Exploring the protective mechanism of Tibetan medicine Potentilla anserine on cyclophosphamide-induced myelosuppression based on metabonomics technology / 药学学报

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Biomechanical analysis of four internal fixations for Pauwels Ⅲ femoral neck fractures with defects / 中国骨伤

OBJECTIVE@#To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture.@*METHODS@#Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared.@*RESULTS@#When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS.@*CONCLUSION@#For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.

Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology / 中国中药杂志

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Construction of TRAF6 ubiquitin site 331 mutant colorectal cancer cell stable line and its effect on biological behavior of colorectal cancer cells / 中华肿瘤杂志

Objective: To investigate the effect of ubiquitin mutation at position 331 of tumor necrosis factor receptor related factor 6 (TRAF6) on the biological characteristics of colorectal cancer cells and its mechanism. Methods: lentivirus wild type (pCDH-3×FLAG-TRAF6) and mutation (pCDH-3×FLAG-TRAF6-331mut) of TRAF6 gene expression plasmid with green fluorescent protein tag were used to infect colorectal cancer cells SW480 and HCT116, respectively. The infection was observed by fluorescence microscope, and the expressions of TRAF6 and TRAF6-331mut in cells was detected by western blot. Cell counting kit-8 (CCK-8) and plate cloning test were used to detect the proliferation ability of colorectal cancer cells in TRAF6 group and TRAF6-331mut group, cell scratch test to detect cell migration, Transwell chamber test to detect cell migration and invasion, immunoprecipitation to detect the ubiquitination of TRAF6 and TRAF6-331mut with ubiquitinof lysine binding sites K48 and K63. Western blot was used to detect the effects of TRAF6 and TRAF6-331mut over expression on the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinase mitogen-activated protein kinase (MAPK)/activating protein-1(AP-1) signal pathway. Results: The successful infection of colorectal cancer cells was observed under fluorescence microscope. Western blot detection showed that TRAF6 and TRAF6-331mut were successfully expressed in colorectal cancer cells. The results of CCK-8 assay showed that on the fourth day, the absorbance values of HCT116 and SW480 cells in TRAF6-331mut group were 1.89±0.39 and 1.88±0.24 respectively, which were lower than those in TRAF6 group (2.09±0.12 and 2.17±0.45, P=0.036 and P=0.011, respectively). The results of plate colony formation assay showed that the number of clones of HCT116 and SW480 cells in TRAF6-331mut group was 120±14 and 85±14 respectively, which was lower than those in TRAF6 group (190±21 and 125±13, P=0.001 and P=0.002, respectively). The results of cell scratch test showed that after 48 hours, the percentage of wound healing distance of HCT116 and SW480 cells in TRAF6-331mut group was (31±12)% and (33±14)%, respectively, which was lower than those in TRAF6 group [(43±13)% and (43±7)%, P=0.005 and 0.009, respectively]. The results of Transwell migration assay showed that the migration numbers of HCT116 and SW480 cells in TRAF6-331mut group were significantly lower than those in TRAF6 group (P<0.001 and P<0.002, respectively). The results of Transwell invasion assay showed that the number of membrane penetration of HCT116 and SW480 cells in TRAF6-331mut group was significantly lower than those in TRAF6 group (P=0.008 and P=0.009, respectively). The results of immunoprecipitation detection showed that the ubiquitin protein of K48 chain pulled by TRAF6-331mut was lower than that of wild type TRAF6 in 293T cells co-transfected with K48 (0.57±0.19), and the ubiquitin protein of K63 chain pulled down by TRAF6-331mut in 293T cells co-transfected with K63 was lower than that of wild type TRAF6 (0.89±0.08, P<0.001). Western blot assay showed that the protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-HCT116 cells were 0.63±0.08, 0.42±0.08 and 0.60±0.07 respectively, which were lower than those in TRAF6-HCT116 cells (P=0.002, P<0.001 and P<0.001, respectively). The expression level of AP-1 protein in TRAF6-HCT116 cells was 0.89±0.06, compared with that in TRAF6-HCT116 cells. The difference was not statistically significant (P>0.05). The protein expression levels of NF-κB, p-NF-κB and p-AP-1 in TRAF6-331mut-SW480 cells were 0.50±0.06, 0.51±0.04, 0.48±0.02, respectively, which were lower than those in TRAF6-SW480 cells (all P<0.001). There was no significant difference in AP-1 protein expression between TRAF6-331mut-SW480 cells and TRAF6-SW480 cells. Conclusion: The ubiquitin site mutation of TRAF6 gene at 331 may prevent the binding of TRAF6 and ubiquitin lysine sites K48 and K63, and then affect the expressions of proteins related to downstream NF-κB and MAPK/AP-1 signal pathways, and inhibit the proliferation, migration and invasion of colorectal cancer cells.

Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis / 中草药·英文版

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus Disease 2019 Pneumonia in Lung Cancer Patients: A Single-center Retrospective Study / 中国肺癌杂志

BACKGROUND@#Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population.@*METHODS@#From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models.@*RESULTS@#(1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity.@*CONCLUSIONS@#Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Histogram analysis of based on two-dimensional ultrasound images to differentiate medullary thyroid carcinoma and thyroid adenoma / 中华肿瘤杂志

Objective: To investigate the feasibility and value of histogram analysis based on two-dimensional gray-scale ultrasonography in the differential diagnosis of medullary thyroid carcinoma (MTC) and thyroid adenoma (TA). Methods: The preoperative ultrasound images of 86 newly diagnosed MTC patients and 100 TA patients treated in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2015 to October 2021 were collected. Histograms were performed based on the regions of interest (ROIs) delineated manually by two radiologists, thereafter, mean, variance, skewness, kurtosis, percentiles (1st, 10th, 50th, 90th, 99th) were generated. The histogram parameters between the MTC group and the TA group were compared, and the independent predictors were screened by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to compare the individual diagnostic efficacy and joint diagnostic efficacy of independent predictors. Results: Multivariate regression analysis showed that mean, skewness, kurtosis and 50th percentile were independent factors. The skewness and kurtosis in the MTC group were significantly higher than those in the TA group, and the mean and 50th percentile were significantly lower than those in the TA group. The area under the individual ROC curve of mean, skewness, kurtosis and 50th percentile is 0.654-0.778. The area under the combined ROC curve is 0.826. Conclusion: Histogram analysis based on two-dimensional gray-scale ultrasonography is a promising tool to distinguish MTC from TA, in which the joint diagnosis value of mean, skewness, kurtosis and 50th percentile is the highest.

Comparison of the diagnostic effect on different machine learning predictive model of imipenem sensitivity of Klebsiella pneumoniae based on MALDI-TOF MS / 中华检验医学杂志

Objective:Machine learning is not only an important branch of artificial intelligence, but also supporting technologies for bioinformatics analysis. In the presence work, four machine-learning-predictive model for the drug-sensitivity of Klebsiella pneumoniae to imipenem were established based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and the diagnostic effect of these methods was exmained. Methods:A retrospective study was performed and the data of MALDI-TOF-MS and imipenem sensitivity of a total number of 684 cases Klebsiella pneumoniae isolated from clinical specimens in the laboratory of microbiology department of Tianjin Haihe Hospital from 2019 January to 2020 December were collected. The mass spectrometry and imipenem sensitivity data of 70 cases identified as imipenem-sensitive and 70 resistant cases were simple randomly selected to establish the training set model; whereas 30 cases of sensitive and 30 cases of resistant cases were randomly selected to establish the test set model. Mass spectral peak data were subjected to Orthogonal Partial least squares Discriminant Analysis (OPLS-DA). The training set data model was established by machine learning least absolute shrinkage and selection operator (LASSO) algorithm, Logistic Regression (LR) algorithm, Support vector machines (SVM) algorithm, neural network (NN) algorithm. The area under the curve (AUC) and confusion matrix of training set and test set model were calculated and selected by Grid search and 10-fold Cross-validation respectively, the accuracy of the prediction model was verified by test set confusion matrix. Results:The R2Y and Q2 of OPLS-DA were 0.546 3 and 0.017 8. The AUC of the best training set and test set models were 1.000 0 and 0.858 1, 1.000 0 and 0.820 1, 0.940 8 and 0.756 1, 1.000 0 and 0.697 2 evaluated by LASSO, LR, SVM and NN model respectively. The accuracy of the model were 99% (69/70), 100% (70/70), 91% (64/70) and 100% (70/70) for prediction of drug resistance, 100% (70/70), 100% (70/70), 90% (63/70) and 100% (70/70) for drug sensitivity prediction, the correct rate were 99% (139/140), 100% (140/140), 91% (127/140) and 100% (140/140) in training set, the test set showed that the accuracy were 93% (28/30), 87% (26/30), 60% (18/30) and 60% (18/30) for prediction of drug resistance, 100% (30/30), 80% (24/30), 93% (28/30) and 67% (20/30) for drug sensitivity prediction, the correct rate were 97% (58/60), 83% (50/60), 77% (46/60) and 63% (38/60) by LASSO, LR, SVM and NN model respectively.Conclusion:The LASSO prediction model of Klebsiella pneumoniae sensitivity to imipenem established in this study has a high accuracy rate and has potential clinical decision support ability.

