The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Metaanalysis

AIM:To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia.METHODS:A systematic search was conducted across the Cochrane Library,PubMed,Web of Science,EMBASE,CNKI,CBM,VIP,and Wanfang database,encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17,2024.Data extraction and quality assessment were performed,and a network Meta-analysis was executed using Stata version 14.0 Software.Results were visually represented through graphs.RESULTS:Fourteen papers comprising 2475 cases were included;five different concentrations of atropine solution were used.The network Meta-analysis,along with the surface under the cumulative ranking curve(SUCRA),showed that 1%atropine(100%)>0.05%atropine(74.9%)>0.025%atropine(51.6%)>0.02%atropine(47.9%)>0.01%atropine(25.6%)>control in refraction change and 1%atropine(98.7%)>0.05%atropine(70.4%)>0.02%atropine(61.4%)>0.025%atropine(42%)>0.01%atropine(27.4%)>control in axial length(AL)change.CONCLUSION:In Chinese children and teenagers,the five various concentrations of atropine can reduce the progression of myopia.Although the network Meta-analysis showed that 1%atropine is the best one for controlling refraction and AL change,there is a high incidence of adverse effects with the use of 1%atropine.Therefore,we suggest that 0.05%atropine is optimal for Chinese children to slow myopia progression.

Relationship between primary caregivers’social support function,anxiety,and depression after interventional therapy for acute myocardial infarction patients

BACKGROUND An acute myocardial infarction(AMI)is often treated with direct coronary intervention and requires home-based rehabilitation.Caregivers of patients with AMI need adequate social support to maintain high-quality care;however,their social support function is low,and relevant indicators for intervention must be identified.AIM To analyze the correlation between social support for primary caregivers,their anxiety,and depression,when caring for patients with AMI after interventional therapy.METHODS Using convenience sampling,we selected 300 primary caregivers of patients with AMI who had undergone interventional therapy.The Social Support Rating Scale(SSRS),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to assess the primary caregivers.A Pearson’s correlation analysis was used to analyze the correlations between the SSRS,SAS,and SDS,and a multiple logistic regression analysis was used to analyze the factors influencing the low social support function of primary caregivers.The receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the predictive ability of the SAS and SDS for low social support function in primary caregivers.RESULTS Considering the norm among Chinese people,AMI caregivers’objective support,subjective support,support utilization,and SSRS scores were lower,while their SAS and SDS scores were higher.The SSRS scores of female caregivers were higher than those of the male caregivers(t=2.123,P=0.035).The Pearson correlation analysis showed that objective support,subjective support,support utilization,and SSRS total scores were significantly correlated with both SAS(r=-0.414,-0.460,-0.416,-0.535)and SDS scores(r=-0.463,-0.379,-0.349,-0.472).Among the 300 AMI caregivers,56 cases(18.67%)had a low level of support function(SSRS≤22 points).Logistic regression model analysis showed that SAS and SDS were independent risk factors for low social support function of AMI caregivers,regardless of adjustment for other variables(P<0.05).SAS and SDS predicted that the AUC of AMI caregivers with low support function was 0.84,sensitivity was 67.9 and 71.4,and specificity was 84.0 and 70.9,respectively.CONCLUSION The social support function of the primary caregiver of patients with AMI after interventional therapy was lower and negatively correlated with anxiety and depression in the primary caregiver.

The efficacy and safety of endoscopic ultrasound-guided fine-needle biopsy in gallbladder masses

Background: Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. Methods: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. Results: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89%(24/27) and 93%(25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval(CI): 75.12%-99.76%], 100%(95% CI: 46.29%-10 0%), 10 0%(95% CI: 80.76%-100%), 83.33%(95% CI: 36.48%-99.12%), and 96.30%(95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. Conclusions: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further largescale studies are needed to confirm our conclusion.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.

Multiple Magnetic Phase Transitions and Critical Behavior in Single-Crystal SmMn_(2)Ge_(2)

Magnetic materials with noncollinear spin configurations have engendered significant interest in condensed matter physics due to their intriguing physical properties.We direct our attention towards the magnetic properties and critical behavior of single-crystal SmMn_(2)Ge_(2),an itinerant magnet with numerous temperature-dependent magnetic phase transitions.Notably,SmMn_(2)Ge_(2)displays significant magnetic anisotropy with easy magnetization direction switching from the c axis to the ab plane as temperature decreases.The critical behavior of the ferromagnetic transition occurring above room temperature is thoroughly examined.Reliable and self-consistent critical exponents,includingβ=0.292(2),γ=0.924(8),andδ=4.164(6),along with the Curie temperature T_c=347 K,are extracted through various methods,which provide evidence for the coexistence of multiple magnetic interactions in SmMn_(2)Ge_(2).Further analysis reveals that the magnetic interaction of SmMn_(2)Ge_(2)is a long-range type with the interaction distance decaying as J(r)~r^(-4.35).

