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Objective:To investigate the efficacy and safety of using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch to guide intravenous thrombolysis in patients with ischemic stroke beyond a 4.5-h time window.Methods:Patients with acute ischemic stroke received intravenous thrombolysis with alteplase in the Stroke Center of Hefei Second People's Hospital from July 2019 to June 2021 were retrospectively enrolled. According to the time of onset, they were divided into the time window group and the beyond time window group. The demographic and baseline clinical data of both groups were recorded and compared. The primary outcome measure was the clinical outcome assessed by the modified Rankin Scale (mRS) at 90 d after onset. 0-2 points were defined as good outcome, and >2 were defined as poor outcome. The secondary outcome measure was symptomatic intracranial hemorrhage (sICH). Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcomes. Results:A total of 244 patients with acute ischemic stroke were enrollded, including 146 males (58.8%), aged 61.4±8.47 years. The median time from onset to thrombolysis was 142 min, and the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Thirty-six (14.8%) patients exceeded the 4.5 h time window, and 69 (28.3%) patients had poor outcomes. There were no significant differences in the good outcome rate (71.2% vs. 75.0%; χ2=0.224, P=0.636), any intracranial hemorrhage (9.6% vs. 13.9%; χ2=0.233, P=0.629) and the incidence of sICH (5.3% vs. 5.6%; χ2=0.000, P=1.000) between the time window group and the beyond time window group. Univariate analysis showed that the proportion of patients with atrial fibrillation or cardiogenic embolism and the baseline NIHSS score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05), while there was no statistical difference in the proportion of patients receiving intravenous thrombolysis beyond the time window. Multivariate logistic regression analysis showed that only the baseline NIHSS score was an independent risk factor for poor outcomes (odds ratio 1.681, 95% confidence interval 1.457-1.940; P<0.001). Conclusions:Compared with the patients who received intravenous thrombolysis within 4.5 h after onset, intravenous thrombolysis in patients with acute ischemic stroke beyond the 4.5 h time window guided by DWI-FLAIR mismatch results in similar clinical outcomes, and does not increase the incidence of intracranial hemorrhage.
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Autoimmune diseases of the nervous and muscle systems constitute a major disease category in neurology, characterized by high disability and heterogeneity. However, incidences for this group of disorders are still unknown in China at the national level. The emergence of the national Hospital Quality Monitoring System (HQMS) provides comprehensive data for epidemiological studies of rare diseases, and the systematism, accuracy and consistency during data collection of HQMS information provide a unique advantage for the investigation of the incidence of rare diseases. Currently, the incidence of major neurological autoimmune diseases based on HQMS has been accomplished and published. In conjunction with clinical practice and research progress of this field, the incidence studies of multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, Guillain-Barré syndrome, and myasthenia gravis are summarized. The completion of survey of disease incidence is instrumental to investigate the prevalence of this group of diseases. Ultimately, the outcome would benefit neurologists as well as health care policy makers.
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PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.
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Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.
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Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.
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Objective@#To investigate the prevalence of anxiety and depression among inpatients with AIDS and its influencing factors, so as to provide the evidence for improving the psychological health among inpatients with AIDS.@*Methods@#The inpatients with AIDS that were hospitalized in an infectious disease hospital in Chengdu City were recruited using the convenient sampling method. The demographic features, depression and anxiety were collected using a self-designed questionnaire, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale ( SDS ), respectively, and factors affecting the development of depression and anxiety were identified using a multivariable linear regression model among inpatients with AIDS.@*Results@#The 228 AIDS inpatients included 186 men (81.58%) and 42 women ( 18.42% ), and had a mean age of ( 48.04±16.03 ) years. There were 113 inpatients ( 49.56% ) with a CD4+T cell count of ≤200 cells/μL, and the mean SAS and SDS standardized scores were 35.87±8.01 and 42.07±11.08 among AIDS inpatients, which were both significantly greater than in normal populations ( P<0.05 ). The prevalence rates of anxiety, depression, and comorbid anxiety and depression were 5.26%, 16.23% and 4.82% among the participants, respectively. Multivariable linear regression analysis identified unemployment as a risk factor of anxiety ( β'=0.168, P<0.05 ), and CD4+T cell count as a risk factor of anxiety ( β'=-0.151, P<0.05 ) and depression ( β'=-0.238, P<0.05 ) among inpatients with AIDS.@*Conclusions@#Anxiety and depression are prevalent among inpatients with AIDS. Unemployment and a low CD4+T cell count may cause a rise in the risk of developing anxiety and depression among inpatients with AIDS.
