Keratocyst Odontogenic Tumor (KCOT): Treatment Methods at the Second Affiliated Hospital of Jiamusi University

Many studies have been done about the treatment of KCOT, but the recurrence rate still remains high despite the combination of surgical techniques used, associated with or without the use chemical solutions such as Carnoy’s solution or Cryosurgery. Currently, there is no consensus concerning the therapeutic choice for the KCOT. The purpose of this study was to evaluate the different treatment methods used for the management of KCOT in the Second Affiliated Hospital of Jiamusi University and the results obtained from those treatment methods. Settings and Design: Clinical study was done at the Second Affiliated Hospital of Jiamusi University. Materials and Methods: Analytical retrospective review of 63 cases treated surgically from 2009 to 2015 at the Maxillofacial and Oral Surgery Department of the Second Affiliated Hospital of Jiamusi University. All cases diagnosed as KCOT and registered in the archives were used. The level of statistical significance was set at P < 0.05. Results: Of the 63 cases, 55.56% were male and 44.44% female. The sex ratio was 1.25 in favor of male and the average age was 42 years. 81% of the lesions were located in the mandible. Of 40 cases treated by enucleation with peripheral ostectomy, curettage and electric cauterization with application of 2% iodine tincture, no recurrence was found. Of 20 cases treated by the same surgical method but without the application of 2% iodine tincture, recurrence was found in 3 cases (4.76%). 3 cases treated by resection had no recurrence. Significant relation between recurrence and type of treatment was found (P < 0.05). Conclusion: In our series, those cases that were treated by combination of surgical methods used with 2% iodine tincture showed an “improvement” in the reduction of recurrence, suggesting a future question to be examined in experimental study is to test the effectiveness of 2% iodine tincture.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Factors influencing ruminative thinking behaviours in nurses:a cross-sectional study of 858 subjects in a tertiary care hospital

To the editor:Nurses play a vital role in healthcare by providing direct medical care to patients,and their mental well-being significantly impacts the quality of service and patient satisfaction.^(1)Ruminative thinking involves repetitive thoughts about negative feelings,their causes and consequences.This common psychological behaviour innurses can significantly impact their self-evaluation and result in feelings of worthlessness.

Transepithelial photorefractive keratectomy without mitomycin-C for irregular astigmatism after femtosecond laser-assisted in situ keratomileusisflap complications

Dear Editor,W e write to present a case report of transepithelial photorefractive keratectomy(TPRK)without mitomycin-C(MMC)for irregular astigmatism after femtosecond laser-assisted in situ keratomileusis(FS-LASIK)flap complications.Written informed consent was obtained from the patient to allow the publication of this case and associated accompanying images.The study was conducted in accordance with the Helsinki Declaration.TPRK is a surgical procedure which uses an excimer laser to ablation of both the corneal epithelium and stroma,which is widely used in clinic[1-2].The procedure may be conducted in cases where there is notable topographic irregularity or scarring following complications with the LASIK flap.Corneal haze is a potential complication following TPRK,and the use of MMC as a prophylactic agent against postoperative corneal haze has been demonstrated to significantly reduce its formation after TPRK/photorefractive keratectomy(PRK).

Five-year analysis of isolated pathogens and antibiotic resistance of ocular infections from two large tertiary comprehensive hospitals in east China

