Objective To investigate the safety and efficacy of flow-directed devices(flow diverter,FD)in the treatment of intracranial anterior cerebral artery aneurysms(ACAA).Methods The clinical data of 21 patients with ACAA,who were admitted to the Department of Neurointerventional Medicine of the First Affiliated Hospital of Zhengzhou University of China to receive FD treatment between February 2019 and August 2022,were retrospectively analyzed.After the treatment,O'Kelly Marotta(OKM)grading criteria was used to determine the degree of occlusion of the aneurysm,and the modified Rankin Scale(mRS)score was adopted to assess the clinical prognosis(0-2 points being defined as a good prognosis,and 3-5 points being defined as a poor prognosis).Results A total of 24 FD stents were implanted in 24 patients(24 aneurysms in total),and the technical success rate of stent implantation was 100％.During the perioperative period,complications occurred in 2 patients(8.3％),including hemorrhagic event(n=l)and ischemic event(n=l).The mRS score in all the 24 patients was ≤2 points.Follow-up imaging examination showed that OKM grade B was seen in 2 patients(8.3％),grade C in 6 patients(25％),and grade D(complete healing)in 16 patients(66.7％).Conclusion For the treatment of ACAA,the FD stent implantation is a safe and effective method.During the postoperative and the long-term follow-up period,neither serious ischemic or hemorrhagic complications nor neurological complications are observed.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

OBJECTIVE: To observe the effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle (LMM) in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy (PTED). METHODS: A total of 104 patients with lumbar disc herniation treated with PTED were randomly divided into an observation group (52 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). Patients of both groups received rehabilitation training of two weeks 48 h after PTED treatment. The observation group was treated with acupotomy (L₃-L₅ Jiaji [EX-B 2]) once within 24 h after PTED. In the two groups, the fat infiltration cross sectional area (CSA) of LMM was compared before and 6 months after PTED, the visual analogue scale (VAS) score and Oswestry disability index (ODI) score were observed before and 1, 6 months after PTED. The correlation between fat infiltration CSA of LMM in each segment and VAS score was analyzed. RESULTS: Six months after PTED, the fat infiltration CSA of LMM in L₄/L₅ and the total L₃-S₁ segments of the observation group was lower than that before PTED (P<0.05), and the fat infiltration CSA of LMM in L₄/L₅ of the observation group was lower than the control group (P<0.01). One month after PTED, the ODI and VAS scores of the two groups were lower than those before PTED (P<0.01), and those in the observation group were lower than the control group (P<0.05). Six months after PTED, the ODI and VAS scores of the two groups were lower than those before PTED and 1 month after PTED (P<0.01), and those in the observation group were lower than the control group (P<0.01). There was a positive correlation between the fat infiltration CSA of LMM in the total L₃-S₁ segments and VAS scores in the two groups before PTED (r = 0.64, P<0.01). Six months after PTED, there was no correlation between the fat infiltration CSA of LMM in each segment and VAS scores in the two groups (P>0.05). CONCLUSION Acupotomy can improve the fat infiltration degree of LMM, pain symptoms and activities of daily living in patients with lumbar disc herniation after PTED.
Humans ; Intervertebral Disc Displacement ; Activities of Daily Living ; Paraspinal Muscles ; Treatment Outcome ; Lumbar Vertebrae ; Retrospective Studies ; Endoscopy ; Diskectomy ; Acupuncture Therapy

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 Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective　To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy).　Methods　Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry.　Results　Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P<0.05). The expression of FABP4 mRNA (5.34±0.28) and the expression of FABP4 protein (11.94±0.22) in Hcy group were higher than those in control group (4.00±0.17, 5.10±0.20)(P<0.05). After infection with FABP4 adenovirus, the mRNA expression levels (3.05±0.22) and protein expression (4.07±0.20) of FABP4 in Ad-GFP group were not significantly different from those in control group (3.07±0.15, 3.93±0.15) (P>0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05).　FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05).　Conclusion　FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.
Animals ; Baroreflex ; physiology ; Blood Pressure ; drug effects ; Hypertension ; metabolism ; Hypoxia ; chemically induced ; Kidney ; drug effects ; metabolism ; Male ; Nitric Oxide Synthase Type I ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Solitary Nucleus ; metabolism

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
China ; Core Binding Factor Alpha 2 Subunit ; Humans ; Leukemia, Myeloid, Acute ; RUNX1 Translocation Partner 1 Protein ; Real-Time Polymerase Chain Reaction ; Transcription, Genetic ; WT1 Proteins

Objective To investigate the influence of body mass index(BMI) on the prognosis of patients who had received elective PCI.Methods The study population consisted of 2964 consecutive patients with electivePCIs performed between July 2009 and September 2011. The patients were divided into three groups based on their preoperative BMI levels:the normal group( BMI<24.0 kg/m2,n=810); the overweight group( 24.0 kg/m2≤BMI<28.0 kg/m2,n=1454) and the obese group(BMI≥28.0 kg/m2,n=700). We examined the association between baseline BMI levels and postoperative mortality through a mean(571.5±130.8)days of follow up.Results Patients with high BMI had a higher percentage of comorbidities compared with the normal BMI group. The results of multivariate Cox regression analysis revealed that preoperative BMI was inversely associated with mortality after adjustment for other factors (HR 0.896,95％ CI 0.821-0.977,P=0.031). Compared with the obese group, the hazard ratios for risk of mortality in the overweight and the normal groups were 1.908(95％CI 0.689-5.291,P=0.213) and 2.241(95％CI 1.154-4.350,P=0.017).Conclusions For patients undergoing elective PCI, individuals with obesity and overweight had the better prognosis than those with normal BMI.