Role of TRPV1/NF-κB signaling pathway in dexmedetomidine-induced alleviation of VILI in rats / 中华麻醉学杂志

Objective:To evaluate the role of transient receptor potential vanilloid receptor 1 (TRPV1)/nuclear factor-κB (NF-κB) signaling pathway in dexmedetomidine-induced alleviation of ventilator-induced lung injury (VILI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), AMG9810 group (group A), dexmedetomidine group (group D), and dexmedetomidine + RTX group (group DR). VILI model was prepared by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h. In group A, TRPV1 inhibitor AMG9810 30 mg/kg was intraperitoneally injected at 1 h before mechanical ventilation.Dexmedetomidine 5.0 μg/kg was intravenously infused at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μ g·kg -1·h -1 during ventilation in group D and group DR.In group DR, RTX 70 μ g/kg was intraperitoneally injected for 3 consecutive days before mechanical ventilation.At 4 h of mechanical ventilation, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 in bronchoalveolar lavage fluid (BALF) were detected, oxygenation index (OI) and wet/dry lung weight (W/D) ratio were measured, the histopathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of TRPV1 and NF-κB in lung tissues was detected by Western blot, and real-time polymerase chain reaction was used to detect the expression of TRPV1 and NF-κB mRNA. Results:Compared with group C, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group V ( P<0.05). Compared with group V, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly decreased, OI was increased, the W/D ratio and lung injury scores were decreased, and the expression of TRPV1 and NF-κB protein and mRNA was down-regulated in A, D and DR groups ( P<0.05). Compared with group D, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group DR ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates VILI is partially related to inhibition of the activation of TRPV1/NF-κB signaling pathway and inhibition of the inflammatory responses in lung tissues of rats.

Transform routine medical accelerators to achieve Flash-RT and physical performance measurements / 中华放射肿瘤学杂志

Objective:To investigate the feasibility of transforming conventional medical accelerator to achieve ultra-high dose rate required to achieve Flash radiotherapy (Flash-RT), and to understand the physical properties of the Flash-RT beam.Methods:By transforming the Varian 23CX medical accelerator, the radiation average dose rate at the isocenter was not less than 40 Gy/s. The relevant physical measurement scheme was designed to accurately measure the actual radiation dose rate of different source skin distance (SSD) conditions, the percent depth dose (PDD) curve and the off-axis dose distribution of the beam.Results:The average dose rate of 9 MeV electron beam after the transformation was measured using the HD-V2 type film, the average dose rate of 3 s was 97.9 Gy/s, and the average dose rate of 6 s was 99.27 Gy/s. When the SSD was 100 cm, 80 cm and 60 cm, the average dose rate of 9 MeV electron beam after the transformation was 99.3 Gy/s, 168 Gy/s and 297.5 Gy/s, respectively. After the transformation, the R100 of the 9 MeV beam was 2.2 cm underwater, R50 was 3.87 cm underwater, the electron range Rp was 4.58 cm, and the maximum possible energy Ep,0 on the phantom surface was 9.28 MeV. These parameters were slightly higher than those of the conventional 9 MeV beam, manifested with slight increase in the surface dose and widening high dose flat area. The overall deposit dose distribution exhibited the highest central axis and the increase in dose declines from the axis distance. Under the condition that the field size was 20 cm×20 cm and the SSD was 100 cm, the FWHM of the vertical and horizontal off-axis dose distribution curves were 16.6 cm and 16.4 cm, respectively. Conclusion:By transforming conventional medical accelerator, the average dose rate of the beam at the isocycle meets the requirement of Flash-RT, and the average dose rate under the condition of 60 cm SSD is much higher than the requirement of at least 40 Gy/s for Flash-RT.