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Objective:To investigate the efficacy of quetiapine fumarate combined with lithium carbonate in the treatment of bipolar disorder and its effect on cognitive function.Methods:Sixty patients with bipolar disorder, who received treatment in Zhuji Fifth People's Hospital from January 2017 to December 2019, were included in this study. They were randomly assigned to receive either lithium carbonate (control group, n = 30) or quetiapine fumarate combined with lithium carbonate treatment (combined treatment group, n = 30). All patients received 4 weeks of treatment. Manic and depressive symptoms pre- and post-treatment, clinical efficacy, cognitive function, and adverse reactions were compared between the two groups. Fasting venous blood was taken before and 4 weeks after treatment to measure superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px) levels. Results:The scores of the Bech-Rafaelsdn Mania Rating Scale (BRMS) and the Hamilton Rating Scale for Depression (HAMD) in each group were significantly decreased after treatment compared with before treatment ( t = 10.39, 12.47, both P < 0.001). The score of the Mini-Mental State Examination in each group significantly increased after treatment compared with before treatment ( t = 8.36, 14.52, both P < 0.001). The scores of BRMS and HAMD post-treatment were significantly lower in the combined treatment group than in the control group ( t = 5.86, 5.54, both P < 0.001). The score of MMSE post-treatment was significantly higher in the combined treatment group than in the control group ( t = 2.40, P = 0.020). The response rate was significantly higher in the combined treatment group than in the control group ( Z = 2.16, P = 0.030). After treatment, serum MDA level significantly decreased in each group compared with before treatment ( t = 8.72, 15.47, both P < 0.001). After treatment, SOD, CAT and GSH-Px levels were significantly increased in each group compared with before treatment (SOD: tcontrol group = 2.84, P = 0.006, tcombined treatment group = 4.05, P < 0.001; CAT: tcontrol group = 5.20, P < 0.001, tcombined treatment group = 9.86, P < 0.001; GSH-Px: tcontrol group = 2.67, P = 0.010, tcombined treatment group = 3.71, P = 0.001). Serum MDA level post-treatment was significantly lower in the combined treatment group than in the control group ( t = 12.38, P < 0.001). Serum SOD and CAT levels post-treatment were significantly higher in the combined treatment group than in the control group ( tSOD = 2.24, P = 0.029; tCAT = 2.72, P = 0.009). There was no significant difference in the incidence of adverse reactions between the combined treatment and control groups [20.00% (6/30) vs. 16.67% (5/30), χ2 = 1.02, P = 0.907). Conclusion:Quetiapine fumarate combined with lithium carbonate can greatly improve clinical symptoms and cognitive function and reduce the over-activation of oxidative stress in patients with bipolar disorder. The combined therapy is of certain clinical application value.
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Complex systems science (CSS) is an evaluation system that integrates the overall system and draws multilateral conclusions in the form of dynamic and reasonable interpreta-tion. Evaluation of modern hernia and abdominal wall surgery by CSS includes the application of artificial intelligence, data analysis and other methods. It implements the value oriented clinical quality improvement principle in the overall treatment cycle through the measurement of value, combined cost, quality evaluation and patient perspective. Finally, CSS will realize the sustainable development of hernia and abdominal wall surgical diagnosis and treatment system of medical care system.
