Accuracy of a smartphone-assisted novel labeling method for marking target axial position in cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the convenience and accuracy of a novel smartphone-assisted “any-point two-step method” for finding the target axial position in cataract phacoemulsification combined with intraocular lens(IOL)implantation.METHODS: Prospective observational study. A total of 62 cases(62 eyes)of patients with age-related cataracts who underwent cataract phacoemulsification combined with IOL implantation in our hospital from October 2021 to April 2022 were selected. They were randomly divided into two groups: 31 cases(31 eyes)in the control group were applied with the “traditional two-step method” using slit lamp to mark the target axial position of the IOL, and 31 cases(31 eyes)in the experimental group were applied with the smartphone-assisted “two-step method” to mark the target axial position of the IOL. The Callisto eye navigation system was used as a standard reference, and the deviation of the reference marking point(deviation-1), the deviation of the target axial marking point(deviation-total), and the deviation of the angle from the reference marking point to the target axial marking point(deviation-2)were calculated and recorded as the preoperative axial marking time.RESULTS:Both deviation-1 and deviation-total values were lower in the experimental group than those in the control group(1.06°±1.39° vs 2.48°±2.23°, 1.77°±1.54° vs 2.81°±1.58°, all P<0.01), but there was no significant difference in the deviation-2 values between the two groups(1.35°±1.40° vs 1.48°±1.79°, P>0.05). The preoperative axial marking took shorter time in the experimental group than in the control group(1.77±1.70 min vs 2.88±3.20 min, P<0.01).CONCLUSION: The smartphone-assisted “any-point two-step method” for finding the target axial position in cataract phacoemulsification combined with IOL implantation is simple, time-saving, and accurate compared with the “traditional two-step method”.

Evaluation of Cd2+ stress on Synechocystis sp. PCC6803 based on single-cell elemental accumulation and algal toxicological response.

With the development of single cell analysis techniques, the concept of precision toxicology has been proposed in recent years. Due to the heterogeneity of cells, we need to perform toxicological assessments on individual cells. Microalgae, one kind of important primary producers, play as a major pathway by which heavy metals enter the food chain and thus accumulate/transfer to higher trophic levels. Herein, the biosorption of Cd (Ex-Cd) and bioaccumulation of Cd (In-Cd) for Synechocystis sp. PCC 6803 were investigated by online 3D droplet microfluidic device combined with inductively coupled plasma mass spectrometry detection. Meanwhile, the algal toxicological responses of the algae cell to Cd2+ exposure under different concentration (50, 100, and 150 µg L - 1) and time (15 min, 24, 48 and 96 h) were studied. Combining single-cell analysis with toxicological indicators, the toxicity mechanism of Cd2+to algal was discussed. The single cell analysis results revealed heterogeneity in cellular uptake of Cd2+. The proportion of Cd-containing cells and Cd content in single algal cells all reached the maximum at 24 h. The uptake of Cd2+ occurred within 15 min under all tested exposure concentrations and a large part of Cd2+ were adsorbed on the algal cells surface. The Pearson correlation analysis showed that cell density, chlorophyll a and carotenoids were significantly negatively correlated with Cd accumulation, whereas ROS level and SOD activity were significantly positively correlated with Cd accumulation. It suggested that Cd2+accumulated intracellular would show toxic effects on the algal cells and oxidative stress is the main mechanism of Cd toxicity to algal cells. This work promotes our understanding of the toxicological responses of microalgae under Cd stress at single cells level.

A spatiotemporal assessment of occupants' infection risks in a multi-occupants space using modified Wells-Riley model.