Hyperactivation of PI3K/AKT/mTOR signal pathway impairs TNF-α-induced autophagy in mesenchymal stem cells from patients with ankylosing spondylitis / 南方医科大学学报

OBJECTIVE@#To investigate the changes in autophagy of mesenchymal stem cells (MSCs) from patients with ankylosing spondylitis and explore the mechanism for decreased autophagy in ASMSCs.@*METHODS@#MSCs collected from 14 patients with AS (ASMSCs) and from 15 healthy donors (HDMSCs) were cultured in the absence or presence of 25 ng/mL TNF-α for 6 h. Autophagy of the cells was determined by immunofluorescence staining of GFP-LC3B, and the results were confirmed by detecting the protein expressions of autophagy markers LC3 II/LC3 I and P62. The mRNA expressions of the related genes were detected using qRT-PCR, and the protein expressions of the autophagy markers and signaling pathway-related molecules were determined with Western blotting. TG100713 was used to block the PI3K/AKT/mTOR signal pathway, and its effect on autophagy of ASMSCs was evaluated.@*RESULTS@#ASMSCs showed significantly weaker GFP-LC3B puncta staining and lower protein expression levels of LC3 II/LC3 I but higher levels of P62 protein (P < 0.05), indicating a decreased autophagy capacity as compared with HDMSCs. TNF-α-induced ASMSCs showed significantly higher protein expressions of p-PI3K/ PI3K, p-AKT/AKT and p-mTOR/mTOR than HDMSCs (P < 0.05), suggesting hyperactivation of the PI3K/AKT/mTOR signaling pathway in ASMSCs. Blocking PI3K/AKT/mTOR signaling with TG100713 eliminated the difference in TNF-α-induced autophagy between HDMSCs and ASMSCs.@*CONCLUSION@#In patients with AS, hyperactivation of the PI3K/AKT/mTOR signaling pathway results in decreased autophagy of the MSCs and potentially contributes to chronic inflammation.

Correlation between serum VEGF level and clinical symptoms in patients with first-episode drug-naive schizophrenia of different genders / 中华行为医学与脑科学杂志

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.

The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway / 中国天然药物

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Mechanism of emodin in relieving neuropathic pain by regulating serum metabolism / 中国中药杂志

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P<0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P<0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.

Meta-analysis of acupuncture and moxibustion for the therapeutic effect on postoperative gastrointestinal dysfunction of gastric cancer / 中国针灸

OBJECTIVE@#To systematically review the therapeutic effect of acupuncture and moxibustion on postoperative gastrointestinal dysfunction (GID) of gastric cancer with meta-analysis.@*METHODS@#The articles of randomized controlled trials (RCTs) of acupuncture and moxibustion treatment for postoperative GID of gastric cancer were retrieved from the following databases from the time of database establishment to December 31, 2020, including PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database and China Biomedical Literature Database (SinoMed). RevMan5.3 software was used for meta-analysis. Using Stata16.0 software, sensitivity analysis and publication bias test were performed.@*RESULTS@#A total of 16 RCTs were included finally, including 1 360 patients, of which, there were 681 cases in the intervention group and 679 cases in the control group. Meta-analysis results showed that acupuncture and moxibustion shortened the time of first flatus (P<0.000 01, MD =-14.52, 95%CI = [-17.31, -11.74]), the time of first bowel sound (P<0.000 01, MD =-10.50, 95%CI =[-13.99, -7.01]) and the time of first defecation (P<0.000 1, MD =-13.79, 95%CI =[-20.09, -7.50]). Meanwhile, acupuncture and moxibustion shortened the time of the first food intake (P<0.000 1, MD =-3.23, 95%CI = [-3.45, -3.00]) and the hospital stay (P<0.000 01, MD =-1.94, 95%CI =[-2.20, -1.69]) after gastric cancer operation, and reduced the incidences of postoperative adverse reactions, i.e. nausea and vomiting (P =0.000 3, RR =0.43, 95%CI =[0.28, 0.68]) and abdominal distention (P =0.000 5, RR =0.41, 95%CI =[0.25, 0.68]).@*CONCLUSION@#Acupuncture and moxibustion can promote the recovery of postoperative gastrointestinal function in the patients with gastric cancer. But, for the comparison among different measures of acupuncture and moxibustion intervention, it needs more high-quality trials for a further verification.