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Objective:To investigate the efficacy and safety of intravenous thrombolysis based on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch in patients with wake-up stroke (WUS).Methods:Patients with acute ischemic stroke received alteplase intravenous thrombolysis in the Stroke Center, the Second People's Hospital of Hefei from July 2019 to June 2021 were enrolled retrospectively. According to the time of finding the symptoms, they were divided into WUS group and non-WUS group. The demographic and baseline clinical data were documented and compared between the two groups. The efficacy endpoint was the clinical outcome assessed by the modified Rankin Scale (MRS) score at 90 d after onset. 0-2 was defined as a good outcome, and >2 were defined as a poor outcome. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH); the secondary safety endpoint was death within 90 d after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcome. Results:A total of 256 patients with acute ischemic stroke were enrolled, including 155 males (60.5%), aged 63.0±8.53 years. The median time from symptom onset to intravenous thrombolysis was 130.5 min, and the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Forty-eight patients (18.7%) were WUS and 208 (81.3%) were non-WUS; 186 (72.7%) had a good outcome and 70 (27.3%) had a poor outcome. There were no significant differences in 90 d good outcome rate (79.2% vs. 71.2%; χ2=1.260, P=0.262), sICH incidence (4.2% vs. 5.3%; χ2=0.102, P=0.750) and 90 d mortality (2.1% vs. 3.4%; χ2=0.000, P=1.000) between the WUS group and the non-WUS group. The baseline NIHSS score, the time from symptom onset to intravenous thrombolysis and the proportion of patients with cardiogenic embolism in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that the baseline NIHSS score (odds ratio 1.670, 95% confidence interval 1.453-1.919; P<0.001) and the time from symptom onset to intravenous thrombolysis (odds ratio 1.007, 95% confidence interval 1.000-1.015; P=0.043) were the independent risk factors for the poor outcome. Conclusion:The efficacy and safety of intravenous thrombolysis in DWI-FLAIR-mismatched wake-up stroke patients are comparable to those of acute ischemic stroke within the time window.
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Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.
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Animals , Artesunate , Drugs, Chinese Herbal/therapeutic use , Female , Liver Cirrhosis/drug therapy , Mice , Mice, Inbred C57BL , Mitochondria , SchistosomiasisABSTRACT
Objective@#: Extracranial supra-aortic dissections (ESADs) with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke. Endovascular stenting to reconstruct non acute phase ESADs (NAP-ESADs) is an alternative to anticoagulant or antiplatelet therapy. However, its feasibility, safety and efficacy of stenting in NAP-ESADs is unclear. This study aims to investigate the long-term outcomes of the feasibility, safety and efficacy of stenting in NAP-ESADs. @*Methods@#: Seventy-four patients with 91 NAP-ESAD vessels with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke who underwent stent remodeling were enrolled into this respective study from December 2008 to March 2020. Technical success rate, complications, clinical and angiographic results were harvested and analyzed. @*Results@#: Success rate of stent deployment was 99% (90/91) with no procedural mortality or morbidity. Transient ischemic attack occurred in three patients during operation (4.1%, 3/74). Asymptomatic embolisms of distal intracranial vessels were found in two patients (2.7%, 2/74). One hundred and forty-two stents deployed at 85 carotid (135 stents) and six vertebral (seven stents) vessels. Six stent types (Wingspan, 28/135, 20.7%; Solitaire, 10/135, 7.4%; Neuroform, 8/135, 5.9%; LVIS, 2/135, 1.5%; Precise, 75/135, 55.6%; Acculink, 12/135, 8.9%) were deployed at carotid arterial dissection while two types (Wingspan, 5/7, 71.4%; Solitaire 2/7, 28.6%) at vertebral arterial dissection. Digital subtracted angiography (56%, 51/91), computational tomography angiography (41.8%, 38/91) and high resolution magnetic resonance imaging (2.2%, 2/91) were adopted for follow up, with a mean time of 17.2±15.4 months (5–77). All patient modified Rankin Scale scores showed no increase at discharge or follow-up. Angiographically, dissections in 86 vessels in 69 patients (94.5%, 86/91) were completely reconstructed with only minor remnant dissections in four vessels in four patients (4.4%, 4/91). Severe re-stenosis in the stented segment required re-stenting in one patient (1.1%, 1/91). @*Conclusion@#: Stent remodeling technique provides feasible, safe and efficacious treatment of ESADs patients with severe stenosis, occlusion and/or pseudoaneurysm.
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Due to the narrow time window of traditional reperfusion therapy and the presence of the risk of reperfusion injury, it is of great significance to study the pathogenesis of ischemic stroke and explore methods to reduce reperfusion injury from the perspective of pathophysiology. This article expounds the functions of von Willebrand factor (vWF) and platelet glycoprotein (GP) Ⅰb and their roles in hemostasis, thrombosis, and inflammation. It is believed that pharmacological blockade of the interaction of vWF-GP Ⅰb may contribute to the treatment of ischemic stroke. In addition, its clinical significance in ischemic stroke and ischemic brain injury was further discussed.
