Metastatic clear cell sarcoma of the pancreas:A rare case report

BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Clinical efficacy of endovascular revascularization combined with vacuum-assisted closure for the treatment of diabetic foot

BACKGROUND The diabetic foot is a common cause of disability and death,and comorbid foot infections usually lead to prolonged hospitalization,high healthcare costs,and a significant increase in amputation rates.And most diabetic foot trauma is complicated by lower extremity arteriopathy,which becomes an independent risk factor for major amputation in diabetic foot patients.AIM To establish the efficacy and safety of endovascular revascularization(ER)combined with vacuum-assisted closure(VAC)for the treatment of diabetic foot.METHODS Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022.Diabetic foot lesions were graded according to Wagner’s classification,and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries.Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control.Lower limb revascularization was facilitated by percutaneous transluminal balloon angioplasty(BA)or stenting.Wounds were cleaned by nibbling debridement.Wound granulation tissue growth was induced by VAC,and wound repair was performed by skin grafting or skin flap transplantation.RESULTS Of the 35 cases treated with lower limb revascularization,34 were successful with a revascularization success rate of 97%.Of these,6 cases underwent stenting after BA of the superficial femoral artery,and 1 received popliteal artery stent implantation.In the 25 cases treated with infrapopliteal artery revascularization,39 arteries were reconstructed,7 of which were treated by drug-coated BA and the remaining 32 with plain old BA.VAC was performed in 32 wounds.Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed.Two patients underwent major amputations,whereas 17 had minor amputations,accounting for a success limb salvage rate of 95%.CONCLUSION ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates.The use of VAC after ER simplifies and facilitates wound repair.

Diagnostic efficacy of virtual organ computer-assisted analysis in measuring the volume ratio of subchorionic hematoma with serum progesterone

BACKGROUND Subchorionic hematoma(SCH)is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane.SCH can lead to adverse pregnancy outcomes such as miscarriage,preterm birth,and other complications.Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes.AIM To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis(VOCAL)in measuring the volume ratio of SCH to gestational sac(GS)combined with serum progesterone on early pregnancy outcomes in patients with SCH.METHODS A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled.All patients were followed up until a gestational age of 20 wk.The parameters of transvaginal two-dimensional ultrasound,including the circumference of SCH(Cs),surface area of SCH(Ss),circumference of GS(Cg),and surface area of GS(Sg),and the parameters of VOCAL with transvaginal three-dimensional ultrasound,including the three-dimensional volume of SCH(3DVs)and GS(3DVg),were recorded.The size of the SCH and its ratio to the GS size(Cs/Cg,Ss/Sg,3DVs/3DVg)were recorded and compared.RESULTS Compared with those in the normal pregnancy group,the adverse pregnancy group had higher Cs/Cg,Ss/Sg,and 3DVs/3DVg ratios(P<0.05).When 3DVs/3DVg was 0.220,the highest predictive performance predicted adverse pregnancy outcomes,resulting in an AUC of 0.767,and the sensitivity,specificity were 70.2%,75%respectively.VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients,with a high sensitivity of 82.1%and a specificity of 72.1%,which showed a significant difference between AUC.CONCLUSION VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH,while combined serum progesterone better predicts adverse pregnancy outcomes.

Analysis of therapeutic effect of cell reduction combined with intraperitoneal thermoperfusion chemotherapy in treatment of peritoneal pseudomyxoma

