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Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.
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Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.
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Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
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Objective:To investigate the efficacy of galantamine combined with Fufang Haishe Jiaonang in the treatment of Alzheimer's disease and its effects on serum levels of inflammatory factors, Aβ1-42 protein, and Tau protein. Methods:A total of 104 patients with Alzheimer's disease who received treatment in Jiaozhou People's Hospital from January 2019 to January 2021 were included in this study. They were randomly divided into a control group and an observation group ( n = 52/group). The control group was given galantamine treatment. The observation group was given galantamine combined with Fufang Haishe Jiaonang. All patients were treated for 3 months. Clinical efficacy was compared between the two groups. Before and after treatment, serum inflammatory factor, Aβ1-42 protein, Tau protein, Mini-Mental State Examination score, and The Quality of Life in Alzheimer's Disease Seale score were compared between the two groups. Adverse reactions were observed during the treatment. Results:Total response rate in the observation group was significantly higher than that in the control group [92.31% (48/52) vs. 76.92% (40/52), χ2 = 4.73, P < 0.05]. After treatment, serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and Tau protein in the observation group were significantly lower than those in the control group, and Aβ1-42 protein level in the observation group was significantly higher than that in the control group ( t = 16.78, 6.94, 5.16, 2.91, 2.55, all P < 0.05). After treatment, Mini-Mental State Examination score and The Quality of Life in Alzheimer's Disease (QOL-AD) Seale score were increased in each group ( t = 13.48, 6.34, 18.58, 14.45, all P < 0.001), and they were significantly higher in the observation group than the control group ( t = 5.86, 7.25, both P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Galantamine combined with Fufang Haishe Jiaonang for the treatment of Alzheimer's disease can better reduce clinical symptoms and signs, regulate serum levels of inflammatory factors, Aβ1-42 protein, and Tau protein, and improve the mental state and quality of life.
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Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circu-lating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based micro-fluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.
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Traditional Chinese Medicine (TCM) external therapy for sleep disorder of chronic fatigue syndrome (CFS) has good anti-fatigue effect and can improve sleep quality of patients. The treatment for sleep disorders of CFS with TCM external treatment mainly adopts acupuncture, moxibustion, massage, TCM bath, transcutaneous acupoint electrical stimulation and auricular point sticking, etc., or alone, or comprehensive application, or combined with oral Chinese materia medica. The appropriate treatment method can be selected according to the patients' condition and compliance, which reflects the unique advantages of TCM syndrome differentiation and treatment and the treatment according to people and time. The existing research still needs to further form a standardized and recognized diagnosis and treatment system, so as to better guide clinical popularization and application.
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Objective:To explore the clinical characteristics, treatment regimens and prognostic influencing factors of patients with multiple myeloma (MM) involving central nervous system (CNS).Methods:The clinical data of 18 MM patients involving CNS in Second Affiliated Hospital of Naval Medical University from January 2014 to June 2020 were retrospectively analyzed. Their clinical characteristics, treatment and prognosis were also analyzed. Kaplan-Meier method was used to make survival analysis and log-rank was performed; Cox proportional risk model was used to make univariate and multivariate analysis.Results:The cohort of 18 patients included 12 males and 6 females; the median age of patients involving CNS was 54 years (38-71 years). The median time from diagnosis to the involvement of CNS was 22 months (0-126 months).Among 18 patients, 1 case was primary MM involving CNS, and 17 cases were secondary MM involving CNS. All patients had Durie-Salmon (DS) stage Ⅲ; 10 cases had international staging system (ISS) stage Ⅲ, 6 cases had ISS stage Ⅱ, and 2 cases had ISS stage Ⅰ. Involvement sites of CNS included 7 cases of involving the dura mater alone and 4 cases of involving the pia mater alone, 2 cases of involving brain parenchyma and 5 cases of involving both meninges and brain parenchyma. The most common neurological symptoms were headache and cranial nerve palsy, and 9 patients had multiple neurological symptoms. All patients received systemic therapy, 16 patients received an intrathecal injection and/or radiotherapy; and the overall effective rate was 66.7%, including 3 achieving strict complete remission (sCR), 1 achieving complete remission (CR), 3 achieving very good partial remission (VGPR), 5 achieving partial remission (PR). The median overall survival (OS) was 32.7 months. Counting from the point of CNS involvement, the median progression-free survival (PFS) and OS time was 7.5 months, 12.2 months, respectively. The median PFS of MM patients in the dura-involved alone group was longer than that in the non-dura-involved alone group (15.1 months vs. 5.9 months, P = 0.009); the median OS of MM patients in the dura-involved alone group was longer than that in the non-dura-involved alone group (16.9 months vs. 10.7 months, P = 0.175). Multivariate Cox analysis showed that dura mater involvement alone was an independent factor affecting PFS in MM patients with CNS involvement ( HR = 0.191,95% CI 0.038-0.952, P = 0.043). Conclusions:MM involving CNS is rarely found and has a very poor prognosis. Different sites of CNS involvement could affect the prognosis of patients. There is a lack of effective treatment regimens.