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Objective:To investigate whether there is inflammatory reaction and cell pyroptosis in impaired glucose tolerance （IGT） rats induced by high-fat diet and the intervention effect of Huanglian Wendantang. Method:Healthy male SD rats were fed with 45% fat content diet for 20 weeks to replicate the IGT model. The rats in line with the model establish criteria were randomly divided into 3 groups， with 10 rats in each group， another 10 rats were selected as the blank control group. Huanglian Wendantang group was given 7.8 g·kg<sup>-1</sup>·d<sup>-1</sup> compound decoction of Huanglian Wendantang， and the positive control group was given 0.05 g·kg<sup>-1</sup>·d<sup>-1</sup> aqueous solution of metformin hydrochloride， with the dose volume of 10 mL·kg<sup>-1</sup>·d<sup>-1</sup>. The blank group and the model group were given the same volume of distilled water. After continuous intragastric administration for 4 weeks， the body weight， body length and abdominal circumferences were measured， the Lee's obesity index was calculated， and the levels of fasting plasma glucose （FPG） and 2-hour plasma glucose （2 h PG） were detected in each group. Serum interleukin-6 （IL-6） content was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of nuclear factor kappa B （NF-<italic>κ</italic>B）， cysteinyl aspartate specific proteinase-1 （Caspase-1） and NOD-like receptor protein 3 （NLRP3） in liver tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Immunofluorescence was used to detect the expression of Caspase-1 and NLRP3 in rat liver. Hematoxylin and eosin （HE） staining was used to observe the morphology of liver tissue. Result:Compared with blank group， the body weight， abdominal circumference， body length and Lee's index in model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， the levels of FPG and 2 h PG were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， serum IL-6 content and NF-<italic>κ</italic>B， Caspase-1 and NLRP3 gene and protein expressions in liver tissue were significantly increased （<italic>P</italic><0.01）， immunofluorescence technique showed that Caspase-1 and NLRP3 expressions increased obviously in IGT rat model’s liver tissues， and inflammatory cells infiltration was observed obviously in HE stained rat liver tissue model. Compared with model group， Huanglian Wendantang and metformin hydrochloride groups could effectively reduce the body weight of IGT rats （<italic>P</italic><0.01） and abdominal obesity， and correct the levels of FPG and 2 h PG （<italic>P</italic><0.01）， while effectively reducing serum IL-6 content and gene and protein expressions of NF-<italic>κ</italic>B， Caspase-1 and NLRP3 in liver tissues of IGT rats， and alleviating inflammatory cell infiltration. Conclusion:Inflammatory response exists in IGT model rats induced by high-fat diet. Huanglian Wendantang can obviously reduce its inflammatory response and alleviate liver cell pyroptosis.
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Objective:Ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry （UHPLC-Q-Orbitrap-MS） was used to rapidly analyze and assign the chemical constituents of Naizilai granules. Method:An ACQUITY UPLC BEH Shield RP C<sub>18</sub> column （2.1 mm×100 mm， 1.7 µm） was selected for chromatographic analysis， the mobile phase was 0.1% formic acid aqueous solution （A） and acetonitrile （B） for gradient elution （0-3 min， 1%B； 3-16 min， 1%-11%B； 16-30 min， 11%-34%B； 30-37 min， 34%-52%B； 37-42 min， 52%-100%B； 42-44 min， 100%B）， flow rate was 0.3 mL·min<sup>-1</sup> and the column temperature was 35 ℃. Mass spectrometry data of Naizilai granules were collected in positive and negative ion modes， the chemical constituents of this preparation were speculated and identified according to the precise molecular weight， secondary fragmentation and other information， combined with reference substance and literature data. Result:A total of 175 compounds were identified and speculated， including 72 flavonoids， 77 organic acids， 15 sesquiterpenes， 6 coumarins and 5 other compounds. Among these identified chemical constituents， there were 154 from <italic>Artemisia rupestris</italic>， 64 from <italic>Hyssopus cuspidatus</italic>， 33 from <italic>Cordia dichotoma</italic>， 42 from <italic>Viola tianshanica</italic>， 56 from <italic>Lactuca sativa</italic>， 65 from <italic>Mentha haplocalyx</italic>， 78 from <italic>Matricaria chamomilla</italic>， 28 from <italic>Ziziphus jujuba</italic>， 7 of which were common components of these eight herbs. Conclusion:The established analytical method can realize the rapid and accurate identification of the chemical constituents in Naizilai granules， and basically covers the main constituents of each medicinal material in the formula， so as to provide a basis for improving the quality evaluation system of the preparation and lay a foundation for elucidating the pharmacodynamic mechanism.