Escalating demands of assessing airborne disease infection risks had been awakened from ongoing pandemics. An inhalation index linked to biomedical characteristics of pathogens (e.g. TCID 50 for coronavirus delta variant) was proposed to quantify human uptake dose. A modified Wells-Riley risk-assessment framework was then developed with enhanced capability of integrating biological and spatiotemporal features of infectious pathogens into assessment. The instantaneous transport characteristics of pathogens were traced by Eulerian-Lagrangian method. Droplets released via speaking and coughing in a conference room with three ventilation strategies were studied to assess occupants' infection risks using this framework. Outcomes revealed that speaking droplets could travel with less distance (0.5 m) than coughing droplets (1 m) due to the frequent interaction between speaking flow and thermal plume. Quantified analysis of inhalation index revealed a higher inhalation possibility of droplets with nuclei size smaller than 5 µ m , and this cut-off size was found sensitive to ventilation. With only 60-second exposure, occupants in the near-field of host started to have considerable infection risks (approximately 20%). This risk was found minimising over distance exponentially. This modified framework demonstrated the systematic analysis of airborne transmission, from quantifying particle inhalation possibility, targeting specific disease's TCID 50 , to ultimate evaluation of infection risks.

Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats / 中国中药杂志

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

Analysis of occupants' exposure risk of cough-expelled droplets in the workspace with various mixing ventilation layouts.

This study numerically investigated the transport characteristics of the cough-expelled droplets and their corresponding exposure risk of each occupant under various mixing ventilation layouts. Transient simulations were conducted in a conference room, while pathogen-bearing droplets were released by a standing speaker. The results showed that droplet residues (< 40 µm) had a high potential to reach occupant's breathing zone, among which the number fraction of aerosol residues (< 10 µm) could be nearly doubled compared with that of the rest droplet residues in the breathing zone. Occupants' exposure risks were found very sensitive to the ventilation layouts. The strong ventilated flow could significantly promote droplet dispersions when those inlets were closely located to the infectious speaker, resulting in all occupants exposed to a considerable fraction of aerosols and droplets within a given exposure time of 300 s. The mixing ventilation layout did not have a consistent performance on restricting the pathogen spread and controlling the occupant's exposure risk in an enclosed workspace. Its performance could be highly sensitive to the location of the infectious agent. Centralized vent layouts could provide relatively more consistent performance on removing droplets, whilst some local airflow recirculation with locked droplets were noticed.

Effect of hepatocellular carcinoma cell-derived exosomes on M2 polarization of tumor-associated macrophages / 临床肝胆病杂志

Objective To investigate the effect of exosomes derived from hepatocellular carcinoma cells on the polarization of tumor-associated macrophages (TAMs), and to reveal the novel mechanism of hepatocellular carcinoma formation. Methods Hepatocellular carcinoma cell-derived exosomes were isolated by ultracentrifugation, and the characteristics of exosomes were identified by transmission electron microscope (TEM), Dynamic Light Scattering (DLS), and Western blotting. The model of macrophage polarization was induced and verified by quantitative real-time PCR and Western blotting. The t -test was used for comparison of normally distributed continuous data between two groups. A one-way analysis of variance was used for comparison between multiple groups, and the LSD- t -test was used for further comparison between two groups. Results TEM showed that hepatocellular carcinoma cell-derived exosomes were round or oval vesicles, LDS showed that the exosomes had a particle size of 172.65±2.34 nm, and Western blotting showed highly positive expression of the biomarkers TSG101 and CD63 in exosomes. There was a significant increase in the expression of CD68 after the addition of 15 ng phorbol ester to induce human-derived mononuclear macrophages for 24 hours to achieve adherent growth (1.00±0.25 vs 6.67±0.98, t =11.20, P < 0.001). Western blotting showed that compared with the control group (L02 cell-derived exosomes), the hepatocellular carcinoma cell-derived exosomes (at low, middle, and high doses) induced M2 polarization of macrophages and increased the expression of the markers Arg-1 and CD163 (all P < 0.05). Conclusion Hepatocellular carcinoma cell-derived exosomes promote M2 polarization of TAMs.

Demethylenetetrahydroberberine protects dopaminergic neurons in a mouse model of Parkinson's disease / 中国天然药物

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1β and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.

Mutant NPM1-regulated lncRNA HOTAIRM1 promotes leukemia cell autophagy and proliferation by targeting EGR1 and ULK3.