The effects of fast walking on persons with sarcopenia / 中华物理医学与康复杂志

Objective:To observe any effect of fast walking on walking speed, 6-minute walking test (6MWT) time, and on serum levels of growth differentiation factor-8 (GDF-8) and insulin-like growth factor-1 (IGF-1) in patients with sarcopenia.Methods:A total of 61 sarcopenia patients were randomly divided into an observation group ( n=31) and a control group ( n=30). Both groups were given conventional drug therapy. In addition, the observation group underwent 30-minutes of walking at 100-120 steps/min (about 60% of maximum heart rate) three times a week for 12 weeks. The control group also walked, but at 70-90 steps/min (less than 50% of maximum heart rate). Grip strength, walking speed, 6MWT time, skeletal muscle index (ASMI) and serum GDF-8 and IGF-1 were compared before and after the intervention. Results:There were no significant differences in grip strength or ASMI between observation group and control group (comparing males with males and females with females) before the experiment. Afterward, grip strength and ASMI in the observation group had increased significantly on average. Both were then significantly higher than the control groups′ averages, which had not changed significantly. Average walking speed, 6MWT time and serum IGF-1 levels had improved significantly in both groups, but the observation group′s average improvement was significantly greater. A significant decrease the average serum GDF-8 level was observed in the observation group, but not in the control group.Conclusion:Fast walking can improve the walking of persons with sarcopenia, raise serum IGF-1 levels, and significantly reduce serum GDF-8.

Analysis of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice / 中华放射医学与防护杂志

Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.

Clinicopathological features and prognosis of 128 children with idiopathic membranous nephropathy / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in children, and to investigate the factors influencing their prognosis.Methods:The clinical and pathological data of 128 children with IMN hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed.They were divided into 2 groups according to the pathological manifestations: group A[typical membranous nephropathy(MN) group] and group B (atypical MN group), and the clinicopathological characteristics of the 2 groups were compared.Different treatment regimens and their efficacy were summarized, and the prognosis and its influencing factors were analyzed.The primary endpoint event at follow-up was the occurrence of end stage renal disease (ESRD), and the secondary endpoint event was the occurrence of renal insufficiency.Children with IMN were further divided into endpoint event group and non-endpoint event group according to the presence or absence of endpoint events at the last follow-up.Survival analysis was performed using the Kaplan-Meier survival curve method.The Cox proportional risk model method was used to analyze the factors influencing the prognosis of poor kidney outcomes in children with IMN. Results:(1)A total of 128 children were included, with the male-to-female ratio of 1.13∶1.00.The median age of onset and peak age of onset were 13.0 (10.3, 15.0) years, and 12-16 years (68.8%), respectively.Massive proteinuria was detected in 119 cases (93.0%), including 103 cases (80.5%) with massive proteinuria and hematuria, 4 cases(3.1%) with simple hematuria, and 5 cases (3.9%) with non-renal proteinuria.There were 29 cases (22.7%) in group A and 99 cases (77.3%) in group B. (2)Blood triacylglycerol level was significantly higher in group B than that of group A[2.1 (1.5, 3.0) mmol/L vs.1.7(1.1, 2.5) mmol/L], while high-density lipoprotein[1.5(1.1, 1.8) mmol/L vs.1.8(1.4, 2.1) mmol/L], serum albumin[22.0(17.0, 27.3) g/L vs.25.5 (21.0, 32.5) g/L] and complement C3[(1.1±0.2) g/L vs.(1.2±0.2) g/L] were significantly lower in group B than those of group A (all P<0.05). (3)Complete clinical data during hospitalization and follow-up data were obtained from 91 children with IMN, with a median follow-up time of 87.0 (49.0, 104.5) months.Among them, 5 cases (5.5%) progressed to ESRD, involving 3 cases received renal transplantation, and 9 cases (9.9%) had secondary endpoints.Cumulative renal survival rate for ESRD at 5 and 10 years were 96.2% and 92.9%, respectively, which, for the secondary endpoints at 5 and 10 years were 95.2% and 84.8%, respectively.(4)Kaplan-Meier survival analysis showed no significant difference in the cumulative renal survival between group A and group B ( P>0.05). Multifactorial Cox regression analysis showed that tubular atrophy/interstitial fibrosis was an independent risk factor for renal insufficiency in children with IMN ( HR=0.102, 95% CI: 0.011-0.940, P<0.05). Conclusions:Massive proteinuria combined with hematuria is the major clinical manifestation of IMN in children, and atypical MN is the major pathological manifestation.Tubular atrophy/interstitial fibrosis is an independent risk factor for renal insufficiency in children with IMN.