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Background and Objectives@#MiR-148a-3p has been reported to regulate the differentiation of marrow stromal cell osteoblast. In this study, whether miR-148a-3p regulated the odontoblastic differentiation of human dental pulp stem cells (hDPSCs) or not was explored. @*Methods@#and Results: The hDPSCs were isolated and identified via flow cytometry. Targets of miR-148a-3p were identi-fied via bioinformatics and dual-luciferase reporter assay. After the cell was cultured in the odontogenic differentiation medium or infected, cell viability, invasion, and odontoblastic differentiation were detected via MTT, transwell, and Alizarin Red S staining, respectively. The miR-148a-3p, Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions were determined by RT-qPCR and Western blot. The hDPSCs odontoblastic differentiation downregulated the miR-148a-3p expression and upregulated Wnt1 expression. Wnt1 was determined as the target for miR-148a-3p. MiR-148a-3p mimic and siWnt1 suppressed the cell viability, invasion, and odontoblastic differentiation of hDPSCs and inhibited the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. In contrast, miR-148a-3p inhibitor and overexpressed Wnt1 promoted the cell viability, invasion, and odontoblastic differentiation of hDPSCs, and upregulated the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. Also, miR-148a-3p mimic and inhibitor reversed the effects of Wnt1 overexpression and siWnt1. @*Conclusions@#MiR-148a-3p modulated the invasion and odontoblastic differentiation of hDPSCs through the Wnt1/β-catenin pathway.
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Objective:To investigate the method and outcome of reconstruction of thumb soft tissue defect by index finger proximal dorsal island flap supplied by the second dorsal metacarpal artery (SDMA).Methods:From August, 2015 to December, 2017, 12 cases of thumb soft tissue defect were treated by index finger proximal dorsal island flap supplied by SDMA. The site of defect ranged from 2.0 cm×2.4 cm to 5.5 cm×3.0 cm, and the flap area ranged from 2.2 cm×2.6 cm to 6.0 cm×3.3 cm. The donor site was repaired by split-thickness skin graft from the forearm of the injured limb. All patients received regular outpatient follow-up after surgery. The appearance, texture, sensory recovery and donor site of the flap were observed.Results:All the 12 flaps had 5-16 (8.8 in average) months follow-up and survived, the donor site and wounds healed in primary stage. The appearance, sensory and function of the flaps were good. There were no scar contracture on the donor sites, and no pain and limitation of motion in the joints. At the last follow-up, according to the Criteria for Function Assessment of Upper Limbs by the Branch of Hand Surgery of Chinese Medicine Association, the thumb functions were excellent in 11 cases and good in 1 case.Conclusion:Index finger proximal dorsal island flap supplied by SDMA is easy to operate, and has constant blood supply, improved rotation angle of the flap vessel base. It is a good method to repair the soft tissue defect of thumb.
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In the past 20 years, with the development of molecular biology, the treatment of non-small cell lung cancer (NSCLC) has been developing. Targeted therapy has improved the survival period of patients with positive mutation of tumor driver gene. More and more targets have been found gradually. Drugs targeting different driving genes have brought the treatment of NSCLC into a promising target era. Among the many driving genes of NSCLC, the fusion of transfection proto oncogene (RET) is the addition of the epidermal growth factor receptor (EGFR), analytic lymphama kinase (ALK) and c-ros oncogene 1-receptor tyrosine kinase (ROS1) are emerging targets. Targeted drugs for RET gene fusion have been constantly updated. Recently, new high selective RET inhibitors blu-667 and loxo-292 have made important breakthroughs. This paper will review the review of the fusion mutation of RET gene in NSCLC, the detection methods, clinicopathological characteristics, targeted treatment and the research progress after drug resistance. .
