA). RESULTS: There were 79 (62.2%), 34 (26.8%), 14 (11.0%), and 0 (0.0%) patients with CD133 negative, low, moderate, and high expression, respectively; 7 (5.5%), 47 (37.0%), 20 (15.7%), 53 (41.7%) patients with Nestin negative, low, moderate, high expression, respectively. CD133 and Nestin were both correlated with advanced WHO grade but not with age or gender, and positive correlation was observed between CD133 and Nestin. For survival, both CD133 and Nestin were correlated with unfavorable overall survival (OS), and further analysis illustrated that Nestin but not CD133 independently predicted poor OS. Subgroup analysis also revealed that Nestin but not CD133 negatively associated with shorter OS in LGA patients, while both CD133 and Nestin were correlated with poor OS in HGA patients. CONCLUSION: CD133 and Nestin present as potential biomarkers for advanced pathological grade and poor survival in patients with astrocytic tumor.

[Clinical study of Jiawei Xiaoyao Powder(JWXYP) on preventing delirium in elderly patients with hip fracture after operation].

OBJECTIVE: To study the effect of soothing liver, relieving depression, invigorating spleen and reinforcing blood on reducing delirium in elderly patients with hip fracture. METHODS: From December 2014 to June 2018, 180 elderly patients with hip fracture admitted were divided into treatment group and placebo group according to the order of admission:90 patients in treatment group were treated with Jiawei Xiaoyao Powder(JWXYP), including 32 males and 58 females, with an average age of(72.12±4.92), involving 67 cases of femoral trochanter fractures and 23 cases of femoral neck fractures; 35 cases underwent dynamic hip screw fixation, 31 cases underwent intramedullary fixation and 24 cases underwent artificial hip replacement. In the placebo group, 90 patients were treated with placebo, including 37 males and 53 females, with an average age of(72.91±5.43) years old, involving 69 cases of femoral trochanteric fractures and 21 cases of femoral neck fractures, including 37 cases underwent dynamic hip screw fixation, 30 cases underwent intramedullary fixation and 23 cases underwent artificial hip replacement. The age, sex, injury site, intraoperative bleeding volume, postoperative drainage, operation time, anesthesia time, post-operative pain score, post-operative hemoglobin, post-operative CRP, delirium severity(DRS) score and delirium occurrence were observed and compared between the two groups. RESULTS: All patients were followed up until delirium returned to normal, postoperative delirium was found in 12 cases (13.33%) in the treatment group and in 39 cases(43.33%) in the placebo group, the treatment group was significantly better than the placebo group. The monitoring indexes of the two groups were compared:post-operative pain score(P=0.002), post-operative hemoglobin(P=0.012), post-operative CRP(P=0.042). CONCLUSIONS: JWXYP can relieve liver depression, invigorate spleen and invigorate blood circulation, reduce pain, inflammatory stimulation and supplement blood volume after operation, and significantly reduce the incidence of delirium after operation.

Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Inhibiting Intestinal Damage via Increasing the Proliferation of Crypt Cells.

SCOPE: Necrotizing enterocolitis (NEC) is a devastating disease that is highly lethal in premature infants. Human milk oligosaccharides (HMOs) efficiently reduce the incidence of NEC. However, the protective mechanism of HMO treatment is unknown. It is hypothesized that HMOs protect against NEC by inhibiting the damage to intestinal epithelial cells. METHODS AND RESULTS: C57BL/6 pups are challenged with hypoxia and cold stress to induce NEC. All pups are sacrificed after 72 h. It is found that HMO administration reduces the concentrations of IL-8 in the serum and ileum of all NEC mice. Ileum toll-like receptor 4 (TLR4) protein expression and nuclear factor kappa-B (NFκB) pathway activation are inhibited. The proliferative ability of enterocytes in the ileum is restored as determined by labeling with proliferation markers (Ki67, SOX9). In a 3D culture intestinal crypt organoids study, HMO treatment improves the maturation of organoid cells and increases the ratio of proliferative cells under lipopolysaccharides (LPS) treatment. HMO treatment downregulates TLR4 expression in the organoid cells, thus reducing the effect of LPS. CONCLUSION: HMOs protect intestinal epithelial cells from injury by accelerating the turnover of crypt cells by reducing the expression of TLR4 on intestinal epithelial cells.

Overexpression of long noncoding RNA LINC01419 in esophageal squamous cell carcinoma and its relation to the sensitivity to 5-fluorouracil by mediating GSTP1 methylation.

BACKGROUND: Genome-wide sequencing investigations have identified numerous long noncoding RNAs (lncRNAs) among mammals, many of which exhibit aberrant expression in cancers, including esophageal squamous cell carcinoma (ESCC). Herein, this study elucidates the role and mechanism by which LINC01419 regulates the DNA methylation of glutathione S-transferase pi 1 (GSTP1) in relation to ESCC progression and the sensitivity of ESCC cells to 5-fluorouracil (5-FU). METHODS: LINC01419 and GSTP1 levels were quantified among 38 paired ESCC and adjacent tissue samples collected from patients with ESCC. To ascertain the contributory role of LINC01419 in the progression of ESCC and identify the interaction between LINC01419 and GSTP1 promoter methylation, LINC01419 was overexpressed or silenced, and the DNA methyltransferase inhibitor 5-Aza-CdR was treated. RESULTS: Data from the GEO database (GSE21362) and the Cancer Genome Atlas displayed elevated levels of LINC01419 and downregulated levels of GSTP1 in the ESCC tissues and cells. The silencing of LINC01419 led to decreased proliferation, increased apoptosis, and enhanced sensitivity to 5-FU in ESCC cells. Notably, LINC01419 could bind to the promoter region of the GSTP1 gene, resulting in elevated GSTP1 methylation and reduced GSTP1 levels via the recruitment of DNA methyltransferase among ESCC cells, whereby ESCC progression was stimulated accompanied by reduced ESCC cell sensitivity to 5-FU. GSTP1 demethylation by 5-Aza-CdR was observed to reverse the effects of LINC01419 overexpression in ESCC cells and the response to 5-FU. CONCLUSION: Highly expressed LINC01419 in ESCC promotes GSTP1 methylation, which ultimately acts to promote the event of ESCC and diminish the sensitivity of ESCC cells to 5-FU, highlighting a novel potential strategy to improve 5-FU-based chemotherapy in ESCC.