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BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.
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Humans , Quality of Life , China , Arthritis, Rheumatoid/drug therapy , Piperidines/therapeutic use , Treatment Outcome , Antirheumatic Agents/therapeutic use , Pyrroles/therapeutic useABSTRACT
Background@#and Purpose To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). @*Methods@#Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. @*Results@#A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4–53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8–15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. @*Conclusion@#TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.
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Aim To explore the effect of ZLY18 on angiotensin II-induced cardiac fibrosis and the underlying mechanism. Methods Ang II was used to induce cardiac fibrosis in vitro and in vivo. Cardiac fibroblasts were divided into blank control group, model group and medicine group. The medicine group was subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 1, 2, 5 μmol·L-1 respectively. C57BL/6 mice were randomly divided into control group, model group and medicine group. The medicine group were subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 10,20 and 50 mg·kg-1 respectively. Both the model group and the medicine group were given with Ang II to induce cardiac fibrosis. The changes of protein levels were detected by Western blot and immunofluorescence. The changes of cardiac function indexes in C57BL/6 mice were detected by small animal echocardiography. The morphology, cell arrangement and collagen fibers of cardiac fibroblasts were observed by tissue section staining and other methods. Results The model of Ang II-induced myocardial fibrosis was successfully established at the cell and animal levels, and ZLY18 treatment improved the elevated fibrosis-related protein caused by Ang II and abnormal cardiac function in mice. Moreover, ZLY18 was able to inhibit the increased phosphorylation of TGF-1 and Smad3 caused by Ang II and increased Smad2/3 nuclear entry, suggesting that the antifibrotic effect of ZLY18 might be related to the activation of TGF-1/Smads signaling pathway. Conclusions ZLY18 has a protective effect on Ang II-induced cardiac fibrosis. ZLY18 may inhibit TGF-β/Smads signaling pathway activation to exert anti-fibrotic effects.
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The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study. However, few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy. In this study, a decreased level of SNX3 in Dox-induced cardiomyopathy was observed. Cardiac-specific Snx3 knockout (Snx3-cKO) significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly. SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro, and cardiac-specific Snx3 transgenic (Snx3-cTg) mice were more susceptible to Dox-induced ferroptosis and cardiomyopathy. Mechanistically, SNX3 facilitated the recycling of transferrin 1 receptor (TFRC) via direct interaction, disrupting iron homeostasis, increasing the accumulation of iron, triggering ferroptosis, and eventually exacerbating Dox-induced cardiomyopathy. Overall, these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRC-dependent ferroptosis.