BACKGROUND Pseudomyxoma peritonei is a rare tumor that can produce a biological behavior similar to that of a malignant tumor.Surgical resection combined with chemo-therapy is the traditional treatment method,but the effect is not good.Cell reduction(CRS)combined with intraperitoneal thermoperfusion chemotherapy(HIPEC)has become a new method for the treatment of peritoneal pseudomy-xoma(PMP).AIM To find out if CRS and HIPEC can be used safely and effectively to treat PMP.METHODS This is an observational study.Clinical data of PMP patients treated with CRS+HIPEC at our hospital from January 2013 to June 2023 was collated and analyzed.The main outcome measures were overall survival(OS),and the secondary outcome measures were the incidence of surgical complications and serious adverse events.Complications were graded according to common adverse event evaluation criteria.Peritoneal tumor staging was performed using the peritoneal tumor index(PCI)scoring system,and a cell reduction degree(CCR)score was performed after CRS.CCR-0 and CCR-1 were considered satisfactory CRS.RESULTS A total of 186 patients with PMP were included,with a median age of 56(48-64)years,65(34.9%)years in males,and 121(65.1%)years in females.The median PCI score was 28(20-34)points.The median operative time was 300(211-430)minutes,and no significant complications occurred.91.4%(170/186)were from the appendix,53.2%(99/186)were from the low grade,and 30.6%(57/186)were from the high grade.CCR scores showed that 55 patients(29.6%)achieved satisfactory CRS,and 113 patients(60.8%)did not achieve satisfactory CRS.The fatality rate at 30 days after surgery was 2.7%(5/186),1.6%(3/186)needed a second operation,and the fatality rate at 90 days was 4.3%(8/186).The total incidence of III-IV complications was 43.0%(80/186),among which the higher incidence was mainly anemia(27.4%,51/186),electrolyte disturbance(11.6%,21/181),and albumin decrease(7.5%,14/186).The main compli-cations associated with abdominal surgery were gastrointestinal anastomotic leakage(2.2%,4/186),abdominal hemorrhage(2.2%,4/186),and abdominal infection(4.3%,8/186).The median follow-up was 38.1(95%CI:31.2-45.1)months.The 5-year OS of PMP patients treated with CRS+HIPEC was 50.3%(95%CI:40.7%-59.9%),and the median survival time was 66.1(95%CI:43.1-89.1)months.The results of the survival analysis showed that patients with a low pathological grade,a low PCI,and a satisfactory CCR score had a higher survival rate(all P<0.05).5-year OS was 88.9%(95%CI:68.3%-100.0%)in CCR-0 patients,77.6%(95%CI:62.7%-92.5%)in CCR-1 patients,and 42.0%(95%CI:29.5%-54.5%)in CCR-2/3 patients.CONCLUSION The application of CRS+HIPEC in PMP is safe and feasible,and the survival benefit is high,especially in those who achieve satisfactory CRS,which can significantly extend the OS.

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Long non-coding RNA DPP10-AS1 represses the proliferation and invasiveness of glioblastoma by regulating miR-24-3p/CHD5 signaling pathway

This investigation aimed to unveil new prospective diagnosis-related biomarkers together with treatment targets against glioblastoma.Methods:The expression levels of long non-coding RNA(lncRNA)DPP10-AS1 were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)within both the patient tissue specimens and glioblastoma cell lines.The relationship between lncRNA DPP10-AS1 expression in glioblastoma and patient prognosis was investigated.Cell Counting Kit-8(CCK-8),transwell,and clonogenic experiments were utilized to assess tumor cells’proliferation,invasiveness,and migratory potentials after lncRNA DPP10-AS1 expression was up or down-regulated.Using an online bioinformatics prediction tool,the intracellular localization of lncRNA DPP10-AS1 and its target miRNA were predicted,and RNA-FISH verified results.A dual-luciferase reporter experiment validated the relationship across miR-24-3p together with lncRNA DPP10-AS1.MiR-24-3p expression within glioblastoma was identified through RT-qPCR,and potential link across miR-24-3p and lncRNA DPP10-AS1 was assessed using Pearson correlation analysis.Moreover,influence from lncRNA DPP10-AS1/miR-24-3p axis upon glioblastoma cell progression was assessed in vivo via a subcutaneous xenograft tumor model.Results:The expression of lncRNA DPP10-AS1 was notably reduced in both surgical specimens of glioblastoma and the equivalent cell lines.Low level of lncRNA DPP10-AS1 in glioblastoma is following poor prognosis.The downregulation of lncRNA DPP10-AS1 in glioblastoma cells resulted in enhanced cellular proliferation,migration,and invasion capabilities,accompanied by downregulated E-cadherin and upregulated vimentin and N-cadherin.Additionally,the observed upregulation of lncRNA DPP10-AS1 demonstrated a substantial inhibitory function upon proliferation,invasion,and migratory capabilities of LN229 cells.Subcellular localization disclosed that lncRNA DPP10-AS1 had a binding site that interacted with miR-24-3p.Upregulated miR-24-3p was detected in glioblastomas,displaying an inverse correlation with lncRNA DPP10-AS1 expression.MiR-24-3p downstream target has been determined as chromodomain helicase DNA binding protein 5(CHD5).LncRNA DPP10-AS1 affected the invasion and proliferation of glioblastoma by controlling the miR-24-3p/CHD5 axis.Conclusion:The present study demonstrated that lncRNA DPP10-AS1 can inhibit the invasive,migratory,and proliferative properties of glioblastoma by regulating the miR-24-3p/CHD5 signaling pathway.Consequently,lncRNA DPP10-AS1 has potential as a tumor suppressor and might be utilized for accurate diagnosis and targeted treatments of glioblastomas.

