BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

ObjectiveTo examine the protective mechanism of wogonin in SH-SY5Y cells cultured in the conditioned media with lipopolysaccharide （LPS）-induced BV-2 microglia. MethodBV-2 microglia were divided into the blank group， LPS group， low concentration group of wogonin （4 μmol∙L^-1）， medium concentration group of wogonin （8 μmol∙L^-1）， and high concentration group of wogonin （16 μmol∙L^-1）. The LPS group was given 1 mg·L^-1 LPS， and the other three groups were treated with the corresponding concentration of wogonin for 4 h and then given 1 mg·L^-1 LPS. The conditioned media from these groups were used to cultivate SH-SY5Y cells. Cell counting kit-8 （CCK-8） was used to assess the vitality of BV-2 cells in the above groups. The contents of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） in the supernatant of BV-2 cells were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of tyrosine hydroxylase （TH） and α-Synuclein （α-Syn） in SH-SY5Y cells was detected by immunohistochemical staining （IHC）. The nuclear transfer and fluorescence expression intensity of nuclear transcription factor-κB p65 （NF-κB p65） protein in SH-SY5Y cells were detected by immunofluorescence staining （IF）. Western blot was used to detect the expression of Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/NF-κB pathway-related proteins in SH-SY5Y cells. ResultThe levels of IL-6 and TNF-α in the supernatant of BV-2 cells in the LPS group were significantly higher than those in the blank group （P<0.01）. Compared with those in the LPS group， the IL-6 content of BV-2 cells in the low concentration group of wogonin was statistically significantly lower （P<0.05）， whereas the IL-6 and TNF-α contents of the medium and high concentration groups of wogonin were statistically lower （P<0.05，P<0.01）. The IL-6 and TNF-α contents in the high concentration group of wogonin decreased most significantly （P<0.01）， and the intervention effect was the best. Compared with that in the blank group， the expression of α-Syn protein in SH-SY5Y cells cultured with conditioned media in the LPS group was significantly increased， and the expression of TH protein was significantly decreased （P<0.05）. Compared with that in the LPS group， α-Syn protein expression in the medium and high concentration groups of wogonin showed a decreasing trend （P<0.05， P<0.01）. TH protein expression was increased in the low， medium， and high concentration groups of wogonin （P<0.05， P<0.01）. Compared with the blank group， NF-κB p65 protein gradually accumulated into the nucleus， and the fluorescence expression intensity was significantly enhanced （P<0.01）. Compared with the LPS group， the NF-κB p65 protein was gradually dispersed outside the nucleus， and the fluorescence expression intensity was gradually weakened in all concentration groups of wogonin. The fluorescence intensity in the high concentration group of wogonin was significantly reduced （P<0.01）. Compared with those in the blank group， the expression levels of TLR4 protein， phosphorylated（p）-NF-κB p65 protein， and MyD88 protein in the LPS group were significantly increased （P<0.05， P<0.01）. Compared with those in the LPS group， the expressions of TLR4 protein， p-NF-κB p65 protein， and MyD88 protein in the medium concentration group of wogonin were all significantly decreased （P<0.05， P<0.01）. The expressions of TLR4 protein， and MyD88 protein in the high concentration group of wogonin were significantly decreased （P<0.05， P<0.01）. ConclusionWogonin may regulate the TLR4/MyD88/NF-κB signaling pathway to inhibit the release of LPS-induced inflammatory factors in BV-2 microglia and protect SH-SY5Y cells， thereby reducing inflammation and achieving neuroprotective effects.

Objective:To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD.Methods:It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication.Results:A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention.Conclusions:Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.