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Stroke is one of the most common cerebrovascular diseases， including hemorrhagic stroke and ischemic stroke. From a modern medical perspective， stroke is caused by cerebrovascular damage or embolism leading to impaired blood circulation. From the traditional Chinese medicine （TCM） perspective， the pathogenesis of this disease is mainly due to the disorder of Qi and blood， which ascend to the brain， causing either blood extravasation or blockage of brain collaterals. Stasis is a pathological factor that runs throughout the entire course of stroke， and the method of promoting blood circulation and resolving stasis has been a core treatment for stroke for a long time. Hirudo， as a traditional insect drug， has shown good effects in promoting blood circulation and resolving stasis. Modern pharmacological research has confirmed that Hirudo contains anticoagulant components， which provide significant advantages in dissolving thrombi in ischemic stroke and facilitating hematoma absorption in hemorrhagic stroke. Hirudo and its related preparations have been proven to exert an anti-stroke effect through anticoagulation， anti-thrombosis， and protection of vascular endothelium. As a result， they have been widely used in the treatment of stroke. This article explored the theoretical basis and research status of using Hirudo for treating stroke based on its main active components and hemostatic properties and summarized the current research status of commonly used Hirudo-based formulations and preparations， aiming to provide references for the involvement of Hirudo in stroke treatment.
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An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.
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Objective To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival (DFS); univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve (AUC) of 0.674 (95% confidence interval [ CI ]: 0.580-0.767) in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745 (95% CI : 0.652-0.838). The survival analysis showed that high preoperative serum levels of AFP (≥250.0 ng/mL) and ALP (≥95.5 U/L) were significantly associated with the poor prognosis of HCC patients ( P < 0.001). Based on the AFP-ALP score, all HCC patients were further divided into 0-point group (AFP < 250.0 ng/mL and ALP < 95.5 U/L), 1-point group (AFP≥250.0 ng/mL, ALP < 95.5 U/L; or AFP < 250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group (AFP≥250.0 ng/mL and ALP≥95.5 U/L). The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0 (56.7-67.3) months, 20.0 (1.4-36.6) months, and 13.0(7.9-18.0) months, respectively, and there were significant survival differences between the three groups ( P < 0.05). Serum AFP-ALP score (1 point vs 0 point: hazard ratio [ HR ]=4.060, 95% confidence interval [ CI ]: 2.050-8.039, P < 0.001; 2 points vs 0 point: HR =4.583, 95% CI : 2.385-8.805, P < 0.001) was an independent prognostic factor for HCC patients. Conclusion The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC.
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OBJECTIVE To explore the role and underlying mechanism of tournefolic acid B （TAB） on the improvement of glucose metabolism and renal function in diabetic nephropathy （DN） model mice. METHODS DN model mice were established by high-fat diet combined with streptozotocin， and then randomly divided into model group， positive control group （vitamin E， 20 mg/kg）， TAB low-dose， medium-dose and high-dose groups （1， 2， 4 mg/kg）， with 12 mice in each group； normal control group was given regular diet. Each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. The glucose metabolic function was estimated by fasting blood glucose， glucose tolerance test， insulin tolerance test and serum insulin concentration. The renal coefficients and biochemical indicators related to renal function [serum uric acid， blood urea nitrogen， creatinine levels， and ratio of urine microalbumin to creatinine] were detected in mice； the contents of biochemical indicators related to oxidative stress [superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， 8-hydroxydeoxyguanosine （8-OHdG）] were determined in renal tissue of mice； the pathological morphology of renal tissue was observed； the expressions of extracellular matrix （ECM） deposition related factors [transforming growth factor β1 （TGF- β1）， fibronectin （Fn）， type Ⅳ collagen （Col Ⅳ）] and protein kinase B （Akt）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway related proteins were determined in renal tissue of mice. RESULTS Compared with normal control group， fasting blood glucose， area under glucose tolerance curve， area under insulin tolerance curve， serum insulin content， the levels of uric acid， urea nitrogen and creatinine @qq.com and ratio of urinary microalbumin to creatinine in serum， the contents of MDA and 8-OHdG and the protein expressions of TGF-β1， Fn and Col Ⅳ were increased significantly in model group （P＜0.05）， while the contents of SOD， GSH-Px and the protein expressions of p-Akt， Nrf2， HO-1 in renal tissue were decreased significantly （P＜0.05）； the significant thickening of the basement membrane， accumulation of mesangial matrix， glomerulosclerosis and interstitial fibrosis of the renal tubules were all found. Compared with model group， above indexes of mice were all reversed significantly in TAB groups （P＜0.05）， and pathological changes were alleviated in a dose-dependent manner. CONCLUSIONS TAB can improve blood glucose metabolism and kidney function and alleviate renal tubulointerstitial fibrosis in DN model mice， the mechanism of which may be associated with activating the Akt/Nrf2/HO-1 signaling pathway and suppressing ECM deposition.
