This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in adolescents, with potential causes etiologies associated with mesenchymal stem cells, genetic factors, histological features, and biomechanical aspects. Biomechanically, the pelvis, serving as the central and majort load-bearing structure, exhibits morphological and alignment abnormalities highly correlated with the development of AIS. Recent studies have extensively explored three-dimensional pelvic parameters and kinematics, demonstrating that abnormal pelvic characteristics may contribute to AIS onset and progression and are increasingly incorporated into clinical interventions. This review summarizes sagittal and coronal features of the spine-pelvis, as well as the influence of three-dimensional kinematic features on the pathogenesis of AIS, providing insights for advancing the study of spine-pelvis features related to AIS.
Humans ; Scoliosis/pathology* ; Adolescent ; Spine/pathology* ; Pelvis/pathology* ; Biomechanical Phenomena

Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

OBJECTIVE: To systematically review the clinical efficacy of total ankle arthroplasty (TAA) and ankle arthrodesis (AA) in the treatment of end-stage ankle arthritis. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched for articles published in the treatment of end-stage ankle arthritis with AA or TAA from the establishment of the database to June 2021. Bias risk tool was used to evaluate the quality of the literature. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale(AOFAS), visual analog scale (VAS), ankle osteoarthritis scale(AOS), gait analysis (pace, frequency, stride), range of motion (ROM), satisfaction, complications and reoperation rate were analyzed by meta-analysis between AA and TAA groups by RevMan 5.3 software. RESULTS: A total of 12 articles were included, including 1 050 patients in the AA group and 3 760 patients in the TAA group, totaling 4 810 patients. Meta-analysis showed that the total score of AOFAS[MD=-3.12, 95%CI(-9.02, 2.96), P=0.31], pain score [MD=1.60, 95%CI(-1.35, 4.54), P=0.29], alignmentl score[MD=-0.04, 95%CI(-0.52, 0.44), P=0.88], VAS[MD=0.10, 95%CI(-0.49, 0.68), P=0.74], and AOS total score [MD=-4.01, 95%CI(-8.28, 0.25), P=0.06], the difference was not statistically significant (P>0.05). The score of AOFAS functional in TAA group was significantly higher than that in TAA group[MD=44.22, 95%CI(-8.01, -0.43), P=0.03]. There was no significant difference in gait analysis between the two groups (P>0.05). Postoperative ROM [MD=-4.93, 95%CI(-6.35, -3.52), P<0.000 01] and change in ROM from preoperative to follow-up[MD=-5.74, 95%CI(-8.88, -2.61), P=0.0003] between two groups, the difference was statistically significant. There was no significant difference in satisfaction between the two groups [OR=1.011, 95%CI(0.46, 2.23), P=0.98]. Complications [OR=1.61, 95%CI(1.26, 2.06), P=0.0002] and non-revision reoperation [OR=1.61, 95%CI(1.17, 2.21), P=0.003] were significantly lower in the TAA group than in the AA group. There was no significant difference in the rate of revision and reoperation(P>0.05) between the two groups [OR=1.02, 95%CI(0.37, 2.78), P=0.97]. CONCLUSION The clinical efficacy of AA is similar to that of TAA, but the non revision reoperation rate and main surgical complications of TAA are significantly reduced. Therefore, further high-quality methodological research and long-term follow-up are needed to confirm this conclusion.
Humans ; Ankle/surgery* ; Ankle Joint/surgery* ; Arthroplasty, Replacement, Ankle ; Treatment Outcome ; Osteoarthritis/surgery* ; Arthrodesis ; Retrospective Studies

OBJECTIVE: To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients. METHODS: Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression. RESULTS: Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05). CONCLUSION Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.
Humans ; Bone Marrow/pathology* ; Polycythemia Vera ; Hyperplasia/pathology* ; Granulocytes/pathology* ; Janus Kinase 2/genetics* ; Risk Factors ; Lipoproteins, LDL ; Polycythemia/pathology*

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Humans ; Pregnancy ; Female ; Hypertension, Pregnancy-Induced/diagnosis* ; Retrospective Studies ; Pre-Eclampsia/epidemiology* ; Risk Factors ; Incidence

RNA interference induced by small interfering (siR¬NA) has shown great potential in disease treatment.However, due to the poor stability of siRNA and lack of targeting, it is still challenging to deliver siRNA to target tissues/cells and induce gene silencing.Aptamer is a kind of oligonucleotide sequence that can specifically recognize the target.Covalently binding aptamers with siRNA or linking with other siRNA carriers can guide siRNA into target tissues/cells.In this review we summa¬ rize the research progress in the design strategy and application of aptamer-based targeted deliver)' of siRNA in the treatment of diseases in recent years, and discuss the challenges and pros-pects of aptamer-mediated siRNA deliver>r in clinical transforma¬tion.

Aim To investigate the effect of extracellular vesicles secreted by adipose tissue of mice on hippocampal neurons and cognitive behavior of mice with a high-fat diet.Methods Twenty C57BL/6J male mice were randomly divided into normal diet(ND)group(n=10)and high-fat diet(HFD)group(n=10), fed for 28 weeks.The weight of mice was recorded weekly.The level of fasting blood glucose, insulin and the insulin resistance index(HOMA-IR)of mice were tested at week 27.At week 28, the learning and memory abilities of mice were assessed by the Morris water maze.The morphological differences in adipose tissue were observed by HE staining, and the extracellular vesicles secreted from adipose tissue were quantified by TEM and NTA.Extracellular vesicles derived from adipose tissue labeled with PKH 67 were injected into normal mice via the tail vein, and after 30 h, the uptake of extracellular vesicles was detected in the hippocampal slice.The primary hippocampal neurons were treated with extracellular vesicles with the same amount of protein, and the effects of them on neuronal morphology and cell viability were observed.Results Compared with ND group, mice in HFD group were significantly heavier, with hyperglycemia, hyperinsulinemia and higher insulin resistance index.In the Morris water maze test, the HFD group showed a longer escape latency and less swimming time in the target zone.The volume of adipocytes and the amount of extracellular vesicles secreted from them significantly increased in HFD group.Extracellular vesicles secreted by adipose tissue could be internalized by both the primary hippocampal neurons and the hippocampal neurons in the normal mice.Compared with ND group, extracellular vesicles secreted by adipose tissue of the HFD group significantly reduced the length of primary hippocampal neuronal dendrites, the number of primary and secondary dendrites, and the cell viability of neuron cells.Conclusion Long-term high-fat diet could damage the hippocampal neurons by affecting the extracellular vesicles derived from adipose tissue.