Objective To explore the predictive value of soluble fms-like tyrosine kinase-1(sFlt-1)and leukotriene B4(LTB4)in patients with intracranial aneurysms for cerebral vasospasm(CVS)after interventional embolization.Methods A total of 98 patients with intracranial aneurysms admitted to our hospital from January 2019 to September 2023 were regarded as the observation group,and were divided into the CVS group(32 cases)and the non CVS group(66 cases)according to whether CVS occurred or not within 3 to 5 days after surgery;102 healthy examinees in our hospital were selected as the control group.Enzyme-linked immunosorbent assay was used to detect serum levels of sFlt-1 and LTB4;the influencing factors for CVS after interventional embolization of intracranial aneurysms were analyzed by Logistic regression analysis;the predictive value of serum sFlt-1 and LTB4 levels for the occurrence of CVS after interventional embolization of intracranial aneurysms was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of sFlt-1 and LTB4 of patients in the observation group were obviously higher than those in the control group,and the differences were statistically significant(P<0.05).The serum levels of sFlt-1 and LTB4,and the proportions of patients with postoperative blood pressure fluctuation range≥30 mmHg and Hunt-Hess grade Ⅲ in the CVS group were obviously higher than those in the non CVS group,and the differences were statistically significant(P<0.05).SFlt-1(OR:2.985;95%CI:1.684 to 5.291)and LTB4(OR:2.868;95%CI:1.581 to 5.204)were the independent risk factors for CVS after interventional embolization of intracranial aneurysms(P<0.05).The area under the curve(AUC)of sFlt-1 and LTB4 alone and in combination for predicting the occurrence of CVS after interventional embolization of intracranial aneurysms were 0.839,0.825,and 0.915,respectively,with sensitivity of 84.44%,87.59%,and 81.36%,and specificity of 74.26%,75.87%,and 90.98%,respectively.The AUC of the combination of the two was higher than those of sFlt-1 and LTB4 alone,and the differences were statistically significant(Z=2.150,2.546,P<0.05).Conclusion The serum levels of sFlt-1 and LTB4 in patients with CVS after interventional embolization of intracranial aneurysms are increased,and the combination of the two can serve as the important indicators for predicting CVS.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective:To investigate the predictive value of platelet/lymphocyte ratio (PLR) for conversion surgery in patients with small bowel obstruction treated with intestinal obstruction catheter. Methods:The clinical data of patients with intestinal obstruction treated by intestinal obstruction catheter in the 900TH Hospital of Joint Logistics Support the Force were retrospectively collected. Logistic regression analyses were performed to identify independent predictors of conversion surgery. Restricted cubic spline (RCS) curves assessed the dose-response relationship between PLR and conversion surgery. Receiver operating characteristic (ROC) curves assessed the validity of the predictive model. Results:A total of 73 patients with small bowel obstruction treated conservatively with intestinal obstruction catheter were included and 25 (34.2％) patients were referred for surgical intervention after poor outcome of conservative treatment. Multivariate logistic regression analysis showed that PLR was an independent predictor of conversion surgery (P=0.032). The RCS analysis showed a non-linear correlation between a progressively higher risk of conversion surgery as the PLR increased. The ROC curves show that the incorporation of PLR into the prediction model significantly enhances its predictive efficacy (All P<0.05). Conclusion:PLR was found to be significantly associated with conversion surgery in small bowel obstruction patients treated with intestinal obstruction catheter,with a non-linear correlation. Incorporating PLR into the prediction model can significantly enhance the predictive efficacy,thus providing reference value for clinicians' decision-making.

Kidney is an essential organ in human body with multiple physiological functions. However, there is 10 % population worldwide with renal disease. It is urgent to generate a model which is more similar with kidney at structural and functional level to study renal disease. The rise of in vitro differentiation technology from pluripotent stem cells gives regeneration medicine and precise medicine new energy. This study mimics kidney development in vitro by inducing human pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into kidney progenitor cells, and further forming nephrons, which is the structure and function unit in kidney. Human pluripotent stem cells were differentiated into primitive streak through activating WNT pathway while inhibiting TGF-(B signaling. Afterward, the primitive streak spontaneously differentiated into intermediate mesoderm. Then, we induced intermediate mesoderm cells into kidney progenitor cells through FGF pathway. The FACS analysis data indicated kidney progenitor cells were up to 51. 5%-61. 9% in total cell population. Immuno-stai-ning results showed these structures contained podocytes of glomerulus, proximal tubule, and distal tubule. This kidney differentiation protocol is stable, high-efficient, and well repeatable. This research provides a novel platform for early human kidney development study, kidney disease modeling, and drug screening.

Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.
Artificial Intelligence ; Data Warehousing ; Humans ; Tetanus ; Tetanus Toxoid ; Whooping Cough/prevention & control*

OBJECTIVE: To study the inhibitory effect of HDAC6 on proliferation of human leukemia KG1α and to explore its mechanism by ERK signaling pathways. METHODS: .The siRNA interference technology was used to inhibit the HDAC6 gene expression; the expression of HDAC6 and prateins of ERK signal pathway was detected by Western blot; the cell proliferation ability was detected by colony forming experiment and trypan blue staining; cell cycle was detected by FCM; and the expression of Ki67 was detected by immunofluorescence. RESULTS: Western blot showed that HDAC6 expression was up-regulated in leukemia cell lines in comparison with the healthy volunteers and bone marrow stromal cells (P＜0.05). Knockdown of HDAC6 significantly inhibited the proliferation and colony formation ability of leukemia cells, promoted cell arrest at G/G phase. The Western blot and immunefluorescence showed that knockdown of HDAC6 suppressed the expression level of Ki67, CDK4, Cyclin D1 and enhanced the expression level of p16, p21, p-ERK (P＜0.05). CONCLUSION Knockdown of HDAC6 significantly inhibits the proliferation, arrest the cell cycle at G/G phase, and its mechanism probably relates with the activation of ERK signaling pathway.

OBJECTIVE: To retrospectively analyze the risk factors of avascular necrosis of femoral head (ANFH) after internal fixation in young and mid-aged adults. METHODS: From January 2007 to December 2017, femoral neck fracture patients (18-60 years old) treated by reduction and internal fixation were retrospectively studied in Peking University Third Hospital. We recorded their gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) grade, reason of injury, fracture side, interval between injury and surgery, location of fracture line, Garden classification, Pauwels classification, reduction method (open or closed), internal fixation and reduction quality. The diagnosis of ANFH was confirmed based on X-ray and MRI images during the follow-up. The internal fixation method included cannulated compression screw (CCS) or dynamic hip screw (DHS, with or without anti-rotation screw). χ² test and Logistic regression analysis were used to analyze the relationship between the various factors and postoperative ANFH. RESULTS: A total of 113 patients were included in this study, including 63 males and 50 females with an average age of (43.17 ± 12.34) years. They were followed up by (25.08 ± 16.17) months. ASA grade included grade I (21 cases), grade II (55 cases) and grade III (37 cases). The reasons of injury included low-energy trauma (76 cases) and high-energy (37 cases). The fracture line included subcapital type (37 cases), transverse type (74 cases) and basal type (2 cases). Garden classification included type I (3 cases), type II (46 cases), type III (39 cases) and type IV (25 cases). Pauwels classification included type I (21 cases), type II (55 cases) and type III (37 cases). Interval between injury and surgery was (3.88 ± 3.66) days, 108 patients and 5 patients performed closed and open reduction respectively. 63 patients performed CCS, and 50 patients performed DHS. The reduction quality included grade A (91 cases), grade B (18 cases) and grade C (4 cases). 18 patients developed ANFH after surgery, the incidence rate was 15.93% (18/113). The result of χ² test showed the reason of injury (OR=0.19, P < 0.01), Garden classification (OR=0.13, P < 0.01), Pauwels classification (OR=0.12, P = 0.02), internal fixation method (OR=3.29, P = 0.04) and reduction quality (OR=0.33, P < 0.01) were significantly associated with ANFH. These five factors were further included into the Logistic regression analysis, and its results showed that the reason of injury (OR=4.11, P = 0.03) and Garden classification (OR=4.85, P = 0.04) were statistically significant. CONCLUSION The reason of injury, Garden classification, Pauwels classification, internal fixation and reduction quality may increase the risk of ANFH after surgery, and the reason of injury and Garden classification were much more significant.
Adolescent ; Adult ; Female ; Femoral Neck Fractures ; Femur Head Necrosis ; Fracture Fixation, Internal ; Fracture Healing ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVE: To understand the differentiation of mesoderm-derived Flk1 cells on different locations of the early mouse embryonic development and to explore the potential of Flk1 cells to differentiate into mesenchymal lineage, like pericytes during vascular development. METHODS: Based on the Cre-LoxP system conditional knockout study strategy, the Flk1-Cre mice and ROSA26 reporter mice were used for lineage-tracing studies. The fate of the Flk1 progenitor cells was traced with the GFP population. The detection of mesoderm marker Flk1, hematopoietic cell-specific marker CD45, endothelial cell-specific markers CD31, CD144, and Emcn (endomucin), pericyte specific markers PDGFRβ and NG2, using the methods of immunohistochemistry, immunofluorescence, and flow cytometry should be combined to solve the concerned problems. RESULTS: Immunohistochemical staining of different fractions of E8.5-10.5 in the early embryogenesis of Flk1-Cre; ROSA26-EYFP mouse lineage showed that there were multiple populations in the Flk1 cell-derived GFP population surrounding hematopoietic sites, such as dorsal aortas, limb buds and yolk sac. In addition to hematopoietic cells, the CD31/Emcn typical endothelial cells distributed specifically along the blood vessel wall, there were many types of cell populations, such as mesenchymal-like cells. The immunofluorescence demonstrated that the cells of this group are neither hematopoietic, non-endothelial cells around the blood vessels, which are NG2+ pericytes. FACS analysis also confirmed that Flk1 cells contributed to pericytes. In addition, in different hematopoietic sites of the embryo, a small population of CD31+CD140B+ cell populations with a mesenchymal-like morphology was observed in the GFP population. CONCLUSION In the early stages of embryogenesis, mesoderm-derived Flk1 populations not only contribute to hematopoietic, endothelial, and muscle lineages, but also have a differentiation potential for mesenchymal lineage, like pericytes. The presumably observed CD31CD140B cell population may be a group of endothelial cells differentiated from Flk1 progenitor cells and undergoing an endothelium-to-mesenchymal transition, EndMT, gradually losing the endothelial surface-specific marker and also starting to express a pericyte surface-specific marker.
Animals ; Cell Differentiation ; Cell Lineage ; Mesoderm ; Mice ; Stem Cells ; Vascular Endothelial Growth Factor Receptor-2 ; Yolk Sac

