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Objective:To systematically evaluate the efficacy and safety of ruxolitinib in the treatment of Chinese patients with refractory graft-versus-host disease(SR-GVHD) by using meta-analysis.Methods:China National Knowledge Infrastructure(CNKI), WanFang database, VIP database, China Biology Medicine disc, PubMed, Ebscore Medline, EMBASE, Web of Science Core Collection and Cochrane Library were searched by using "ruxolitinib" "Graft vs Host Disease" "graft versus host disease" "Graft-Versus-Host Disease" as key words. The retrieve time was from the establishment of the database to December 7th, 2021. The related literatures of ruxolitinib for Chinese patients with SR-GVHD were screened according to inclusion and exclusion criteria, and the characteristics of the literatures were extracted. Outcomes indexes included overall objective response rate (ORR), proportion of hormone reduction and discontinuation, survival indexes and incidence of adverse events. Meta-analysis of ORR, remission rate of affected organs, 12-month overall survival rate, overall mortality and mortality due to graft-versus-host disease (GVHD) were performed by using Stata 16.0 software or R3.6.3 software. The statistics analysis was performed on the hormone usage and adverse events.Results:A total of 19 literatures involving 775 Chinese patients with SR-GVHD treated by ruxolitinib were included. Meta analysis showed that the ORR of ruxolitinib for treatment of acute GVHD (aGVHD) was 84% (285/339), with moderate heterogeneity among studies ( I2 = 62.04%, P<0.01), and the complete remission (CR) rate, partial remission (PR) rate and non-remission (NR) rate was 56% (190/339), 28% (95/339), and 14%(47/339), respectively. The ORR of ruxolitinib for treatment of chronic GVHD (cGVHD) was 77% (332/431), with moderate heterogeneity among studies ( I2 = 50.17%, P = 0.02), and the CR rate, PR rate and NR rate was 36% (155/431), 41% (177/431) and 21% (91/431), respectively. As for hormone usage, 46.51% of aGVHD patients had steroid reduction and 34.88% patients had steroid discontinuation. Similarly, 28.2% of patients with cGVHD had steroid reduction and 36.9% had steroid discontinuation. The overall 12-month survival rate of patients with SR-GVHD after the treatment of ruxolitinib was 71% (95% CI: 63%-79%, I2 = 72.70%, P<0.01). Adverse events occurred for 760 times in total, among which 287 times (36.0%) of viral infection and 269 times (34.7%) of hemocytopenia were the most common adverse events. Conclusions:Ruxolitinib is effective in the treatment of Chinese patients with SR-GVHD, and it helps reduce hormone-dependency and prolong the survival time.
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Objective:To detect the level of the circulating cell-free mitochondrial DNA (ccf-mtDNA) in plasma of children with primary carnitine deficiency (PCD)-associated cardiomyopathy and evaluate its clinical significance.Methods:In this prospective case-control study, peripheral blood samples were collected from 7 PCD patients with cardiomyopathy (PCD group), 16 dilated cardiomyopathy (DCM) patients (DCM group), and 50 healthy children (healthy control group) in the Pediatric Cardiovascular Department Ward of First Hospital of Jilin University from July 2017 to June 2022.The ccf-mtDNA levels were measured and compared between groups by the real-time fluorescence quantitative polymerase chain reaction.The correlations between plasma ccf-mtDNA level and blood free carnitine level and cardiac function in the PCD group were analyzed.The changes in the ccf-mtDNA level were monitored after L-carnitine treatment in the PCD group.The Kruskal-Wallis test was used for comparison among the three groups.The Mann-Whitney test was used for comparison between the PCD group and the control group.Changes before and after treatment in the PCD group were analyzed using the paired Wilcoxon rank sum test.The correlation between variables was evaluated by Logistic regression.Results:The plasma ccf-mtDNA levels in the PCD and DCM groups were 3.69×10 6 (1.09×10 6-7.26×10 6) copies/L and 0.99×10 6 (0.25×10 6-4.10×10 6) copies/L, respectively, which were significantly higher than that in the healthy control group[0.09×10 6 (0.01×10 6-0.35×10 6) copies/L]( H=33.34, 24.69; all P<0.01). Besides, the plasma ccf-mtDNA level in the PCD group was higher than that in the DCM group ( H=6.31, P<0.05). In the PCD group, the plasma ccf-mtDNA level was negatively correlated with the blood free carnitine level and left ventricular ejection fraction ( r=-0.85, -0.82, all P<0.05) and positively correlated with the modified Ross score and the N-terminal pro B type natriuretic peptide level ( r=0.81, 0.83, all P<0.05) before L-carnitine treatment.After treatment, the plasma ccf-mtDNA level decreased, and the blood free carnitine level and cardiac function recovered in the PCD group.The plasma ccf-mtDNA level declined sharply from the 3 rd month[0.96×10 6(0.50×10 6-2.27×10 6) copies/L] after treatment ( Z=2.24, P<0.05) and got to 0.27×10 6 (0.18×10 6-0.76×10 6) copies/L, 0.29×10 6(0.19×10 6-0.78×10 6) copies/L, and 0.16×10 6(0.10×10 6-1.06×10 6) copies/L at the 6 th, 9 th, and 12 th months after treatment, respectively, with no statistically significant difference compared to the healthy control group[0.09×10 6(0.01×10 6-0.35×10 6) copies/L] ( Z=1.23, 1.09, 2.12; all P>0.05). Conclusions:Plasma ccf-mtDNA may act as one pathogenic factor of cardiomyopathy in PCD, and monitoring its level is clinically important for heart condition assessment in PCD.
