Objective To establish a predictive model using multiple layer perceptron (MLP) for short-term outcome after subacute ischemic stroke.Methods From January, 2019 to September, 2021, 60 readmission-inpatients in Department of Rehabilitation, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were collected the clinical features of first admission (less than 30 days after attack), and the outcomes were assessed with modified Rankin Scale (MRS) three months after the first admission. The risk factors were screened with single factor analysis, and the short-term outcome predictive models were established with multi-factor Logistic regression and MLP. The predictive accuracy of both models was calculated, and the predictive effects were compared with Receiver Operating Characteristic (ROC) curve.Results For multi-factor Logistic regression, the predictive accuracy was 73.3%, and the area under ROC curve was 0.851. For MLP, the predictive accuracy was 88.9%, and the area under the ROC curve was 0.930.Conclusion The prediction of short-term outcome after subacute ischemic stroke can be done with MLP model.

OBJECTIVE: To analyze characteristics and related factors of the plantar pressure during the level walking and single leg standing in the chronic ankle instability (CAI) individuals. METHODS: From April 2019, 75 CAI individuals and 40 healthy individuals were enrolled in this study. Both of the static and dynamic plantar pressure were measured during six times level walking and three times single leg standing testing. The data including peak force, time to peak force in various foot contact areas and the time to boundary (TTB) and velocity of center of pressure (COP) were measured and compared between the affected side and the unaffected side and between the CAI cases and the healthy individuals. The correlations between the plantar pressure and the gender, Beighton score, affected side and body mass index (BMI) were analyzed. RESULTS: The characteristics of plantar pressure distribution in the CAI individuals included: (1) During the level walking, the affected side showed the similar pressure contribution as the unaffected side (P>0.05). While compared with healthy individuals, there was a significantly higher peak force in the 5th metatarsal area (t=-3.86, P=0.03) of the affected side, lower peak force in the 1st (t=2.99, P=0.02), 2nd metatarsal head areas (t=2.09, P=0.01) of the affected side, medial hindfoot areas of both sides (affected, t=2.33, P=0.01; unaffected, t=3.74, P=0.02) and toes areass of both sides (affected, t=2.23, P=0.01; unaffected, t=3.28, P=0.02) and a delay to peak force in the 4th metatarsal head area (t=3.33, P=0.01) of the affected side. (2) During the single leg standing, the CAI individuals showed significantly worse balance control in the anterior/posterior direction (P < 0.05) and lateral/medial direction (P < 0.05) compared with the healthy controls, and the affected side had more severe balance control deficit in the lateral/medial direction (P < 0.05). (3) The women (P < 0.05) and the individuals with higher Beighton scores (P < 0.05) showed worse balance control deficit in the lateral/medial direction. CONCLUSION CAI individuals showed significantly a more lateral shifted plantar distribution during the level walking compared with the healthy individuals and the tendency was worse on the affected sides, and showed worse balance control in the anterior/posterior direction and lateral/medial direction during the single leg standing. The women and those with generalized ligament laxity showed significantly worse balance control.
Ankle ; Ankle Joint ; Case-Control Studies ; Female ; Foot ; Humans ; Joint Instability

OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

BACKGROUNDThe molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family.

METHODSA series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested.

RESULTSThe pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls.

CONCLUSIONSA nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.

Asian Continental Ancestry Group ; Child ; Deafness ; genetics ; Female ; Genetic Predisposition to Disease ; Hearing Loss ; genetics ; Humans ; Male ; Mutation ; genetics ; POU Domain Factors ; genetics ; Pedigree