Objective To investigate the efficacy of unicompartmental knee arthroplasty(UKA) on treating elderly patients with knee osteoarthritis in comparison with total knee arthroplasty(TKA),and discuss the indications of the procedure.Methods The clinical data of elderly patients(≥75 years) undergoing UKA in our institute from October 2011 to May 2015 were retrospectively reviewed.Patients treated with UKA were in UKA group.Patients who had no significant difference in the age,gender,BMI (body mass index) and HSS (hospital for special surgery) compared with UKA group and received TKA were selected as TKA group.The outcomes were assessed by HSS and satisfaction score(range,0 ～ 10).Results A total of 29 cases (41 knees) of UKA group were followed up for (30.3 ± 13.6) months (13 ～49 months),29 cases(39 knees) of TKA group.The postoperative HSS(P =0.00),surgery time(P =0.00),perioperative hemorrhage(P =0.00),hospital stay(P =0.04) and satisfaction(P =0.03) of UKA group were all better than those of TKA group.The pain location of the knee (P =0.86) and patellofemoral degeneration (P =0.24) did not affect the postoperative outcomes,11 knees presented with varus ＞ 15° with an average angle of 18.4 ° (15.7 ° ～ 20.1 °),4 knees were with flexion contracture ＞ 15 °,averaging at 18.8 ° (17.7 ° ～ 20.1 °),range of motion measured ＜ 100° in 6 knees with an average range of 79.0° (66.8° ～ 92.1 °).The aforementioned abnormalities were effectively corrected under anesthesia,the range of motion inproved significantly,but there was no significant difference in postoperative HSS among these patients (P =0.85).One case of UKA group had wound dehiscence and superficial infection,recovery occurred after debridement and suturing.Conclusion UKA is effective for elderly patients with satisfactory outcomes,which is superior to TKA with respect to trauma control and preservation of the limb function.Medial patellofemoral degeneration poses no negative effect on postoperative outcomes,medium knee varus (≤20°) and flexion contracture(≤20°) that are corrective under anesthesia among elderly patients might not be considered as contraindications for UKA.

AIM:To investigate the expression and localization of autophagy related protein microtublule associated protein 1 light chain 3 (LC3) at various stages of follicular development and atresia in the mice.METHODS:On 0,1,2,3,4 and 5 day after intraperitoneal injection of pregnant mare serum gonadotropin (PMSG),expression and positioning situation of autophagy related protein LC3 and apoptosis related protein cleaved caspase-3 were examined by the method of immunohistochemical staining.The protein levels of cleaved caspase-3 and LC3 were determined by Western blot in cultured mouse granulosa cells after incubation under serum-free conditions in the absence or presence of FSH.LC3 subcellular localization in granulosa cells were studied by the method of immunofluorescence.RESULTS:The LC3 protein expressed in granulosa cells during all developmental stages mainly.Granulosa cells of atretic follicles that showed intense staining of cleaved caspase-3 and LC3.The protein levels of cleaved caspase-3 and LC3-Ⅱ in the granulosa cells significantly decreased at 1 d and 2 d after intraperitoneal injection of PMSG (P ＜ 0.05).The protein levels of cleaved caspase3 and LC3-Ⅱ in the granulosa cells increased in turn on 3,4 and 5 day after intraperitoneal injection of PMSG.The positive correlation between LC3-Ⅱ and cleaved caspase-3 protein levels was observed (r2 =0.8299,P ＜ 0.05).The LC3-Ⅱ protein expressed with punctuate structures in granulosa cell cytoplasm cultured under serum-free conditions in the presence of FSH.CONCLUSION:LC3 is expressed in the follicular granulosa cells with cell specificity and regional specificity.Autophagy is induced mainly in granulosa cells during folliculogenesis and shows positive correlation with apoptosis.Ovarian granulosa cell autophagy and apoptosis are gonadotropic hormone dependent.