Profile of biological characterizations and clinical application of corneal stem/progenitor cells

Corneal stem/progenitor cells are typical adult stem/progenitor cells.The human cornea covers the front of the eyeball,which protects the eye from the outside environment while allowing vision.The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role.Corneal stem/progenitor cells include mainly corneal epithelial stem cells,corneal endothelial cell progenitors and corneal stromal stem cells.Since the discovery of corneal epithelial stem cells(also known as limbal stem cells)in 1971,an increasing number of markers for corneal stem/progenitor cells have been proposed,but there is no consensus regarding the definitive markers for them.Therefore,the identification,isolation and cultivation of these cells remain challenging without a unified approach.In this review,we systematically introduce the profile of biological characterizations,such as anatomy,characteristics,isolation,cultivation and molecular markers,and clinical applications of the three categories of corneal stem/progenitor cells.

Clinical study of different modes of repetitive transcranial magnetic stimulation in the treatment of post‑stroke executive dysfunction

Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.

Biochemical characteristics,functions and clinical significance of cofilin

Cofilin is a low molecular weight actin-binding protein widely found in eukaryotic cells in ADF/cofilin family proteins,which has a wide range of biological effects and has gradually become a research hotspot in recent years.We review the structural characteristics of cofilin,the mechanism of regulating actin,biological functions,and the relationship with clinical diseases to explore its role in the development of cancer,nervous system diseases,osteoarthritis,heart and kidney diseases.The use of cofilin phosphorylation pathways as major action-targeting sites in the treatment of these diseases could provide a basis for the development of new drugs,such as Rho related protein kinases inhibitors netarsudil to prevent cancer metastasis,neuroligin C-terminal domain(NLG1-CTD)peptides with high affinity to inhibit LIM kinase thereby preventing nervous system diseases,grape seed proanthocyanidins to inhibit cofilin related oxidative stress in the treatment of heart and kidney diseases.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.

The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Differentiating consistency of meningioma based on grey-level histogram analysis of T2WI

Objective To observe the value of grey-level histogram analysis based on T2WI for differentiating consistency of meningioma.Methods Data of 109 patients with meningioma were retrospectively analyzed.The patients were divided into hard group(n=71)and soft group(n=38)according to the consistency of tumors.Tumor ROI was outlined on axial T2WI showing the largest tumor section,gray levels were extracted and histogram analysis was performed.The value of each histogram parameter were compared between groups.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficiency for differentiating soft and hard meningioma.Results P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI in soft group were all higher than those in hard group(all P<0.05),while the variance,the kurtosis and the skewness were not significantly different between groups(all P>0.05).The differentiating efficiency of P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI were all fine,with AUC of 0.774 to 0.833,and no significant difference was found(all P>0.05).Conclusion Parameters of grey-level histogram analysis such as P 1,P 10,P 50,P 90,P 99 and the mean values based on T2WI were all valuable for differentiating soft and hard meningioma.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses

BACKGROUND Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection(EFTR).Successful perforation repair under endoscopy,thereby avoiding surgical intervention and postoperative complications such as peritonitis,are pivotal for effective EFTR.AIM To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors.METHODS A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted.The total operation time,tumor dissection time,wound closure time,intraoperative bleeding volume,length of hospital stay and incidence of complications were analyzed.RESULTS There were 93 patients,aged 55.1±12.1 years.Complete tumor resection was achieved in all cases,resulting in a 100% success rate.The average total operation time was 67.4±27.0 min,with tumor dissection taking 43.6±20.4 min.Wound closure times varied,with gastric body closure time of 24.5±14.1 min and gastric fundus closure time of 16.6±8.7 min,showing a significant difference(P<0.05).Intraoperative blood loss was 2.3±4.0 mL,and average length of hospital stay was 5.7±1.9 d.There was no secondary perforation after suturing in all cases.The incidence of delayed bleeding was 2.2%,and the incidence of abdominal infection was 3.2%.No patient required other surgical intervention during and after the operation.CONCLUSION Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss,making it a viable approach for gastric submucosal tumors.

