BACKGROUND:Many studies have shown that total hip arthroplasty will improve low back pain in patients with hip-spine syndrome.However,there are few studies on the relationship between postoperative low back pain improvement and changes in spinal-pelvic sagittal parameters.This study aims to reveal their connections between the two. OBJECTIVE:To explore the relationship between the improvement of low back pain and changes in the spinal-pelvic sagittal parameters in patients with hip-spine syndrome after total hip arthroplasty. METHODS:A retrospective analysis was performed on the clinical and imaging data of 93 end-stage hip disease patients who underwent primary total hip arthroplasty and combined with low back pain and were admitted to Affiliated Hospital of Xuzhou Medical University from January 2019 to January 2022.Spinal-pelvic sagittal parameters were measured on lateral lumbar X-rays before surgery and 1 year at the last follow-up:pelvic incidence,pelvic tilt,sacral slope,lumbar lordosis,pelvic incidence-lumbar lordosis(difference between pelvic incident angle and lumbar lordosis angle).Visual analog scale score,Oswestry disability index,and hip Harris score were recorded before and 1 year after arthroplasty.The patients were divided into two groups according to whether the change in visual analog scale scores 1 year after surgery reached the minimal clinically important difference for low back pain treatment,including 45 cases in the low back pain unimproved group and 48 cases in the low back pain improved group.The preoperative general data of patients,differences in spinal-pelvic sagittal parameters,Oswestry Disability Index and hip Harris score before and after surgery were compared between the two groups. RESULTS AND CONCLUSION:(1)There was no significant difference in age,gender,surgical side,body mass index,and etiology between the two groups(P>0.05),and they were comparable.(2)There was no significant difference in visual analog scale scores before surgery(P>0.05).The visual analog scale scores of the low back pain improved group were lower than those of the low back pain unimproved group 1 year after surgery(P<0.01).(3)At 1 year after surgery,the lumbar lordosis of the low back pain unimproved group was significantly smaller than that before surgery,while the lumbar lordosis of the low back pain improved group was significantly smaller than that before surgery(P<0.01).At the same time,the pelvic incidence-lumbar lordosis mismatch in the low back pain unimproved group was greater than before surgery,while the pelvic incidence-lumbar lordosis mismatch in the low back pain improved group was smaller than before surgery,with significant differences between the two groups(P<0.01).There was no significant difference in the changes of other spinal-pelvic sagittal parameters between the two groups(P>0.05).(4)Preoperative lumbar Oswestry disability index and hip Harris score were not significantly different between the two groups(P>0.05).At 1 year after surgery,Oswestry disability index of the low back pain improved group was lower than that of the low back pain unimproved group and the hip Harris score was higher than that of the low back pain unimproved group(P<0.05).(5)The results showed that the improvement of low back pain was related to changes in spinal-pelvic sagittal parameters in patients with hip-spine syndrome after total hip arthroplasty,showing reduced lumbar lordosis and pelvic incidence-lumbar lordosis mismatch.Moreover,patients with improved low back pain after surgery had better functional scores,indicating that total hip arthroplasty improved spinal alignment and spinal-pelvic sagittal balance.For patients with hip-spine syndrome,a total hip arthroplasty performed before the onset of lumbar disease can have a favorable effect on the lumbar spine.

Objective To explore the effectiveness of building block assembly games in the upper limb functional exercise of school-aged children with peripherally inserted central catheter catheterization.Methods Using convenience sampling,90 catheterized children who met the inclusion criteria in the pediatric ward of a tertiary hospital in Henan Province from November 2022 to April 2023 were selected as research subjects.They were randomly divided into an experimental group and a control group,with 45 cases in each group.The experimental group participated in building block assembly games in addition to conventional ball-gripping exercises,while the control group engaged solely in conventional ball-gripping exercises.The compliance rates of upper limb exercises,time average peak flow rate of axillary vein of the catheterization side,and the incidence of catheter-related complications were compared between the 2 groups.Results During the study,2 cases in the experimental group and 3 in the control group dropped out,resulting in 43 cases in the experimental group and 42 in the control group.The compliance rate of upper limb exercises in the experimental group during hospitalization was 93.03％,significantly higher than 64.29％in the control group(P＜0.001).On the third day after catheterization,the time average peak flow rate of axillary vein of the catheterization side was(5.58±1.24)cm/s and(5.37±1.24)cm/s on the seventh day in the experimental group,compared to(3.87±1.06)cm/s and(3.56±0.81)cm/s,respectively,in the control group.These differences were statistically significant(P＜0.001).The incidence of catheter-related thrombosis in the experimental group was 4.65％,significantly lower than 21.43％in the control group(P=0.021).The rates of bleeding at the puncture site and catheter displacement in the experimental group were both 4.65％,compared to 7.14％and 4.76％,respectively,in the control group.These differences were not statistically significant(both P＞0.05).Conclusion Incorporating building block assembly games into routine ball-gripping exercises can improve the compliance of upper limb exercises in children with PICC placement,improve the blood flow velocity in the axillary vein of the catheterization upper limb,and reduce the incidence of catheter-related thrombosis,without increasing the risk of bleeding at the puncture site or catheter displacement.

