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Objective@#: Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. @*Methods@#: A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. @*Results@#: Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). @*Conclusion@#: Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.
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This study aimed to assess the hypoglycemic activity, and in vitro inhibition of α-glucosidase, inhibition of the advanced glycation end products (AGEs), and total antioxidant capacity were used to clarify its bioactivity. Furthermore, the potential hypoglycemic active chemical constituents in the aqueous extract of Osmanthus fragrans var. thunbergii flower were characterized using high performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) method. The result showed that in vitro inhibition of α-glucosidase of the extract (IC50 = 2.11 ± 0.26 mg·mL-1) were similar to acarbose (IC50 = 2.88 ± 0.32 mg·mL-1), and it inhibited the AGEs formation and the total antioxidant capacity in a certain extent. Based on the MS fragmentation pathway analysis of reference chemical acteoside contained in this extract, and related references, 73 constituents were tentatively identified from the aqueous extract of Osmanthus fragrans var. thunbergii flower, including 58 phenylethanoids, 8 caffeoylquinic acids, 1 flavonoid vicenin-2, and 6 common organic chemicals in plant. Furthermore, 8 unknown alkaloids were characterized in this work. Among of these chemicals, 61 phenylethanoids were supposed to be detected for the first time. In conclusion, this work disclosed the potential hypoglycemic active constituents of Osmanthus fragrans var. thunbergii flower.
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Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β1 （TGF-β1） can induce the activation of hepatic stellate cell （HSC）， and TGF-β1/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β1 signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β1/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β1 signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β1/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β1/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β1/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β1/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.
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Objective:To analyze the laboratory detection methods and clinical characteristics of patients with 2019-nCoV Omicron variant infection, to realize the rapid identification and diagnosis of 2019-nCoV Omicron variants.Methods:Totally 80 overseas patients in First Hospital of Changsha from December 16 in 2021 to January 5 in 2022 were selected, the nucleic acids and mutant genes were detected by fluorescent PCR and genome sequencing, and the clinical characteristics of patients with 2019-nCoV Omicron variant infection were analyzed.Results:The specificity was 100% (58/58) and positive predictive value was 100% (21/21) respectively, the sensitivity was 95.5% (21/22), negative predictive value was 98.3% (58/59) by detected with fluorescent PCR. It was found that there were 45-50 nucleotide displacement sites in the genome and 25-30 amino acid mutation sites in S gene fragment by genome sequencing. Clinical analysis showed that mild cases were 59.1% (13/22) in layouts, without severe and critical cases. Ages were positively associated with the clinical classification (ρ=0.698, P<0.001), foundation infections were positively associated with the clinical classification (ρ=0.636, P<0.001). Conclusions:Patients with 2019-nCoV Omicron variant infection had a high viral load and long negative conversion time of nucleic acid. Ages and foundation infections were positively associated with the clinical classification. AST/ALT was higher in the early stage of the disease. Fluorescent PCR method can be used in rapid screening patients with 2019-nCoV Omicron variant infection.
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Objective:To study minimally invasive treatment using percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) to treat complicated hepatolithiasis.Methods:Patients with complicated hepatolithiasis who were treated at the Second Affiliated Hospital of Kunming Medical University from July 2017 to September 2021, were included into this study. There were 48 patients treated with PTCSL (the PTCSL group) and 150 patients treated with conventional open hepatectomy (the OH group). Propensity score matching (PSM) was used to match 40 patients in the PTCSL group with 40 patients in the OH group. There were 11 males and 29 females, aged 32 to 85 (59.3±12.7) years in the PTCSL group and 15 males and 25 females, aged 20 to 74 (55.4±10.9) years in the OH group. Theoperation time, intraoperative blood loss, hospitalization time, hospitalization cost, incidences of major complications (including pleural effusion, biliary bleeding), residual stone rates and recurrence rates were analyzed.Results:Baseline data were comparable between groups after PSM. For the PTCSL group, the operation time was (135.8±42.6) minutes, intraoperative bleeding volume 32.5(20.0, 50.0) ml, hospitalization time 13.5(11.0, 18.0) days, and hospitalization expense 3.4(2.9, 5.0) wanyuan compared with the corresponding figures in the OH group with operation time (350.7±113.8) minutes, intraoperative bleeding volume 475.0(200.0, 900.0) ml, hospitalization time 24.0(17.3, 28.8) days, and hospitalization expense 6.6(5.0, 8.9) wanyuan. The differences between the two groups were statistically significant (all P<0.05). The overall complication rate was 2.5%(1/40) in the PTCSL group and 22.5%(9/40) in the OH group (χ 2=7.31, P=0.007). The residual stone rate of 20.0%(8/40), stone recurrence rate of 17.5%(7/40), compared with the OH group with the stone residual rate of 27.5%(11/40), stone recurrence rate of 12.5%(5/40). There was no significant difference between the two groups in both the stone residual rates and stone recurrence rates (both P>0.05). Conclusion:In treatment of complex hepatolithiasis, the stone residual rate after repeated PTCSL was comparable to traditional open hepatectomy. PTCSL had the advantages of shorter operation time, less bleeding, lower hospitalization time, lower complication rate and lower hospitalization cost. PTCSL is worthy of wider application and popularization.