Evolutionary trend analysis and knowledge structure mapping of endothelial dysfunction in sepsis:a bibliometrics study

BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the fi eld of EDS.METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords).RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolifi c institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest infl uence.The"protein C","tissue factor","thrombin","glycocalyx",“acute kidney injury”,“syndecan-1”and“biomarker”were identifi ed as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function.CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.

Status Quo of Acceptance of Illness among Reproductive Age Cervical Cancer Patients and Its Influencing Factors

Objective: To explore the status quo of acceptance of illness among reproductive-age cervical cancer patients and its influencing factors, to provide a theoretical basis for the implementation of targeted interventions. Methods: The convenience sampling method was used to investigate 256 reproductive-age cervical cancer patients using the general information questionnaire, Acceptance of Illness Scale, Reproductive Concerns After Cancer Scale, and Medical Coping Style Scale. Results: The total score of the acceptance of illness was (18.03 ± 3.24), and reproductive concerns were (57.02 ± 6.30), among reproductive-age cervical cancer patients. Multivariate analysis showed that age, number of children, income level, treatment method, level of reproductive concerns, and the yield and avoidance dimensions of medical coping style were the main influencing factors on patients’ level of illness acceptance (all P Conclusion: The acceptance of illness levels in reproductive-age cervical cancer patients was low to intermediate, and medical staff should timely identify high-risk groups and take preventive management measures based on influencing factors.

Relationship between Stigma and Marital Satisfaction in Cervical Cancer Patients

Objective: To investigate the status quo of stigma and marital satisfaction of patients with cervical cancer, and analyze the correlation between them, to provide a reference for making intervention plans for patients with cervical cancer. Methods: 216 patients in a third-class first-class hospital in Zhengzhou were investigated by convenient sampling method, using a general information questionnaire, social impact scale, and Olson marriage quality questionnaire. Results: The total stigma score of cervical cancer patients was 73.00 (62.00, 76.00), which was high. The total marital satisfaction score is 36.00 (26.00, 38.00), in the middle level. There was a negative correlation between marital satisfaction and stigma (P Conclusion: The stigma of patients with cervical cancer is at a high level, and their marital satisfaction is at a medium level. Medical staff should give them health education through various channels, pay attention to low-income patients, improve marital satisfaction, and reduce stigma.

Giant bile duct dilatation in newborn:A case report

BACKGROUND Giant congenital biliary dilation(CBD)is a rare condition observed in clinical practice.Infants born with this condition often experience a poor overall health status,and the disease progresses rapidly,leading to severe biliary obstruction,infections,pressure exerted by the enlarged CBD on abdominal organs,disturbances in the internal environment,and multiple organ dysfunction.The treatment of giant CBD using laparoscopy is challenging due to the high degree of variation in the shape of the bile duct and other organs,making it difficult to separate the bile duct wall from adjacent tissues or to control bleeding.CASE SUMMARY Herein,we present the details of an 11-d-old male newborn who was diagnosed with giant CBD.The patient was admitted to the neonatal surgery department of our hospital due to a history of common bile duct cyst that was detected more than 3 mo ago,and also because the patient had been experiencing yellowish skin for the past 9 d.The abnormal echo in the fetal abdomen was first noticed by the patient’s mother during a routine ultrasound examination at a local hospital,when the patient was at 24 wk+6 d of pregnancy.This finding raised concerns about the possibility of congenital biliary dilatation(22 mm×21 mm).Subsequent ultrasound examinations at different hospitals consistently confirmed the presence of a congenital biliary dilatation.No specific treatment was administered for biliary dilatation during this period.A computed tomography scan conducted during the hospitalization revealed a large cystic mass in the right upper quadrant and pelvis,measuring approximately 9.2 cm×7.4 cm×11.3 cm.Based on the CONCLUSION The analysis reveals that prenatal imaging techniques,such as ultrasound and magnetic resonance imaging,play a crucial role in the early diagnosis,fetal prognosis,and treatment plan for giant CBD.Laparoscopic surgery for giant CBD presents certain challenges,including difficulties in separating the cyst wall,anastomosis,and hemostasis,as well as severe biliary system infection and ulceration.Consequently,there is a high likelihood of converting to laparotomy.The choice between surgical methods like hepaticojejunostomy(HJ)or hepaticoduodenostomy has not been standardized yet.However,we have achieved favorable outcomes using HJ.Preoperative management of inflammation,biliary drainage,liver function protection,and supportive treatment are particularly vital in improving children’s prognosis.After discharge,it is essential to conduct timely reexamination and close follow-up to identify potential complications.