BACKGROUND: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1), which displays a distinct long noncoding RNA (lncRNA) expression profile, has been defined as a unique subgroup in the new classification of myeloid neoplasms. However, the biological roles of key lncRNAs in the development of NPM1-mutated AML are currently unclear. Here, we aimed to investigate the functional and mechanistic roles of the lncRNA HOTAIRM1 in NPM1-mutated AML. METHODS: The expression of HOTAIRM1 was analyzed with a public database and further determined by qRT-PCR in NPM1-mutated AML samples and cell lines. The cause of upregulated HOTAIRM1 expression was investigated by luciferase reporter, chromatin immunoprecipitation and ubiquitination assays. The functional role of HOTAIRM1 in autophagy and proliferation was evaluated using western blot analysis, immunofluorescence staining, a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, flow cytometric analyses and animal studies. The action mechanism of HOTAIRM1 was explored through RNA fluorescence in situ hybridization, RNA pulldown and RNA immunoprecipitation assays. RESULTS: HOTAIRM1 was highly expressed in NPM1-mutated AML. High HOTAIRM1 expression was induced in part by mutant NPM1 via KLF5-dependent transcriptional regulation. Importantly, HOTAIRM1 promoted autophagy and proliferation both in vitro and in vivo. Mechanistic investigations demonstrated that nuclear HOTAIRM1 promoted EGR1 degradation by serving as a scaffold to facilitate MDM2-EGR1 complex formation, while cytoplasmic HOTAIRM1 acted as a sponge for miR-152-3p to increase ULK3 expression. CONCLUSIONS: Taken together, our findings identify two oncogenic regulatory axes in NPM1-mutated AML centered on HOTAIRM1: one involving EGR1 and MDM2 in the nucleus and the other involving the miR-152-3p/ULK3 axis in the cytoplasm. Our study indicates that HOTAIRM1 may be a promising therapeutic target for this distinct leukemia subtype.

Deposition features of inhaled viral droplets may lead to rapid secondary transmission of COVID-19.

Inhaled viral droplets may immediately be expelled and cause an escalating re-transmission. Differences in the deposition location of inhaled viral droplets may have a direct impact on the probability of virus expelling. This study develops a numerical model to estimate the region-specific deposition fractions for inhalable droplets (1-50 µ m) in respiratory airways. The results identified a higher deposition fraction in the upper airways than the lower airways. Particularly for droplets larger than 10 µ m, the relatively high deposition fraction in the oral/laryngeal combined region warns of its easy transmission through casual talking/coughing. Moreover, considering droplet sizes' effect on virus loading capacity, we built a correlation model to quantify the potential of virus expelling hazards, which suggests an amplified cascade effect on virus transmission on top of the existing transmission mechanism. It therefore highlights the importance of considering the instant expelling possibilities from inhaled droplets, and also implies potentials in restricting a rapid secondary transmission by measures that can lower down droplet deposition in the upper airways.

NPM1 mutant maintains ULK1 protein stability via TRAF6-dependent ubiquitination to promote autophagic cell survival in leukemia.

Nucleophosmin (NPM1) mutations are the most frequent genetic alteration in acute myeloid leukemia (AML) and aberrant cytoplasm-dislocated NPM1 mutant is a distinct biological characterization of this disease. Our group previously reported that NPM1 mutant elevated autophagy activity and autophagy activation contributed to leukemic cell survival. However, the molecular mechanisms by which cytoplasmic NPM1 mutant involving in the autophagy pathway has not been fully elucidated. Here, we showed that Unc-51-like kinase 1 (ULK1) as a core autophagy protein was highly expressed in NPM1-mA positive OCI-AML3 cells and primary NPM1-mutated AML blasts. Meanwhile, we found that NPM1-mA could interact with ULK1 protein and positively regulated ULK1 protein levels. Mechanically, NPM1-mA promoted TRAF6-dependent K63 ubiquitination and further maintained ULK1 stability and kinase activity via miR-146a. In addition, ULK1 high expression-mediated autophagy activation and facilitated to leukemic cell proliferation. Finally, we demonstrated that restoring ULK1 expression, ULK1 inhibitor SBI-0206965 treatment and using shULK1 partially rescued the effect of NPM1-mA on autophagy and cell survival. In conclusion, our findings suggest that NPM1 mutant interacts with ULK1, and thus, maintains its protein stability, which is required for NPM1 mutant-mediated autophagic cell survival. These data extend our understanding of the functions of NPM1 mutant in the regulation of autophagy activation in NPM1-mutated AML.