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Objective:To investigate the effect of different drainage methods on pancreatic fistula after pancreaticoduodenectomy (PD).Methods:The data of all patients with PD in Xijing Hospital, the First Affiliated Hospital of the Fourth Military Medical University from January 2007 to December 2018 were retrospectively analyzed. A total of 670 patients were enrolled, including 415 males and 255 females, aged (58.4±7.3) years, ranging from 24 to 82 years. According to the different method of pancreatic duct drainage, the propensity score was matched, and the patients were divided into internal drainage group ( n=529) and external drainage group ( n=141). The pancreatic fistula rate was compared between the two groups. Factors influencing pancreatic fistula after PD were analyzed by univariate and multivariate logistic regression. Results:The incidence of pancreatic fistula in the internal drainage group was 12.5% (66/529), which was significantly higher than that in the external drainage group 6.4% (9/141) (χ 2= 4.16, P=0.041). Multivariate logistic regression analysis showed that age ≥65 years ( OR=2.004, 95% CI: 1.185-3.390), complicated with digestive diseases ( OR=3.087, 95% CI: 1.599-5.959), history of upper abdominal surgery ( OR=2.031, 95% CI: 1.104-3.734) increased the risk of pancreatic fistula after PD (all P<0.05), decreased the risk of pancreatic fistula after PD in patients with external drainage ( OR=0.470, 95% CI: 0.223-0.989, P=0.047), and decreased the risk of pancreatic fistula after PD with the tumor size ( OR=0.725, 95% CI: 0.556-0.944, P=0.017), tumor located in the common bile duct after PD increased the risk of pancreatic fistula ( OR=1.497, 95% CI: 1.192-1.880, P=0.001). Conclusions:Compared with pancreatic duct drainage, external pancreatic duct drainage is better because of preventing postoperative pancreatic fistula.
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This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.
Subject(s)
Chromatography, High Pressure Liquid , Ginkgo biloba , Lactones/analysis , Least-Squares Analysis , Spectroscopy, Near-Infrared/methodsABSTRACT
OBJECTIVE@#To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses.@*METHODS@#Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice.@*RESULTS@#Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05).@*CONCLUSION@#A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.
Subject(s)
Animals , Mice , Acupuncture Points , Dermatitis, Atopic/therapy , Dinitrobenzenes , Dinitrochlorobenzene , Immunoglobulin E , Interferon-gamma , Interleukin-4 , Mice, Inbred BALB C , Saline SolutionABSTRACT
Five universities with health policy and management ranked top level worldwide, including Harvard University, John Hopkins University, Stanford University, University of North Carolina at Chapel Hill and National University of Singapore were selected in our study. From above universities, we found that the curriculum of PHD students was focused on research concentration, methodology courses, and numerous elective courses. Hence, in China, the curriculum of PHD students should be improved with emphasis on course studying, management courses and highlighting curriculum content according to research area to enhance the quality of doctoral education.