Role of Iron Accumulation in Osteoporosis and the Underlying Mechanisms

Osteoporosis is prevalent in postmenopausal women.The underlying reason is mainly estrogen deficiency,but recent studies have indicated that osteoporosis is also associated with iron accumulation after menopause.It has been confirmed that some methods of decreasing iron accumulation can improve the abnormal bone metabolism associated with postmenopausal osteoporosis.However,the mechanism of iron accumulation-induced osteoporosis is still unclear.Iron accumulation may inhibit the canonical Wnt/β-catenin pathway via oxidative stress,leading to osteoporosis by decreasing bone formation and increasing bone resorption via the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL)/receptor activator of nuclear factor kappa-B(RANK)system.In addition to oxidative stress,iron accumulation also has been reported to inhibit either osteoblastogenesis or osteoblastic function as well as to stimulate either osteoclastogenesis or osteoclastic function directly.Furthermore,serum ferritin has been widely used for the prediction of bone status,and nontraumatic measurement of iron content by magnetic resonance imaging may be a promising early indicator of postmenopausal osteoporosis.

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing

BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

Expert consensus on the clinical application of totally implantable venous access devices in the upper arm(2022 Edition)

With the widespread adoption of ultrasound guidance,Seldinger puncture techniques,and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years,an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices(TIVADs)in the upper arm.This approach has the advantage of completely avoiding the risks of hemothorax,pneumothorax,and neck and chest scarring.Medical specialties presently engaged in this study in China include internal medicine,surgery,anesthesiology,and interventional departments.However,command over implantation techniques,treatment of complications,and proper use and maintenance of TIVAD remain uneven among different medical units.Moreover,currently,there are no established quality control standards for implantation techniques or specifications for handling complications.Thus,this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach,reduce complication rates,and ensure patient safety.This consensus elaborates on the technical indications and contraindications,procedures and technical points,treatment of complications,and the use and maintenance of upper-arm TIVAD,thus providing a practical reference for medical staff.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Identification of EML4 as a key hub gene for endometriosis and its molecular mechanism and potential drug prediction based on the GEO database

Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls were obtained from the Gene Expression Omnibus database.Significant differentially expressed genes were screened using the limma package.Correlation pathways were screened by Spearman correlation analysis on the echinoderm microtubule-associated protein-like 4(EML4)and enrichment in endometriosis pathways and estimated by the GSVA package.Immune characteristics were assessed by the“ESTIMATE”R package.Potential regulatory pathways were determined by enrichment analysis.The SWISS-MODE website was used in homology modeling with EML4 and EML4 protein activity was predicted.VarElect was employed in molecular docking for screening potential compound inhibitors targeting endometriosis.Results:Ten endometriosis and 10 normal samples were included.EML4 was significantly upregulated in endometriosis(p<0.05).Thirty significantly correlated pathways involving 18 positive and 12 negative correlations,including GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE and GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES were screened between EML4 and endometriosis.Immunocorrelation analysis showed a significant difference in immune-related pathways in endometriosis and normal samples(p<0.05).In endometriosis,EML4 was associated with T-cell CD4 resting memory,activated mast cells,plasma cells,activated NK cells,M2 macrophages,and follicular helper T cells(p<0.05).Molecular docking identified five potential inhibitors of EML4,and compound DB05104(asimadoline)bound well to EML4 protein to exert its physiological effects.Conclusion:Differential gene expression and immune correlation analyses revealed that EML4 may affect endometriosis through multiple targets and pathways,the mechanism of which involved immune cell activation and infiltration.Molecular docking and dynamics simulation verified DB05104 as a potential inhibitor of EML4 and a powerful target for endometriosis treatment.

Knockdown Annexin A8 inhibits the proliferation and invasion of cervical cancer cells

This study aimed to explore the expression,function,and molecular mechanism of ANXA8,the gene for annexin 8,in cervical cancer.Methods:The gene expression of the ANX family members in cervical cancer tissues was classified via The Cancer Genome Atlas(TCGA)database.The expression of ANXA8 in paracancerous tissues,cervical cancer tissues,and cell lines was identified by fluorescence quantitative polymerase chain reaction(PCR)and immunohistochemistry.The effects of ANXA8 knockdown on the cellular growth and cell invasion of cervical cancer were examined by MTT,clone-formation assay,scratch test,and Transwell assay.The effect of ANXA8 knockdown on the proliferative potency of cervical cancer cells was assessed through an in vivo nude-mouse tumor-formation test.The gene expression levels of Ki-67 and ANXA8 in tumor-bearing tissues were measured through Immunohistochemical analysis.Results:TCGA data analysis and fluorescence quantitative PCR exhibited significantly increased expression of ANXA8 in cervical cancer tissues.Further examination exhibited that ANXA8 was expressed exceedingly in cervical cancer tissue,and it was associated with lymph node metastasis,FIGO stage,degree of differentiation,and infiltration depth of cancer patients.Cell-function assays revealed that knocking down ANXA8 may substantially suppress the propagation,colony formation,invasion,and migration of cervical cancer cells.In vivo experiments demonstrated that ANXA8 knockdown had a substantial inhibitory effect on the propagation of cervical cancer cells in nude mice and inhibited the expression of Ki-67.Conclusion:ANXA8 is specifically and significantly upregulated within cervical cancer tissues.The knockdown of this gene showed remarkable outcomes,as evidenced by the substantial inhibition of cervical cancer cell proliferation in in vitro and in vivo experimentations.Therefore,ANXA8 is a potential target or a marker that can serve as a therapeutic or diagnostic tool for cervical cancer.

