Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells

Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism.To further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating chemosensitivity.Methods This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC cells.Additional experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these findings.Results Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic proteins.Additionally,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression.Conversely,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above.The results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 treatment.Conversely,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by HLY78.Conclusion Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.

Meibomian glands segmentation in infrared images with limited annotation

●AIM:To investigate a pioneering framework for the segmentation of meibomian glands(MGs),using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis.●METHODS:Totally 203 infrared meibomian images from 138 patients with dry eye disease,accompanied by corresponding annotations,were gathered for the study.A rectified scribble-supervised gland segmentation(RSSGS)model,incorporating temporal ensemble prediction,uncertainty estimation,and a transformation equivariance constraint,was introduced to address constraints imposed by limited supervision information inherent in scribble annotations.The viability and efficacy of the proposed model were assessed based on accuracy,intersection over union(IoU),and dice coefficient.●RESULTS:Using manual labels as the gold standard,RSSGS demonstrated outcomes with an accuracy of 93.54%,a dice coefficient of 78.02%,and an IoU of 64.18%.Notably,these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%,2.06%,and 2.69%,respectively.Furthermore,despite achieving a substantial 80%reduction in annotation costs,it only lags behind fully annotated methods by 0.72%,1.51%,and 2.04%.●CONCLUSION:An innovative automatic segmentation model is developed for MGs in infrared eyelid images,using scribble annotation for training.This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs.It holds substantial utility for calculating clinical parameters,thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

psk1 virulence gene-induced pulmonary and systemic tuberculosis in a young woman with normal immune function:A case report

BACKGROUND Tuberculosis is a chronic infectious disease and an important public health pro-blem.Despite progress in controlling tuberculosis,the incidence of tuberculosis in China is still very high,with 895000 new cases annually.This case report des-cribes the investigation of a case of severe disseminated tuberculosis in a young adult with normal immune function,conducted to ascertain why a Mycobacterium tuberculosis(M.tuberculosis)strain caused such severe disease.CASE SUMMARY A previously healthy 28-year-old woman presented to our hospital with a 1-mo-nth history of fever and fatigue.She was diagnosed with severe disseminated pulmonary tuberculosis,spinal tuberculosis with paravertebral abscesses,and tuberculous meningitis.M.tuberculosis was isolated from bronchoal-veolar lavage fluid.She was treated with standard antituberculous therapy and underwent debridement,bone graft,and internal fixation surgery for spinal tuberculosis.She responded to therapy and regained her ability to walk following the surgery.We analysed the whole-genome sequence of the strain and designated it BLM-A21.Additional M.tuberculosis genomes were selected from the Virulence Factor Database(http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Mycobacterium)for comparison.An evolutionary tree of the BLM-A21 strain was built using PhyML maximum likelihood software.Further gene analysis revealed that,except for the pks1 gene,BLM-A21 had similar virulence genes to the CDC 1551 and H37Rv strains,which have lower dissemination.CONCLUSION We speculate that the pks1 virulence gene in BLM-A21 may be the key virulence gene responsible for the wide-spread dissemination of M.tuberculosis infection in this previously healthy adult with normal immune function.

Clinical efficacy and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in gastrectomy

BACKGROUND With the continuous progress of surgical technology and improvements in medical standards,the treatment of gastric cancer surgery is also evolving.Proximal gastrectomy is a common treatment,but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options.Each of these two surgical methods has advantages and disadvantages,so it is particularly important to compare and analyze their clinical efficacy and safety.AIM To compare the surgical safety,clinical efficacy,and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy.METHODS The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study.According to the different anastomosis methods used,the patients were divided into a double-channel anastomosis group(50 patients)and a tubular gastroesophageal anastomosis group(49 patients).In the double-channel anastomosis,Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection,and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux.In the tubular gastroesophageal anastomosis group,after the proximal end of the stomach was cut,tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube.The main outcome measure was quality of life 1 year after surgery in both groups,and the evaluation criteria were based on the postgastrectomy syndrome assessment scale.The greater the changes in body mass,food intake per meal,meal quality subscale score,and total measures of physical and mental health score,the better the condition;the greater the other indicators,the worse the condition.The secondary outcome measures were intraoperative and postoperative conditions,the incidence of postoperative long-term complications,and changes in nutritional status at 1,3,6,and 12 months after surgery.RESULTS In the double-channel anastomosis cohort,there were 35 males(70%)and 15 females(30%),33(66.0%)were under 65 years of age,and 37(74.0%)had a body mass index ranging from 18 to 25 kg/m2.In the group undergoing tubular gastroesophageal anastomosis,there were eight females(16.3%),21(42.9%)individuals were under the age of 65 years,and 34(69.4%)had a body mass index ranging from 18 to 25 kg/m2.The baseline data did not significantly differ between the two groups(P>0.05 for all),with the exception of age(P=0.021).The duration of hospitalization,number of lymph nodes dissected,intraoperative blood loss,and perioperative complication rate did not differ significantly between the two groups(P>0.05 for all).Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group.Specifically,they had lower scores for esophageal reflux[2.8(2.3,4.0)vs 4.8(3.8,5.0),Z=3.489,P<0.001],eating discomfort[2.7(1.7,3.0)vs 3.3(2.7,4.0),Z=3.393,P=0.001],total symptoms[2.3(1.7,2.7)vs 2.5(2.2,2.9),Z=2.243,P=0.025],and other aspects of quality of life.The postoperative symptoms[2.0(1.0,3.0)vs 2.0(2.0,3.0),Z=2.127,P=0.033],meals[2.0(1.0,2.0)vs 2.0(2.0,3.0),Z=3.976,P<0.001],work[1.0(1.0,2.0)vs 2.0(1.0,2.0),Z=2.279,P=0.023],and daily life[1.7(1.3,2.0)vs 2.0(2.0,2.3),Z=3.950,P<0.001]were all better than those of the tubular gastroesophageal anastomosis group.The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score[3.0(2.0,4.0)vs 3.5(2.0,5.0),Z=2.345,P=0.019]compared to the dual-channel anastomosis group.Hemoglobin,serum albumin,total serum protein,and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups(P>0.05 for all).CONCLUSION The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery.Compared with tubular gastric surgery,double-channel anastomosis is a preferred surgical technique for proximal gastric cancer.It offers advantages such as less esophageal reflux and improved quality of life.