Clinical diagnosis and prognostic value of serum TLR4 and VEGFA expression in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and clinical significance of Toll-like receptor 4(TLR4)and vascular endothelial growth factor A(VEGFA)in the serum of patients with diabetic retinopathy(DR).METHODS: A total of 183 patients with type 2 diabetes mellitus(T2DM)admitted to our hospital from January 2021 to January 2022 were collected as the study subjects. They were grouped into non diabetic retinopathy(NDR)group(n=54), proliferative diabetic retinopathy(PDR)group(n=68)and non proliferative diabetic retinopathy(NPDR)group(n=61). In the same period, 70 volunteers who underwent physical examination in our hospital were randomly stratified according to age and sex. After discharge, DR patients were followed up for 1a and grouped into a poor prognosis group(n=40)and a good prognosis group(n=89)based on whether they had visual impairment. Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of TLR4 and VEGFA in serum; Logistic regression was applied to analyze the influencing factors of DR; receiver operating characteristic(ROC)curve was applied to analyze the clinical value of serum TLR4 and VEGFA levels in diagnosing DR and predicting prognosis.RESULTS: There were statistical significance in TLR4 and VEGFA levels among the control group, NDR group, PDR group, and NPDR group(F=935.753, 516.936, all P&#x003C;0.05), and further pairwise comparisons showed statistical significance(P&#x003C;0.05); the expression levels of TLR4 and VEGFA in the serum of patients with poor prognosis were higher than those of patients with good prognosis(P&#x003C;0.01); the results of Logistic regression analysis showed that TLR4, VEGFA, course of disease, and HbA1c were all risk factors for the occurrence of DR(P&#x003C;0.05); the ROC results showed that the AUC of serum TLR4, VEGFA levels, and their combination for predicting DR was 0.869, 0.862, and 0.931, respectively, the AUC of serum TLR4, VEGFA levels, and their combined prediction of visual disability in DR patients was 0.864, 0.863, and 0.938, respectively.CONCLUSION: The expression of TLR4 and VEGFA in serum of DR patients is up-regulated, and the combined detection of TLR4 and VEGFA can be used as a potential indicator to evaluate the occurrence and poor prognosis of DR.

Research progress on the mechanism of exosomes in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Protective effect and mechanism of Ershiwuwei Zhenzhu Pills on cerebral apoplexy rats / 中国中药杂志

To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1β and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.

Comparison of therapeutic effects of non-vitrectomy versus vitrectomy for idiopathic epiretinal membrane / 中华眼底病杂志

