Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

At present, interdisciplinary integration has become a major feature of the development of science and technology, and multi-disciplinary integration will gradually become the norm. Professional and technological multi-disciplinary integration has unpredictable potential, which will produce new disciplinary frontiers, new fields of science and technology and new patterns of innovation. Organ donation is a new discipline in China's new era. Constructing and promoting an organ donation disciplinary system with the overall goal of safeguarding legal and reasonable rights and interests of donors and their families and the health rights and interests of the recipients are in line with the fundamental requirements of maintaining high-quality development of organ donation and transplantation in China. Meantime, organ donation is a complex medical and social behavior, and organs donated by citizens belong to national resources, which also endows organ donation with a social welfare attribute and relevance with all parties in society. In this article, the essence of current problems encountered during organ donation in China, the whole process of organ donation and theoretical knowledge, professional skills and personnel support required by donors in different clinical stages were analyzed to illustrate the necessity and feasibility of establishing an organ donation disciplinary system based on multi-disciplinary integration. Besides, how to integrate organ donation disciplinary construction into the national policy was also investigated. Taking safeguarding the rights and interests of donors, family members and recipients as the core and taking organ donation and transplantation as the main line, cooperative principles of co-creation, co-construction, mutual promotion, sharing and win-win should be upheld, aiming to promote multi-disciplinary integration and comprehensive talent cultivation of organ donation, jointly enhance the recognition rate and donation rate of organ donation, and make organ donation widely recognized by citizens from all walks of life.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To investigate the triggering factors of ischemic stroke and their correlation with stroke severity and traditional risk factors.Methods:The clinical data of patients with ischemic stroke within 2 weeks of the onset were collected retrospectively. They were divided into two groups according to the questionnaire of triggering factors. The demographic and baseline data of the two groups were compared. According to the National Institutes of Health Stroke Scale (NIHSS) score, the patients were divided into low NIHSS score group (≤8) and high NIHSS score group (>8). The demographic and baseline data were compared. Multivariate logistic regression analysis was used to determine the independent related factors of the existence of triggering factors in patients with ischemic stroke and the correlation between the existence of triggering factors and the severity of stroke. Results:A total of 217 patients were enrolled in the study. Their age was 63.4±12.8 years and 148 were male (68.2%). One hundred and nine patients had at least one triggering factor. Common triggering factors were sleep disorders (46.8%), infection (18.4%), and missed medication (13.8%). Multivariate logistic regression analysis showed that after adjusting for confounding factors, diabetes mellitus (odds ratio [ OR]2.496, 95% confidence interval [ CI]1.347-4.626; P=0.047), large artery atherosclerosis ( vs. small vessel occlusion: OR 2.168, 95% CI 1.060-4.343; P=0.034) and baseline NIHSS score (the fourth quartile vs. the first quartile: OR 2.320, 95% CI 1.043-5.162; P=0.039) were independently associated with the existence of triggering factors in patients with ischemic stroke, and any of the triggering factors was independently associated with stroke severity ( OR 2.042, 95% CI 1.106-3.770; P=0.023). Conclusion:Diabetes and the severity of stroke are associated with the existence of triggering factors in patients with ischemic stroke. Stroke severity in ischemic stroke patients with triggering factors is more severe.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Objective:To observe the effect of sagittal traction on the internal fixation with proximal femoral nail anti-rotation (PFNA) for femoral intertrochanteric fractures in the elderly patients.Methods:A retrospective study was conducted to analyze the clinical data of 61 elderly patients with intertrochanteric fracture who had been treated from January 2016 to January 2018 at Department of Orthopaedics, The Ninth Hospital of Ningbo. Of them, horizontal traction of the affected limb was performed in 31 (16 males and 15 females with an age of 73.6 years ± 9.4 years) while 10°-20° sagittal traction of the affected limb in 30 (15 males and 15 females with an age of 75.0 years ± 7.2 years). The 2 groups were compared in terms of operation time, intraoperative blood loss, times of intraoperative fluoroscopy, fracture healing time, hip function at 6 months after operation by Harris scoring and complications.Results:There was no statistically significant difference between the 2 groups in the general clinical data, showing comparability ( P>0.05). The operation time (47.1 min ± 4.7 min), intraoperative blood loss (72.3 mL ± 9.1 mL), and times of intraoperative fluoroscopy (11.5 ± 1.4) in the sagittal traction group were significantly less than those in the horizontal traction group (56.7 min ± 4.6 min, 103.9 mL ± 19.2 mL, and 14.6±1.6) ( P< 0.05). This cohort was followed up for 6 to 18 months (12.6 months on average). There were no significant differences between the 2 groups in quality of postoperative fracture reduction, fracture healing time or hip Harris scores at postoperative 6 months ( P>0.05). Internal fixation loosening and hip pain occurred in one patient in the sagittal traction group. Follow-ups observed no complications like wound infection, bedsores, deep vein thrombosis or hip varus deformity in either group. Conclusion:As 10°-20° sagittal traction can lift the affected limb upward to avid blockage by the iliac wing, hip soft tissue and lateral abdominal wall, it lends convenience to surgeons, reducing intraoperative bleeding volume, times of fluoroscopy and operation time.