AIM:To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China.METHODS:Ocular specimen data were collected from January 2019 to October 2023.The pathogen spectrum and positive culture rate for different infection location,such as keratitis,endophthalmitis,and periocular infections,along with antibiotic resistance were analyzed.RESULTS:We included 2727 specimens,including 827(30.33%)positive cultures.A total of 871 strains were isolated,530(60.85%)bacterial and 341(39.15%)fungal strains were isolated.Gram-positive cocci(GPC)were the most common ocular pathogens.The most common bacterial isolates were Staphylococcus epidermidis(25.03%),Staphylococcus aureus(7.46%),Streptococcus pneumoniae(4.59%),Corynebacterium macginleyi(3.44%),and Pseudomonas aeruginosa(3.33%).The most common fungal genera were Fusarium spp.(12.74%),Aspergillus spp.(6.54%),and Scedosporium spp.(5.74%).Staphylococcus epidermidis strains showed more than 50%resistance to fluoroquinolones.Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90%resistance to erythromycin.The percentage of bacteria showing multidrug resistance(MDR)significantly decreased(χ^(2)=17.44,P=0.002).CONCLUSION:GPC are the most common ocular pathogens.Corynebacterium macginleyi,as the fourth common bacterium,may currently be the local microbiological feature of east China.Fusarium spp.is the most common fungus.More than 50%of the GPC are resistant to fluoroquinolones,penicillins,and macrolides.However,the proportion of MDR strains has been reduced over time.

Correlation Study of Neurotransmitter and Immune Levels in Pre-Hospital Emergency Nurses with Post-Traumatic Stress Disorder

Objective: To investigate the occurrence of PTSD in pre-hospital emergency nurses and its related factors, and to compare the differences of neurotransmitter and immune-related factors between pre-hospital emergency nurses who experienced traumatic events and those who did not develop PTSD and healthy people. How: Post-traumatic Stress Disorder Self-Rating Scale (PCL-C) tests were performed on pre-hospital emergency nurses in PTSD group, non-PTSD group and healthy control group, and the plasma monoamine neurotransmitters and serum cytokines were determined by double-antibody sandwich ABC-ELISA assay using enzyme-linked adsorption kit provided by Shanghai Xitang Biotechnology Co., Ltd. Results: 1) There were statistically significant differences in PCL-C scores between PTSD group, non-PTSD group and healthy group (p α between PTSD group, non-PTSD group and healthy group (p Conclusion: Pre-hospital emergency nurses should have early psychological intervention and guidance to reduce the occurrence of PTSD in emergency and emergency nurses.

Small incision lenticule extraction and femtosecond-assisted laser in situ keratomileusis in patients with deep corneal opacity:case series

AIM:To report the safety,efficacy,and accuracy of small-incision lenticule extraction(SMILE)or femtosecondassisted laser in situ keratomileusis(FS-LASIK)for the correction of myopia or myopic astigmatism in patients with deep corneal opacity denoted by anterior segment optical coherence tomography(AS-OCT).METHODS:Four patients with monocular corneal opacity(3 due to mechanical injury,1 due to a firecracker wound)were recruited and treated with refractive surgery(3 for SMILE,1 for FS-LASIK combined with limbal relaxing incision(LRI).Preoperative ocular manifestations,surgical details,postoperative visual outcomes,corneal opacity parameters,and corneal topography were analyzed.RESULTS:Preoperatively,spherical diopter ranged from-3.0 D to-4.75 D with cylinder ranging from-0.75 to-5.0 D,and corrected distance visual acuity(CDVA)ranging from 20/25 to 20/20.One eye’s corneal opacity was located in the central zone and three were in the mid-peripheral optical zone.Three patients underwent uneventful SMILE in both eyes,whilst one patient underwent FS-LASIK for high astigmatism in both eyes and LRI in the right eye.CDVA of the eye with corneal opacity ranged from 20/22to 20/20 one to six weeks postoperatively.Two patients achieved better CDVA and no patients lost Snellen lines.The postoperative diopter was within±0.75 D for all eyes.Significant edema existed above the corneal opacity in one eye and dissipated soon.No eccentric corneal topography or morphological anomaly of the corneal cap or flap was observed.CONCLUSION:The cases demonstrate that SMILE or FS-LASIK is safe and effective to treat myopic astigmatism combined with deep corneal opacity lesions after comprehensive preoperative evaluation and appropriate candidate selection.FS-LASIK combined with LRI is also sufficient for correcting high astigmatism due to corneal scarring.

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.