Analysis of load status and management strategies of main caregivers of patients with malignant tumors of digestive tract

Caregiver load refers to the subjective and objective negative impact of caregivers in the care of patients,and excessive load will have a serious impact on patients and caregivers themselves and can reduce their quality of life.For the main caregivers,it not only needs to care for the patients in life and daily life,but also needs to pay the cost of treatment for the patients,coupled with the need to carry out their own original work,life,etc.excessive life pressure,economic pressure,work pressure,emotional pressure,etc.lead to heavy load of the main caregivers,which can easily cause caregivers to have different degrees of psychological problems,which will cause serious adverse effects on the caregivers themselves and cancer patients,not conducive to the construction of a harmonious family and society.This article analyzes the current situation of primary caregiver burden in patients with gastrointestinal malignant tumors,analyzes its influencing factors,and specifies specific treatment strategies.It is hoped to provide scientific guidance for later related research and application.

Giant myxofibrosarcoma of the esophagus treated by endoscopic submucosal dissection:A case report

BACKGROUND Myxofibrosarcoma(MFS)is a fibroblast-derived sarcoma that mainly occurs in subcutaneous tissue.MFS rarely occurs in the gastrointestinal tract,especially in the esophagus.CASE SUMMARY A 79-year-old male patient was admitted to our hospital for dysphagia for a week.Computed tomography and electronic gastroscopy showed that a giant mass was located 30 cm from the incisor and extended to the cardia.There was incomplete esophageal stenosis.Endoscopic pathology showed spindle cell lesions,which were considered inflammatory myofibroblast like hyperplasia.Considering the strong demands of the patient and his family,and the fact that most inflammatory myofibroblast tumors are benign,we decided to perform endoscopic submucosal dissection(ESD)even if the tumor size was giant(9.0 cm×3.0 cm).Postoperative pathological examination resulted in a final diagnosis of MFS.MFS rarely occurs in the gastrointestinal tract,especially in the esophagus.Surgical resection and local adjuvant radiotherapy are the first choices to improve the prognosis.This case report firstly described the ESD for esophageal giant MFS.It suggests that ESD may be an alternative treatment for primary esophageal MFS.CONCLUSION This case report for the first time describe the successful treatment of a giant esophageal MFS by ESD,suggesting that ESD may be an alternative treatment for primary esophageal MFS,especially in elderly high-risk patients with obvious dysphagia symptoms.

Relationship between intestinal microbiota and ulcerative colitis:Mechanisms and clinical application of probiotics and fecal microbiota transplantation

Ulcerative colitis(UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. however, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation(FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in thepathogenesis and treatment of UC.

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15th, 25th and 40th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Prognostic significance of lymphovascular invasion in colorectal cancer and its association with genomic alterations

BACKGROUND Lymphovascular invasion (LVI) is suggested to be an early and important step in tumor progression toward metastasis, but its prognostic value and genetic mechanisms in colorectal cancer (CRC) have not been well investigated. AIM To investigate the prognostic value of LVI in CRC and identify the associated genomic alterations. METHODS We performed a retrospective analysis of 1219 CRC patients and evaluated the prognostic value of LVI for overall survival by the Kaplan-Meier method and multivariate Cox regression analysis. We also performed an array-based comparative genomic hybridization analysis of 47 fresh CRC samples to examine the genomic alterations associated with LVI. A decision tree model was applied to identify special DNA copy number alterations (DCNAs) for differentiating between CRCs with and without LVI. Functional enrichment and protein-protein interaction network analyses were conducted to explore the potential molecular mechanisms of LVI. RESULTS LVI was detected in 150 (12.3%) of 1219 CRCs, and the presence was positively associated with higher histological grade and advanced tumor stage (both P < 0.001). Compared with the non-LVI group, the LVI group showed a 1.77-fold (95% confidence interval: 1.40-2.25, P < 0.001) increased risk of death and a significantly lower 5-year overall survival rate (P < 0.001). Based on the comparative genomic hybridization data, 184 DCNAs (105 gains and 79 losses) were identified to be significantly related to LVI (P < 0.05), and the majority were located at 22q, 17q, 10q, and 6q. We further constructed a decision tree classifier including seven special DCNAs, which could distinguish CRCs with LVI from those without it at an accuracy of 95.7%. Functional enrichment and proteinprotein interaction network analyses revealed that the genomic alterations related to LVI were correlated with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling. CONCLUSION LVI is an independent predictor for survival in CRC, and its development may correlate with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.