Effectiveness and safety evaluation of lidocaine hydrochloride ophthalmic gel for ocular anesthesia: a multicenter randomized double-blind trial / 中华实验眼科杂志

Objective:To evaluate the effectiveness and safety of 3.5% lidocaine hydrochloride ophthalmic gel for eye surface anesthesia.Methods:A multicenter, randomized, double-blind, placebo controlled clinical trial was conducted in 10 hospitals in China from August 2018 to April 2019 under the approval of an Ethics Committee of Beijing Hospital (No.2018BJYYEC-014-02). A total of 220 fellow eyes of 220 subjects who received ocular surgery in one eye were actually enrolled according to a same included criteria in different institutes.The 220 eyes were randomly divided into control group and trail group.Two drops of lidocaine hydrochloride gel were dropped at about 5 mm away from corneal limbus at 6 o'clock direction of experimental eye of the trail group, and the blank gel was used in the eyes of the control group in the same way.The pain sensation was assessed with a 0.3 mm toothless micro forceps on conjunctiva within a specified time, and ''pain'' or ''no pain'' was answered by the subjects.The primary effective indexes, namely the number of eyes and percentage of ''no pain'' within 5 minutes following dropping, as well as the secondary indexes including the onset time point of the drug and the duration of anesthesia were recorded and evaluated.Safety evaluation took ocular and system adverse events into account.Results:Within 5 minutes after dropping, ''no pain'' occurred in 104 eyes (94.55%) and 29 eyes (26.36%) in the trail group and control group, respectively, showing a significant difference between the two groups ( χ2=106.948, P<0.001). And there was a significant difference in anesthesia onset time between the trail group and control group (40.0 seconds vs. 300.0 seconds) ( Z=-15.17, P<0.001). The duration of anesthesia was 860.5 (577.5, 1 180.0) seconds in the trail group and 676.0 (280.0, 1 401.0) seconds in the control group, with no statistically significant difference between the two groups ( Z=0.898, P>0.05). The incidence of adverse events in the trail group and control group were 5.45% (6/110) and 4.55% (5/110), respectively, without statistical significance between them ( P=1.000). Conclusions:The 3.5% lidocaine hydrochloride is a safe, effective, easy to use and high-quality surface anesthesia drug for eye surgery.

Exploration of Serum Exosomal LncRNA TBILA and AGAP2-AS1 as Promising Biomarkers for Diagnosis of Non-Small Cell Lung Cancer.

Non-small cell lung cancer is the most common type of cancer with a poor prognosis, and development of an effective diagnostic method is urgently needed. Exosomal lncRNAs, a class of transcripts longer than 200 nucleotides packaged into exosomes, have been defined as an ideal diagnostic biomarker for cancer. However, little is known about the clinical utility of exosomal lncRNAs in NSCLC. Here, we aimed to identify exosomal lncRNAs as promising biomarkers for NSCLC diagnosis. First, serum exosomes from NSCLC patients were successfully isolated by a polymer precipitation kit and then identified by TEM, NTA and western blot analysis. A total of nine candidate lncRNAs were detected by qRT-PCR in a training set. The two exosomal lncRNA TBILA and AGAP2-AS1 were screened out for the higher levels in NSCLC patients than that of healthy controls in a validation set. And there was a significant positive correlation between these exosomal lncRNAs levels and tumor size, lymph node metastasis and TNM stage. Additionally, we validated that these exosomal lncRNAs were stable in serum. Next, we evaluated the diagnostic efficiency of exosomal lncRNAs in NSCLC patients by ROC curve analysis. The data showed that individual TBILA or AGAP2-AS1 exhibited better diagnostic efficiency in NSCLC patients with different tumor pathologic subtypes and early stage, whereas the combination of lncRNAs did not provide better results than individual lncRNAs. Notably, the combination of two exosomal lncRNAs and the serum tumor biomarker Cyfra21-1 widely used in clinical practices further improved the diagnostic accuracy for NSCLC patients. This study suggests that exosomal lncRNA TBILA and AGAP2-AS1 may be promising biomarkers for diagnosis of NSCLC.