Objective To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology,which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails'entry point,and to verify its clinical value through clinical tests.Methods After matching the locating module with the developing board,which are the two components of the locating device,they were placed on the skin surface of the proximal femur of the affected side.Anteroposterior fluoroscopy was performed.The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image,and then the yaw angle of the locating module was reset to zero.After resetting,the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire.The ideal direction of entry point was accurately located based on the angle guidance.By setting up an experimental group and a control group for clinical surgical operations,the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss with or without the locating device was recorded.Results Compared to the control group,the experimental group showed significant improvement in the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss,with a statistically significant difference(P<0.01).Conclusion The locating device can assist doctors in quickly locating the entry point of intramedullary nail,effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot,improving surgical efficiency,and possessing certain clinical value.

Objective:To explore the relationship between the long-term dynamic change in alanine aminotransferase(ALT) level and metabolic associated fatty liver disease(MAFLD).Methods:A retrospective study was conducted on 6 864 subjects who underwent four consecutive physical examinations from 2017 to 2020 in a cohort study of physical examination population in Henan Province. The relation between ALT level and the shift of MAFLD risk was analyzed using a multi-state Markov model, and the bidirectional relationship between ALT level and MAFLD was explored using a random intercept cross-lagged model.Results:Multi-state Markov model after adjusting for confounding factors showed that the risk of MAFLD in ALT Q2, Q3, Q4 group was gradually higher than that in Q1 group; Compared with health status, non-alcoholic fatty liver disease and MAFLD status gradually increased the risk of ALT shifting from normal to abnormal. The random intercept cross-lagged model after adjusting for confounding factors showed that there was a significant positive bidirectional relationship between MAFLD and ALT level. The cross-lag effect of MAFLD→ALT level was 0.083(95% CI 0.078-0.087), and the cross-lag effect of ALT→MAFLD was 0.044(95% CI 0.039-0.050). And with the extension of time, the cross-lag effect gradually decreased. Conclusions:There is a significant bidirectional relationship between the long-term dynamic change of ALT level and MAFLD. The occurrence of MAFLD is more likely to increase the risk of elevated ALT level, emphasizing the need for enhanced early prevention and treatment of MAFLD.

Objective:To explore the effectiveness of the Exowalk gait training robot in improving the walking ability of stroke survivors.Methods:Forty stroke survivors were randomly divided into a control group and an experimental group, each of 20. In their rehabilitation, the control group was given routine walking training, while the experimental group′s training was assisted with the Exowalk robot. Both groups trained for 60 minutes a day, five days a week for four weeks. Before as well as after 2 and 4 weeks of training functional ambulatory categories (FACs), the Berg balance scale (BBS), the 6-minute walking test (6MWT), the 10-minute walking test (10MWT), the Rivermead mobility index and an exercise index were used to evaluate those in both groups.Results:After 2 weeks significant improvement was observed in the average FAC, BBS, 6MWT and 10MWT results of both groups, without significant differences between them. After 4 weeks there was still no significant difference in the groups′ average BBS scores. However, the average FAC rating in the experimental group had improved significantly while there was no significant increase in the control group′s average score.Conclusions:The Exowalk robot can help to improve the balance and walking ability of hemiplegic stroke survivors.

Objective:To determine any effect of repeated thermal stimulation on the viability and functioning of inflamed human umbilical vein endothelial cells (HUVECs).Methods:Well-cultured HUVECs were divided into a normal group, a model group, a thermal stimulation 5 times group (group A), a thermal stimulation 9 times group (group B) and a thermal stimulation 13 times group (group C) and cultured under the same conditions. The normal group was not given any intervention. The model group was stimulated with 1μg/mL lipopolysaccharide for 1 hour. Groups A, B and C were first subjected to 5, 9 and 13 rounds of repeated thermal stimulation, each round lasting 4 minutes at 43℃ and 1 minute at room temperature. They were then incubated for one hour at 37℃ under a 5% CO 2 atmosphere with 1μg/mL lipopolysaccharide. Cell viability and the expression of NF-κB were evaluated using methyl thiazolyl tetrazolium and immunofluorescence assays. The levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined by enzyme-linked immunosorbent assay. Results:After the intervention, the average cell viability of the model group and of groups A and C was significantly lower than that of the normal group, while that of group B was significantly higher. After the intervention, the average NF-κB expression in the normal group was significantly different from that in the others, with group B′s level significantly different from that of the model group. After the treatment, the average expression of ICAM-1 and VCAM-1 in the model group had increased significantly, while that in groups A, B and C had decreased significantly compared with the normal group. The levels of groups A, B and C were then significantly different from that of the model group. The average ICAM-1 level of group B was significantly different from those of groups A and C.Conclusions:Repeated thermal stimulation can protect inflamed HUVECs and reduce the expression of HUVEC adhesion molecules.

