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 monitor heart-related parameters of hypoxic pulmonary hypertension(PH)mouse models induced by hypoxia alone and hypoxia combined with vascular endothelial growth factor receptor inhibitor SU5416 using echocardiography,and to construct the prediction equation of right ventricular systolic pressure(RVSP).Twenty-four C57BL/6J male mice were randomly divided into simple hypoxia group(group A),hypoxia combined with SU5416 group(group B),control group(group C),each group 8 mice.Hypoxic PH models were constructed with hypoxia alone and hypoxia combined with SU5416 in group A and group B,respectively.Echocardiography was performed before and during modeling(2,3,4 weeks after interventions),and the relevant parameters were obtained.RVSP was measured using right heart catheterization after the last echocardiography.The changes of ultrasonic parameters were observed,the correlations of ultrasonic parameters 4 weeks after intervention with RVSP were observed,and linear equations for predicting RVSP were established.Results With time going,during modeling,pulmonary artery diameter(PAD),PAD/aorta diameter(AOD)and right ventricle anterior wall thickness(RVAWT)increased,while heart rate,pulmonary artery acceleration time(PAAT),PAAT/pulmonary artery ejection time(PAET)and tricuspid annular plane systolic excursion(TAPSE)decreased in group A and B(all P＜0.05).Three and 4 weeks after interventions,PAET,PAAT/PAET and TAPSE in group B decreased compared with those in group A(all P＜0.05).Four weeks after interventions,RVSP in group A and B were highly correlated with PAD/AOD,RVAWT,PAAT,PAAT/PAET and TAPSE(all P＜0.05).The linear regression equations of PAAT/PAET and TAPSE for predicting RVSP in simple hypoxic PH mice models included RVSP=-161.7 ×(PAAT/PAET)+63.85,as well as RVSP=-36.53 ×TAPSE+71.55,while of predicting RVSP in hypoxia combined with VEGFR-2 inhibitor PH mouse models were as follows:RVSP=-266.4 ×(PAAT/PAET)+91.59,RVSP=-69.14 × TAPSE+116.5.Conclusion Four weeks after inerventions,the phenotypes of hypoxic PH mouse models induced by hypoxia alone and hypoxia combined with SU5416 became obvious.Prediction equations of RVSP established based on PAAT/PAET and TAPSE obtained with echocardiography could provide references for relevant research.

Diabetic kidney disease(DKD)is one of the serious microvascular complications of diabetes.Immune disorder-mediated chronic inflammation is an essential mechanism underlying the occurrence of DKD.Macrophages,as important participants in the immune-inflammatory response,can polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype under different microenvironments.The two are functionally antagonistic to each other.They can be transformed into each other in different developmental stages of DKD,which is similar to the connotation of yin and yang in the theory of"yin-yang theory"in TCM,such as restriction of opposites,mutual root and mutual use,balance of growth and decline,and mutual transformation.The imbalance of M1 and M2 macrophages is an important factor leading to DKD inflammatory response and renal fibrosis.Therefore,based on the yin-yang theory in TCM,this article clarified the effects of macrophage polarization on DKD,and proposed that the basic treatment method is to"tonify deficiency and damage excess"to adjust the polarization of macrophages and restore the balance of yin and yang,in order to provide ideas for the clinical treatment of DKD.

This article discusses the overview of virtual reality (VR) technology and chronic pain kinesiophobia, elucidating the principles by which VR technology reduces chronic pain kinesiophobia and its effectiveness in the treatment and rehabilitation training of patients with this condition. The advantages and limitations of VR technology are summarized, aiming to provide references for clinical practitioners to better apply VR technology in the treatment and rehabilitation management of chronic pain kinesiophobia. The goal is to improve patients' fear of movement, fear-avoidance beliefs, pain related to movement injuries, physical function, motivation for training, and patient satisfaction.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.

Objective:To explore the motivation of the formation of the breastfeeding mission and education behavior of nurses in NICU, analyze the deep reasons, and construct the motivation and path theoretical model of the formation of the breastfeeding mission and education behavior of nurses in NICU.Methods:Through semi-structured interviews, the qualitative research method of grounded theory was used to study 20 nurses in the Second Affiliated Hospital, University of South China from July to September 2020, to construct the motivation and path theoretical model of the formation of the breastfeeding mission and education behavior of nurses in NICU.Results:The research identified five main categories: attitude factor, ability factor, behavior factor, internalization and externalization. Under the influence of three dimensions of attitude level, ability level and behavior level and their cross-layer interaction effects, the NICU nurses were driven to form stable breastfeeding mission and education behaviors through internalization and externalization.Conclusions:Based on the evolutionary context of "multi-dimensional factors and their interaction drivers-internalization-externalization", the relationship between attitude factors, ability factors, behavioral factors, internalization, and externalization are clarified. It provides a theoretical reference basis for managers in managing the breastfeeding propaganda and education of nurses in the NICU, and enriches the theoretical framework of breastfeeding behavior in the NICU.