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Objective:To investigate the application value of preoperative clinical and magnetic resonance imaging (MRI) targetoid enhancement combined with alpha-fetoprotein in evaluating the expression of cytokeratin 19 (CK19) in patients undergoing radical resection for single hepatocellular carcinoma (HCC) without macrovascular invasion.Methods:The retrospective cohort study was conducted. The clinicopathological data of 220 patients who underwent radical resection for single HCC without macrovascular invasion in the General Hospital of Ningxia Medical University from January 2016 to December 2020 were collected. There were 171 males and 49 females, aged (56±11)years. Of the 220 patients, 52 cases showed positive CK19 expression, while 168 cases showed negative CK19 expression. Observation indicators: (1) MRI and immunohistochemical staining results of patients with different status of CK19 expression; (2) comparison of clinical features of patients with different status of CK19 expression; (3) comparison of MRI features in patients with different status of CK19 expression; (4) analysis of influencing factors for CK19 expression in patients and predictive value. The normality of continuous variables was tested using the Shapiro-Wilk test. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers and (or) percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The relevant clinical and imaging features with P<0.05 were included in the binary Logistic regression model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the predictive efficiency of the model. Results:(1) MRI and immunohistochemical staining results of patients with different status of CK19 expre-ssion. Results of MRI examination in patients with positive CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, annular high enhancement in the arterial phase, clear boundaries in the portal venous phase, central enhance-ment in the delayed phase and targetoid high signals on diffusion-weighted imaging (DWI). Immuno-histochemical staining revealed a positive CK19 expression. Results of MRI examination in patients with negative CK19 expression showed the tumors with low-signal intensity on plain T1-weighted imaging, non-annular high enhancement in the arterial phase, unclear boundaries in the portal venous phase, low signals compared with peripheral liver tissue in the delayed phase and uniform high signals on DWI. Immunohistochemical staining revealed a negative CK19 expression. (2) Clinical features of patients with different status of CK19 expression. The neutrophil count and cases with alpha-fetoprotein (AFP) ≥400 μg/L were 3.07(2.21,4.41)×10 9/L and 26 in patients with positive CK19 expression, versus 2.72(2.05, 3.51)×10 9/L and 48 in patients with negative CK19 expression, showing significant differences between them ( Z=?2.06, χ2=8.17, P<0.05). (3) Compari-son of MRI features in patients with different status of CK19 expression. Cases with tumor diameter ≥ 5 cm and cases with tumor showing targetoid enhancement were 34 and 22 in patients with positive CK19 expression, versus 82 and 24 in patients with negative CK19 expression, showing significant differences between them ( χ2=4.38, 18.86, P<0.05). (4) Analysis of influencing factors for CK19 expression in patients and predictive value. Results of multivariate analysis showed that AFP ≥ 400 μg/L and targetoid enhance-ment were independent risk factors for positive CK19 expression in HCC patients [ odds ratio=2.09, 3.23, 95% confidence interval ( CI) as 1.06?4.13, 1.49?6.99, P<0.05]. Results of ROC curve analysis showed that the AUC of targetoid enhancement for predicting positive CK19 expression was 0.64 (95% CI as 0.57?0.71), with the sensitivity and specificity as 42.31% and 85.71%. The AUC of AFP ≥400 μg/L for predicting positive CK19 expression was 0.61 (95% CI as 0.53?0.68), with the sensitivity and specificity as 51.00% and 71.43%. The AUC of targetoid enhancement combined with AFP ≥400 μg/L for predicting positive CK19 expression was 0.69 (95% CI as 0.61?0.77), with the sensitivity and specificity as 67.31% and 63.10%, respectively. Conclusions:Targetoid enhancement and AFP ≥400 μg/L are independent risk factors for positive CK19 expression in patients with single HCC without macrovascular invasion. Their combination has clinical value for preoperative evaluation of CK19 expression.