Acute diffuse peritonitis secondary to a seminal vesicle abscess:A case report

BACKGROUND Seminal vesicle abscess(SVA)is the manifestation of a relatively rare urinary system infection.In response to urinary system inflammation,an abscess forms in special locations.However,acute diffuse peritonitis(ADP)induced by SVA is unusual.CASE SUMMARY We report a case of a left SVA in a male patient complicated with pelvic abscess,ADP,multiple organ dysfunction syndrome,infectious shock,bacteremia,and acute appendiceal extraserous suppurative inflammation as a result of a long-term indwelling urinary catheter.The patient received a course of morinidazole+cefminol antibiotics but showed no obvious relief,so the perineal SVA underwent puncture drainage and abdominal abscess drainage+appendectomy was performed.The operations were successful.After the operation,anti-infection,anti-shock,and nutritional support treatments were continued and various laboratory indicators were regularly reviewed.The patient was discharged from the hospital after recovery.This disease is a challenge for the clinician because of the unusual spreading path of the abscess.Moreover,appropriate intervention and adequate drainage of abdominal and pelvic lesions are necessary,especially when the primary focus cannot be determined.CONCLUSION The etiology of ADP varies,but acute peritonitis secondary to SVA is very rare.In this patient,the left SVA not only affected the adjacent prostate and bladder but also spread retrogradely through the vas deferens,forming a pelvic abscess in the loose tissues of the extraperitoneal fascia layer.Inflammation involving the peritoneal layer led to ascites and pus accumulation in the abdominal cavity,and appendix involvement led to extraserous suppurative inflammation.In clinical practice,surgeons need to consider the results of various laboratory tests and imaging examinations to make comprehensive judgments involving the diagnosis and treatment plan.

Establishment of Microbial Limit Test Methods for Two Hospital Preparations

[Objectives] This study was conducted to establish microbial limit test methods for traditional Chinese medicine preparations Yunpi Granules and Bupi Qiangli Paste. [Methods] According to General Rules of Part IV of Chinese Pharmacopoeia, applicability tests were conducted on microbial limit test methods for the above two traditional Chinese medicine preparations by the plate method. [Results] The established methods showed recovery values in the range of 0.5-2.0 for both experimental strains, and the control bacteria could be detected in the experimental group, but not in the negative control group. [Conclusions] The microbial limit test methods were reliable for the two traditional Chinese medicine preparations and could be used for quality control.

Neuro-11:a new questionnaire for the assessment of somatic symptom disorder in general hospitals

Background Somatic symptom disorder(SSD)commonly presents in general hospital settings,posing challenges for healthcare professionals lacking specialised psychiatric training.The Neuro-11 Neurosis Scale(Neuro-11)offers promise in screening and evaluating psychosomatic symptoms,comprising 11 concise items across three dimensions:somatic symptoms,negative emotions and adverse events.Prior research has validated the scale’s reliability,validity and theoretical framework in somatoform disorders,indicating its potential as a valuable tool for SSD screening in general hospitals.Aims This study aimed to establish the reliability,validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD.Through this comparative analysis,we aimed to validate the effectiveness and precision of the Neuro-11,enhancing its utility in clinical settings.Methods Between November 2020 and December 2021,data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People’s Hospital in China for various physical discomforts.The patients completed multiple questionnaires,including the Neuro-11,Short Form 36 Health Survey,Patient Health Questionnaire 15 items,Hamilton Anxiety Scale and Hamilton Depression Scale.Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD.Results The Neuro-11 demonstrated strong content reliability and structural consistency,correlating significantly with internationally recognised and widely used questionnaires.Despite its brevity,the Neuro-11 exhibited significant correlations with other questionnaires.A test-retest analysis yielded a correlation coefficient of 1.00,Spearman-Brown coefficient of 0.64 and Cronbach’sαcoefficient of 0.72,indicating robust content reliability and internal consistency.Confirmatory factor analysis confirmed the validity of the three-dimensional structure(p<0.001,comparative fit index=0.94,Tucker-Lewis index=0.92,root mean square error of approximation=0.06,standardised root mean square residual=0.04).The threshold of the Neuro-11 is set at 10 points based on the maximum Youden’s index from the receiver operating characteristic curve analysis.In terms of diagnostic efficacy,the Neuro-11 has an area under the curve of 0.67.