Creep damage characterization of UNS N10003 alloy based on a numerical simulation using the Norton creep law and Kachanov–Rabotnov creep damage model

The calculation of inelastic creep damage is important for the structural integrity evaluation of the elevated temperature structure in a thorium molten salt reactor(TMSR). However, a creep damage theory model and numerical simulation method have not been proposed for the key materials(UNS N10003 alloy) in the TMSR. In this study, creep damage characterization of UNS N10003 alloy is investigated using the Norton creep law and Kachanov–Rabotnov(K–R) creep damage model. First, the creep experimental data of the UNS N10003 alloy at 650 °C were adopted to fit the material constants of the two models. Then, the creep damage behavior of the UNS N10003 alloy was analyzed and discussed under uniaxial and multi-axial stress states. The results indicated that the K–R creep damage model is more suitable for the UNS N10003 alloy than the Norton model. Finally, the numerical simulation method was developed by a user-defined UMAT subroutine and subsequently verified through a finite element analysis(FEA). The FEA results were in agreement with the theoretical solutions. This study provides an effective method for the inelastic creep damage analysis of the elevated temperature structure in the TMSR.

Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy

AIM: To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy. METHODS: Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and nonCOPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO 2 ), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded. RESULTS: All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO 2 , systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001). CONCLUSION: The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.

Significance of Bcl-xL in human colon carcinoma

AIM:To investigate the clinical significance of Bcl-xL gene in the pathogenesis of human colon carcinoma. METHODS:Fifty-six pair tissue samples from patients with colon cancer were collected, and protein level of the Bcl-xL gene was measured by immunohistochemistry method. The correlation of Bcl-xL expression with clinical index was evaluated. After human colon cancer cell line HT29 was transfected with Bcl-xL small interfering RNA (siRNA), the anchorage-independent growth of cancer cells was detected by colony formation in soft agar and invasion ability of cancer cells was determined by a transwell model. RESULTS:The Bcl-xL expression was higher in cancerous tissue samples than in normal tissue samples (38.78 ± 11.36 vs 0.89 ± 0.35, P < 0.001), and was associated with the pathological grade, lymphnode metastasis and Duke’s stage of colorectal carcinoma. Transfection with Bcl-xL siRNA inhibited the colony formation and invasion ability of human colon cancer cell line HT29 in vitro. CONCLUSION:Bcl-xL gene plays an important role in carcinogenesis of human colorectal carcinoma and is associated with malignant biological behaviors of human colorectal carcinoma.

Gastrointestinal insights during the COVID-19 epidemic

Coronavirus disease-2019(COVID-19)has so far caused hundreds of mortalities worldwide.Although respiratory symptoms are the main complication in COVID-19 patients,the disease is also associated with gastrointestinal problems,with diarrhea,nausea,and vomiting being primary COVID-19 symptoms.Thus,cancer and inflammatory bowel disease(IBD)management,stool viral tests,and virus exposure are major concerns in the context of COVID-19 epidemic.In patients with colorectal cancer and IBD,the colonic mucosa exhibits elevated angiotensin-converting enzyme 2 receptor levels,enhancing COVID-19 susceptibility.In some cases,positive viral stool tests may be the only indicator of infection at admission or after leaving quarantine.Without supplemental stool tests,the risk of undetected COVID-19 transmission is high.Moreover,viral exposure during the regular or emergency endoscopic examination should be avoided.We carefully discuss key gastrointestinal concerns with regard to COVID-19 and call for more attention to such problems.

Prostate artery embolization on lower urinary tract symptoms related to benign prostatic hyperplasia: A systematic review and metaanalysis

BACKGROUND Prostate artery embolization(PAE)is a promising minimally invasive therapy that improves lower urinary tract symptoms(LUTS)related to benign prostatic hyperplasia(BPH).Transurethral resection of the prostate(TURP)is the gold standard therapy for LUTS/BPH.AIM To evaluate the efficacy and safety of PAE vs TURP on LUTS related to BPH.METHODS A literature review was performed to identify all published articles on PAE vs TURP for LUTS/BPH.Sources included PubMed,Embase,Cochrane library databases,and Chinese databases before June 2022.A systematic review and meta-analysis were conducted.Outcome measurements were combined by calculating the mean difference with a 95%confidence interval.Statistical analysis was carried out using Review Manager 5.3.RESULTS Eleven studies involving 1070 participants were included.Compared with the TURP group,the PAE group had a similar effect on the International Index of Erectile Function(IPSS)score,Peak urinary flow rate(Qmax),postvoid residual volume(PVR),Prostate volume(PV),prostatic specific antigen(PSA),The International Index of Erectile Function short form(IIEF-5)scores,and erectile dysfunction during 24 mo follow-up.Lower quality of life(QoL)score,lower rate of retrograde ejaculation and shorter hospital stay in the PAE group.There was no participant death in either group.A higher proportion of haematuria,urinary incontinence and urinary stricture was identified in the TURP group.CONCLUSION PAE may be an appropriate option for elderly patients,patients who are not candidates for surgery,and patients who do not want to risk the potential adverse effects of TURP.Studies with large cases and long follow-up time are needed to validate results.