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Objective:To evaluate the efficacy of Zhongfeng Xingnao liquid combined with conventional treatment for acute ischemic stroke (AIS).Methods:A total of 92 patients with AIS in our hospital from May 2020 to March 2021 who met the inclusion criteria were selected and divided into 2 groups according to the end number of the medical records, with 46 cases in each group. Both groups were given conventional western medicine therapy, and the control group added intravenous drip of edaravone injection, and the study group added Zhongfeng Xingnao liquid on the basis of the control group. Both groups were treated continuously for 2 weeks. Before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) were used to evaluate the degree of neurological deficit and prognosis. The whole blood high-shear viscosity, hematocrit, whole blood low-shear viscosity, fibrinogen were detected by automatic blood rheometer, and the levels of high-sensitivity C-reactive protein (hs-CRP), IL-6 and endothelin-1 (ET-1) were detected by ELISA. Adverse events were recorded, and clinical effect rate was evaluated.Results:After treatment, the mRS score (2.06±0.18 vs. 2.73±0.23, t=15.56) and NIHSS score (5.25±2.36 vs. 10.61±2.48, t=14.58) of the study group were significantly lower than those in the control group ( P<0.01). The total clinical effective rate was 89.1% (41/46) in the study group and 69.6% (32/46) in the control group, with a statistically significant difference between the two groups ( χ2=5.37, P=0.020). After treatment, the serum levels of hs-CRP [(9.04±1.98)mg/L vs. (14.36±2.09)mg/L, t=12.57], IL-6 [(23.14±1.46)ng/L vs. (39.37±2.51)ng/L, t=12.39] and ET-1[(67.18±13.22)ng/L vs. (98.14±22.29)ng/L, t=19.37] in the study group were significantly lower than those in the control group ( P<0.01). The whole blood high shear viscosity [(7.53± 1.37)mPa·s vs. (9.24±1.42)mPa·s, t=5.89], hematocrit [(0.27±0.06)% vs. (0.39±0.08)%, t=8.14], whole blood low shear viscosity [(5.92±1.09)mPa·s vs. (8.35±1.24)mPa·s, t=9.98] and fibrinogen [(1.63±0.42) g/L vs. (2.47±0.58) g/L, t=7.96] were significantly lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse events was 8.70% (4/46) in the control group and 15.22% (7/46) in the study group, and there was no significant difference between the two groups ( χ2=0.93, P=0.335). After treatment, the good outcome rate was 73.9% (34/46) in the control group and 93.5% (43/46) in the study group, with a statistically significant difference between the two groups ( χ2=6.45, P=0.011). Conclusion:The Zhongfeng Xingnao liquid combined with edaravone injection can reduce the level of inflammatory cytokines in patients with AIS, improve hemorheological indicators, and play a role in brain protection.
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Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.
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Acupoint autohemotherapy at bilateral Zusanli (ST36) and Xuehai (SP10) was used to treat a 26-year-old female patient who had suffered from recalcitrant atopic eczema (AE) for five years. The treatment was applied at a frequency of once per week for the first month, followed by a three-month period of once every other week. At the end of treatment, the patient's AE symptoms were entirely resolved, and by the end of a six-month follow-up her immunoglobulin E level had returned to the normal range. Further, there was no relapse of AE symptoms during the six-month follow-up. Therefore, we hypothesized that after the repeated treatments the local inflammatory reaction induced by autologous blood injection triggered a local immune response, followed by a systemic immune response after the repeated treatment, finally leading to the anti-inflammation and immunomodulation effects. This case suggests that acupoint autohemotherapy could be used as an effective complementary treatment for recalcitrant AE, especially in cases where other treatments have failed. Further comparative studies are needed to corroborate the value and mechanisms of this therapy.
Subject(s)
Female , Humans , Acupuncture Points , Adult , Dermatitis, Atopic/therapy , Inflammation , Treatment OutcomeABSTRACT
Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.
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This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.
Subject(s)
Animals , Male , Mice , Diabetes Mellitus , Diabetic Nephropathies/genetics , Iridoids , Kidney , Signal TransductionABSTRACT
Objective: To guide the patients with vertigo who are suitable for vestibular rehabilitation therapy (VRT), and to evaluate the curative effect through a remote guidance platform based on mobile internet. Methods: Adult outpatients, who were diagnosed as vestibular disorders and required VRT, were selected and conducted baseline evaluation and formulated vestibular rehabilitation plan according to their symptoms, diagnosis and vestibular function examination results. These patients downloaded and installed the mobile internet remote guidance platform app for VRT, and then registered and uploaded medical records. According to the VRT plan formulated by clinicians for patients, the platform launched corresponding exercise guidance videos to guide them to complete 4-week VRT exercise at home. Before and after VRT, the patients were scored with Visual Analogue Scale (VAS), Activities-specific Balance Confidence (ABC), Dizziness Handicap Inventory (DHI) and Self-rating Anxiety Scale (SAS). The rehabilitation effects were statistically analyzed by SigmaStat 4.0 software. Results: From October 2019 to October 2021, 233 patients with vertigo completed the registration of vestibular rehabilitation guidance platform, of whom 187 patients insisted on 4-week rehabilitation training and completed the scale evaluation. Among 187 patients, 65 were male and 122 were female; Age was (49.8±16.0) years; The medical history ranged from one to 192 months, with a median of eight months. Compared with that before rehabilitation exercise, the subjective feeling of vertigo in 170 patients was improved, and the overall effective rate was 90.9% (170/187). The subjective symptoms of vertigo were basically improved after rehabilitation training in patients with unilateral vestibular dysfunction, vestibular neuritis, sudden deafness with vertigo, Hunt syndrome and acoustic neuroma. There were significant differences in ABC, DHI and SAS scores before and after VRT (P<0.05). Of those patients with Meniere's disease in the intermittent period and the patients with Meniere's disease who underwent surgical treatment, more than 90% of their subjective symptoms of vertigo or dizziness improved after VRT, and there were significant differences in the scores of ABC, DHI and SAS before and after VRT exercise (P<0.05). In patients with vestibular migraine, 36.7% (11/30) had no improvement or even aggravation of subjective symptoms of vertigo after VRT, however, the DHI score after rehabilitation exercise was lower than that before exercise, and the difference was statistically significant (P<0.05). In patients with bilateral vestibular dysfunction, although most (6/8) subjective symptom scores were improved compared with those before exercise, there was no significant difference in ABC, DHI and SAS scores before and after rehabilitation (P>0.05). Conclusion: VRT with the help of vestibular rehabilitation mobile internet remote guidance platform can effectively improve the subjective symptoms of vertigo, balance ability and anxiety in patients with unilateral vestibular lesions.