Low ambient temperature and air pollution are associated with hospitalization incidence of coronary artery disease:Insights from a cross-sectional study in Northeast China

Background:Previous studies have established a link between fluctuations in climate and increased mortality due to coronary artery disease(CAD).However,there remains a need to explore and clarify the evidence for associations between meteorological changes and hospitalization incidences related to CAD and its subtypes,especially in cold regions.This study aimed to systematically investigate the relationship between exposure to meteorological changes,air pollutants,and hospitalization for CAD in cold regions.Methods:We conducted a cross-sectional study using hospitalization records of 86,483 CAD patients between January 1,2009,and December 31,2019.Poisson regression analysis,based on generalized additive models,was applied to estimating the influence of hospitalization for CAD.Results:Significant associations were found between low ambient temperature[-10℃,RR=1.65;95%CI:(1.28-2.13)]and the incidence of hospitalization for CAD within a lag of 0-14 days.Furthermore,O_(3)[95.50μg/m^(3),RR=12;95%CI:(1.03-1.21)]and NO_(2)[48.70μg/m^(3),RR=1.0895%CI:(1.01-1.15)]levels were identified as primary air pollutants affecting the incidence of CAD,ST-segment-elevation myocardial infarction(STEMI),and non-STEMI(NSTEMI)within the same lag period.Furthermore,O_(3)[95.50μg/m^(3),RR=1.12;95%CI:(1.03-1.21)]and NO_(2)[48.70μg/m^(3),RR=1.0895%CI:(1.01-1.15)]levels were identified as primary air pollutants affecting the incidence of CAD,ST-segment-elevation myocardial infarction(STEMI),and non-STEMI(NSTEMI)within the same lag period.The effect curve of CAD hospitalization incidence significantly increased at lag days 2 and 4 when NO_(2)and O_(3)concentrations were higher,with a pronounced effect at 7 days,dissipating by lag 14 days.No significant associations were observed between exposure to PM,SO_(2),air pressure,humidity,or wind speed and hospitalization incidences due to CAD and its subtypes.Conclusion:Our findings suggest a positive correlation between short-term exposure to low ambient temperatures or air pollutants(O_(3)and NO_(2))and hospitalizations for CAD,STEMI,and NSTEMI.These results could aid the development of effective preparedness strategies for frequent extreme weather events and support clinical and public health practices aimed at reducing the disease burden associated with current and future abnormal weather events.

The effects of cold region meteorology and specific environment on the number of hospital admissions for chronic kidney disease:An investigate with a distributed lag nonlinear model

Objective:To explore the effects of daily mean temperature(°C),average daily air pressure(hPa),humidity(%),wind speed(m/s),particulate matter(PM)2.5(μg/m3)and PM10(μg/m3)on the admission rate of chronic kidney disease(CKD)patients admitted to the Second Affiliated Hospital of Harbin Medical University in Harbin and to identify the indexes and lag days that impose the most critical influence.Methods:The R language Distributed Lag Nonlinear Model(DLNM),Excel,and SPSS were used to analyze the disease and meteorological data of Harbin from 01 January 2010 to 31 December 2019 according to the inclusion and exclusion criteria.Results:Meteorological factors and air pollution influence the number of hospitalizations of CKD to vary degrees in cold regions,and differ in persistence or delay.Non-optimal temperature increases the risk of admission of CKD,high temperature increases the risk of obstructive kidney disease,and low temperature increases the risk of other major types of chronic kidney disease.The greater the temperature difference is,the higher its contribution is to the risk.The non-optimal wind speed and non-optimal atmospheric pressure are associated with increased hospital admissions.PM2.5 concentrations above 40μg/m3 have a negative impact on the results.Conclusion:Cold region meteorology and specific environment do have an impact on the number of hospital admissions for chronic kidney disease,and we can apply DLMN to describe the analysis.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.

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.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

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.