Accuracy of pipeline blood glucose monitoring in patients with severe liver injury undergoing artificial liver support system treatment

Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, subacute liver failure, acute-on-chronic liver failure, or further worsening of end-stage liver disease [1].

ELEMENTAL CONTENTS IN ORGANS AND TISSUES OF CHINESE ADULT MEN

Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.

Expression of nucleus accumbens-1 in colon cancer negatively modulates antitumor immunity

BACKGROUND Nucleus accumbens-1(NAC-1)is highly expressed in a variety of tumors,including colon cancer,and is closely associated with tumor recurrence,metastasis,and invasion.AIM To determine whether and how NAC-1 affects antitumor immunity in colon cancer.METHODS NAC-1-siRNA was transfected into RKO colon cancer cells to knock down NAC expression;tumor cells with or without knockdown of NAC-1 were treated with CD8+T cells to test their cytocidal effect.The level of the immune checkpoint programmed death receptor-1 ligand(PD-L1)in colon cancer cells with or without knockdown of NAC-1 was analyzed using Quantitative real-time polymerase chain reaction and Western blotting.A double luciferase reporter assay was used to examine the effects of NAC-1 on the transcription of PD-L1.Mice bearing MC-38-OVA colon cancer cells expressing NAC-shRNA or controlshRNA were treated with OT-I mouse CD8+T cells to determine the tumor response to immunotherapy.Immune cells in the tumor tissues were analyzed using flow cytometry.NAC-1,PD-L1 and CD8+T cells in colon cancer specimens from patients were examined using immunohistochemistry staining.RESULTS Knockdown of NAC-1 expression in colon cancer cells significantly enhanced the cytocidal effect of CD8+T cells in cell culture experiments.The sensitizing effect of NAC-1 knockdown on the antitumor action of cytotoxic CD8+T cells was recapitulated in a colon cancer xenograft animal model.Furthermore,knockdown of NAC-1 in colon cancer cells decreased the expression of PD-L1 at both the mRNA and protein levels,and this effect could be rescued by transfection of an RNAi-resistant NAC-1 expression plasmid.In a reporter gene assay,transient expression of NAC-1 in colon cancer cells increased the promoter activity of PD-L1,indicating that NAC-1 regulates PD-L1 expression at the transcriptional level.In addition,depletion of tumoral NAC-1 increased the number of CD8+T cells but decreased the number of suppressive myeloid-derived suppressor cells and regulatory T cells.CONCLUSION Tumor expression of NAC-1 is a negative determinant of immunotherapy.

Primary pancreatic lymphoma diagnosed by endoscopic ultrasound-guided fine needle biopsy

To the Editor:Primary pancreatic lymphoma(PPL)is extremely rare,account-ing for 1%of extra-nodal lymphomas and less than 0.5%of pan-creatic masses[1].Both cytological and histological analyses are required to confirm the diagnosis of PPL.The main treatments include chemotherapy and radiotherapy[2].Pancreatic resection alone does not improve the survival rate[3].Hence,it is necessary to differentiate PPL from other malignant tumors before surgery.

Antagomir Dependent MicroRNA-205 Reduction Enhances Adhesion Ability of Human Corneal Epithelial Keratinocytes

Objective To investigate the effect of microRNA-205 reduction by antagomirs on adhesion ability of normal human corneal epithelial keratinocytes(NHCEKs).Methods Antagomir-205,complementary and inhibitory to microRNA-205,was used to suppress endogenous microRNA-205 in NHCEKs.The adhesion ability of treated NHCEKs was then assessed by cell adhesion assay.Immunoblot and immunohistochemistry were conducted to determine the level of two focal adhesion-related proteins,focal adhesion kinase(FAK) and paxillin(Pax).Phalloidin staining was performed to measure the level of filamentous actin in antagomir-treated NHCEKs.Results Antagomir-205 markedly reduced the level of microRNA-205 in NHCEKs and significantly enhanced adhesion ability of NHCEKs(P<0.01).Further protein analysis validated that inhibition of mi-croRNA-205 increased the number of phosphorylated FAK and phosphorylated Pax,and decreased filamen-tous actin.Conclusion Our findings suggest that microRNA-205 has down-regulating effect on cell motility in NHCEKs.