Subject(s)
Female , Humans , Male , Adult , Dizziness , Internet , Postural Balance , Vertigo , Vestibular Neuronitis/diagnosisABSTRACT
Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Aortic Valve , Aortic Valve Stenosis/surgery , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation , Prospective Studies , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
We predicted the anti-hepatitis B virus (HBV) active components and mechanism of Salvia miltiorrhiza based on network pharmacology. The active components of S. miltiorrhiza were obtained through TCMSP, PubChem database and literature research. The potential targets of the active components and HBV infection were predicted by SwissTargetPrediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID platform. The molecular docking of key components and core targets was carried out by AutoDock Vina software. We screened out a total of 38 active components and 178 disease-component overlapping targets. Enrichment analyses obtained 405 related GO items and 68 signaling pathways, such as T/B cell receptor signaling pathways, PI3K/AKT signaling pathway, and mTOR signaling pathway. According to the results of molecular docking, most characteristic components of S. miltiorrhiza (miltionone Ⅱ, miltirone, protocatechuic acid, lithospermic acid, protocatechualdehyde) showed good affinity with the key targets (PIK3CA, APP, STAT3,AKT1 and mTOR). Furthermore, the anti-HBV activity of lithospermic acid, the representative active component of S. miltiorrhiza, and its regulation on PI3K/AKT and mTOR signaling pathways were investigated in an HBV replicating mouse model. Animal welfare and experimental procedures follow the regulations of the Animal Ethics and Welfare Committee of Hubei University. The results showed that lithospermic acid significantly inhibited HBV DNA replication, reduced serum HBsAg and HBeAg levels, and decreased the phosphorylation protein expression levels of AKT and mTOR in liver, indicating that lithospermic acid might exert the anti-HBV activity by regulating PI3K/AKT and mTOR signaling pathways.
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To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.
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AIM:To analyze the compliance and curative effect of comprehensive vision training in patients with amblyopia. METHODS:A prospective study was conducted among 200 patients(294 eyes)with amblyopia who were treated in the hospital from July 2018 to August 2019. The patients were divided into a control group(98 patients, 140 eyes, traditional comprehensive vision training)and an experimental group(102 patients, 154 eyes, intelligent multi-dimensional comprehensive vision training)according to the random number table method. Curative effect, compliance, and the correlation between the two groups were observed.RESULTS:The overall response rate and compliance rate in the experimental group(93.5%, 45.1%)were higher than those in the control group(80.0%, 35.7%, all P<0.05). The curative effect was different in patients of different age, with different types and severity of amblyopia, different nature of fixation, and different compliance(all P<0.001). Age and the severity of amblyopia were negatively correlated with the curative effect(r=-0.342, -0.459, P<0.001), while compliance was positively correlated with the curative effect(r=0.378, P<0.001). Patients aged 3-6 had significantly better compliance, followed by those aged 7-10(P<0.05). Age was negatively correlated with treatment compliance(r=-0.398, P<0.001).CONCLUSION:Intelligent multi-dimensional comprehensive vision training can improve the compliance of patients with amblyopia, thereby achieving better curative effect. The curative effect is closely related to age, the type and severity of amblyopia, the nature of fixation and compliance. Compliance is related to age. Clinically, early treatment should be conducted bases on these features.