Synchronous vs sequential laparoscopic cholecystectomy for cholecystocholedocholithiasis

AIM: To compare synchronous laparoscopic cholecystectomy (LC) combined with endoscopic sphincterotomy (EST) and sequential LC combined with EST for treating cholecystocholedocholithiasis. METHODS: A total of 150 patients were included and retrospectively studied. Among these, 70 were selected for the synchronous operation, in which the scheme was endoscopic retrograde cholangiopancreatography combined with EST during LC. The other 80 patients were selected for the sequential operation, in which the scheme involved first cutting the papillary muscle under endoscopy and then performing LC. The indexes in the two groups, including the operation time, the success rate, the incidence of complications, and the length of the hospital stay, were observed.RESULTS: There were no significant differences between the groups in terms of the numbers of patients, sex distribution, age, American Society of Anesthesiologists score, serum bilirubin, γ-glutamyl transpeptidase, mean diameter of common bile duct stones, and previous medical and surgical history (P = 0.54, P = 0.18, P = 0.52, P = 0.22, P = 0.32, P = 0.42, P = 0.68, P = 0.70, P = 0.47 and P = 0.57). There was no significant difference in the surgical operation time between the two groups (112.1 ± 30.8 min vs 104.9 ± 18.2 min). Compared with the sequential operation group, the incidence of pancreatitis was lower (1.4% vs 6.3%), the incidence of hyperamylasemia (1.4% vs 10.0%, P < 0.05) was significantly reduced, and the length of the hospital stay was significantly shortened in the synchronous operation group (3 d vs 4.5 d, P < 0.001). CONCLUSION: For treatment of cholecystocholedo-cholithiasis, synchronous LC combined with EST reduces incidence of complications, decreases length of hospital stay, simplifies the surgical procedure, and reduces operation time.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

Long-term acupuncture treatment has a multitargeting regulation on multiple brain regions in rats with Alzheimer＇s disease：a positron emission tomography study

The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.

Dictamine Stimulates Cystic Fibrosis Transmembrane Conductance Regulator Cl-Transport

Dictamine is a furoquinoline alkaloid isolated from Dictamus dasycarpus Turcz.In the present study,we found that dictamine is able to stimulate the chloride transport activity of wild-type and ΔF508 mutant CFTR.The activity is cAMP-dependent and can be completely reversed by specific CFTR inhibitor CFTRinh-172.In addition,dictamine can further increase the chloride transport activity when CFTR is maximally activated by the combination of cAMP stimulators forskolin（FSK）and IBMX,suggesting direct interaction of dictamine with CFTR.Dictamine may be useful for probing CFTR channel gating mechanisms and used as a lead compound to develop the pharmacological therapy of CFTR-related diseases such as idiopathic chronic pancreatitis and keratoconjunctivitis sicca and cystic fibrosis.