Retrospective Clinical Analysis on Treatment of Coronavirus Disease 2019 with Traditional Chinese Medicine Lianhua Qingwen / 中国实验方剂学杂志

Objective:To analyze the clinical effect of traditional Chinese medicine Lianhua Qingwen in the treatment of coronavirus disease 2019 (COVID-19) and provide the basis for medication guides through a retrospective study in a cohort of COVID-19 confirmed patients. Method:A retrospective analysis of clinical records was conducted in COVID-19 confirmed patients at The Ninth Hospital of Wuhan and CR&WISCO General Hospital including the treatment group (21 patients, basic treatment in combination with Lianhua Qingwen granules, 1 packet/time, 3 times/day) and the control group (21 patients, basic treatment). Comparison between the two groups was made in terms of the disappearance rates of cardinal symptoms (fever, cough and weakness), duration of fever, and disappearance rates of other symptoms (muscle pain, expectoration, nasal obstruction, running nose, dry throat, pharyngalgia, shortness of breath, chest distress, dyspnea, dizziness, headache, nausea, vomiting, loss of appetite and diarrhea). Result:The baseline data were similar between the two groups. When compared with the control group, patients in the treatment group had the higher clinical effect, including the disappearance rate of fever (85.7% vs 57.1%, χ2=4.200, P=0.040), the disappearance rate of cough (46.7% vs 5.6%, P=0.012), the disappearance rate expectoration (64.3% vs 9.1%, P=0.012), the disappearance rate of shortness of breath (77.8% vs 0, P=0.021), and the duration of fever [(4.6±3.2) d vs (6.1±3.1) d, P=0.218]. Conclusion:Lianhua Qingwen can significantly relieve cardinal symptoms in COVID-19 confirmed patients by inhibiting fever and cough, reducing their duration, as well as improving individual symptoms. All these results provide preliminary clinical evidence for Lianhua Qingwen granules in the COVID-19 treatment.

Advance in Repeatitive Transcranial Magnetic Stimulation for Dysphagia after Stroke (review) / 中国康复理论与实践

Repeatitive transcranial magnetic stimulation can adjust cortical excitability and improve swallowing function in patients with dysphagia after stroke. High frequency stimulations with 90% to 130% resting motor threshold (rMT) in the early stage, as well as low frequency stimulations with 100% to 130% rMT for 1200 pulse in the recovery period, may be beneficial to the recovery of swallowing function, and bilateral stimulation may be more effective.

Imaging Features of Abnormal Neural Connectivity in Autistic Children / 中国康复理论与实践

Objective:To analyze the structure and function of white matter in autistic children by using diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS), to explore the imaging features of abnormal neural connectivity in children with autism. Methods:Autism group (n = 14) and control group (n = 8), aged two to nine years, underwent DTI and MRS scan. Bilateral frontal lobe, hippocampus, genu and splenium of corpus callosum and cerebellum white matter were selected as regions of interest. The data of DTI and MRS were processed by Functool 2.6 software of GEAW4.2 workstation. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of DTI, the absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatinine (Cr) and the ratios of NAA/Cr and Cho/Cr were recorded respectively. Results:Compared with the control group, the FA of left hippocampus (F = 5.922, P = 0.033) and the absolute concentration of Cr in left and right hippocampus (F > 4.715, P < 0.05) decreased significantly in the autism group. The FA was lower in left corpus callosum genu than in the right one (F = -2.335, P = 0.042), and the ADC was higher in left corpus callosum splenium than in the right one (F = 3.520, P < 0.01) in the autism group. The absolute concentration of NAA, Cho and Cr in left frontal lobe (|t| > 2.648, P < 0.05), the absolute concentration of NAA in left corpus callosum splenium (t = -3.076, P = 0.009) and Cho/Cr in left cerebellum (t = -2.225, P = 0.044) were significantly lower than those in the right cerebral hemisphere in the autism group. The DTI and MRS indexes were not different between left and right hemispheres in the control group (P > 0.05). Conclusion:Abnormal metabolite or functional alternations were found in the frontal lobe, hippocampus, cerebellum and the genu and splenium of the corpus callosum in autistic children, suggesting underconnectivity intra- or inter-hemispheric neural, especially in left hemisphere.