Objective To explore the expressions of Bcl-2 and Bax proteins in the neurons of spinal cord after tibial nerve and common peroneal nerve injuries in rats.Methods A total of 90 male SD rats were randomly divided into three groups, the group A was as control group, group B as suture of tibial nerve cut group, and group C as suture of the common peroneal nerve cut group.The L4-6 segment spinal cord of the rats were removed for HE staining and immumohistochemical staining on 3, 7, 14, 28 days after the operation.The number of motor neurons in the spinal anterior horn were calculated.The expressions differences of Bcl-2 and Bax proteins were detected by immuno-histochemistry, and values of Bcl-2/Bax were calculated.Results The number of motor neurons in the anterior horn of spinal cord in group B were less than that in group C on 1, 3, 7, 14, 28 days after the operation (P< 0.01).The expression of Bcl-2 protein in group B and group C showed an upward and then declining trend.It decreased to the lowest on the postoperative 3 d in group B and 7 d in group C, respectively.The expressions of Bax protein in group B and C showed an upward and then declining trend, and it increased to the highest on the postoperative 3 d in groups B and C.The values of Bcl-2/Bax in groups B and C were showed an decreased and then increased trend and it was lower in group B than group C on the postoperative 3, 7, 14, 28 d(P< 0.01).Conclusion Injuries of tibial nerve and common peroneal nerve of the rats would lead the apoptosis of motor neurons in the spinal cord, but compared with the injury of common peroneal nerve, tibial nerve injury would lead less apoptosis of motor neurons.

Objective To explore the expressions of Bcl-2 and Bax proteins in the neurons of spinal cord after tibial nerve and common peroneal nerve injuries in rats.Methods A total of 90 male SD rats were randomly divided into three groups, the group A was as control group, group B as suture of tibial nerve cut group, and group C as suture of the common peroneal nerve cut group.The L4-6 segment spinal cord of the rats were removed for HE staining and immumohistochemical staining on 3, 7, 14, 28 days after the operation.The number of motor neurons in the spinal anterior horn were calculated.The expressions differences of Bcl-2 and Bax proteins were detected by immuno-histochemistry, and values of Bcl-2/Bax were calculated.Results The number of motor neurons in the anterior horn of spinal cord in group B were less than that in group C on 1, 3, 7, 14, 28 days after the operation (P< 0.01).The expression of Bcl-2 protein in group B and group C showed an upward and then declining trend.It decreased to the lowest on the postoperative 3 d in group B and 7 d in group C, respectively.The expressions of Bax protein in group B and C showed an upward and then declining trend, and it increased to the highest on the postoperative 3 d in groups B and C.The values of Bcl-2/Bax in groups B and C were showed an decreased and then increased trend and it was lower in group B than group C on the postoperative 3, 7, 14, 28 d(P< 0.01).Conclusion Injuries of tibial nerve and common peroneal nerve of the rats would lead the apoptosis of motor neurons in the spinal cord, but compared with the injury of common peroneal nerve, tibial nerve injury would lead less apoptosis of motor neurons.

OBJECTIVETo investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation.

METHODSThe expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA).

RESULTSExpression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples.

CONCLUSIONThe loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

Animals ; Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Down-Regulation ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Mice, Nude ; PTEN Phosphohydrolase ; genetics ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Transfection ; Up-Regulation ; Xenograft Model Antitumor Assays

OBJECTIVETo study relationships between serum ferritin and bone metabolism in patients with hip fragility fractures.

METHODSThis cross-sectional study included 76 postmenopausal women with hip fracture from Feburary 2011 to June 2012. The mean age of the women was (73 ± 10) years (range, 55-93 years) and the mean duration of menstruation was (22 ± 10)years (range, 5-50 years). Serum concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino-terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of type I collagen (β-CTX)and femoral and lumbar bone mineral density by dual-energy X-ray absorptiometry were measured. Bone metabolism was compared between normal and elevated ferritin groups with t-test, Pearson linear, partial correlation and multiple regression analysis examined associations between iron- and bone-related markers.

RESULTSSerum ferritin concentration raised to (230 ± 146)µg/L, transferrin concentration reduced to (1.89 ± 0.33)g/L. P1NP concentration raised to (61 ± 32) ng/L when the concentration of serum ALP and β-CTX were in the normal range. T-scores for bone mineral density in the femoral neck (-2.0 ± 1.1) and lumbar (-2.1 ± 1.2) were below the normal ranges(-1.0-1.0). The subjects were divided into two groups according to serum ferritin concentration, normal group(serum ferritin concentration ≤ 150 µg/L, n = 25) and elevated group(serum ferritin concentration > 150 µg/L, n = 51). Patients of elevated group had lower bone mineral density in femoral neck and lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, β-CTX concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis adjusted for confounders, serum ferritin concentration was correlated negatively with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P < 0.05), and positively with P1NP and β-CTX (r = 0.467,0.414, P < 0.05), but not correlated with ALP (r = 0.188, P > 0.05). Transferrin concentration tended to be correlated positively with bone mineral density in both femoral neck and lumbar (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and β-CTX(r = -0.326,-0.285,-0.278, P < 0.05).