Positron emission tomography and magnetic resonance imaging combined with computed tomography in tumor volume delineation: A case report

BACKGROUND Accurate delineation of the target area for patients with hypopharyngeal cancer is the key to achieving an ideal radiotherapy effect.Since computed tomography(CT)alone can no longer meet the treatment needs,fusing CT images with magnetic resonance imaging(MRI)or positron emission tomography(PET)images can overcome the disadvantages of CT.Herein,we present a clinical case of hypopharyngeal cancer to delineate the tumor volume using combined MRI-CT and PET-CT fusion images to examine if they could accurately cover the tumor volume.CASE SUMMARY A 67-year-old male patient with hypopharyngeal carcinoma could not tolerate chemotherapy and surgery due to complicated health issues such as diabetic nephropathy and other underlying diseases.After multidisciplinary consultations,clinicians eventually agreed to undergo radiotherapy to control the progression of his tumor.He was examined by CT,MRI,and 18-fluorodeoxyglucose-PET for treatment planning,and CT images were fused with PET and MRI images while delineating tumor volume.CONCLUSION The image fusion of MRI-CT and PET-CT has both advantages and disadvantages.Compared with CT images alone,the combination of MRI-CT and PET-CT fusion images can precisely cover the gross tumor volume in hypopharyngeal carcinoma and avoid overestimation or incomplete coverage of tumor volume.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

Correction to"Liu LP,Sheng XP,Shuai TK,Zhao YX,Li B,Li YM.Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.World J Gastroenterol 2018;24:4565-4577[PMID:30386106 DOI:10.3748/wjg.v24.i40.4565]."In this article,we have identified some of the images in Figure 2A,C,E,G,and I are identical to the images in Figures 1B,2A,3B,3E,and 3G of another paper entitled"Liu L,Zhao Y,Fan G,Shuai T,Li B,Li Y.Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.",which was published by us in the Molecular Medicine Reports in December,2018[PMID:30320396 DOI:10.3892/mmr.2018.9558].The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology(WJG)and Molecular Medicine Reports,we uploaded the wrong pictures to the WJG,which were same as those submitted to the Molecular Medicine Reports.We apologize for this negligence and any inconvenience that this may cause.We would be grateful if you could replace the wrong pictures with the correct ones attached.

Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45

AIM：To clarify the role of activated Notch2 in the invasiveness of gastric cancer.METHODS：To investigate the invasiveness of silencing Notch2 gene expression,we established a Notch2small interfering RNA（siRNA） transfected cell line using the MKN-45 gastric cancer cell line.After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction（RT-PCR） and Western blotting,migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer.RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9（MMP9）,Akt,p-Akt.To confirm the relationship between PI3KAkt and MMP9,the PI3K inhibitor LY294002 was used to treat MKN-45 cells.RESULTS：Notch2 expression was dramatically decreased after Notch2 siRNA transfection（100.00% ± 9.74% vs 11.61% ± 3.85%,P 〈 0.01 by qRT-PCR）.There was also a marked reduction of Notch target gene Hes1（100.00% ± 4.74% vs 61.61% ± 3.58%,P 〈 0.05） at the mRNA,indicating an inhibition of Notch signaling.Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels（100.00% ± 9.74% vs 65.61% ± 7.58%,P 〈 0.05）.Down-regulation of Notch2 by siRNA enhanced tumor cell invasion（100.00% ± 21.64% vs 162.22% ± 16.84%,P 〈 0.05） and expression of MMP9（1.56 fold,P 〈 0.05）,and activated the pro-MMP9 protein to its active form（1.48 fold,P 〈 0.05）.There was no significant difference in the protein levels of Akt between the two groups（100.00% ± 10.87% vs 96.61% ± 7.33%,P 〉 0.05）,while down-regulation of Notch2 elevated p-Akt expression（100.00% ± 9.87% vs 154.61% ± 13.10%,P 〈 0.05）.Furthermore,p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002（p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%,P 〈 0.05;MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%,P 〈 0.05）.CONCLUSION：Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling pathway

Myeloperoxidase: a new target for the treatment of stroke?

Myeloperoxidase is an important inflammatory factor in the myeloid system,primarily expressed in neutrophils and microglia.Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke,including damage to the blood-brain barrier and brain.As a specific inflammatory marker,myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke,and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis.Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke.The occurrence of stroke not only refers to the first occurrence but also includes recurrence.Therefore,myeloperoxidase is significant for the clinical evaluation and prognosis of stroke.This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis.This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.