Objective:To compare the efficacy of pars plana vitrectomy (PPV) and nonvitrectomizing vitreous surgery (NVS) in the treatment of idiopathic epimacular membrane (IMEM).Methods:A prospective , randomized and comparative clinical study. From April 2019 to May 2020, 21 eyes of 21 patients with IMEM diagnosed in Chongqing Aier Eye Hospital were included in the study. Among them, 11 males had 11 eyes, and 10 females had 10 eyes. Best-corrected visual acuity (BCVA), optical coherence tomography angiography (OCTA), and corneal, intraocular, and global aberration measurements were performed in all eyes. The international standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted into logarithm of minimum angle of resolution (logMAR) during statistics. The iTrace visual function analyzer was used to measure the corneal, intraocular and whole ocular aberrations, and the dysfunction lens index (DLI) was calculated. Lens density in Scheimpflug images was calculated using Pentacam three-dimensional anterior segment analysis and diagnosis system. The 6 mm×6 mm area of the macular area was scanned by OCTA, which was divided by the software automatically into three concentric circles with the fovea as the center, namely the central area with a diameter of 1 mm, the inner ring area with a diameter of 1-3 mm, The outer ring area of 3-6 mm was used to measure the superficial vessel density (SVD) and superficial perfusion density (SPD) of the entire macular area, the central area, the inner ring area, and the outer ring area. The patients were divided into PPV combined with epimacular membrane (MEM) peeling group (PPV group) and NVS direct peeling MEM group (NVS group) by random number table method, 10 cases with 10 eyes and 11 cases with 11 eyes, respectively. The age of the two groups ( t=-0.72), logMAR BCVA ( t=-0.98), lens density ( t=-1.10), DLI ( t=1.15), SVD ( t=0.82) and SPD ( t=1.19) of entire macular area, corneal aberration ( t=0.45), intraocular aberration ( t=-0.22), and whole eye aberration ( t=0.83), there was no significant difference ( P>0.05). All eyes were operated on with a 27G vitrectomy system. The MEM was removed from the eyes of the NVS group under NVS condition, and the MEM was removed from the eyes of the PPV group under the condition of PPV, and the operation time was recorded at the same time. The follow-up period after surgery was 12 months. Relevant examinations were performed using the same equipment and methods before surgery. Taking the last follow-up as the time point for efficacy judgment, the BCVA, lens opacity, DLI, visual quality, SVD, SPD and MEM recurrence in the macula were compared between the two groups. The two groups were compared by paired t test. Results:The operation time of eyes in PPV group and NVS group was 20.81±3.52 and 5.70±1.30 min, respectively, and the difference was statistically significant ( t=7.23, P<0.001). At the last follow-up, the logMAR BCVA of PPV group and NVS group were 0.65±0.25 and 0.44±0.20, respectively, and the difference was statistically significant ( t=-2.16, P=0.04); compared with before operation, the BCVA of eyes of the two groups was significantly improved, and the difference was statistically significant. ( t=2.52, 4.41; P=0.033, P<0.001). The lens density and DLI of the affected eyes in the PPV group and NVS group were 10.64±1.58, 6.24±3.99 and 5.77±1.63, 7.74±1.55, respectively, and the differences were statistically significant ( t=-3.90, 2.85; P<0.05). The macular area SVD ( t=1.03), SPD ( t=1.77), corneal aberration ( t=-0.42), intraocular aberration ( t=-1.10), and whole-eye aberration ( t=-1.17) of eyes of the two groups, the difference was not statistically significant ( P>0.05). During the follow-up period, there were 2 eyes with MEM recurrence, 1 eye in the PPV group and 1 eye in the NVS group; there was no significant difference in the recurrence rate of MEM between the two groups ( χ2=0.005, P=0.94). Conclusion:Compared with PPV combined with MEM stripping, the BCVA after NVS surgery increases more, has a better protective effect on the lens, and has a shorter operation time.

Effects of thromboelastography guided blood transfusion on blood potassium, coagulation parameters and prognosis in patients with post-traumatic massive hemorrhage / 中国医师进修杂志

Objective:Analyze the influence of blood transfusion therapy under the guidance of thromboelastography on the blood potassium and coagulation indicators and prognosis of patients with post-traumatic hemorrhage.Methods:The clinical data of 73 patients with post-traumatic hemorrhage in Liyang People′s Hospital from March 2018 to February 2021 were retrospectively analyzed. Among them, TEG blood transfusion guidance group (group A) and conventional coagulation indicator guidance group (group B) were divided according to whether TEG test was performed. Repeated measurement analysis of variance and post LSD- t test were used to observe serum potassium, coagulation indexes and prognosis of 2 groups at each time point. Results:The amount of various drugs used in group A was significantly lower than that in group B ( P<0.05). Comparison of serum potassium levels between the two groups before transfusion: (3.94 ± 0.85) mmol/L vs. (3.98 ± 0.71) mmol/L; and on the first day after transfusion: (4.33 ± 0.48) mmol/L vs. (4.57 ± 0.73) mmol/L, there were statistically significant ( P<0.05); on day one. day two and day three after blood transfusion, the indexes of PT and APTT in group A were significantly lower than those in group B: PT: (14.30 ± 1.43) s vs. (16.25 ± 1.74) s, (14.41 ± 1.55) s vs. (16.27 ± 1.48) s, (14.73 ± 1.50) s vs. (16.30 ± 1.45) s; APTT: (32.3 ± 3.6) s vs. (36.7 ± 3.5) s, (32.6 ± 3.4) s vs. (36.8 ± 3.6) s, (32.2 ± 3.2) s vs. (36.3 ± 3.3) s; the above indexes of the two groups before treatment were significantly higher than those at each time point after treatment ( P<0.05). The total effective rate of hemostasis in group A was higher than that in group B: 97.37%(37/38) vs. 80.00%(28/35), P<0.05. Conclusions:Patients with post-traumatic hemorrhage can be recovered by blood transfusion under the guidance of thromboelastography, and the disorder of blood coagulation indicators can be restored, and at the same time, it has a better hemostatic effect.