Application of lung ultrasonography score on clinical evaluating in patients with acute respiratory distress syndrome / 中华急诊医学杂志

Objective:To evaluate the value of lung ultrasound (LUS) in the early assessment of patients with acute respiratory distress syndrome (ARDS).Methods:A prospective double-blind cohort study was conducted. Patients with ARDS conformed to the Berlin diagnosis criteria admitted to the Intensive Care Unit (ICU) of Ningbo Yinzhou People’s Hospital from July 2016 to January 2020. According to the oxygenation index (OI), the patients were divided into the mild to moderate group (100 mmHg<OI≤300 mmHg) and the severe group (OI≤100 mmHg); Patients underwent LUS and transpulmonary thermodilution technique (TPTD) monitoring and chest CT on the first day after diagnosis. Acute physiology and chronic health status (APACHEⅡ) score, lung injury score (LIS), and PaO 2/FiO 2 (OI) were recorded at admission. LUS score, EVLWI, OI, APACHEⅡ score and LIS were compared. The correlation between LUS and EVLWI, OI, APACHEⅡ score and LIS score was measured by Pearson linear correlation anaysis. Receiver operating characteristic (ROC) curve were used to evaluate LUS score in predicting ARDS. Results:A total of 52 patients with ARDS were enrolled, 34 patients in the mild to moderate group and 18 patients in the severe group. Compared with chest CT scans, the accuracy of LUS diagnosis was 93.12%, the sensitivity was 91.33%, the specificity was 95.31%, the positive predictive value was 95.95%, and the negative predictive value was 90.03%. Pearson linear correlation analysis showed that LUS was positively correlatied with EVLWI ( r=0.756, P<0.01), LIS score ( r=0.817, P<0.01), and APACHEⅡ score ( r=0.655, P<0.01), while was negatively correlated with OI ( r=-0.823, P<0.01). The areas under the receiver operating characteristic curves of LUS and EVLWI measured by TPTD were 0.922 ( P<0.01) and 0.972 ( P<0.01), LUS score threshold value of 19.5 had the sensitivity of 0.833 and specificity of 0.791 for prediction of severe ARDS. Conclusions:LUS is convenient and easy to perform, and LUS score has a high value, which is a better prognostic indicator for early assessment of ARDS patients.

Study on the relationship between tear ferning image and the abnormality of tear lipid layer in dry eye patients / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the clinical significance of outer zona pellucid in tear ferning image in dry eye patients and explore a new method for evaluation tear lipid layer. <p>METHODS:Forty-seven patients were randomly selected from the outpatient department of ophthalmology, He Eye hospital, Shenyang from May 2018 to July 2019. The right eye was selected as the study object. All patients were investigated by the ocular surface disease index(OSDI)questionnaire and performed lipid layer classification by DR-1 tear interferometry, NIBUT and tear meniscus height examination by OCULUS Keratograph. Then tears were collected and tear ferning tests was performed. The whole tear crystallization images were observed and photographed by microscopy, then measured by Digimizer software and the area ratios of outer transparent belt were calculated. Pearson correlation analysis were performed between area ratios of outer transparent belt and OSDI scores, lipid layer levels, tear meniscus height values, NIBUT values. <p>RESULTS: The area ratios of outer transparent belt were negatively correlated with OSDI scores(<i>r</i>=-0.764, <i>P</i><0.05), negatively correlated with lipid layer levels(<i>r</i>=-0.838, <i>P</i><0.05), positively correlated with NIBUT values(<i>r</i>=0.575, <i>P</i><0.05)and the correlation between tear meniscus height values was not significantly(<i>r</i>=-0.237, <i>P</i>=0.112). <p>CONCLUSION: The outer transparent belt in tear crystallization image can be used to evaluate the lipid layer of tear film; the larger area ratios of outer transparent belt, the thicker the lipid layer. This method has the advantages of quantified results, good repeatability, low requirement on equipment, and is worth popularizing.