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Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive technique. In recent years, many studies have demonstrated that rTMS can improve cognitive function in Alzheimer's disease (AD) patients and has potential as a therapeutic method for AD. However, the efficacy varies greatly with different rTMS treatment regimens, which is related to the frequency, type, location, duration, intensity and focusing power of stimulation. Recent studies have shown that high-frequency stimulation is superior to low-frequency stimulation; efficacy of intermittent theta burst stimulation (iTBS) is similar to that of conventional rTMS, but iTBS treatment session is shorter and might be more acceptable for AD patients; rTMS stimulation sites targeting AD-damaged brain regions or associated networks would be more effective; short-term intensive treatment combined with long-term maintenance treatment can gain long-term efficacy; dynamic adjustment of stimulus intensity combined with the degree of cognitive impairment can enhance the efficacy; functional connection based on functional magnetic resonance imaging may improve the focusing power of rTMS. In this article, we review the factors related to the efficacy of rTMS, to provide reference for feasible rTMS therapeutic regimens of AD.
Subject(s)
Alzheimer Disease/therapy , Brain , Cognition , Humans , Magnetic Resonance Imaging , Transcranial Magnetic StimulationABSTRACT
Food-borne parasitic diseases include meat-borne, fish-borne, plant-borne, water-borne, mollusk-borne and freshwater crustacean-borne parasitic diseases. The review summarizes the current status and control of 6 major food-borne parasitic diseases in China, including clonorchiasus, paragonimiasis, Taenia solium taeniasis, toxoplasmosis, trichinellosis and angiostrongyliasis, aiming to increase the understanding of food-borne parasitic diseases and provide insights into the development of the control strategy for food-borne parasitic diseases. The transmission of food-borne parasitic diseases are predominantly associated with diet, and neither eating raw nor semi-cooked food is the most effective measure to prevent the development of food-borne parasitic diseases.
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Objective@#To evaluate the effect of functional training on the improvement of Cobb Angle, ATR and quality of life in adolescent idiopathic scoliosis.@*Methods@#Database of CNKI, WanFang, WeiPu, Web of Science, PubMed were reconnoitered for the purpose of research articles of Interest. Literature was screened according to the inclusion criteria, randomized controlled trials (RCTS) were collected and Cochrane risk bias assessment methodology quality was used, and Revman 5.3 software was used to conduct combined effector subgroup analysis on outcome indicators (Cobb Angle, ATR, SRS-22 patient questionnaire).@*Results@#A total of 10 RCT (398 AIS patients) were included in the study. There were two high , five moderate and three low quality studies, respectively. Compared with other non operative treatments, functional training could reduce Cobb horn in patients, MD = -6.56 (95% CI =-7.30--5.83, P <0.01, I 2=0). Further subgroup analysis showed that there were no statistically significant differences in effect size between the subgroups of Cobb Angle, age, intervention period and control method at the time of inclusion ( P >0.05). Compared with the non intervention blank group, the functional training group could reduce the Cobb Angle of patients ( MD = -5.25 , 95% CI =-8.27- -2.98 , P < 0.01 ), with high heterogeneity ( I 2=61%). Effect on angle of trunk rotation(ATR):functional training group could reduce patients ATR, MD =-1.91 (95% CI =-2.25--1.57, P <0.01, I 2=0). The impact on the quality of life:functional training of patients with SRS-22 questionnaire function, pain had no statistical significance ( P >0.05), and self image ( MD =0.64, 95% CI =0.53- 0.75 , P <0.01), mental health ( MD =0.44, 95% CI =0.15-0.74, P <0.01), satisfaction ( MD = 0.58 , 95% CI =0.11- 1.06 , P = 0.02 ) were statistically significant.@*Conclusion@#Functional training can not only reduce the Cobb Angle and ATR of AIS patients, but also improve the quality of life in terms of self image, mental health and satisfaction of the patients. However, due to heterogeneity and bias, more high quality studies are needed to verify.