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).

Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

Metabolic reprogramming: a new option for the treatment of spinal cord injury

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Boosting Chemodynamic Therapy by the Synergistic Effect of Co‑Catalyze and Photothermal Effect Triggered by the Second Near‑Infrared Light

In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction(i.e.,chemodynamic therapy,CDT)has been attracted more attentions in recent years,the limited Fenton reaction efficiency is the important obstacle to further application in clinic.Herein,we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin(FeO/MoS2-BSA)with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared(NIR II)light.In the tumor microenvironments,the MoS2 nanosheets not only can accelerate the conversion of Fe3+ions to Fe2+ions by Mo4+ions on their surface to improve Fenton reaction efficiency,but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy(PTT).Consequently,benefiting from the synergetic-enhanced CDT/PTT,the tumors are eradicated completely in vivo.This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.

An Investigation of Oxidative DNA Damage in Pharmacy Technicians Exposed to Antineoplastic Drugs in Two Chinese Hospitals Using The Urinary 8-OHdG Assay

Objective To investigate oxidative DNA damage in pharmacy technicians preparing antineoplastic drugs at the PIVAS （Pharmacy Intravenous Admixture Service） in two Chinese hospitals. Methods Urinary 8-OHdG served as a biomarker. 5-Fluorouracil （5-FU） concentrations in air, masks and gloves were determined. The spill exposure of each PIVAS technician to antineoplastic drugs was investigated. Eighty subjects were divided into exposed group t, II, and control group I, II. Results 5-FU concentration ratios for gloves and masks in exposed group I were significantly higher than those in exposed group II （P〈0.05 or P〈0.01）. The average urinary 8-OHdG concentrations in exposed group I, control group I, exposed group II, and control group II were 24.69＋0.93, 20.68＋1.07, 20.57＋0.55, and 12.96_＋0.73 ng/mg Cr, respectively. Urinary 8-OHdG concentration in exposed group I was significantly higher than that in control group I or that in exposed group 11 （P〈0.02）. There was a significant correlation between urinary 8-OHdG concentrations and spill frequencies per technician （P〈0.01）. Conclusion There was detectable oxidative DNA damage in PIVAS technicians exposed to antineoplastic drugs. This oxidative DNA damage may be associated with their spill exposure experience and contamination of their personal protective equipment.

Application of refined management in prevention and control of the coronavirus disease 2019 epidemic in non-isolated areas of a general hospital

Objective:This article summarizes the experience in the prevention and control of coronavirus disease 2019(COVID-19)epidemic in non-isolated areas in a general hospital.Methods:Based on refined management theory,we professionally developed the standards for prevention and control of COVID-19 in non-isolated areas,systematically implemented various prevention and control measures,performed gridding audits,effectively communicated among teams and between medical staff and patients assisted by information techniques,and reported results for quality improvement.Results:There was no hospital-acquired COVID-19 infections among staff in the hospital.The rates of mask-wearing,epidemiological history screening,and the medical supplies disinfection were all 100%in the hospital.The accuracy rate of mask-wearing of patients and their families was 73.79%and the compliance rate of their hand hygiene was 40.78%.Conclusion:Refined management strategies for the prevention and control of COVID-19 infection in non-isolated areas of the general hospital are effective.The accuracy rate of mask-wearing and hand hygiene compliance of patients and their families need to be further improved.

An overview of the construction of emergency and pre-hospital first aid platform

To further improve the ability of pre-hospital and in-hospital collaborative treatment, strengthen emergency multidisciplinary cooperation and construct a scientific, rational and efficient emergency system, under the support of former chairman Yu Xue-zhong, Dr. Li Chun-sheng and numerous colleagues in the industry, the Emergency Medicine Society of the Chinese Medical Association appeal to us to draft Construction of Emergency and Pre-hospital Platform. Based on this background, the platform of emergency and pre-hospital first aid helps to build a 'one horizontal and one Longitudinal' treatment model, using the horizontal and longitudinal patterns to integrate emergency medical resources to satisfy the automatic information integration and intelligent analysis sharing, realizing the emergency management visualization and medical information digitization, simplifying the medical process and establishing a perfect standard for the emergent diseases, thereby ultimately achieving efficient diagnosis and scientific treatment.

Endoscopic ablation of Barrett's esophagus using the second generation argon plasma coagulation:a prospective randomized controlled trail

Objective：To investigate the efficacy and safety of the second generation argon plasma coagulation（VIO APC） in the ablation of Barrett＇ s Esophagus. Methods：A total of 35 patients with uncomplicated Barrett＇ s esophagus entered into a prospective, randomized, unblinded study comparing the treatment VIO APC combined with a proton pump inhibiter with a proton pump inhibiter administered alone. VIO APC was performed at a power setting of 40W, and argon gas flow at 1.5-2.0 L/min, and＂ forced＂ mode. Ablative treatment was repeated until either no Barrett＇ s epithelium remained or a maximum of 5 treatment sessions occurred. Results：In the ablation group, macroscopic complete ablation was achieved in 14 of 18 patients, and complete ablation confirmed by histology in 12 of 18 patients （P 〈 0.01）. Buried glands were observed in 2 patients who had achieved macroscopic ablation. The Barrett＇s mucosa averaged a reduction of 65%（range 50-75%） in the remaining 4 patients. In the control group, only 2 patients had partial regression, median 30%（range 20-40%）. In the ablation group, post-treatment 4 patients had transient retrosternal pain, and 3 patients had mild epigastric discomfort. One patient had a small hemorrhage during the procedure, which ceased after norepinephrine and thrombosin were administered through the endoscope biopsy channel. No adverse events were observed in the control group. During 11.8（4-15） months follow-up, patients who had achieved the complete ablation have no evidence of relapse of Barrett＇ s esophagus. Conclusion：VIO APC with a relatively low power setting can effectively ablate the Barrett＇ s mucosa. No severe adverse events were observed. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium.