Peiminine inhibits myocardial injury and fibrosis after myocardial infarction in rats by regulating mitogen-activated protein kinase pathway

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

Research on cost-benefit analysis of in-hospital falls: based on real world data / 中国实用护理杂志

Objective:Based on the real-world clinical data of hospital electronic medical records, to analyze the length of stay and healthcare costs associated with in-hospital falls and fall injuries in hospitals.Methods:Based on the electronic medical record system of the First Affiliated Hospital of Nanjing Medical University, a retrospective cohort study was conducted on patients admitted to these departments reported falls in nursing management information system from January 2017 to December 2019. A total of 38 481 patients from 74 units were enrolled in this study. The patients′ characteristics, falls, falls injury, and explore the length of hospital stay and bottom-up direct cost were analyzed.Results:A total of 243 cases (0.6%) fell and 154 cases (63.4%) were injured by falls from January 2017 to December 2019. Compared with non-fallers, the median length of stay of patients with falls was 19 days, which was significantly increased compared with 7 days of patients without falls ( Z=-15.18, P<0.05). The median hospitalization cost of patients with falls was 39 000 yuan, which was significantly higher than 16 300 yuan of patients without falls ( Z=-11.47, P<0.01). There was no statistical difference between non-injuried fallers and injuried fallers for length of stay and healthcare costs ( Z=-0.92, -0.64, P>0.05). Linear regression model analysis showed that gender, age, comorbidity, inpatient department unit, reason of hospitalization were significantly correlated with inpatient cost and length of stay ( F=280.05, 217.31, all P<0.05). Conclusions:Patients who have an in-hospital fall have significantly longer hospital stays and higher direct costs, mainly can be attributed to the fall itself, not the injury. Our findings have important financial implications for real world in light of optimal intervention strategies, resource allocation and economic evaluation of fall prevention.

Evaluation of the treatment of functional dyspepsia of deficiency cold of spleen and stomach by He Style fire acupuncture / 国际中医中药杂志

Objective:To observe the curative effect of He Style fire acupuncture on functional dyspepsia of deficiency cold of spleen and stomach syndrome.Methods:Sixty patients who met the inclusion criteria from March 2017 to March 2019 in Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were divided into 2 groups according to the random number table method, with 30 in each group. The control group was given mosapride tablets, one tablet (5 mg) each time half an hour before meals. On the basis of the control group, the treatment group was given fire acupuncture on Zusanli(ST36), Zhongwan(CV12), Pishu(BL20), Weishu(BL21), Guanyuan(CV4) and Qihai (CV6) twice a week. The course of treatment for both groups of patients was 4 weeks. A follow-up was visited at 1 month after the treatment. The total Symptom Scores and Health-Related Quality of Life Scale (SF-36) scores were performed before and after treatment, and the total scores of syndromes of patients with Deficiency cold of spleen and stomach before and after treatment were used for clinical efficacy evaluation, and adverse events during treatment were recorded.Results:The total efficiency of the treatment group was 93.3% (28/30), and 76.7% (23/30) in the control group, and the 2 groups were statistically significant ( χ2=4.78, P<0.05). After treatment, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort, early satiety, and total scores in the treatment group were significantly lower than those in the control group ( t values were 4.27, 5.16, 3.93, 4.69, 4.28, respectively, all Ps<0.05); during follow-up, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort and the total scores in the treatment group were significantly lower than those in the control group ( t values were 3.63, 3.22, 4.03, 3.04, respectively, all Ps<0.05). In terms of SF-36, after treatment, the treatment group showed significantly higher scores in the control group of physical function, physiology, mental health, and health changes compared with the control group ( t values were 2.97, 4.05, 4.22, 3.05, respectively, all Ps<0.05). During follow-up, the treatment group with physiological function, physical function, physical pain, overall health, life vitality, mental health, health changes scores were significantly higher than those in the control group ( t values were 3.27, 4.23 3.85, 3.15, 3.25, 6.15, 3.85, respectively, all Ps<0.05). Conclusion:He Style fire acupuncture combined with western medicine treatment can improve the symptoms of upper abdominal pain and upper abdominal burning, and the quality of lifein the patients with functional dyspepsia.

