ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Atherosclerosis(AS)is the common pathological basis of ischemic cardiovascular diseases,and its formation mechanism is complex.Western medical treatment has problems such as a long cycle and a high relapse rate.Ethnic medicine is an important part of traditional medicine,which has unique efficacy in treating cardiovascular diseases.Studies have shown that the Mongolian medicine Eldon-Uriel regulates blood lipids and improves blood rheology in the treatment of AS.This paper aims to pro-vide new ideas for the prevention and treatment of AS by collecting,organizing,and summarizing the relevant literature on Eldon-Uriel and introducing its unique concept,mechanism of action,and clinical studies in the treatment of AS.

Objective To investigate the intervention effects of Yangqing Chenfei Fang (YCF), Baojin Chenfei Fang (BCF), and Jinshui Chenfei Fang (JCF) at different pathological stages of silicosis in a rat model. Methods A total of 216 specific pathogen free rats were randomly divided into control group, silicosis group, tetrandrine group, YCF group, BCF group and JCF group, with 35-36 rats in each group (11-12 rats at each time point). The rats in control group were treated with intragastric administration of pure water [administration volume at 2.5 mL/(kg·time)], while the rats of other five groups were treated with silica suspension at 250 mg/kg body weight to induce a silicosis model using the one-time non-exposed tracheal method. Intragastric administration of the corresponding drugs was performed at three time points at days 1-14 (early stage of silicosis), days 15-28 (middle stage of silicosis), and days 29-42 (late stage of silicosis) after modeling. Pulmonary function enhanced pause (Penh), forced vital capacity (FVC), and dynamic lung compliance (Cdyn) of rats in the six groups was assessed on days 15, 29, and 43 after modeling. Histopathological changes in lung tissues were observed, and relative expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, hydroxyproline, collagenⅠ(COL-Ⅰ), and α-smooth muscle actin (α-SMA) were detected in lung tissues. Results i) Pulmonary function index. The index of Penh in three stages of silicosis of rats in YCF group, BCF group and JCF group was lower than that in the silicosis group at the same stage (all P<0.05), and the index of Penh was higher than that in the tetrandrine group at the same stage (all P<0.05). The index of FVC of rats in YCF group, BCF group and JCF group at the middle stage was higher than that in the silicosis group at the same stage (all P<0.05), as well as the index of Cdyn was higher than that in the tetrandrine group at the same stage (all P<0.05). ii) Histopathology of lung tissue. Rats of the silicosis group exhibited alveolitis, fibro stripe, and collagen deposition in lung tissues in the early stage compared with rat of the control group, with fibrosis progressively worsening over time and inflammation persisting throughout the disease course. Pathological changes of lung tissues were alleviated to varying degrees in the tetrandrine groups, YCF group, BCF group and JCF group compared with that of the silicosis group. Compared with the same stage of silicosis group, the Ashcroft scores of lung tissues in the YCF group and BCF group were lower in the middle and late stages (all P<0.05). The Ashcroft score of lung tissues in the BCF group in the middle and late stages was lower than that in tetrandrine group at the same stage (all P<0.05), while the Ashcroft score in the middle stages was lower than that in YCF group at the same stage (P<0.05). The Ashcroft score of lung tissue in the JCF group was lower than that in the silicosis group, tetrandrine group and YCF group at all three stages (all P<0.05), and was lower than that in BCF group at the early and late stage of silicosis (all P<0.05). iii) Inflammatory factors. IL-6 level in the lung tissues in the YCF group, BCF group and JCF group decreased compared with that in the silicosis group at the same stage (all P<0.05), while IL-1β and TNF-α levels decreased at the early and middle stages (all P<0.05), hydroxyproline level decreased at all three stages (all P<0.05). iv) Collagen. The relatively expression of COL-Ⅰ in the lung tissues in the YCF group decreased at the late stage of silicosis compared with that in the silicosis group at the same stage (all P<0.05), while the relatively expression of α-SMA decreased at the middle and late stages (all P<0.05). Compared with the same stage of silicosis group, the relative expression of COL-Ⅰ and α-SMA of the lung tissues reduced in the BCF group and JCF group at all stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the BCF group at the late stage compared with that in the YCF group in the same stage (all P<0.05), while the relative expression of α-SMA decreased at the early and middle stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the JCF group at late stage of silicosis (all P<0.05), while the relative expression of α-SMA decreased at all three stages (all P<0.05), compared with the same stage of YCF group. Conclusion All three formulations of Chinese herbs are effective in improving lung function and alleviating the progress of lung inflammation and fibrosis. YCF is the most effective in suppressing inflammation in the early stage of silicosis. BCF excels in delaying fibrosis in the early and middle stages. JCF is the most effective in improving lung function and delaying fibrosis progression in the late stage.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Objective    To explore the early results of Ozaki operation in children with aortic regurgitation. Methods    We retrospectively analyzed the clinical data of 15 patients with aortic regurgitation who received the Ozaki operation in our hospital from April 2017 to July 2019. There were 11 males and 4 females with an average operation age of 10.7±3.7 years. Besides preoperative evaluation, aortic regurgitation and cardiac function were evaluated on 1 day, 1 week, 1 month, 3 months, and 6-12 months after surgery. Results    In 14 (93.3%) patients , the aortic valve leaflets functioned well on 1 day, 1 month, 3 months, and 6-12 months, and the regurgitation grade was Ⅰ-Ⅱ, which was improved than before (P=0.001). The cardiac function of children recovered quickly after operation. There was no statistical difference in ejection fraction on 1 day, 1 month, 3 months, and 6-12 months after operation (P>0.05). No children died, and no other clinical event was found. Conclusion    The Ozaki technique of reconstructing a tricuspid aortic valve leaflet for the treatment of severe aortic regurgitation in children is effective in short term, and the persistence of its valve function remains to be determined in the long-term follow-up.

