The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.

With the increasing attention of domestic and foreign scholars to death with dignity, the importance of death with dignity in the field of hospice care is becoming increasingly prominent. This study reviews the fundamental concept of death with dignity, comprehensively analyzes the content, application scenarios, advantages, and limitations of various cognition and practice assessment tools for death with dignity at home and abroad, aiming to provide reference for promoting the development and appropriate use of cognition and practice assessment tools for death with dignity in China.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

Objective To explore the value of the corrected-size ratio(c-SR)value of intracranial volume computed tomography angiography(CTA)in predicting the risk of intracranial aneurysm rupture.Methods A total of 81 patients with aneurysms who had follow-up records were selected.Among them,39 patients with unruptured aneurysms and underwent regular follow-ups,while 9 patients with unruptured aneurysms opted for surgical intervention.Additionally,surgery was performed on 33 patients with ruptured aneu-rysms.Three-dimensional reconstruction of CTA was performed to obtain the morphological parameters of aneurysms.The initial size ratio(SR)value of aneurysm and the follow-up SR value or postoperative c-SR value were obtained.The changes in SR values of unruptured aneurysms were analyzed,the preoperative SR values and postoperative c-SR values of aneurysms were analyzed.Finally,the correla-tion between the intial SR value of unruptured aneurysms and the c-SR value of ruptured aneurysms was compared.Results No sig-nificant difference was observed between the initial SR value of unruptured aneurysms and the follow-up SR value(P>0.05).Simi-larly,no significant difference was noted between the preoperative SR value of unruptured aneurysms and the postoperative c-SR value(P>0.05).The preoperative SR value of ruptured aneurysms differed significantly from the postoperative c-SR value(P<0.05).There was a significant difference between the initial SR value of unruptured aneurysms and the postoperative c-SR value of ruptured aneurysms(P<0.05).The receiver operating characteristic(ROC)curve analysis was performed on the initial SR value of unrup-tured aneurysms and the postoperative c-SR value of ruptured aneurysms.The area under the curve(AUC)was 0.860 and the best cut-off value was 1.045.Conclusion Unruptured aneurysms remain stable for an extended period of time,exhibiting no significant change in morphological parameters.It can be concluded that surgical intervention does not affect the SR value of aneurysms.In the case of subarachnoid hemorrhage caused by ruptured aneurysms,the parent artery become thinner,then the preoperative SR value of ruptured aneurysms may be exaggerated,which results in the distortion of the preoperative SR value of ruptured aneurysms.However,the postoperative c-SR value is the true SR value before the rup-ture of aneurysms.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

To summarize the postoperative nursing experience for a child with Uhl's anomaly undergoing complex heart surgery.Nursing key points include implementing goal-oriented liquid negative balance management to promote the recovery of cardiac function;carrying out pressure load management and closely monitoring the heart rate and rhythm to maintain the stability of the circulatory system;closely monitoring the central venous pressure in the upper chamber and paying attention to the changes of the pulmonary artery pressure in real time;adopting a refined integrated management to avoid an abnormal rise in the pulmonary artery pressure;withdrawing invasive mechanical ventilation as early as possible and carrying out the non-invasive ventilator deconditioning training in an orderly manner;the synergistic management of bleeding and anticoagulation;the adoption of various measures to actively prevent complications;the prevention and control of infections in an all-round and multi-angle manner;the formulation of individualized cardiac rehabilitation training and nutritional intervention programs.The child was transferred from the pediatric intensive care unit back to the pediatric ward on postoperative day 9,transferred back to the pediatric intensive care unit on postoperative day 11 for 13 d for right atrial thrombus,stabilized and transferred back to the pediatric ward,and discharged after 10 d for recovery.The prognosis showed good recovery after 1 month and 3 months.

Objective To explore the value of the corrected-size ratio(c-SR)value of intracranial volume computed tomography angiography(CTA)in predicting the risk of intracranial aneurysm rupture.Methods A total of 81 patients with aneurysms who had follow-up records were selected.Among them,39 patients with unruptured aneurysms and underwent regular follow-ups,while 9 patients with unruptured aneurysms opted for surgical intervention.Additionally,surgery was performed on 33 patients with ruptured aneu-rysms.Three-dimensional reconstruction of CTA was performed to obtain the morphological parameters of aneurysms.The initial size ratio(SR)value of aneurysm and the follow-up SR value or postoperative c-SR value were obtained.The changes in SR values of unruptured aneurysms were analyzed,the preoperative SR values and postoperative c-SR values of aneurysms were analyzed.Finally,the correla-tion between the intial SR value of unruptured aneurysms and the c-SR value of ruptured aneurysms was compared.Results No sig-nificant difference was observed between the initial SR value of unruptured aneurysms and the follow-up SR value(P>0.05).Simi-larly,no significant difference was noted between the preoperative SR value of unruptured aneurysms and the postoperative c-SR value(P>0.05).The preoperative SR value of ruptured aneurysms differed significantly from the postoperative c-SR value(P<0.05).There was a significant difference between the initial SR value of unruptured aneurysms and the postoperative c-SR value of ruptured aneurysms(P<0.05).The receiver operating characteristic(ROC)curve analysis was performed on the initial SR value of unrup-tured aneurysms and the postoperative c-SR value of ruptured aneurysms.The area under the curve(AUC)was 0.860 and the best cut-off value was 1.045.Conclusion Unruptured aneurysms remain stable for an extended period of time,exhibiting no significant change in morphological parameters.It can be concluded that surgical intervention does not affect the SR value of aneurysms.In the case of subarachnoid hemorrhage caused by ruptured aneurysms,the parent artery become thinner,then the preoperative SR value of ruptured aneurysms may be exaggerated,which results in the distortion of the preoperative SR value of ruptured aneurysms.However,the postoperative c-SR value is the true SR value before the rup-ture of aneurysms.