Identification of pathological characteristics in pulmonary tuberculosis using polarization-sensitive optical coherence tomography

The low detection rate of Mycobacterium tuberculosis in clinical practice leads to a high rate of missed diagnosis for pulmonary tuberculosis(PTB).As a noninvasive,high-resolution,real-time imaging technology,polarization-sensitive optical coherence tomography(PS-OCT)may be feasible for the rapid identification of pathological feature.This study aimed to explore the feasibility of using PS-OCT to identify pathological features of PTB.In the experiments,PTB samples containing some surrounding lung tissues were imaged using PS-OCT.It is demonstrated that PS-OCT images showed good consistency with the corresponding pathological images and were able to identify PTB-related characteristic pathological regions.We think PS-OCT can serve as an effective supplement for the diagnosis of PTB,enabling rapid and accurate diagnosis,and aiding in the understanding of the pathological characteristics and pathophysiological processes of PTB.

Prognostic value and predictive model of tumor markers in stageⅠtoⅢgastric cancer patients

BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients.However,few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators.AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients.METHODS From October 2018 to April 2020,a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study.The relationship between serum tumor markers and clinical and pathological data were analyzed.We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis.Overall survival(OS)was also compared across different stages of gastric cancer.RESULTS The deadline for follow-up was May 31,2023.A total of 1236 patients were included in our study.Univariate analysis found that age,clinical stage,T and N stage,tumor location,differentiation,Borrmann type,size,and four serum tumor markers were prognostic factors of OS(P<0.05).It was shown that clinical stage,tumor size,alpha foetoprotein,carcinoembryonic antigen,CA125 and CA19-9(P<0.05)were independent prognostic factors for OS.According to the scoring results obtained from the statistical model,we found that patients with high scores had poorer survival time(P<0.05).Furthermore,in stage I patients,the 3-year OS for scores 0-3 ranged from 96.85%,95%,85%,and 80%.In stage II patients,the 3-year OS for scores 0-4 were 88.6%,76.5%,90.5%,65.5%and 60%.For stage III patients,3-year OS for scores 0-6 were 70.9%,68.3%,64.1%,50.9%,38.4%,18.5%and 5.2%.We also analyzed the mean survival of patients with different scores.For stage I patients,the mean OS was 55.980 months.In stage II,the mean OS was 51.550 months.The mean OS for stage III was 39.422 months.CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population:A prospective,multicenter,randomized,two-stage study

BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.

Analysis of the Application and Effect of Homemade Medical Scrotal Support Shorts

Objective:To design and manufacture medical scrotal support shorts for patients with enlarged scrotum and observe its application and effect.Methods:40 patients with enlarged scrotum admitted to the basic surgery department from February 2021 to March 2023 were selected and divided into a test group and a control group according to their time of admission,with the test group using scrotal support shorts and the control group using ordinary shorts without scrotal support pockets or diapers.Results:The complication rate of skin injury in the scrotum and the surrounding inguinal area of the patients in the test group was significantly lower than that of the control group(P<0.01).The medical cost covered by patients in the test group was significantly lower than that of the control group(P<0.01)and the hospitalization satisfaction of the patients in the test group was significantly higher than that of the control group(P<0.01).The difference in the therapeutic effect of the test groups was statistically significant when compared with the control group(P<0.05).Conclusion:Homemade medical scrotal support shorts reduced the local enlargement of the scrotum and bleeding,but also protected the scrotum and the surrounding skin to prevent secondary injuries.The process of patient care was simple and promoted their recovery.The length of hospitalization was also decreased,the burden of health care costs was reduced,and the overall comfort and satisfaction of the patient was improved.

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).