Correlation of serum testosterone level with coronary artery disease features and its prognosis in elderly male patients with coronary heart disease / 中华老年医学杂志

Objective:To investigate the correlation of serum testosterone level with severity and characteristics of coronary plaque, stent implantation rate and major cardiovascular adverse events(MACE)in elderly male patients with coronary heart disease(CHD).Methods:In this retrospective study, a total of 63 elderly male patients of the Third People's Hospital of Hangzhou with coronary angiography(CAG)-confirmed CHD and to undergo percutaneous coronary intervention(PCI)were selected.According to serum testosterone level, they were divided into the low testosterone(low T)group and the normal testosterone(normal T)group.Optical coherence tomography(OCT)was performed in both groups to define the characteristics of coronary artery lesions and guide stent implantation.The correlation of serum testosterone level with blood lipids, glycated hemoglobin(HbA1c), degree of coronary artery lesions, plaque characteristics, stent implantation and MACE in two groups were analyzed.The in-stent restenosis rate after stent implantation and the variation of minimum lumen diameter of stent were determined during 12 months follow up in both groups.Results:Total cholesterol(TC), low-density lipoprotein(LDL-C)and HbA1c were higher in the low T group than in the normal T group( t=7.808、-5.871、6.611, all P<0.05). When taking testosterone as the independent variable, and TC, triglycerides(TG), LDL-C, high density lipoprotein cholesterol(HDL-C)and HbA1c as the dependent variables, linear regression analysis showed that TC, LDL-C and HbA1c were negatively correlated with testosterone level( β=-0.733, -0.716, -0.581, P<0.05). More than 2 vascular lesions were more common in low testosterone group versus the control group( χ2=8.66, P<0.05). Mixed plaques, lipid plaques, and calcified plaques were more commonly found in low testosterone group versus the control group( χ2=7.87, P<0.05). Unstable plaques were more common in the low T group( χ2=6.14, P<0.05). The low T group vs the normal T group, coronary stent implantation rate were 93.3%(28/30 cases) vs.66.7%(22/33 cases), the difference was statistically significant( χ2=6.82, P<0.05). When testosterone, TC, TG, LDL-C, HDL-C, HbA1c were taken as the independent variables, and the stent implantation rate was the dependent variable, logistic regression analysis results showed that only testosterone, TC and HbA1c were independently correlated with stent implantation rate( OR=0.971、425.523、0.004, P<0.05). There was no statistically significant difference in minimum stent lumen diameters between the two groups under OCT-guided coronary stent implantation( t=-1.064, P>0.05). During 12 months follow up, the MACE0 incidence was 26.7%(8/30 cases, in low T group)than 6.1%(2/33 cases, in normal T group), with statistically significant difference( χ2=5.00, P<0.05). When taking testosterone, TC, TG, LDL-C, HDL-C and HbA1c as the independent variables, and MACE as the dependent variable, logistic regression analysis results showed that only testosterone and LDL-C were independently correlated with MACE( OR=0.968, 0.008, P<0.05). Conclusions:Serum testosterone level is negatively correlated with TC, LDL-C and HbA1c, and may be correlated with the degree of coronary artery lesions, plaque properties, MACE and stent implantation rate of CHD patients.Serum testosterone can be used to evaluate the characteristics and conditions of CHD, and help to predict the prognosis of CHD.The OCT is a good guide tool for coronary stent implantation.

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

Analysis of Differential Proteins Related to Platelet Activation in Patients with Essential Thrombocythemia Based on Label-Free Quantitative Technology / 中国实验血液学杂志

OBJECTIVE@#To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation.@*METHODS@#Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P＜0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P＜0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology.@*RESULTS@#A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing.@*CONCLUSION@#Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.