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

A case of Rickettsia felis infection-induced encephalitis in a pregnant woman

Rickettsia felis is an exclusively cytozoic Gram-negative prokaryote with cat fleas as the major vectors.[1]As early as 1918,Rickettsia felis was detected in cat fleas in Europe and named Rickettsia ctenocephali.[2]Symptoms of fever,malaise,headache,maculopapular rash and eschar are observed in patients with Rickettsia felis infection.

Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

Correction: Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA

In the article“Long non-coding RNA LINC02163 accelerates malignant tumor behaviors in breast cancer by regulating the microRNA-511-3p/HMGA2 axis as a competing endogenous RNA”(Oncology Research,2020,Vol.28,No.5,pp.483–495.doi:10.3727/096504020X15928179818438),there was an error in the processing of data.To further confirm our observation,we repeated multiple experiments involving in this study,including Flow Cytometry,Transwell Cell Migration and Invasion Assays,Xenograft Tumor Model,and Western Blotting.We have revised the figures to correct these errors.Corrected versions of the Figs.2,4,5,6,and 7 are provided.The corrections do not change any results or conclusion of the article.We apologize for any inconvenience caused.

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury:not by immediately improving cerebral oxygen saturation and oxygen partial pressure

Although hyperbaric oxygen （HBO） therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury （TBI）, the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation （rSO2） and oxygen partial pressure （PaO2）. To test this idea, we compared two groups： a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO2 were measured. The controls were also examined for rSO2 and PaO2, but received no treatment, rSO2 levels in the patients did not differ significantly after treatment, but levels before and after treatment were significantly lower than those in the control group. PaO2 levels were significantly decreased after the 30-minute HBO treatment. Our findings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.

Eosinopenia is a predictive factor for the severity of acute ischemic stroke

Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke.However,the relationship of eosinopenia with infarct volume,infection rate,and poor outcome of acute ischemic stroke is still unknown.The retrospective study included 421 patients(273 males,65%;mean age,68.0± 13.0 years)with first acute ischemic stroke who were hospitalized in the Second Affiliated Hospital of Soochow University,China,from January 2017 to February 2018.Laboratory data,neuroimaging results,and modified Rankin Scale scores were collected.Patients were divided into four groups according to their eosinophil percentage level(<0.4%,0.4-1.1%,1 1-2.3%,≥2.3%).Spearman’s correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume(rs=-0.514,P<0.001).Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia;the area under curve was 0.906 and 0.876,respectively;a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas.Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke(P=0.002).Moreover,eosinophil percentage was significantly associated with large infarct volume,high infection rate(pulmonary and urinary tract infections),and poor outcome(modified Rankin Scale score>3)after adjusting for potential confounding factors(P-trend<0.001).These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke.This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University,China(approval number:K10)on November 10,2015.

Paired eye-control study of unilateral opaque bubble layer in femtosecond laser assisted laser in situ keratomileusis

AIM: To investigate the predictive factors of the opaque bubble layer(OBL) compared to the fellow eye of same patients in FS200 femtosecond laser assisted laser in situ keratomileusis(FS-LASIK).METHODS: This study consisted of 60 consecutive patients(120 eyes) with unilateral OBL during FS-LASIK. Eyes were divided into OBL(the OBL eyes) and OBL-free groups(the fellow eyes) based on the occurrence of OBL. The preoperative demographic data, refraction, keratometry, corneal astigmatism, pachymetry, intraocular pressure and intraoperative data including the outlet location of gas diffusing canal were collected. Conditional logistic regression analysis was performed to find the associated factors with OBL in the two groups by determining odds ratios(OR) and 95%CI.RESULTS: The preoperative demographic data, mean spherical errors, mean K value, suction time, intraocular pressure and central cornea thickness were not significantly different between the two groups. The outlet location of gas diffusing canal(P<0.01, OR 7.16, 95%CI 2.53-20.32) and the corneal astigmatism(P=0.013, OR 0.13, 95%CI 0.03-0.65) were significantly associated with the incidence of OBL by multivariate logistic regression analysis. Visual acuity, efficacy, and safety were comparable between the two groups two months after surgery except for a slightly lower predictability value for the hard OBL eyes.CONCLUSION: The reduction of the incidence of OBL is obvious when the outlet of gas diffusing canal located at the posterior border of the corneoscleral limbus. This is probably consequent to more effectiveness of gas diffusing canal. Corneal astigmatism is also an independent protective factor for OBL formation.