The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.

Histone H3K27 methylation modulates the dynamics of FANCD2 on chromatin to facilitate NHEJ and genome stability.

Dysregulation of the homeostatic balance of histone H3 di- and tri-methyl lysine 27 (H3K27me2/3) levels caused by the mis-sense mutation of histone H3 (H3K27M) is reported to be associated with various types of cancers. In this study, we found that reduction in H3K27me2/3 caused by H3.1K27M, a mutation of H3 variants found in patients with diffuse intrinsic pontine glioma (DIPG), dramatically attenuated the presence of 53BP1 (also known as TP53BP1) foci and the capability of non-homologous end joining (NHEJ) in human dermal fibroblasts. H3.1K27M mutant cells showed increased rates of genomic insertions/deletions and copy number variations, as well as an increase in p53-dependent apoptosis. We further showed that both hypo-H3K27me2/3 and H3.1K27M interacted with FANCD2, a central player in the choice of DNA repair pathway. H3.1K27M triggered the accumulation of FANCD2 on chromatin, suggesting an interaction between H3.1K27M and FANCD2. Interestingly, knockdown of FANCD2 in H3.1K27M cells recovered the number of 53BP1-positive foci, NHEJ efficiency and apoptosis rate. Although these findings in HDF cells may differ from the endogenous regulation of the H3.1K27M mutant in the specific tumor context of DIPG, our results suggest a new model by which H3K27me2/3 facilitates NHEJ and the maintenance of genome stability.This article has an associated First Person interview with the first author of the paper.

Incidence and risk factors of pancreatitis in obstructive jaundice patients after percutaneous placement of self-expandable metallic stents.

BACKGROUND: Percutaneous transhepatic biliary drainage is an alternative treatment for patients with malignant distal biliary obstruction. The aim of this study was to investigate the occurrence of pancreatitis in patients who had undergone percutaneous placement of a biliary stent and to assess the risk factors for pancreatitis and the treatment outcomes. METHODS: From January 2010 to October 2016, 980 patients in our hospital who underwent percutaneous placements of self-expandable metallic stents for obstructive jaundice were retrospectively analyzed. The incidence of pancreatitis and risk factors were assessed by univariate and multivariate logistic regression analysis. Therapeutics, such as somatostatin, which were also adminstrated to release the symptom and promote the restoration of normal function of pancreas, were also analyzed. RESULTS: Pancreatitis occurred in 45 (4.6%) patients. One patient died from severe acute pancreatitis. Multivariate logistic regression analysis showed that common bile duct stent placement was the only independent risk factor that related to pancreatitis (odds ratio = 2.096, 95% CI: 1.248-5.379; P = 0.002). By using somatostatin, the concentrations of serum amylase and lipase were decreased in 44 patients with pancreatitis. No major complications were found during the treatment. CONCLUSIONS: Pancreatitis is a relatively low complication of percutaneous placement of biliary stents. The common bile duct stent placement is the only independent risk factor that related to pancreatitis. In this case, the percutaneous transhepatic biliary drainage is a preferred method for treatment. Furthermore, somatostatin is a secure and efficacious method to release the symptom and promote the restoration of pancreatic function.

8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation.

The refractoriness of acute promyelocytic leukemia (APL) with t(11;17)(q23;q21) to all-trans retinoic acid (ATRA)-based therapy concerns clinicians and intrigues basic researchers. By using a murine leukemic model carrying both promyelocytic leukemia zinc finger/retinoic acid receptor-α (PLZF/RARα) and RARα/PLZF fusion genes, we discovered that 8-chlorophenylthio adenosine-3', 5'-cyclic monophosphate (8-CPT-cAMP) enhances cellular differentiation and improves gene trans-activation by ATRA in leukemic blasts. Mechanistically, in combination with ATRA, 8-CPT-cAMP activates PKA, causing phosphorylation of PLZF/RARα at Ser765 and resulting in increased dissociation of the silencing mediator for retinoic acid and thyroid hormone receptors/nuclear receptor corepressor from PLZF/RARα. This process results in changes of local chromatin and transcriptional reactivation of the retinoic acid pathway in leukemic cells. Meanwhile, 8-CPT-cAMP also potentiated ATRA-induced degradation of PLZF/RARα through its Ser765 phosphorylation. In vivo treatment of the t(11;17) APL mouse model demonstrated that 8-CPT-cAMP could significantly improve the therapeutic effect of ATRA by targeting a leukemia-initiating cell activity. This combined therapy, which induces enhanced differentiation and oncoprotein degradation, may benefit t(11;17) APL patients.

Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1.

As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-ß superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.

P300 regulates histone crotonylation and preimplantation embryo development.

Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia.

Acquisition of additional genetic and/or epigenetic abnormalities other than the BCR/ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast crisis (BC). To gain insights into the underlying mechanisms of progression to BC, we screened DNA samples from CML patients during blast transformation for mutations in a number of transcription factor genes that are critical for myeloid-lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of GATA-2, a negative regulator of hematopoietic stem/progenitor cell differentiation. A L359V substitution within zinc finger domain (ZF) 2 of GATA-2 was found in eight cases with myelomonoblastic features, whereas an in-frame deletion of 6 aa (delta341-346) spanning the C-terminal border of ZF1 was detected in one patient at myeloid BC with eosinophilia. Further studies indicated that L359V not only increased transactivation activity of GATA-2 but also enhanced its inhibitory effects on the activity of PU.1, a major regulator of myelopoiesis. Consistent with the myelomonoblastic features of CML transformation with the GATA-2 L359V mutant, transduction of the GATA-2 L359V mutant into HL-60 cells or BCR/ABL-harboring murine cells disturbed myelomonocytic differentiation/proliferation in vitro and in vivo, respectively. These data strongly suggest that GATA-2 mutations may play a role in acute myeloid transformation in a subset of CML patients.

[Changes of contractility and relaxation of corpus cavernosum in hyperlipidemic rabbit in vitro].

OBJECTIVE: To investigate the mechanisms of erectile dysfunction induced by hyperlipidemia through studying the changes of contractility and relaxation of corpus cavernosum in hypercholesterolemic rabbit in vitro. METHODS: New Zealand white rabbits were randomly divided into control and experiment groups. The control group (n = 20) received a regular diet for 8 weeks while the experimental group (n = 20) were fed a 1% cholesterol diet for 8 weeks. The authors conducted isometric tension studies with phenylephrine, endothelium-dependent vasodilators (acetylcholine), endothelium-independent vasodilators (sodium nitroprusside) and rho kinase inhibitor (Fasudil) on isolated strips of corpus cavernosum. RESULTS: The weight and total serum cholesterol significantly improved (P < 0.01) in experimental group as compared with the non-fed experimental group. The total serum cholesterol significantly improved (P < 0.01) in experimental group as compared with the control group. The contractility responses to phenylephrine in experiment group in doses (0.5, 1, 5, 10, 50, 100 micromol) were 4.79% +/- 2.00%, 8.84% +/-2.95%, 12.81% +/- 3.77%, 14.63% +/- 5.38%, 25.01% +/- 6.14% and 34.69% +/- 8.53% respectively. The contractility responses to phenylephrine in control group were 1.00% +/- 0.3%, 2.60% +/- 0.72%, 4.28% +/- 1.27%, 5.91% +/- 2.09%, 6.49% +/- 4.02% and 5.64% +/- 11.87% respectively. The contractility responses to phenylephrine significantly improved (P < 0.01) in experimental group in these doses as compared with the control group. The relaxation responses to acetylcholine in experimental group in doses (1, 10 and 100 micromol) were 36.28% +/- 4.71%, 48.81% +/- 4.36% and 56.27% +/- 11.93% respectively. The relaxation responses in control group were 48.04% +/- 4.78%, 69.12% +/- 5.27% and 78.23% +/- 5.30% respectively. There was significant reduction (P < 0.01) in experimental group in these doses as compared with the control group. No difference were found among the two groups in the relaxation response to sodium nitroprusside. The relaxation responses to fasudil in experimental group in doses (0.25, 1.25, 2.5 and 12.5 micromol) were 1.56% +/- 0.43%, 5.03% +/- 1.02%, 8.28% +/- 1.35% and 16.77% +/- 3.57% respectively. The relaxation responses in control group were 4.69% +/- 1.23%, 10.39% +/- 2.05%, 15.08% +/- 3.04% and 25.22% +/- 3.72% respectively. There was significant reduction (P < 0.01) in experimental group in these doses as compared with the control group. CONCLUSION: The improvement of cavernous smooth muscle contractility and the impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli are the mechanisms of erectile dysfunction induced by hyperlipidemia.

[Differentiation of rat adipose-derived stem cells into smooth-muscle-like cells in vitro].