Pleomorphic rhabdomyosarcoma of the spermatic cord and a secondary hydrocele testis:A case report

BACKGROUND Pleomorphic rhabdomyosarcoma(RMS)of the spermatic cord is a group of rare neoplasms,and a secondary hydrocele testis occasionally occurs.The misdiagnosis of paratesticular mass may lead to a therapeutic delay.CASE SUMMARY A 79-year-old man presented to our clinic complaining of a 1-mo history of painless scrotal swelling.Physical examination revealed approximately a 15 cm×10 cm×5 cm inguinal mass with limited mobility.Contrast-enhanced magnetic resonance imaging showed a hydrocele testis,several enlarged inguinal lymph nodes,and a heterogeneously enhanced lesion with a relatively well-defined margin in the left inguinal region.Due to the imaging findings,he was diagnosed with pleomorphic RMS and received a wide resection of the mass,an inguinal incision with a high section of the left spermatic cord,and a left radical orchiectomy.He experienced local relapse 1 mo postoperatively and received radiotherapy and anlotinib hydrochloride-based immunotherapy as adjuvant therapy.The patient died 3 mo after the surgery.CONCLUSION The optimal interventions for advanced-stage pleomorphic RMS patients should be investigated by more preclinical studies and clinical trials.Physicians need to be aware of the occurrence of pleomorphic RMS in unusual locations,especially when accompanied by a hydrocele testis.

Nanosecond pulsed electric feld interrupts the glycogen metabolism in hepatocellular carcinoma by modifying the osteopontin pathway

To the Editor:Hepatocellular carcinoma (HCC) is one of the most common lethal cancers and is the leading cause of cancer mortality worldwide [1].In recent years,developments in locoregional therapies have provided new options for the treatment of HCC,which are recommended by the international guidelines including the Barcelona Clinic Liver Cancer (BCLC) and the American Joint Committee on Cancer (AJCC)[2].

Exploration of transmission chain and prevention of the recurrence of coronavirus disease 2019 in Heilongjiang Province due to inhospital transmission

The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become the first core infection area of China's COVID-19 outbreak.Since March 2020,the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases.Herein,we reported the major COVID-19 outbreak,which caused a rebound of the epidemic in Harbin,China.After the rebound,different levels of causes for the recurrence of COVID-19,including citylevel,hospital-level,and medical staff-level cause,were investigated.Meanwhile,corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level,hospital level,and medical staff level,which eventually showed the effect of infection control function in a pandemic.In this study,we described the complete transmission chain,analyzed the causes of the outbreak,and proposed corresponding countermeasures from our practical clinical experience,which can be used as a valuable reference for COVID-19 control.

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.

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.

Hospital ethical climate associated with the professional quality of life among nurses during the early stage of COVID-19 pandemic inWuhan,China:A cross-sectional study

Objectives:To describe the professional quality of life and explore its associated factors among nurses coming from other areas of China to assist with the anti-epidemic fight inWuhan and especially examine whether the hospital ethical climate was independently associated with nurses’professional quality of life.Methods:A cross-sectional online survey was conducted from March 2020 to April 2020.The nurses working in Wuhan from the other parts of China were the target population.The Professional Quality of Life Scale version 5,the Hospital Ethical Climate Survey,and a basic information sheet were used to collect data.Descriptive statistics,t-test,ANOVA,Pearson correlation,and multiple linear regression analysis were used to analyze the data.Results:In total,236 nurses participated in this study,and 219 valid questionnaires were analyzed.The average age of the participants was 31.2±5.0 years.Most nurses were female(176/219;80.4%)and married(145/219;66.2%).In term of professional quality of life,nurses reported moderate(129/219;58.9%)to high(90/219;41.1%)levels of compassion satisfaction,low(119/219;54.3%)to moderate(100/219;45.7%)levels of burnout,and low(67/219;36.0%)to high(10/219;4.6%)levels of secondary traumatic stress.Regarding hospital ethical climate,nurses reported moderately high hospital ethical climates with an average score of 4.46.After controlling for socio-demographic characteristics,the multiple linear regression models showed that the hospital ethical climate subscale of“relationship with physicians”was independently associated with the compassion satisfaction(b=0.533,P<0.01)and burnout(b=0.237,P<0.05);the hospital ethical climate subscale of“relationship with peers”(b=0.191,P<0.01)was independently associated with the secondary traumatic stress.Conclusions:During the early stage of the pandemic,nurses demonstrated moderate to high level of compassion satisfaction,low to moderate level of burnout,and all nurses experienced secondary traumatic stress.Nurses perceived a high level of hospital ethical climate,and the perceived hospital ethical climate played an important role in promoting nurses’professional quality of life during a lifethreatening infectious disease pandemic.

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.