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Rosacea is a common chronic inflammatory skin disease whose exact pathogenesis has not been fully elucidated. Metabolomics has been widely used in the field of life science to provide strong evidence for exploring the pathogenesis and biomarkers of diseases. In recent years, researchers have applied metabolomics to rosacea-related fields using sebum, tear, saliva, and serum samples. This review summarizes research progress on current metabolomics methods and the application of metabolomics in rosacea.
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Rosacea is a chronic recurrent inflammatory skin disease, and correct assessment of clinical symptoms and severity may facilitate treatment options. This review summarizes a range of subjective, semi-subjective and objective methods currently used in the assessment of rosacea severity, in order to provide useful tools for clinical assessment of rosacea severity and give guidance on treatment modification according to the therapeutic effect.
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Rosacea is a chronic facial inflammatory skin disease. It has been proved that heredity, immunity, neurovascular disorders, microorganisms, skin barrier damage and ultraviolet rays are closely related to the occurrence of rosacea. However, the exact pathogenesis of rosacea has not been fully elucidated. This review summarizes recent advances in the pathogenesis of rosacea in the past 5 years.
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By organizing and studying on the original works of LI Wenrong， this paper aimed to explore his theories and methods for treating liver diseases. LI Wenrong believes that the liver is easily prone to physiological disturbances， difficult to pacify， and can be compared to a “chariot” that moves horizontally and vertically， acting as a “general” for both civil and military affairs. Pathologically， liver diseases tend to spread to other organs， resulting in ever-changing pathological changes， often affecting emotional health. In terms of therapeutic methods， LI Wenrong proposes ten methods including draining fire to calm the liver， nourishing water to moisten wood， clearing metal to calm the liver， calming gallbladder and harmonizing liver， subduing yang with shell-drug， treating liver diseases by supplementing spleen， soothing the liver with sweetness， astringing the liver with sourness， relieving the liver with spiciness， and draining the liver with excess-fire. These methods have great guidance and reference value for contemporary clinical practice in traditional Chinese medicine.