OBJECTIVE: To study the feasibility of inducing the differentiation of rat adipose-derived stem cells (ADSCs) into smooth-muscle-like cells in monolayer culture in vitro. METHODS: ADSCs were obtained from the adipose of the inguinal region of the SD rat. A growth curve of the ADSCs was drawn. The fourth passage ADSCs were induced to differentiate into adipocytes with adipogenic inducing fluid and determined by Oil Red O staining, into osteoblasts with osteogenic inducing fluid and determined by Von Kossa staining, as well as into smooth-muscle-like cells with inducing fluid containing beta-mercaptoethanol, and the expression of alpha-smooth muscle actin (alpha-SMA) was detected by the immunohistochemical method. RESULTS: The ADSCs presented spindle and polygon shapes and proliferated rapidly in vitro. The growth curve showed the ADSCs in the logarithmic growth phase two days after subculture. The fourth passage ADSCs exhibited red stained lipid droplets characteristic of adipocytes in the cytoplasm on Oil Red O staining after induction with adipogenic inducing fluid, and calcium nodes on Von Kossa staining after induction with osteogenic inducing fluid. The immunohistochemical results of the ADSCs induced into smooth-muscle-like cells showed that the positive rate of alpha-SMA in the beta-mercaptoethanol induced cells was (29.80 +/- 6.89)%, significantly higher than in the uninduced ones ([2.89 +/- 1.24]%, P < 0.01). CONCLUSION: ADSCs displayed obvious characteristics of smooth muscle cells after induction, and could be a new source of cells in the tissue engineering studies of smooth muscle related diseases.

Content Determination of Alkaloids and Catalpol in Different Proportions of Qianjin Huanglian Pills / 医药导报

Objective To establish an HPLC method for the determination of alkaloids(epiberberine,coptisine,palma-tine,berberine)and catalpol in different ratios(1∶1,1∶10)of ancient and modern Qianjin Huanglian Pills,and to compare the differences in their contents.The content differences were compared to preliminarily evaluate the differences in the efficacy of Qianjin Huanglian Pills in the treatment of diabetes under different preparation processes and different ratios.Methods The alkaloid solvent was methanol∶ hydrochloric acid(100∶1).The detection conditions were as follows:C18 column,acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate solution(50∶50),detection wavelength 345 nm,column temperature 30℃,flow rate 1 mL·min-1,injection volume 10 μL.The catalpol solution was methanol∶ water(20∶80).The detection conditions were as follows:chromatographic column C18 column,methanol-0.1%phosphoric acid solution(1∶ 99),detection wavelength 210 nm,column temperature 30℃,flow rate 1 mL·min-1,injection volume 10 μL.Results The established method was spe-cific,and the separation effect of the five components was good.It exhibited a good linear relationship(R2＞0.999)in their respec-tive linear ranges.The repeatability,precision,stability,and sample recovery rate all met the requirements.The content of four alka-loids in the ancient method 1∶1 was the highest,and the content of catalpol was the lowest.The content of four alkaloids in the ancient method 1∶10 was the lowest;the content of 1∶1 in the present method was higher than that in the ancient method 1∶10,and the content of berberine in the present method 1∶10 was slightly lower than that in the present method 1∶1,and the rest were higher than that in the present method 1∶1.The PCA results showed that the chemical composition contents of the four kinds of Qianjin Huanglian pills were very different.Conclusion The method is simple,accurate,and reproducible,making it suitable for the quality control of Qianjin Huanglian Pills.It provides a theoretical basis for exploring the difference in efficacy of Qianjin Huanglian Pills.

Atropine 0.01% eye drops slow myopia progression: a systematic review and Meta-analysis.

AIM: To evaluate the effects of atropine 0.01% on slowing myopia progression. METHODS: We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey (System for Information on Grey Literature in Europe), the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from the dates of inception to June 30, 2018. RESULTS: Seven randomized controlled trials (RCTs) with a total of 1079 subjects were included (505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group [MD=-0.12, 95%CI (-0.19, -0.06)]. There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI (-0.25, -0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure [MD=0.08, 95%CI (-0.27, 0.42); MD=0.09, 95%CI (-0.17, 0.36); MD= -0.01, 95%CI (-0.02, 0.00); MD=0.08, 95%CI (-0.56,0.40)]. The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups [OR=0.26, 95%CI (0.11, 0.61)]. CONCLUSION: Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.