OBJECTIVE：To stu dy the improvement effects o f Trillium tschonos kii total sapo nins（TTM）on adjuvant-induced arthritis model rats and its mechanism. METHODS ：SD rats were randomly divided into model group （n＝44）and blank group （n＝6）. Model group was given Complete Freund ’s adjuvant to induce the adjuvant-induced arthritis model ；blank group was given constant volume of normal saline with same method. Model group were divided into model group ，Tripterygium wilfordii polyglycoside tablets group （40 mg/kg），TTM low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；blank group and model group were given normal saline intragastrically ，once a day ，for consecutive 9 days. After last intragastric administration ，the body weight and foot swelling degree （bilateral）were detected ，and arthritis score was performed. The contents of tumor necrosis fator α（TNF-α）， interleukin 1β（IL-1β）and IL- 6 were detected ；the pathomorphological changes of rat ankle were observed ；protein expression of NOD-like receptor protein 3 （NLRP3），apoptosis associated spot-like protein （ASC），caspase-1 were detected ；the protein expression of NLRP 3 in synovial tissue of ankle joint were also determined. RESULTS ：Compared with blank group ，foot swelling degree，serum contents of TNF-α，IL-1β and IL-6，the protein expression of NLRP 3，ASC and caspase- 1 in knee tissue as well as the protein expression of NLRP 3 in synovial tissue of ankle joint were increased significantly in model group （P＜0.05 or P＜ 0.01），while the body weight was decreased significantly （P＜0.05）. The obvious proliferation of synovial cells ，the congestion and inflammatory cell infiltration of synovial tissue were all observed. Compared with model group ，most of the above indexes were all reversed significantly in TTM groups （P＜0.05 or P＜0.01）；the pathological changes such as synovial cell proliferation ， congestion of synovial tissue and chondrocyte destruction were all relieved ，and inflammatory cell infiltration was alleviated.CONCLUSIONS：TTM can improve rheumatoid arthritis of rats， the mechanism of which may be associated with 用。E-mail：yulingling@ctgu.edu.cn inhibiting the activity of NLRP 3/caspase-1 signaling pathway and decreasing the expression of inflammatory factors TNF-α，IL-1β，IL-6.

OBJECTIVES: To investigate the effect of icariin (ICA) on early β-defensin-2 and T cell subsets in rats after tracheotomy. METHODS: A total of 54 SPF male Sprague-Dawley rats were randomly divided into a normal control group (group A), a model group (group B), and a model+ICA treatment group (group C), with 18 rats in each group. A tracheotomy intubation model of the B and C group was prepared. After 6 h of surgery, ICA intervention was given to group C. Groups A and B were given the same amount of normal saline. Lung tissue, alveolar lavage fluid and peripheral blood were taken at 24 h, 72 h and 168 h, respectively. The expression of rat β-defensin-2 mRNA in lung tissue was detected by RT-PCR. The content of β-defensin-2 in alveolar lavage fluid and peripheral blood serum was detected by ELISA. The content of peripheral blood T cell subsets (CD3, CD4, CD8) was detected by flow cytometry, and the ratio of CD4/CD8 was calculated. RESULTS: After tracheotomy, the levels of β-defensin-2 mRNA and β-defensin-2 in lung tissue from the group B were increased significantly at 24 h, then they were decreased gradually, and decreased most significantly at 168 h (<0.05). The content of β-defensin-2 in peripheral blood of group B decreased gradually, and the content of β-defensin-2 in 168 h was significantly lower than that in 24 h (<0.05), but there was no significant difference between group B and group A (>0.05). The level of CD3 T cells in peripheral blood was significantly lower than that in the group A (<0.05), but their was no significant difference in CD4 and CD8 T cells compared with group A (>0.05). After ICA intervention in group C: lung tissue, alveolar lavage fluid, peripheral blood serum β-defensin-2 content, and peripheral blood CD3 and CD4 T cell levels were gradually increased, significantly higher than those in the group B (<0.05). CD8 T cell level was significantly lower than that in the group A at 24 h (<0.05), the CD4/CD8 ratio was significantly higher at 168 h than those in the group A or B (both <0.01). CONCLUSIONS ICA can improve the early lung immune function in rats with tracheotomy, which might be related to up-regulation of β-defensin-2 in lung tissue and alveolar lavage fluid, concomitant with increases in CD3 and CD4 T cells and CD4/CD8 ratio in peripheral blood while reduction in CD8 cells.
Animals ; Flavonoids ; Male ; Rats ; Rats, Sprague-Dawley ; T-Lymphocyte Subsets ; Tracheotomy ; beta-Defensins

Objective:To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN) .Methods:Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET) , 24 with polycythemia vera (PV) , and 29 with primary myelofibrosis (PMF) ] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed.Results:Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59% ) , per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2% , 89/211) , methylation genes (17.6% , 36/211) , and chromatin-modified genes (16.1% , 34/211) . There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ2=13.445, P=0.001) . MPN-SAF-TSS (MPN 10 score) ( P=0.006) and myelofibrosis level ( P=0.015) in patients with ≥ 3 mutant genes were higher and the HGB level ( P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1% ) carried high-risk mutation (HMR) , and patients with HMR had lower PLT ( P=0.017) , HGB levels ( P<0.001) , and higher myelofibrosis level ( P=0.010) and MPN10 score ( P<0.001) . The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2% , P=0.005) . PMF patients with ASXL1 had lower levels of PLT and HGB ( P=0.029 and 0.019) . Conclusion:69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.