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The UV cross-linking immunoprecipitation (CLIP) technique was first established in 2003. Sequences of target RNAs and binding sites of specific RNA-binding proteins (RBPs) were identified within the entire transcriptome by UV cross-linking, immunoprecipitation, reverse transcription, and subsequent high-throughput sequencing. Over the last 20 years, CLIP has been continuously modified and improved. Advanced operability and accuracy have extended its application category. Currently, the widely used CLIP technologies include high-throughput sequencing with crosslinking-immunoprecipitation (HITS-CLIP), photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP), individual nucleotide resolution CLIP (iCLIP), enhanced CLIP (eCLIP), infrared-CLIP (irCLIP), etc. HITS-CLIP combines high-throughput sequencing with UV cross-linking immunoprecipitation. The 254 nm UV cross-linking and RNAase digestion steps allow the technology to capture transient intracellular RBP-RNA interactions. However, there are limitations in the efficiency of UV cross-linking, with low resolution and high intrinsic background noise. For PAR-CLIP, photoactivatable ribonucleoside was incorporated into RNA molecules, and RBP cross-linked with RNA by 365 nm UV light to improve cross-linking efficiency and resolution. Cross-linking mediated single-base mutations provide more accurate binding site information and reduce interference from background sequences. Long-term alternative nucleotide incorporation, on the other hand, can be cytotoxic and may skew experimental results. iCLIP can identify RBP-RNA cross-linking sites at the single nucleotide level through cDNA circularization and subsequent re-linearization steps, but it has more experimental procedures, and partial cDNAs lost in the circularization step are inevitable. eCLIP discards the radioisotope labeling procedure and reduces RNA loss by ligating adaptors in two separate steps, greatly improving the library-building efficiency, and reducing bias associated with PCR amplification; however, the efficiency of immunoprecipitation cannot be visually assessed at the early stage of the experiment. The irCLIP technique replaces radioisotopes with infrared dyes and greatly reduces the initial number of cells required for the experiment; however, an infrared imaging scanner is essential for the irCLIP application. To address more particular scientific issues, derivative CLIP-related techniques such as PAPERCLIP, cTag-PAPERCLIP, hiCLIP, and tiCLIP have also been developed in recent years. In practice, the aforementioned CLIP approaches have their advantages and disadvantages. When deciding on a technical strategy, we should take into account our experimental objectives and conditions, such as whether we need to precisely define the RNA site for binding to RBP; whether we have the necessary experimental conditions for working with radioisotopes or performing infrared imaging; the amount of initial sample size, and so on. In addition, the CLIP technique has a relatively large number of procedures and can be divided into several successive experimental modules. We can try to combine modules from different mainstream CLIP technologies to meet our experimental requirements, which also gives us more opportunities to improve and refine them and to build more targeted derivative CLIP technologies according to our research objectives.
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Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.
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Child , Humans , Quality of Life , Vaccination , Vaccines , Neoplasms/prevention & control , Communicable DiseasesABSTRACT
Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.
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Child , Humans , Quality of Life , Vaccination , Vaccines , Neoplasms/prevention & control , Communicable DiseasesABSTRACT
Apolipoprotein E (apoE) is a critical molecule in lipid metabolism, which also plays important roles in the occurrence and development of several kinds of cancers by regulating processes including cell proliferation, energy metabolism, oxidative stress and innate immune, etc., and shows influence in patients’ response to treatment. Therefore, apoE has become a potential biomarker and treatment target for cancer. Further research of apoE will help us build deep and systematic understanding of etiology of cancer to promote the prevention and to develop new therapeutic strategies for cancer. In this review, we introduced the properties of apoE from the views of biophysics, biochemistry, molecular biology, evolution and epidemiology, in which we demonstrated the similarities and differences among the structures of 3 subtypes of apoE; we also recapitulated the role of apoE in the genesis and development of cancers in main types of malignancies including gastric cancer, colorectal cancer, hepatobiliary cancer, melanoma, pancreatic cancer, etc.; we summarized the relationship between apoE and the hallmarks of cancer, highlighting the position of apoE in immune system and its critical role for understanding the different nature of immunological background of cancers originated from different organs, and discussed its potential value for application as tumor biomarkers and therapeutic targets by demonstrating the structures of its subtypes. We further discussed the possibility of transferring the drug designing strategy of “structure corrector” from neurology to oncology.