Emergency Biosafety Management Practice in Laboratory of Shelter Hospital

At the end of 2019,the novel coronavirus infection outbroke in Wuhan,Hubei Province.On Feb.2,2020,Wuhan,as the worst-hit region,began to build“shelter hospital”rapidly to treat patients with mild ilness.The shelter hospital has multiple functions such as emergency treatment,surgical treatment and clinical test,which can adapt to emergency medical rescue tasks.Based on the characteristics that shelter hospital only treats patients with mild ilness,tests of shelter laboratory,including coronavirus nucleic acid detection,IgM/IgG antibody serology detection,monitoring and auxiliary diagnosis and/or a required blood routine,urine routine,C-reactive protein,calcitonin original,biochemical indicators(liver enzymes,myocardial enzymes,renal function,etc.)and blood coagulation function test etc,were used to provide important basis for the diagnosis and treatment of the disease.In order to ensure laboratory biosafety,it is necessary to first evaluate the harm level of various specimens.In the laboratory biosafety management,the harm level assessment of microorganisms is the core work of biosafety,which is of great significance to guarantee biosafety.As an emergency deployment afcted by the environment,shelter laboratory must possess strong mobility.This paper will explore how to combine the biosafety model of traditional laboratory with the particularity of shelter laboratory to carry out effective work in response to the current epidemic.

Theoretical framework construction on care complexity in Chinese hospitals: A grounded theory study

Objectives: This study aims to construct a theoretical framework to analyze risk factors and explore hospital nurses' perspectives on care complexity.Methods: The grounded theory method was adopted,and semi-structured in-depth interviews regarding the understanding of care complexity were conducted among the participants,including 31 nurses and nine doctors.In addition,data were coded and strictly analyzed in accordance with the coding strategy and requirements of grounded theory.Results: Our study reveals three factors that are closely related to care complexity,namely,(1) patient factors,including patients' condition,age,self-care abilities,compliance,social support systems,psy chological conditions,expectations,and requirements;(2) nursing staff factors,including work experiences,education,knowledge and operational skills of caring,and communication skills;and (3) organization and equipment factors,including nursing workforce,nursing workload,support from multidisciplinary teams and ancillary departments,and the conditions of medical and hospital services.Conclusions: This study defines care complexity on the basis of its factors.Care complexity refers to the difficulty of nursing tasks during patient care plan implementation,which are affected by patients,nurses,and other factors in nursing and multisectoral,multidisciplinary cooperation.The framework can be beneficial for nursing education and for the improvement of the quality and efficiency of clinical nursing practice.

Angiogenesis in hepatocellular carcinoma:mechanisms and anti-angiogenic therapies

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

Performance of novel 3D printing tools in removing coronary-artery calcification tissue

Rotational atherectomy is an effective treatment for severe vascular calcification obstruction,and relies on high-speed grinding(typically 130,000–210,000 r/min)with miniature grinding tools to remove calcified tissue and restore blood flow.However,reports of intraoperative complications are common because of the grinding force,temperature,and debris directly acting on the body during the grinding process,which can easily cause damage to patients.In this study,three novel grinding tools were designed and fabricated and a series of experiments have been conducted to analyze the effects of tool geometry and parameters on grinding performance,that is,force,temperature,and specimen surface morphology.The results show that these tools can effectively remove simulated calcified tissue and that they have two motions,rotation and revolution,in the tube.At higher rotational speeds,grinding force and temperature increase noticeably,while the amount of debris decreases significantly.In addition,by observing the surface morphology of the specimens,we concluded that the material removal rate per unit time is influenced by both rotational speed and tool geometry,and that high rotational speed and a rough tool surface can improve the material removal rate efficiently.

Changes in the pathogen spectrum of hospitalized adults with community-acquired pneumonia in Fujian Province: A multicenter, retrospective study from 2012 to 2018

To the Editor:Community-acquired pneumonia(CAP)in adults refers to inflammation of the lung parenchyma involving the alveolar wall.It occurs in the community environment(outside the hospital),including pneumonia caused by pathogens with definite latency after admission.

Cardiogenic shock and asphyxial cardiac arrest due to glutaric aciduria typeⅡ

Lipid storage myopathy(LSM)is a manifestation of lipid dysmetabolism,presenting with lipid accumulation in muscles.The mechanism includes defects in intracellular triglyceride catabolism,transport of long-chain fatty acids and carnitine,or fatty acidβ-oxidation.[1]Among LSMs,the most common type is multiple acyl-coenzyme A dehydrogenase deficiency(MADD).

The Mesenchymal stem cell regulates the immune system: secretion of cytokines, cell-to-cell contact and extracellular vesicles

MSCs are pluripotent stem cells which have multipotent differentiation potential and immunosuppressive ability.Therefore,MSCs play an important role in regenerative medicine;the study of their mechanisms of regulating immune responses will also lead to new strategies for the treatment of immune-inflammatory diseases.Studies have shown that MSCs can modulate adaptive and innate immunity by secreting cytokines or cell-to-cell contact and play an immunosuppressive role.In addition,the secretion of extracellular vesicles by MSCs is also an important immunomodulatory mechanism.MSCs need to be cultured in vitro before they can be used to modulate immunity.It has been shown that pretreatment of MSCs during culture can improve cell survival rate and further enhance the ability of immunomodulation.In this paper,the mechanism of MSCs regulating immune response is discussed to deepen the understanding of MSCs regulating immunity.