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Objective@# To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. @*Methods@# (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis.@*Results@#(i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levelsof the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). @*Conclusion@#LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.
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Objective:To explore the value of Glasgow coma score (GCS) combined with optic nerve sheath diameter (ONSD) in predicting the death risk of patients with cerebrocardiac syndrome (CCS).Methods:From January 2021 to September 2021, 83 patients with CCS secondary to severe traumatic brain injury (sTBI) in our hospital were collected and divided into a survival group ( n = 37) and death group ( n = 46) according to CCS-related death. The clinical data including age, sex, underlying diseases, head CT imaging manifestations, electrolytes, blood glucose, C-reactive protein (CRP), neuron-specific enolase (NSE), lactate dehydrogenase (LDH), creatine kinase (CK), creatine phosphokinase isoenzyme (CKMB), intracranial pressure (ICP), ONSD, cardiac color ultrasound, acute physiology and chronic health evaluationII (APACHEⅡ ) and GCS were analyzed and compared between the two groups. The proportion and dosage of vasoactive drugs used at admission, daily fluid balance volume during hospitalization, total amount of sedative and analgesic drugs, and average daily dose were analyzed and compared between the two groups. The independent risk factors for CCS-related death were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the independent risk factors in CCS-related death. Results:In this study, 55.4% of the patients died of CCS. The ONSD, ICP change rate, right ventricular Tei index and NSE in the death group were higher than those in the survival group, with statistically significant differences ( P < 0.05), while the GCS in the death group was significantly lower than that in the survival group, with a statistically significant difference ( P < 0.01). ONSD ( OR = 23.890, 95% CI: 5.526-103.286, P < 0.001), GCS ( OR = 17.066, 95% CI: 1.476-197.370, P = 0.023) and ICP change rate ( OR = 0.060, 95% CI: 0.007-0.477, P = 0.008) were the independent risk factors for CCS-related death. The area under the ROC curve (AUC = 0.897) of ONSD combined with GCS in evaluating CCS-related death was larger than that of ONSD, ICP change rate alone and the corresponding AUC of 1/GCS (0.876, 0.785, 0.800, respectively), with the advantages of non-invasive, dynamic monitoring and low inspection costs. Conclusions:The mortality rate of CCS is high. ONSD, GCS and ICP change rates are independently correlated with the death of CCS patients. ONSD combined with GCS is an ideal indicator for clinical prediction of CCS-related death.