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Abstract Objective To investigate whether additional Cognitive Behavior Therapy (CBT) combined with conventional therapy improves outcomes for patients with Persistent Postural-Perceptual Dizziness (PPPD) compared with conventional therapy alone. Methods Two reviewers independently searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant Randomized Controlled Trials (RCTs) examining CBT for PPPD which were conducted and published in English from January 2002 to November 2022. RCTs reporting any indicators for assessing corresponding symptoms of PPPD were included, such as Dizziness Handicap Inventory (DHI), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Two independent reviewers conducted extraction of relevant information and evaluation of risk of bias. The Cochrane Collaboration risk of bias tool version 1.0 was used to evaluate risks and assess the quality of the included studies, and Cochrane Review Manager 5.3 software (RevMan 5.3) was used to perform meta-analyses. Results The results of six RCTs indicated that combining additional CBT with conventional therapy significantly improved outcomes for PPPD patients compared with conventional therapy alone, especially in DHI-Total scores (Mean Difference [MD = −8.17], 95% Confidence Interval [95% CI: −10.26, −6.09], p< 0.00001), HAMA scores (MD = −2.76, 95% CI: [−3.57, −1.94], p< 0.00001), GAD-7 scores (MD = −2.50, 95% CI [−3.29, −1.70], p< 0.00001), and PHQ-9 scores (MD = −2.29, 95% CI [−3.04, −1.55], p< 0.00001). Subgroup analysis revealed a significant benefit of additional CBT compared with conventional therapies alone, including Vestibular Rehabilitation Therapy (VRT) (MD = −8.70, 95% CI: [−12.17, −5.22], p< 0.00001), Selective Serotonin Reuptake Inhibitor (SSRI) (with controlled SSRI: MD = −10.70, 95% CI: [−14.97, −6.43], p< 0.00001), and VRT combined with SSRI (MD = −6.08, 95% CI [−9.49, −2.67], p= 0.0005) in DHI-Total scores. Conclusion Additional CBT combined with conventional therapy may provide additional improvement for patients with PPPD compared with conventional therapy alone. However, more RCTs are needed to support and guide the application of CBT in treating PPPD. Level of evidence: I; Systematic review of RCTs.
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NK/T cell leukemia/lymphoma is a type of malignancy originating from T cells or natural killer cells with low incidence and poor clinical prognosis. There is still no effective treatment strategy. In recent years, targeted therapy has made great progress in the treatment of hematological malignancies, including monoclonal antibody and chimeric antigen receptor T cells (CAR-T), among which CD30, CD7, CD5, CD52, CCR4 and other target antigens are effective in the treatment of NK/T cell leukemia/lymphoma, but its widespread application still faces a great challenge. This article reviews the progress of immunotherapy for NK/T cell leukemia/lymphoma.
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AIM: To investigate the characteristics of changes in corneal epithelial thickness at the early postoperative stage of femtosecond assisted laser in situ keratomileusis(FS-LASIK)and its related influencing factors.METHOD: Retrospective study. A total of 120 patients(240 eyes)of myopia undergoing FS-LASIK from May 2021 to June 2022 were selected. The corneal epithelium thickness in the central area, inner ring area, and outer ring area of patients before and at 1d, 1wk, 1 and 3mo after operation was recorded. The relationship between the variation of corneal epithelium thickness and spherical equivalent, optical zone diameter, depth of cut and cutting ratio was analyzed by Pearson correlation.RESULTS: There was no statistical significance in corneal epithelial thickness in the central area, inner ring area and outer ring area at 1d after FS-LASIK compared with that before operation(P>0.05). At 1wk, 1 and 3mo after surgery, the corneal epithelial thickness in the central area, inner ring area and outer ring area increased compared with that before surgery, and the corneal epithelial thickness in the central area and inner ring area at 1 and 3mo after surgery was greater than that in the outer ring area(all P<0.05). The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thicker than that of low and moderate myopia patients before operation. The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thinner than that of low and moderate myopia patients at 1wk after operation(P<0.05). At 1 and 3mo after operation, the corneal epithelial thickness in the central, inner and outer ring areas of patients with high myopia was greater than that of patients with low and moderate myopia, and the changes of corneal epithelial thickness in the central, inner and outer ring areas were greater than those of patients with low and moderate myopia(P<0.05). The results of Pearson correlation showed that the changes in corneal epithelial thickness in the central and inner ring area were positively correlated with the corneal curvature, depth of cut and cutting ratio at 3mo after surgery, and they were in negative correlation with the age, spherical equivalent and optical zone diameter(P<0.05).CONCLUSION: The corneal epithelial thickness of patients thickened after the FS-LASIK operation, and it was correlated with age, corneal curvature, preoperative depth of cut, cutting ratio, spherical equivalent and the optic zone diameter.
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Rosacea is a chronic inflammatory disease. In addition to subjective evaluation, some objective quantifiable indices are needed for the diagnosis and treatment of rosacea. Some skin imaging and noninvasive measurement tools have been applied to clinical practice, and can provide quantitative or semi-quantitative indices to assist the diagnosis and treatment of rosacea. This review summarizes relevant research progress to provide evidence for clinical standardized application.