Research on the participation of exosomes in pathogenesis and prognosis of multiple myeloma(MM)has made encouraging progress.However,the specific mechanism has not yet been clarified.Recently,domestic and foreign researchers have pressed forward on deeper study on exosomes.This article mainly summarizes the role of exosomes in the pathophysiological processes,such as bone marrow microenvironment changes,immunosuppression,myeloma bone disease generation and myeloma drug resistance,so as to provide new reference for further clinical research of exosomes as potential biomarkers for MM.

Objective:To explore the causal relationship between body mass index (BMI) and hypothyroidism using the two-sample Mendelian randomization model.Methods:A large-scale anthropometric genome-wide association study published in the GIANT database was used to select single nucleotide polymorphisms (SNPs) which were statistically significantly associated with BMI as an instrumental variable ( P<5×10 -8, linkage disequilibrium r 2<0.1). The causal relationship between BMI and hypothyroidism was determined by the inverse variance weighted (IVW), weighted median method and the MR-Egger method, respectively. A heterogeneity test, gene pleiotropy test, and sensitivity analysis were performed to evaluate the stability and reliability of the results. Results:A total of 89 SNPs related to BMI were screened out as instrumental variables. IVW analysis suggested that for every standard deviation increase in BMI, the risk of hypothyroidism increased by 0.9% (odd ratio ( OR)=1.009, 95% confidence interval ( CI): 1.006-1.012, P<0.001). Similar results were obtained with the weighted median method ( OR=1.007, 95% CI: 1.002-1.011, P=0.003) and the MR-Egger method ( OR=1.008, 95% CI: 1.001-1.015, P=0.006). The MR-Egger analysis showed that genetic pleiotropy did not bias the results (intercept=0.000 1, P=0.776), the one-by-one exclusion method did not show that a single instrumental variable SNP had a significant impact on the results, and the difference was not statistically significant ( P>0.05). Conclusion:Mendelian randomized analysis showed a positive causal relationship between BMI and hypothyroidism.

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.
Humans ; Rats ; Male ; Animals ; Interleukin-10 ; Rats, Sprague-Dawley ; Interleukin-4/metabolism* ; Bombyx ; Interleukin-6/metabolism* ; Microglia/metabolism* ; Saline Solution/metabolism* ; Reperfusion Injury/metabolism* ; Brain Ischemia/metabolism* ; Cerebral Infarction ; Reperfusion ; Neurons

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Sphingosine-1-phosphate (SIP) is an important bio- active phospholipid molecule, which is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis, myocardial ischemia and reperfusion injury, myocardial infarction, myocardial fibrosis and myocardial remodeling, and it plays a wide range of biological effects in human cardiovascular system.SIP acts mainly in the form of binding of sphingosine-1-phosphate receptor (SI Pits), selectively binding vascular endothelial cells and smooth muscle cells, which plays a role in the fight against cardiovascular diseases.This paper reviews the biological effects of SIP in cardiovascular system, i- dentifies effective targets in cardiovascular diseases, and alleviates the damage caused by SI P.aiming to provide new ideas for the study of SIP in cardiovascular direction.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

OBJECTIVE: To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL. METHODS: Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours. RESULTS: DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771). CONCLUSION DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.
Dimethyl Fumarate/pharmacology* ; HEK293 Cells ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; Ubiquitin-Protein Ligases