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@#AIM:To investigate the clinical efficacy and safety of trans-epithelial accelerated corneal collagen cross-linking in the treatment of progressive keratoconus.METHODS: A prospective before-after self-control study. A total of 47 eyes of 37 patients with progressive keratoconus who underwent trans-epithelial accelerated corneal collagen cross-linking in our hospital from August 2016 to November 2019 were collected. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refractive status, corneal transparency, maximum keratometry value of the anterior corneal surface, thinnest corneal thickness, corneal endothelial cell counts and intraocular pressure(IOP)were analysed preoperatively and at 1, 3, 6 and 12mo postoperative.RESULTS: UCVA of patients 1, 3, 6 and 12mo after surgery was higher than that before surgery, but there was no difference(<i>F</i>=1.372, <i>P</i>=0.261). BCVA at 1, 3, 6 and 12mo after surgery was higher than that before surgery, the difference was statistically significant(<i>F</i>=3.308, <i>P</i>=0.019). There were no differences in the spherical and cylindrical power, Kmax and thickness of the thinnest point of cornea at 1, 3, 6 and 12mo postoperatively compared with those before surgery(<i>F</i>=0.293, 1.378, 2.448, 1.970; <i>P</i>=0.881, 0.258, 0.061, 0.116). There was no difference in corneal endothelial cell counts between 1mo after surgery and before surgery(<i>t</i>=1.156, <i>P</i>=0.25). There was no difference in IOP at all postoperative time points compared with that before surgery(<i>F</i>=1.221, <i>P</i>=0.321). The corneal Haze(grade 1-2)appeared in 7 eyes after surgery, and subsided in 5 eyes from 3-6mo after surgery, and the corneal transparency recovered. The corneal nebula remained in 1 eye, and the corneal central stroma linear opacity existed in 1 eye, but the visual acuity of both eyes was not affected.CONCLUSION: Trans-epithelial accelerated corneal collagen cross-linking can significantly improve BCVA, stabilize refractive status, corneal morphology and thickness, prevent or delay the progression of keratoconus, and enable patients to obtain better visual function. At the same time, the operation time is short, postoperative complications are less, and the operation has good safety.
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Objective:To use quantitative computed tomography (QCT) technology to measure the bone mineral density of the spine of the Chinese healthy population, and to explore its correlation with hemoglobin and serum albumin.Methods:The data in this study came from the China Health Quantitative CT Big Data Project (China Biobank). The spine bone density was measured by using QCT Pro Image Analysis System and all cooperating centers used the European spine phantom (NO.145) for quality control. Total of 50 053 healthy persons who met the criteria for entry were selected as the research subjects. The subjects were divided into 7 groups according to age. The general data, spine bone density, serum albumin, hemoglobin of the subjects were collected. The single-factor analysis of variance, Pearson correlation analysis and multi-classification logistic regression model were applied to analyze the correlation between bone density and hemoglobin and serum albumin.Results:The bone mineral density of healthy people decreased with age ( P<0.05), and there were significant differences in hemoglobin, serum albumin and body mass index (BMI) among different age groups (all P<0.05). Linear correlation analysis showed that there were positive correlation between bone mineral density and hemoglobin in healthy males in different age groups ( r=0.086, 0.101, 0.076, 0.090, 0.072, 0.123, 0.100, all P<0.01). There were negative correlation between bone mineral density and hemoglobin in certain age groups in women (40-49 years group: r=-0.027; 70-79 yearsgroup: r=-0.077; both P<0.05). And corelation were found between bone mineral density and serum levels of albumin in certain age groups of healthy subjects (among men, 30-39 years group: r=-0.048; 40-49 years group, r=-0.027; 70-79 years group, r=-0.051; among women, 30-39 years group: r=-0.044; 40-49 years group, r=-0.042; 50-59 years group, r=-0.086; 70-79 years group, r=-0.070; all P<0.05). After adjusting for age and BMI, the multi-category logistic regression analysis showed that the hemoglobin level was protective factor of normal bone density ( OR=1.022, 95% CI:1.017-1.027) and decreased bone density ( OR=1.012, 95% CI:1.007-1.016) in healthy males, and the serum albumin was risk factor for normal bone density ( OR=0.926, 95% CI:0.905-0.948) and decreased bone density ( OR=1.006, 95% CI:0.951-1.011) in healthy women. Conclusion:There is a correlation between bone mineral density and hemoglobin and serum albumin in Chinese healthy population. Hemoglobin is a protective factor for bone mineral density in men, and serum albumin is a risk factor for bone mineral densityin women.
ABSTRACT
Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.