BACKGROUND: In vitro isolation and culture of neural stem/progenitor cells will provide a good cell model for the study of neurodevelopment, neurological diseases, and neural transplantation. OBJECTIVE: To study the highly effective method for isolation and expansion of hippocampal neural stem/progenitor cells from newborn mice, and to identify the proliferation and differentiation of hippocampal neural stem/progenitor cells using improved adherent culture method. METHODS: Neural stem/progenitor cells were isolated from the hippocampus of newborn C57BL/6 mice and were expanded for several passages. Combination of polylysine and laminin were used for adherent culture to promote cell attachment. Morphological observation and immunofluorescence cytochemical staining were conducted to detect the expression of neural progenitor-specific marker protein Nestin and proliferation index Ki-67. After 7 days of induction and differentiation, the expression of GFAP, DCX, Tuj1 and S100β was detected by immunofluorescence. RESULTS AND CONCLUSION: About 82％ of the cultured neural stem/progenitor cells expressed Nestin, and about 49％ expressed Ki-67. A small number of cells were DCX-positive neurons after induction and differentiation, while most of the cells were positive for GFAP. The ratio of neurons to astrocytes was 1:1.7 identified by Tuj1 and S100β double staining. The neural stem/progenitor cells derived from the hippocampus were efficiently isolated and cultured. The cell proliferation and differentiation abilities were effectively identified after adherent culture, which can provide sufficient cell sources for further experimental research.

Objective To investigate the changes of corneal biomechanics of intrastromal correction (INTRACOR) femtosecond technique to treat presbyopia.Methods A prospective,clinical self-control clinical trial was designed.Twenty-four presbyopic patients with emmetropia or mild hyperopia were enrolled in this study.The INTRACOR procedure was performed using the Technolas femtosecond laser in the nondominant eye.Uncorrected distance visual acuity (UCDVA),uncorrected near visual acuity (UCNVA) and spherical equivalent (SE) were recorded in preoperation and postoperative 12 months,and the quality of life of postoperative patients was evaluated.The corneal deformation parameters including highest concavity deformation amplitude (HC-DA),highest concavity peak distance (HC-PD),highest concavity radius (HC-R),non-contact intraocular pressure and the central corneal thickness (CCT) were measured using the Corvis ST visualization biomechanical analyzer in preoperation and postoperative 1 month,3,6 and 12 months,respectively.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering study cohort.This study protocol was approved by Ethic Committee of Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.SDZYYDXYKYYLL2011.06).Results Compared with preoperation,UCNVA of all 24 (100％) eyes was improved at 12 months postoperatively with minimal or no change in UCDVA.The mean spherical equivalent was (+0.35± 0.29)D and (-0.37 ± 0.29)D before and 12 months after operation,with a significant difference beteeen them (t=-7.39,P＜0.01).No significant differences were seen in the intraocular pressure,CCT and HC-PD values between preoperation and postoperative 1 month,3,6,12 months (F =1.273,1.347,2.434;all at P ＞ 0.05).Compared with preoperation,the postoperative 1 month,3,6,12 months HC-R values were significantly declined,HC-DA values were significantly increased,with significant differences between them (all at P＜0.05),and no significant differences were found in HC-R and HC-DA between the postoperative adjacent time points (all at P＞0.05).Corneal aspherical index (Q Value) was-0.28±t0.10 at 12 months postoperatively,which was increased compared with the preoperation,and the maximum value added value (diff-K) of the central corneal curvature was (2.55±0.81)D.Conclusions INTRACOR treatment of presbyopia can effectively improve near vision,increase postoperative corneal biomechanical maximum HC-R and HC-DA,negatively increase the corneal central curvature increased aspheric index,which suggests that corneal biomechanics of central cornea is weakened after intrastromal femtosecond presbyopic treatment,and the hyperprolate mutifocal corneal shape is formed under normal intraocular pressure.

Objective To investigate the therapeutic effect of the transcatheter closure of antegrade pulmonary blood flow with high-risk Fontan operations.Methods Retrospective analysis of 6 Fontan surgical patients, 4 males and 2 females, who received surgical treatment in the cardiothoracic surgery of Shanghai Children's Medical Center from May 2016 to August 2018;Age(5.7 ±2.9) years;(19.8 ±5.5) kg weight.All 6 patients were treated with primary pulmonary artery banding operation and secondary bilateral Glenn operation(BDG) and re-PAB.Before Fontan surgery, cardiac catheterization was performed in the department of cardiology to close the antegrade pulmonary blood flow .Results These six patients received interventional therapy in the department of cardiology.The mean pulmonary artery pressure(Pp) before occlusion was(17.0 ±0.8) mmHg (1 mmHg=0.133 kPa), the ventricular diastolic pressure(VEDP) was (11.2 ±0.9) mmHg, and the mean pulmonary artery pressure after occlusion was effectively decreased to(14.2 ±0.7) mmHg and VEDP to(9.7 ±0.7) mmHg.Fontan surgery was performed 6 to 12 months after the occlusion.No death was found after the operation, and all the clinical indicators were normal after the operation.Follow-up was conducted for 2-24 months, and the cardiac function and the function of each organ recov-ered well.Conclusion For some patients with high risk Fontan before operation , this method can safely and effectively reduce the average pulmonary artery pressure and reduce the ventricular and pulmonary vascular load , which is of positive help for the successful Fontan operation.