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.

Naringenin (4,5,7-trihydroxyflavonoid) is a naturally occurring bioflavonoid found in citrus fruits, which plays an important role in metabolic syndrome, neurological disorders, and cardiovascular diseases. However, the pharmacological mechanism and biological function of naringenin on anti-angiogenesis and anti-tumor immunity have not yet been elucidated. Our study firstly demonstrates that naringenin inhibits the growth of hepatocellular carcinoma (HCC) cells both in vivo and in vitro. Naringenin diminishes the ability of HCC cells to induce tube formation and migration of human umbilical vein endothelial cells (HUVECs) and suppresses neovascularization in chicken chorioallantoic membrane (CAM) assays. Meanwhile, in vivo results demonstrate that naringenin can significantly upregulate level of CD8⁺ T cells, subsequently increasing the level of immune-related cytokines in the tumor immune microenvironment. Mechanistically, we found that naringenin facilitate the K48-linked ubiquitination and subsequent protein degradation of vascular endothelial growth factor A (VEGFA) and mesenchymal-epithelial transition factor (c-Met), which reduces the expression of programmed death ligand 1 (PD-L1). Importantly, combination therapy naringenin with PD-L1 antibody or bevacizumab provided better therapeutic effects in liver cancer. Our study reveals that naringenin can effectively inhibit angiogenesis and anti-tumor immunity in liver cancer by degradation of VEGFA and c-Met in a K48-linked ubiquitination manner. This work enlightens the potential effect of naringenin as a promising therapeutic strategy against anti-angiogenesis and anti-tumor immunity in HCC.

African swine fever(ASF)is a virulent,hemorrhagic disease of swine caused by African swine fever virus(ASFV),which seriously affects the healthy development of Chinese pig indus-try.The genome of ASFV is large and encodes more than 165 proteins.Among them,the p54 pro-tein is encoded by the E183L gene,which has various functions such as participating in viral as-sembly,inducing apoptosis and inducing immune response.The conventional Chinese vaccine(C-strain)is a safe and effective attenuated vaccine developed by Chinese scientists.It can efficiently protect against attacks from various genotypes of classical swine fever virus(CSFV).The aim of this study was to investigate whether C-strain can express ASFV p54 protein serve as a delivery vector for ASF genetically engineered vaccines.An infectious clone of pHCLV-p54 was constructed by homologous recombination,the recombinant virus rHCLV-p54 was rescued by transfecting it into SK6 cells by blind passaging.Its genetic stability and growth curve were determined in vitro,while rabbits were immunized to evaluate its immunity effect.The results showed that the E183L gene remained genetically stable in the recombinant virus,indicating that the E183L gene could be stably inherited in recombinant viruses,but the inserted exogenous gene affected the replication of the C-strain.The results of the rabbit immunization test showed that the recombinant virus rHCLV-p54 was able to induce ASFV-specific antibodies.The above results indicated that we have successfully constructed a recombinant C-strain that stably expresses the ASFV p54 protein.In summary,the recombinant virus rHCLV-p54 has a good immunogenicity and is warranted for fur-ther evaluation as a vaccine candidate.

Objective:To compare the efficacy and safety of bi-level positive airway pressure (BiPAP) ventilation and heated humidified high flow nasal cannula (HHHFNC) ventilation as initial respiratory support for premature infants with respiratory distress syndrome (RDS).Methods:From January 2019 to June 2021, premature infants [gestational age (GA) 28~35 weeks)] with grade Ⅰ to Ⅲ RDS admitted to Suining County People's Hospital were prospectively enrolled. The infants were randomly assigned into BiPAP group and HHHFNC group. The clinical characteristics, ventilation efficacy and complications were analyzed.Results:A total of 33 infants were in BiPAP group and 32 in HHHFNC group. No significant differences existed between the two groups in the following items: the frequency of apnea within 24 h of ventilation, FiO 2 and PaCO 2 at 24 h, the use of pulmonary surfactant (PS), the incidence of non-invasive ventilation failure within 72 h, non-invasive ventilation duration and the age achieving total enteral nutrition. HHHFNC group had lower score in premature infants pain profile (PIPP) than BiPAP group at 24 h of non-invasive ventilation [4 (3, 6) vs. 8 (6, 11), P<0.001]. No significant differences existed in nasal injury, pneumothorax, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and mortality rate between the two groups ( P>0.05). Conclusions:As the initial treatment for premature infants with grade Ⅰ to Ⅲ RDS, BiPAP and HHHFNC has similar rates of non-invasive ventilation failure within 72 h,non-invasive ventilation duration and adverse events. HHHFNC may ease the pain of the infants.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-β1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Bone Density Conservation Agents/adverse effects* ; Humans ; Quality of Life ; Risk Factors