Electrocardiogram data recognition algorithm based on variable scale fusion network model / 生物医学工程学杂志

The judgment of the type of arrhythmia is the key to the prevention and diagnosis of early cardiovascular disease. Therefore, electrocardiogram (ECG) analysis has been widely used as an important basis for doctors to diagnose. However, due to the large differences in ECG signal morphology among different patients and the unbalanced distribution of categories, the existing automatic detection algorithms for arrhythmias have certain difficulties in the identification process. This paper designs a variable scale fusion network model for automatic recognition of heart rhythm types. In this study, a variable-scale fusion network model was proposed for automatic identification of heart rhythm types. The improved ECG generation network (EGAN) module was used to solve the imbalance of ECG data, and the ECG signal was reproduced in two dimensions in the form of gray recurrence plot (GRP) and spectrogram. Combined with the branching structure of the model, the automatic classification of variable-length heart beats was realized. The results of the study were verified by the Massachusetts institute of technology and Beth Israel hospital (MIT-BIH) arrhythmia database, which distinguished eight heart rhythm types. The average accuracy rate reached 99.36%, and the sensitivity and specificity were 96.11% and 99.84%, respectively. In conclusion, it is expected that this method can be used for clinical auxiliary diagnosis and smart wearable devices in the future.

Relationship between mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury and p38MAPK/NLRP3 pathway in lung tissues of rats / 中华麻醉学杂志

Objective:To evaluate the relationship between the mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury (VILI) and p38 mitogen-activated protein kinase (p38 MAPK)/nucleotide binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway in lung tissues of rats.Methods:Sixty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), mechanical ventilation group (group V), and methylprednisolone group (group M). Group C breathed air spontaneously for 4 h without mechanical ventilation.Group V was mechanically ventilated (RR 40 times/min, V T 40 ml/kg, I∶E 1∶1, PEEP 0, FiO 2 21%) for 4 h. Group M received intravenous methylprednisolone 10 mg/kg at 20 min before mechanical ventilation.At 4 h of mechanical ventilation, broncho-alveolar lavage fluid (BALF) was collected to measure the concentrations of interleukin-1beta (IL-1β), IL-18, and tumor necrosis factor-alpha (TNF-α) and wet/dry lung weight ratio (W/D ratio), and lung tissues were obtained for microscopic examination of the histopathological changes and for detection of the expression of p38MAPK, phosphorylated p38MAPK (p-p38MAPK), NLRP3, apoptosis-related speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific protease-1 (caspase-1) (using Western blot). Results:Compared with group C, the W/D ratio of lung tissues and concentrations IL-1β, IL-18 and TNF-α in BALF were significantly increased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was up-regulated in group V ( P<0.05), and no significant change was found in group M ( P>0.05). Compared with group V, the W/D ratio of lung tissues and concentrations of IL-1β, IL-18 and TNF-α in BALF were significantly decreased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was down-regulated in group M ( P<0.05). Conclusion:The mechanism by which methylprednisolone alleviates VILI may be related to inhibition of p38MAPK/NLRP3 pathway activity and reduction of inflammatory responses in lung tissues of rats.

Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Development of a CRISPR/Cpf1 gene editing system in silkworm Bombyx mori / 生物工程学报

The CRISPR/Cas9 gene editing system has been widely used in basic research, gene therapy and genetic engineering due to its high efficiency, fast speed and convenience. Meanwhile, the discovery of novel CRISPR/Cas systems in the microbial community also accelerated the emergence of novel gene editing tools. CRISPR/Cpf1 is the second type (V type) CRISPR system that can edit mammalian genome. Compared with the CRISPR/Cas9, CRISPR/Cpf1 can use 5'T-PAM rich region to increase the genome coverage, and has many advantages, such as sticky end of cleavage site and less homologous recombination repair. Here we constructed three CRISPR/Cpf1 (AsCpf1, FnCpf1 and LbCpf1) expression vectors in silkworm cells. We selected a highly conserved BmHSP60 gene and an ATPase family BmATAD3A gene to design the target gRNA, and constructed gHSP60-266 and gATAD3A-346 knockout vectors. The efficiency for editing the target genes BmATAD3A and BmHSP60 by AsCpf1, FnCpf1 and LbCpf1 were analyzed by T7E1 analysis and T-clone sequencing. Moreover, the effects of target gene knockout by different gene editing systems on the protein translation of BmHSP60 and BmATAD3A were analyzed by Western blotting. We demonstrate the CRISPR/Cpf1 gene editing system developed in this study could effectively edit the silkworm genome, thus providing a novel method for silkworm gene function research, genetic engineering and genetic breeding.

Comparison on short-term safety outcomes between off-pump and on-pump coronary artery bypass grafting by experienced surgeons: a single center study with 31 075 cases / 中华心血管病杂志

Objective: To compare the short-term outcomes between off-pump and on-pump coronary artery bypass graft (CABG) by experienced surgeons with similar surgical team in a single large-volume cardiac surgery center. Methods: A total of 31 075 patients with multivessel coronary disease who underwent isolated off-pump or on-pump CABG between January 1, 2009 and December 31, 2019 by experienced surgeons in Fuwai hospital were enrolled in this retrospective study. Patients was divided into on-pump CABG group and on-pump CABG group on an intention-to treat basis. Short term safety endpoints, including 30 days mortality, composite endpoint of major morbidity or mortality, prolonged postoperative length of stay (PLOS), and prolonged ICU length of stay (PICULOS), and distal anastomosis were compared between the two groups. Mortality was evaluated on 30 days post operation, other endpoints were collected before discharge. After 1∶1 propensity-score matching of baseline characteristics for on-pump and off-pump CABG, postoperative endpoints were compared with use of McNemar's test and further adjusted with the use of a logistic regression model. Results: After propensity-score matching, 10 243 matched pairs of patients were included in the final analysis, there were 4 605(22.5%) females and mean age was (60.7±8.6) years. The standardized differences were less than 5% for all baseline variables in matched cohort. Univariate analysis indicated lower risk of 30 days mortality (0.2% vs. 0.7%, P<0.001), major morbidity or mortality (5.7% vs. 8.8%, P<0.001), PLOS (3.2% vs. 4.9%, P<0.001), PICULOS (9.4% vs. 12.2, P<0.001), and lower number of distal anastomosis ((3.3±0.8) vs. (3.6±0.8), P<0.001) in off-pump CABG group than in on-pump CABG group. After adjustment of cofounders, multivariate analysis showed that off-pump CABG was still associated with a lower risk of 30 days mortality (OR=0.29, 95%CI: 0.09-0.87, P=0.027), composite endpoint of major morbidity or mortality (OR=0.60, 95%CI: 0.53-0.68, P<0.001), PLOS (OR=0.64, 95%CI 0.54-0.75, P<0.001), PICULOS (OR=0.76, 95%CI: 0.69-0.84, P<0.001). Conclusions: Off-pump CABG is related with superior short-term safety outcomes than on-pump CABG by experienced surgeons in our center.