Objective To systematically review the efficacy and safety of Jinlian Qingre Effervescent Tablet (JQET) compared to Ribavirin for acute upper respiratory tract infection in children.Methods CNKJ,CBM,WanFang Data,VIP,PubMed,EM base,Web of science,and Cochrane Library databases were searched from the date of establishment to December 2016 for all randomized controlled trials (RCTs) and quasi-RCT on the use of JQET in children with acute respiratory infections.Meta-analysis by using Rev Man 5.3.Results A total of seven RCTs involving 782 patients were included,while the group of JQET involving 392 patients,Ribavirin involving 390 patients.The results ofmeta-analysis indicated that the efficacy in Jinlianqingre group was superior to that of Ribavirin control group,such as clinical effectiveness [RR=l.26,95％CI=(1.18,1.34),P＜0.000 01],fever subsidence time [MD=-1.54,95％CI (-1.79,-1.30),P＜0.000 01],the time of subsided cough [MD=-1.53,95％CI (-1.79,-1.27),P＜0.000 01],the disappearance time of pharyngalgia [MD=-1.29,95％CI (-1.88,-0.70),P＜0.000 1],and Pharyngeal congestion disappearance time [MD=-2.80,95％CI(-3.11,-2.49),P＜0.000 01].The difference was statistically significant.There were three adverse reactions reported in JQET group.Conclusion JQET is superior to the Ribavirin control group in clinical effectiveness,fever subsidence time,time of subsided cough,disappearance time of pharyngalgia,and pharyngeal congestion disappearance time to treat acute upper respiratory tract infection in children.However,these results should be carefully interpreted,and this conclusion has to be further verified by high quality,large scale RCTs.

Aim To investigate the preventive effect of Polygonum Multiflorum (PM)on the deteriorated mi-cro-structure and biomechanical properties induced by prednisone.Methods Ninety 6-month-old male Sprague-Dawley rats were randomly divided into nine groups,which were control,prednisone,CAL,30%ethanol eluent of the PM(H,M,L),PM(H,M,L). Prednisone was gavaged to rat for 21 weeks as model group of osteoporosis.Meanwhile,tested herbal ab-stract were orally administrated to the modeled rats in-duced by prednisone.At the end of the experiment, the right femur was collected for micro-CT scanning, three-dimensional reconstruction and biomechanical test.Results Compared with the control group,mod-el group showed destruction of bone microarchitecture, BV /TV fell 28.6%(P <0.05),bone biomechanical parameters decreases,and stiffness fell 29.7%(P <0.01 ). Compared with the model group, positive group had significantly improved effect on bone micro-architecture,and biomechanical parameters,BV /TV increased 46.7%(P <0.01 ),and stiffness increased 25.9%(P <0.01 ).30% ethanol eluent of the PM (M,L)dose may improve bone microstructure by in-creasing BV /TV 46.7% (P <0.01 ),40.0% (P <0.05)respectively,PM(H)may improve the biome-chanical parameters by increasing stiffness 24.7%(P<0.05),and 30% ethanol eluent of the PM(H)and PMhigh-dose may improve the biomechanical parame-ters,but not as positive group.Conclusions Predni-sone reduces biomechanical properties of rat femur and deteriorates femoral microstructure.30% ethanol eluent of the PM(M,L)and PM(H)plays a preventive role in the changes of micro-structural and biomechanical properties by prednisone,and increases BMD,whereas other groups have no significant preventive effect.