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Rosacea is a chronic recurrent inflammatory skin disease that mainly occurs on the face. A large number of studies have confirmed that rosacea is related to a variety of systemic diseases, including neuropsychiatric diseases such as anxiety, depression, migraine, Alzheimer′s disease and Parkinson′s disease. This review summarizes research progress in the correlation between rosacea and neuropsychiatric diseases, as well as the underlying mechanisms.
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Frailty is a nonspecific state with the decline of physiological reserve leading to the increased vulnerability and decreased anti-stress ability in the elderly. Frailty can cause cognitive impairment and physical function decline, and increase the risk of a series of adverse events such as hospitalization, disability and death in the elderly. Studies have shown that early intervention can reverse debilitating condition; therefore, early and timely intervention of frailty has important practical significance for improving the health status of the elderly and reducing the pressure on the medical system. This article reviews frailty interventions and their effects in the elderly, including sports intervention, nutrition intervention, drug intervention and integrated intervention, focusing on the research progress of frailty intervention, to provide reference for clinical management of frailty in the community-dwelling elderly.
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Objective:To establish a risk prediction model for neonatal asphyxia in cesarean section and test its application effect.Methods:This was a retrospective study. We retrospectively analyzed the clinical data of 2 244 infants (modeling group) who were delivered by cesarean section in Affiliated Hospital of Weifang Medical University from April 2021 to December 2021. Newborns were divided into asphyxia group ( n=176) and non-asphyxia group ( n=2 068) according to the occurrence of neonatal asphyxia. Logistic regression was used to screen the risk factors of neonatal asphyxia in cesarean section and a line chart model was established to predict the risk. Another 683 neonates were selected as validation group for external validation of the model from January to March in 2022. Results:Five factors including preterm birth, fetal distress, fetal growth restriction, abnormal S/D value of umbilical artery and umbilical cord around the neck were included in the prediction model. The area under ROC curve of the modeling group was 0.902, the Youden index was 0.687, the sensitivity was 0.837, and the specificity was 0.850. Hosmer-lemeshow test showed that χ2=1.79, and P=0.877. In the validation group, the area under ROC curve was 0.823, the Youden index was 0.555, the sensitivity was 0.835, and the specificity was 0.720. It showed that the model had a good fitting effect and identification validity. Conclusions:The risk prediction model has a good clinical application value in the prediction of neonatal asphyxia in cesarean section, and provides reference for obstetricians to take preventive management measures of neonatal asphyxia in time.
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ObjectiveTo explore the mechanism of Buyang Huanwutang combined with bone marrow mesenchymal stem cell （BMSC） transplantation in the treatment of spinal cord injury （SCI）. MethodDifferent concentrations （12.5， 25， 50 g·kg-1） of Buyang Huanwutang were administrated to rats by gavage. The spinal cord function of rats was measured by modified Tarlov score， and the most suitable concentration of Buyang Huanwutang was screened out. SD rats were then divided into 6 groups， namely， the sham operation group （gavage of equal amount of normal saline）， the model group （gavage of equal amount of normal saline）， the Buyang Huanwutang group （gavage of 25 g·kg-1 Buyang Huanwutang）， the BMSC transplantation group （tail vein injection of BMSCs 1 mL）， the Buyang Huanwutang+BMSC group （gavage of 25 g·kg-1 Buyang Huanwutang and tail vein injection of BMSCs 1 mL）， the Buyang Huanwutang+BMSC+LY294002 group （gavage of 25 g·kg-1 Buyang Huanwutang and tail vein injection of BMSCs 1 mL and 40 mg·kg-1 LY294002）， with 10 rats in each group. The spinal cord function was measured by the modified Tarlov score， inclined plate test， and latency of cortical somatosensory evoked potential. Immunohistochemistry was used to detect the number of 5-bromo-2-deoxyuracil nucleoside （Brdu）-labeled positive cells in the spinal cord tissue. The protein expression levels of phosphorylated protein kinase B （p-Akt）， glycoprotein 130 （gp130）， and interleukin-6 （IL-6） in spinal cord were detected by Western blot. ResultAs compared with the sham operation group， the Tarlov score and the critical angle of tilt plane in the model group were significantly decreased （P<0.05）， and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt， gp130， and IL-6 were significantly increased （P<0.05）. As compared with the model group， the Tarlov score and the critical angle of tilt plane in the sham operation group and each treatment group were significantly increased （P<0.05）， and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt， gp130， and IL-6 were significantly decreased （P<0.05）. As compared with the BMSC group， the Tarlov score and the critical angle of inclined plane in the Buyang Huanwutang+BMSC group increased （P<0.05）， the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt， gp130， and IL-6 decreased （P<0.05）， and the number of Brdu-labeled positive cells increased 5 weeks after transplantation （P<0.05）. As compared with the Buyang Huanwutang+BMSC group， the Tarlov score and the critical angle of the inclined plane in the Buyang Huanwutang+BMSC+LY294002 group increased （P<0.05）， and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt， gp130， and IL-6 decreased significantly （P<0.05）. Five weeks after transplantation， the number of Brdu-labeled positive cells increased significantly in the Buyang Huanwutang+BMSC+LY294002 group （P<0.05）. ConclusionBuyang Huanwutang can promote BMSCs migration and restore spinal cord function by inhibiting phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal.