The clinical application value of potentially inappropriate drug assessment system in elderly inpatients / 中华老年医学杂志

Objective:To explore the clinical value of the geriatric potentially inappropriate medication(PIM)evaluation system in elderly inpatients.Methods:As a prospective cohort study, 203 elderly inpatients with polypharmacy were randomly divided into the control group and experimental group.Geriatric PIM evaluation system(based on the criteria for judging potential inappropriate drug use in Chinese elderly 2017 edition)on wechat platform was applied to patients of experimental group.During the 6 months, the number of elderly syndromes, types of drugs, the days in hospitalization, readmission rates and all-cause mortality were compared between two groups.Results:The age of 203 elderly inpatients ranged from 60 to 94(77.30±10.34)years, including 121 males and 82 females.The morbidity proportion of top five diseases were 69.95%(142/203)in cerebral infarction(non-acute phase), 62.07%(126/203)in hypertension, 24.14%(49/203)in coronary heart disease, 9.85%(20/203)in atrial fibrillation, and 6.40%(13/203)in cardiac insufficiency.The 97.53%(198/203)of elderly hospitalized patients had at least one senile syndrome, the average was 4.3±2.0.Insomnia, fall and frailty accounted for 32.87%(15/198), 28.45%(56/198)and 13.66%(27/198)respectively.Compared with the control group, the average length of stay in hospital in the experimental group significantly decreased[(16.38±4.29) vs.(21.32±6.10)d, t=2.438、 P=0.025], the number of senile syndrome, the score of fall, weakness and the re-admission rate were also decreased significantly(3.11±2.14 vs.4.32±1.50, t=0.854、 P=0.032; 6.19±1.35 vs.8.61±3.22, t=4.078、 P=0.044; 3.94±1.92 vs.5.65±1.34, t=2.843、 P=0.038; 9.81%(10/102) vs.1.98%(2/101), χ2=4.772、 P=0.029), and the frequency of PIM was significantly different between two groups(417.36±49.21 vs.210.25±38.23, t=2.136、 P=0.034). Conclusions:After making the drug adjustment on the elderly inpatients with multiple drugs, PIM evaluation system for the elderly are able to reduce the incidence of geriatric syndrome, shorten the length of stay in hospital, improve the rational use of drugs, and enhance the quality of life of the elderly patients.

Case report of bronchial Dieulafoy disease in children / 中华实用儿科临床杂志

The clinical data of a child with bronchial Dieulafoy disease treated in Wuhan Children′s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, was analyzed retrospectively.The patient was a 9-month-old boy, who was admitted to hospital due to " intermittent hematemesis vomiting blood for 6 hours" . Chest CT suggested ground-glass opacity in both lungs.Electronic bronchoscopy showed that the neoplasm bulged into the lumen at the opening of the right inferior lobar bronchus, and fresh blood oozed from the basal segment of the neoplasm during the operation.Bronchial arteriography and transcatheter bronchial artery embolization were performed due to recurrent hemoptysis, during which the patient was diagnosed with bronchial arterial vascular malformation and finally diagnosed with bronchial Dieulafoy disease after consulting the relevant literatures.The disease is infrequent and characterized by rupture hemorrhage of bronchial submucosal malformed artery, the etiology and pathogenesis of which are still unclear, and it may be related to congenital vascular malformation in children.Bronchoscopy for hemoptysis of unknown cause in children should be performed with caution.If small and smooth protruded nodular lesions are seen under the bronchoscope, the bronchial Dieulafoy disease should be considered, and the lesions should not be touched too much or subjected to biopsy blindly.Fatal massive hemorrhage can be avoided by bronchial arteriography and bronchial artery embolization.

Research Progress on Heterogeneity of Tumor Mutation Burden in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

Programmed death ligand 1 (PD-L1) is a well known biomarker for targeted immunotherapy. However, the relationship between the expression of PD-L1 and the immunotherapy efficacy is not always consistent in different cases. Some patients who are PD-L1 negative still can benefit from immunosuppressive therapy, while some non-small cell lung cancer (NSCLC) patients with PD-L1 positive, even strongly positive, can not. Therefore, PD-L1 is not a completely reliable immunotherapy biomarker. Tumor mutation burden (TMB) estimated by whole exome sequencing (WES) is a biomarker recently approved by Food and Drug Administration (FDA). In this paper, we briefly reviewed the factors that result in the variaty of TMB in order to improve the reliability of the TMB and help clinicians to select patients who can get benefit from immunotherapy more wisely.
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Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study / 医学前沿

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10