Objective To investigate the value of serum IgG4 level for the diagnosis of IgG4-related hepatobiliary diseases and the differentiation from other hepatobiliary diseases.Methods A total of 270 patients with hepatobiliary diseases in the People's Hospital of Hunan Province from August 2015 to April 2017 were enrolled in this study,and 20 healthy subjects were selected as controls.The 270patients were divided into eight groups:liver cirrhosis group (n =17),acute pancreatitis group (n =52),chronic pancreatitis group (n =33),cholecystitis and gallstone group (n =27),bile duct carcinoma group (n =30),cholangitis and biliary calculi group (n =41),pancreatic cancer group (n =47),IgG4-related hepatobiliary disease group (n =23).The levels of serum IgG4 were measured by rate nephelometery assay.The sensitivity and specificity of IgG4 levels for distinguishing IgG4-associated hepatobiliary diseases were evaluated by receiver operating characteristic curve.Results The levels of IgG4 of the cirrhosis group and the IgG4 related hepatobiliary disease group were significantly higher than those of the control group (P ＜ 0.05).The IgG4 level in the hepatobiliary disease group was significantly higher than those of the other seven groups (Z =-5.267,-6.802,-5.921,-6.005,-6.173,-6.513,-6.014,P all ＜ 0.01).The area under curve (AUC) for IgG4 level in distinguishing IgG4 associated hepatobiliary diseases and other hepatobiliary diseases was 0.982.When 4.13 g/L was used as the cut off value of diagnosis,the sensitivity and specificity of IgG4for diagnosis were 95.7％ and 96.0％ respectively.The IgG4 levels in twelve patients with IgG-associated hepatobiliary diseases after 2 months of glucocorticoid therapy were significantly lower than those before glucocorticoid therapy (Z =-2.021,P =0.043).Conclusion The elevated serum IgG4 level may not be specific just for IgG4-related hepatobiliary diseases.The cut off value of 4.13 g/L should be very useful for diagnosing IgG4-related hepatobiliary diseases,differentiating from other hepatobiliary diseases and evaluating the therapeutic effect of glucocorticoid therapy.The further detailed verification for these findings should be necessary in clinical practice by increasing the sample size.

Epidemiological data,clinical observation and animal experiments have shown that cold wave is closely associated with the onset of stroke.When a population with stroke etiology or risk factors is under pre-stroke state,they will have stroke under the influence of various inducing factors.Cold wave is the external factor that causes the body to enter the pre-stroke state and there are many possible mechanisms.The drug intervention of stroke-prone hypertensive rats at 1 week before the cold wave can reduce the occurrence of stroke during cold wave,suggesting that it is of great significance to conduct preventive intervention to the pre-stroke population before the cold wave coming.

[Objective] To study the factors relative to the delayed diagnosis of spontaneous dual arteriovenous fistulas (DAVF) and its influence on the prognosis.[Methods] We included 102 continuous patients diagnosed DAVF in the First Affiliated Hospital of Sun Yat-sen University,and analyzed the correlative factors and impact on outcome of diagnostic delay.Outcome was whether symptoms were non-improvement,improvement or restoration at discharge.[Results] Median delay from onset to diagnosis was 3 months (interquartile range,1 to 6).Compared with patients diagnosed carlier(diagnose time≤3 months),patients diagnosed later (diagnose time ＞ 3 months) had a lower frequency of headache (P =0.012),ptosis (P =0.035) and parenchymal lesions (P =0.001),a higher frequency of conjunctival congestion (P =0.004),tinnitus (P =0.021),visual dysfunction (P ＜ 0.001),isolated visual dysfunction (P =0.007) and delayed imaging scan (P ＜ 0.001),a higher frequency of endovascular treatment,and a lower frequency of improvement or restoration at discharge (P =0.033),in which patients with visual dysfunction had a lower frequency of improvement or restoration than those without visual dysfunction (P =0.023).Compared to those with visual dysfunction and other symptoms,patients with isolated visual dysfunction had a higher frequency of onset with paroxysmal blurring or blinding (P ＜ 0.001),two eyes involved (P ＜ 0.001) and more severe visual loss (P =0.057),a higher frequency of draining into transversesigmoid sinus (P ＜ 0.001) instead of cavernous sinus (P ＜ 0.001),and suffered intracranial hypertension all (median intracranial pressure,405 mmH2O;interquartile range,370 ～ 512 mmH2O).However,no statistically significant differences were found in the frequency of improvement or restoration at discharge between two groups (P =0.739).[Conclusion] Diagnostic delay was considerable in this cohort and was associated with outcome,especially in patients with visual dysfunction.

Objective To optimize the method of isolating ,culturing and screening fetal mouse liver stem cells in vitro ,and to identify the potential of bi‐directional differentiation .Methods The fetal liver stem cells of mouse were isolated by the density gra‐dient centrifugation and cell difference adherence method ,the proliferation of stem cells was determined by cell plate cloning tech‐nique and MTT method;stem cells were induced for differentiation by adding DMSO and HGF .Results The isolated stem cells showed adherence within 24 h ,which were orbicular‐ovate ,closely packed ,activated within 1~2 weeks ;the positive rates of CD133 , CD49f and EPCAM were (97 .95 ± 1 .21)% ,(92 .71 ± 3 .49)% and (50 .73 ± 3 .45)% respectively ;AFP and CK19 proteins were expressed;red glycogen granules were seen by PAS after induced differentiation;ALB and HNF‐4αwere expressed .Conclusion Fe‐tal hepatic stem cells are successfully isolated by the density gradient centrifugation combined with difference adherence method ,and the isolated cells have strong stemness and proliferation ability ,as well as the ability of bi‐directional differentiation towards hepato‐cytes and bile duct epithelial cells .