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【Objective】 To investigate the role and mechanism of dapagliflozin (Dapa), a sodium glucose co-transporter 2 inhibitor, in acute liver injury. 【Methods】 Eight-week-old C57BL6/J mice were given a single intraperitoneal injection of CCl4 to induce acute liver injury. The mice were preventively given 5 mg/kg Dapa by gavage 24 h and 2 h before CCl4 injection, while those in the control group were given an equal volume of solvent gavage. After 24 h, the mice were anesthetized and sacrificed. H&E staining, plasma biochemistry, RT-qPCR, and Western blotting were used to detect the severity of liver injury and the expressions of macrophage-related genes. 【Results】 In the CCl4 group, hepatic infiltration of inflammatory cells increased, and liver and renal functions significantly deteriorated, which was further aggravated by Dapa. CCl4 could promote the expressions of M1 macrophages and fibrosis-related genes in the liver, but reduce those of M2 and antioxidant-related genes, and the latter was further inhibited by Dapa. In addition, the protein expression of arginase 1 decreased and that of SGLT2 increased after Dapa intervention, while NF-κB pathway did not change significantly, suggesting that Dapa might directly affect the energy metabolism homeostasis in the liver and aggravate acute liver injury induced by CCl4. 【Conclusion】 Dapa can exacerbate hepatic and renal damage in acute stage of liver injury, inhibit macrophages M2 polarization, and aggravate oxidative stress and inflammatory injury induced by CCl4.
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【Objective】 To investigate the predictive value of preoperative controlled nutritional status (CONUT) score and ratio of hemoglobin to red cell distribution width (HRR) for survival of patients with upper urinary tract urothelial carcinoma (UTUC) after radical surgery. 【Methods】 A retrospective analysis was performed on 145 UTUC patients who underwent surgical treatment in the Affiliated Hospital of Xuzhou Medical University during May 2011 and Jun. 2017. Clinic opathologic data were collected, the best cut-off values of CONUT score and HRR were determined with receiver operating characteristic (ROC) curve, and the CONUT-HRR scoring system was established. The correlation between different CONUT-HRR scores and clinic opathological indicators of UTUC patients was compared. The application value of CONUT-HRR score in predicting the prognosis of UTUC patients was evaluated with Kaplan-Meier survival curve and Cox proportional risk regression model. 【Results】 The optimal cut-off values of preoperative CONUT score and HRR for predicting cancer specific survival (CSS) were 3 and 10.41, respectively. The patients were divided into three groups: CONUT-HRR 0 group (n=62, CONUT score <3 and HRR ≥10.41), CONUT-HRR 1 group (n=51, CONUT score <3 and HRR <10.41, or CONUT score ≥3 and HRR≥10.41), and CONUT-HRR 2 group (n=32, CONUT score ≥3 and HRR <10.41). CONUT-HRR score was correlated with age, surgical method, pathological T stage, lymph node metastasis and vascular invasion (all P<0.05). Kaplan-Meier survival curve results showed that the 5-year CSS of CONUT-HRR 0, 1 and 2 groups were 96.4%, 65.8% and 30.9%, respectively, with statistically significant differences (P<0.001). Cox regression model showed that CONUT-HRR score, pathological T stage, lymph node metastasis and vascular infiltration were independent factors of CSS. 【Conclusion】 Preoperative CONUT-HRR score can be used as a simple and reliable indicator to evaluate the prognosis of UTUC patients. Higher score indicates worse prognosis.