[Evaluation of the effectiveness of the evidence base multi-discipline critical strategies on the temperature and clinical outcomes in very preterm infants].

To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.

[Analysis of intestinal microbial diversity in Leopoldamys edwardsi based on illumina sequencing technique].

To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and ß diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.

PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells.

BACKGROUND: The PIAS4 protein belongs to the family of protein inhibitors of activated STAT, but has since been implicated in various biological activities including the post-translational modification known as sumoylation. In this study, we explored the roles of PIAS4 in pancreatic tumourigenesis. METHODS: The expression levels of PIAS4 in pancreatic cancer cells were examined. Cell proliferation and invasion was studied after overexpression and gene silencing of PIAS4. The effect of PIAS4 on hypoxia signalling was investigated. RESULTS: The protein was overexpressed in pancreatic cancer cells compared with the normal pancreas. Gene silencing by PIAS4 small interfering RNA (siRNA) suppressed pancreatic cancer cell growth and overexpression of PIAS4 induced expression of genes related to cell growth. The overexpression of PIAS4 is essential for the regulation of the hypoxia signalling pathway. PIAS4 interacts with the tumour suppressor von Hippel-Lindau (VHL) and leads to VHL sumoylation, oligomerization, and impaired function. Pancreatic cancer cells (Panc0327, MiaPaCa2) treated with PIAS4 siRNA suppressed expression of the hypoxia-inducible factor hypoxia-inducible factor 1 alpha and its target genes JMJD1A, VEGF, and STAT3. CONCLUSION: Our study elucidates the role of PIAS4 in the regulation of pancreatic cancer cell growth, where the suppression of its activity represents a novel therapeutic target for pancreatic cancers.

[Evidential research on the literature quoted in Compendium of Medicine].

One of the characteristics of Yixue Gangmu(, Compendium of Medicine) is collecting a large number of medical literatures before Ming Dynasty. And it quoted not only from medical books, but also other literature, with a time span from Han to Yuan Dynasty. From frequency of citation, we found that Lou Ying, the writer's ideas had more resonance with Zhu Danxi and Yi Shui School from academic point of view.

Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia.

Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in a patient-derived xenograft murine model of B-ALL. Interestingly, although KPT-9274 is a dual PAK4/NAMPT inhibitor, B-ALL cell growth inhibition by KPT-9274 was largely abolished with nicotinic acid supplementation, indicating that the inhibitory effects on B-ALL cells are mainly exerted by NAD+ depletion through NAMPT inhibition. Moreover, we have found that the extreme susceptibility of B-ALL cells to NAMPT inhibition is related to the reduced cellular NAD+ reserve. NAD+ depletion may be a promising alternative approach to treating patients with B-ALL.

Skin and soft tissue infection caused by non-tuberculous mycobacteria.

SETTING: A medical centre in Taipei, Taiwan. OBJECTIVE: To investigate the trend and characteristics of patients with non-tuberculous mycobacteria (NTM) related skin and soft tissue infection. DESIGN: A total of 63 patients with culture-proven diseases were identified from January 1997 to December 2004. The medical records of all patients were reviewed. RESULTS: Twenty-seven patients were infected with rapidly growing mycobacteria (RGM), 19 with Mycobacterium marinum, six with M. avium complex (MAC), five with M. kansasii and six with other species. Most patients presented with a protracted cutaneous lesion without systemic symptoms, and two thirds of the patients had a history of exposure. Seventy-three per cent of the lesions involved the extremities. Underlying illness with suppressed immunity was documented in 30.2% of the patients, and was most prevalent in patients with MAC (100%) and M. kansasii (60%). Of the patients, 62% underwent at least one surgical intervention, and 77.8% received treatment with different antimicrobial combinations. Most patients (86%) recovered completely. Granulomatous inflammation was found in 88.9% of biopsied tissue associated with M. marinum infection, 31.8% with RGM and 25.0% with MAC. CONCLUSION: A combination of surgery and antimicrobials cured most patients with microbiologically proven localised NTM skin and soft tissue infection.

Bone hydatid disease.

Bone hydatid disease lacks a typical clinical appearance and image characteristics on x ray or CT are similar to those of tuberculosis, metastases and giant cell tumour or bone cysts. However, MRI does show distinctive diagnostic features of bone hydatid disease, especially in the spine. Until recently, treatment of osseous hydatid disease has been entirely surgical. Effective chemotherapy using benzimidazoles, particularly mebendazole, albendazole and combination treatments, has now been achieved in experimental studies and clinical practice. However, most of these drugs are still in the experimental stage or are in the early stages of clinical use.

ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.

Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD).

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers.

Laryngeal ultrasound: a useful method in predicting post-extubation stridor. A pilot study.

The cuff-leak test was widely used for the prediction of post-extubation stridor, but controversial results limit its clinical application. The current study used real-time ultrasonography to evaluate the air-leak and hypothesised that the air-column width, measured by ultrasonography, may be correlated to the development of post-extubation stridor. From June 1, 2001 to March 1, 2002, a total of 51 planned extubations in 51 consecutively intubated patients were included. All of the patients received ultrasonographical examinations of their vocal cords and larynx in addition to an air-column width measurement within 24 h prior to extubation. The overall post-extubation stridor rate was 7.8%. The air-leak volume presented as median (interquartile range) were 300 (350) mL and 25 (20) mL, respectively, for the nonstridor and stridor groups. The air-column width during cuff deflation was 6.4 (2) mm and 4.5 (0.8) mm, respectively. They were found to be statistically significant. In conclusion, the authors demonstrated that laryngeal ultrasonography could be a reliable, noninvasive method, in the evaluation of vocal cords, laryngeal morphology and the ease of airflow, which passed through vocal cords or subglottic area due to laryngeal oedema. The air-column width during cuff deflation was a potential predictor of post-extubation stridor.

Disease caused by non-tuberculous mycobacteria in a university hospital in Taiwan, 1997-2003.

From January 1997 to December 2003, all patients with non-tuberculous mycobacteria (NTM) isolation who were treated at a university hospital in Taiwan were evaluated. Among the 2650 NTM isolates, 1225 (46.2%) were from 412 patients with clinically significant diseases. The annual incidence (per 100000 patients) of disease caused by NTM was 8.96 in 1997, 21.53 in 2002, and 16.55 in 2003. The major types of infections caused by NTM included isolated pulmonary infection and pleurisy (59.5%), skin/soft-tissue infections and osteomyelitis (13.8%), and disseminated diseases (13.3%). The two most common groups of organisms involved were rapidly growing mycobacteria (RGM) (41.4%) and Mycobacterium avium complex (MAC) (39%). The most common organism involved in isolated pulmonary infection and pleurisy was MAC (44.1%). RGM predominated in keratitis (94%), skin/soft-tissue infections and osteomyelitis (43.9%), and lymphadenitis (66.7%). This retrospective 7-year study demonstrated an increase in the incidence of NTM disease in a university hospital.