Pancreatic carcinoma remains one of the most challenging malignant tumor with an increasing morbidity in China.The significance of multidisciplinary and comprehensive treatment of pancreatic cancer has been recognized in recent years.Moreover,several novel clinical staging standards of pancreatic cancer have emerged to help optimize the treatment strategies and improve patients' prognosis in precise treatment era.Currently,in addition to the traditional TNM stage,usage of histologic grade (G),resection marginstatus (M),lymphatic invasion status (L),vascular invasion status (V),perineurial invasion status (P) and combination of these stages recommended by NCCN guideline as GTNMLVP stage have emerged.Other novel staging standards include respectability status,standardized pancreatic surgery classification,genetics classification,etc.This review summarized the characteristics and clinical significance of these novel established methods for pancreatic cancer precise staging.

Starting from the practices of grade protection assessment on the information system of Peking Union Medical College Hos -pital, the paper introduces the information system grade and assessment contents and processes , discusses common problems found in specific work and risk analysis approaches so as to provide a reference for work related to information security .

Objective To explore the prevalence of polycystic ovary syndrome (PCOS) in nurse of reproductive age and compare the characteristics of four phenotypic subgroups.Methods A cross-sectional survey was carried out in nurses aged 18-45 years in Renji Hospital in 2011.Questionnaire and anthropometric and biochemical assessments were made.Pelvic ultrasound evaluations were made and blood androgen levels were determined.Diagnosis of PCOS was based on Rotterdam 2003 criteria,consisting of anovulation/oligo-ovulation (ANOVU),clinical and/or biochemical hyperandrogenism (HA) and polycystic ovaries (PCO).Results There were 520 participants and finally 486 individuals finished questionnaire and androgen level determination.283 subjects were totally normal,48 suffered from PCO,129 HA,and 89 ANOVU.54 out of 486 women were diagnosed as PCOS,a prevalence of 11.1％.A significant difference exited only in age among four phenotypic subgroups (P＜0.05).There was no statistic difference in other parameters.Conclusion Establishing an explicit definition of each condition in PCOS criteria has important investigational implications and increase the comparability of published researches.Application of Rotterdam criteria is feasible for earlier diagnosis and timely intervention in order to prevent serious complications.

Objective To investigate the MR findings of fetal cleft lip (CL) and evaluate the advantages and limitations of MRI in the diagnosis. Methods Twelve pregnant women suspicious of fetal CL/cleft palate(CP) on ultrasonography were enrolled in the study. The findings of ultrasonography, MRI and following-up were compared. Results MRI and ultrasonography detected 12 fetuses with CL/CP. The following-up results showed 1 case with incomplete cleft lip and the other 11 cases with complete cleft lips and cleft palates. MRI and unltrasonography were consistent with the follow-up in CL detection, showing completed or uncompleted soft tissue interruption of the fetal lips with amniotic fluid filling which is high signal on T_2WI. On MRI, CP showed discontinuous of the soft tissue which were interrupted by long T_2 signal and communicating with oral cavity and nasal cavity. MRI missed 1 case and excluded 1 case of CP. Ultrasonography predicted 5 case of CL, excluded 1 CP but missed 6 cases. The accuracy, sensitivity and specificity in detection CL/CP was 91.7% (11/12), 90.9% (10/11), 100% (1/1) for MRI and 50.0% (6/12),45.5% (5/11), 100% (1/1) for ultrasonography, respectively. Conclusion MR imaging had advantage over ultrasonography in detecting CP, MRI is an essential when CP is suspicious on ultrasonography.