CONCLUSIONSIron overload has a high prevalence in postmenopausal women with fragility fracture. Increased iron stores, which might lead to bone loss and lower bone mineral density by enhancing the activity of bone turnover, could be an independent factor to take effects on bone metabolism on postmenopausal women.

Aged ; Aged, 80 and over ; Bone Density ; Bone Remodeling ; Collagen Type I ; blood ; Cross-Sectional Studies ; Female ; Hip Fractures ; metabolism ; Humans ; Iron Overload ; Iron-Binding Proteins ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; metabolism ; Postmenopause ; Retrospective Studies

OBJECTIVETo explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications.

METHODSRecruited 40 Goto-Kakisaki (GK) Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil, and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight, and then, by blood glucose level from high to low, randomly divided into the DGR group (at the daily dose of 8 mL/kg), the metformin group (MET, at the daily dose of 150 mg/kg), the simvastatin group (SIM, at the daily dose of 2 mg/kg), and the model group (MOD, fed with pure water, at the daily dose of 8 mL/kg) according to the random number table, 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose (FBG) and body weight were monitored. The HbA1c, TC, LDL-C, HDL-C, TG, serum ROS were determined. The aortic NF-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (P65) mRNA in the aorta was detected with Real-time PCR.

RESULTSThe body weight in the normal control group was eventually heavier than others (P < 0.01). There was no difference among the four groups of GK modeled rats (P > 0.05). The FBG in the four GK modeled groups were higher than that in the normal control group (P < 0.01, P < 0.05). There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups (P > 0.05). The last FBG level was obviously lower in the MET and DGR groups than in the MOD group (P < 0.01) and the SIM group (P < 0.05). Twenty-four weeks after intervention, the level of FBG, HbA1c, TC, LDL-C, HDL-C, and NF-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB mRNA expression in the thoracic aorta in the MOD group, the MET group, and the DGR group were significantly higher than those in the normal control group (P < 0.01, P < 0.05). The TG level, serum ROS in the MET, DGR, and SIM groups, and the NF-kappaB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group (P < 0.01, P < 0.05). The levels of FBG, TC, LDL-C, serum ROS, NF-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB positive expression rate in the DGR and MET groups, and the levels of HbA1c, TG in the DGR group were significantly lower than those in the MOD group (P < 0.01, P < 0.05). The level of FBG in the MET and DGR groups were lower than that in the SIM group (P < 0.05). The level of NF-kappaB mRNA expression in the thoracic aorta of the SIM and DGR groups, and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group (P < 0.01).

CONCLUSIONDGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids, as well as down-regulating oxidative stress.

Animals ; Aorta, Thoracic ; metabolism ; Atherosclerosis ; complications ; drug therapy ; metabolism ; Blood Glucose ; analysis ; Diabetic Angiopathies ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Lipid Metabolism ; Male ; NF-kappa B ; metabolism ; Oxidative Stress ; Phytotherapy ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; blood

A total of 127 type 2 diabetic patients were divided into low glycemic index meal replacements (intervention) group and standard food-based diet (reference) group in an experiment for 12 weeks.The results showed that fasting plasma glucose,postprandial 2 h plasma glucose,fasting insulin,and homeostasis model assessment insulin resistance(HOMA-IR) in the intervention group decreased significantly after 12 weeks trial ( P＜0.05 or P＜0.01 ).However,there were no significant changes in lipid profile and HbA1C in intervention group.In addition,percentage of body fatty,visceral fatty area,and waist-hip ratio also decreased in intervention group( all P＜0.01 ).Superoxide dismutase and glutathione levels increased significantly in intervention group by the end of trial (both P＜0.01 ),while malondialdehyde was decreased (P＜0.01 ).There were no significant changes in the aforementioned indices in the reference group.Weight,body mass index,and waist circumferences were decreased in both groups,but without significant difference between the two groups.