[Stable isotopes of zooplankton and their applications in the research of aquatic ecosystems]. / æµ®æ¸¸åŠ¨ç‰©ç¨³å®šç¢³ã€æ°®åŒä½ç´ ç‰¹å¾åŠå ¶åœ¨æ°´ç”Ÿæ€ç³»ç»Ÿç ”ç©¶ä¸­çš„åº”ç”¨.

Zooplankton plays a mediating role in the food web of aquatic ecosystems, the stable carbon and nitrogen isotopes (δ13C and δ15N) of which have been widely used to study the utilization of food resources, material cycling pathways, and trophic relationships. The δ13C and δ15N values of zooplankton have been used to predict primary productivity, sources and sinks of pollutants and environmental changes. To better use δ13C and δ15N of zooplankton as ecological and environmental indicators, it is particularly important to understand their temporal and spatial variations and the influencing factors. Based on related literature, we synthesized spatial and temporal variations in δ13C and δ15N of zooplankton in different aquatic ecosystems and taxa groups, and the use of δ13C and δ15N indicators for ecological processes and environmental changes. The δ13C and δ15N of zooplankton are largely affected by its food sources, and its stable isotope compositions are in turn affected by primary productivity and nitrogen sources. We proposed that the combination of δ13C and δ15N in zooplankton with transportation and transformation of emerging pollutants would form a multi-means, multi-disciplinary and multi-scale research direction in the fields of earth science and biology.

Effect of prone position management on preventing ventilator-associated pneumonia in children with congenital heart disease complicated with acute respiratory distress syndrome / 中国实用护理杂志

Objective:To develop a prone position management program and evaluate its effectiveness in preventing ventilator-associated pneumonia (VAP) in children with congenital heart disease combined with acute respiratory distress syndrome, in order to provide experience for clinical application.Methods:This was a quasi-experimental study. Convenient sampling method was used to select children with congenital heart defect who underwent mechanical ventilation in the Cardiothoracic Surgical Care Unit of Shanghai Children′s Medical Center, Shanghai Jiao Tong University, School of Medicine from June 2018 to December 2021 as the study subjects. The control group consisted of 80 hospitalized children from June 2018 to December 2019. They were used general nursing interventions to prevent VAP. The 42 hospitalized children from January 2020 to December 2021 were the intervention group, who usd the prone position management program on the basis of the control group. The differences in the incidence of VAP, duration of mechanical ventilation, duration of ICU stay, oxygenation index and the incidence of adverse events between the two groups were compared.Results:The incidence of VAP and mechanical ventilation duration in the intervention group were 4.8% (2/42) and 67.50 (55.00/101.50), which were lower than 35.0% (28/80) and 92.50 (68.00/142.00) of the control group, and the differences were statistically significant ( χ2=11.98, Z=3.40, both P<0.01). And the trend of increasing oxygenation index with the intervention group was better than the control group ( F=8.38, P<0.05). There was no statistical difference in the incidence of adverse events between the two groups (all P>0.05). Conclusions:The application of prone ventilation program with congenital heart disease children complicated with acute respiratory distress syndrome is safe and can significantly improve the oxygenation index, shorten the duration of mechanical ventilation and reduce the incidence of VAP.

Study on "Spectrum-material-effect" relationship of Compound Muji Granules against liver tumor based on microfluidic chip / 中国药理学通报

Aim To explore the material basis of anti-tumor effect of Compound Muji Granules. Methods The anti-tumor pharmacodynamics of Compound Muji Granules in vitro was studied by microfluidic chip technology. The fingerprint of Compound Muji Granules was established by HPLC. The "Spectrum-Material-Effect" of Compound Muji Granules was analyzed by grey correlation analysis,partial least squares regression analysis and network pharmacology approach. Results Seven batches of Compound Muji Granules with different extraction methods were successfully established. The results of grey correlation analysis showed that there was a positive correlation between Compound Muji Granules and 7 of the 14 components with pharmacodynamic correlation coefficient >0.80. The contribution of anti liver tumor was peak number 48(luteolin)>6(gallic acid)>19(chlorogenic acid)>59(quercetin)>67(kaempferol)>65(naringin)>38(ellagic acid),in that order. Conclusions Through the establishment of "Spectrum-Material-Effect" research method,it is clear that the above seven active monomers may be the anti-tumor material basis of Compound Muji Granules.

Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.

Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a meta-analysis.

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.