Evaluation of continuous metabolic syndrome score as a screening tool for metabolic syndrome in Xinjiang urban population aged 15-18 years / 中国学校卫生

Objective@#The purpose of the present study was to evaluate of continuous metabolic syndrome score (cMetS) in screening metabolic syndrome (MetS) and to determine the cut-off values in a representative sample of Xinjiang population aged 15 to 18 years old.@*Methods@#A stratified cluster sampling was used to select participants aged 15-18 years from 13 cities in Xinjiang. cMetS was calculated by summing up the Zscores of standardized waist circumference, mean arterial pressure, high-density lipoprotein, triglyceride, and fasting blood glucose by age and gender.@*Results@#Totally 16.3% of subjects were overweight, and 5.2% were obese. The proportion of overweight and obesity in males was significantly higher than that in females (18.1% vs 13.8%)(6.0% vs. 4.1%)(χ2=15.36，7.89，P<0.05). The prevalence of total MetS was 6.1%, with 6.6% and 5.4% for men and women, respectively. There was a correlation between cMetS and MetS components, and the average cMetS value increased with increasing MetS component(P<0.05). The total cut-off value of cMetS was 0.99 (sensitivity 68.0%, specificity 80.7%), and the area under the ROC curve was 84.9%. The cMetS scores for boys and girls were 0.80 and 1.48, respectively.@*Conclusion@#Compared with MetS, cMetS shows more accuracy in screening MetS among youth aged 15-18 years in both gender.

Up-regulation of EMT-related gene VCAN by NPM1 mutant-driven TGF-ß/cPML signalling promotes leukemia cell invasion.

Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) is acknowledged as a distinct leukemia entity in the 2016 updated World Health Organization (WHO) classification. NPM1-mutated AML patients are correlated with higher extramedullary involvement. Epithelial-mesenchymal transition (EMT) is one of the key steps which cause distant metastasis in tumor. However, whether EMT-related programs contribute to cell invasion in NPM1-mutated AML remains unclear. In this study, we identified the EMT-related gene versican (VCAN) in NPM1-mutated AML across three patient datasets. Further experiments validated the elevated VCAN expression in NPM1-mutated AML primary blasts and OCI-AML3 cells with NPM1 mutation. Mechanistic studies revealed that increased VCAN expression was at least partially regulated by NPM1 mutant via TGF-ß/cPML/Smad signalling. Functional evaluations showed that silencing VCAN by shRNA significantly suppressed cell migration and invasion capacity, whereas increased VCAN by overexpressing NPM1-mA enhanced migration and invasion ability of leukemia cells. Finally, we found that high expression of VCAN was associated with poor prognosis in AML patients. These findings provide insights into the involvement of EMT-related gene VCAN in the pathogenesis of NPM1-mutated leukemia, which suggests that VCAN is an attractive target for novel diagnostic and therapeutic strategies in NPM1-mutated AML.

Glycolytic Enzyme PKM2 Mediates Autophagic Activation to Promote Cell Survival in NPM1-Mutated Leukemia.

Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been defined as a distinct leukemia entity in the 2016 updated WHO classification of myeloid neoplasm. Our previous report showed that autophagic activity was elevated in NPM1-mutated AML, but the underlying molecular mechanisms remain elusive. Mount of study provides evidence that glycometabolic enzymes are implicated in the autophagic process. Pyruvate kinase isoenzyme M2 (PKM2), a key glycolytic enzyme, has been recently reported as a tumor supporter in leukemia. However, little is known about the roles of PKM2 in autophagic activity in NPM1-mutated AML. In this study, PKM2 highly expressed in NPM1-mutated AML, and partially, high levels of PKM2 were upregulated by PTBP1. Further experiments demonstrated that PKM2 mediated autophagic activation and increased the phosphorylation of key autophagy protein Beclin-1. Importantly, functional experiments demonstrated that PKM2 contributed to cell survival via autophagic activation. Ultimately, high PKM2 expression was associated with short overall and event-free survival time in NPM1-mutated AML patients. Our findings indicate for the first time that glycolytic enzyme PKM2 mediates autophagic activation and further contributes to cell survival in NPM1-mutated AML, suggesting that PKM2 may serve as a promising target for treatment of NPM1-mutated AML.