OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

OBJECTIVE To compare the efficacy and safety of lacosamide （LCM） and carbamazepine （CAR） as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis， 84 adult patients with newly diagnosed epilepsy， were admitted to the Department of Neurology， Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022， were divided into the control group （40 cases， receiving CAR treatment） and the observation group （44 cases， receiving LCM treatment） according to different medication regimens. Total response rate， epilepsy seizure frequency， blood lipid levels， and the occurrence of adverse events （AEs） of patients were compared between the 2 groups. RESULTS In the first month after treatment， there was no statistically significant difference in the total response rate between the observation group （63.64%） and the control group （55.00%， P＞0.05）； the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment （P＜0.05）， but there was no statistically significant difference between 2 groups （P＞0.05）. In the third month after treatment， the total response rate of the observation group （90.91%） was significantly higher than control group （67.50%， P＜0.05）； the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment， and the observation group was significantly lower than the control group （P＜0.05）. In the third month after treatment， the levels of total cholesterol （TC）， triglyceride （TG） and low-density lipoprotein cholestrol （LDL-C） in the control group and the level of LDL-C in the observation group were significantly higher than before treatment， and the levels of TC， TG and LDL-C in the observation group were significantly lower than those in the control group （P＜0.05）. There was no statistically significant difference in the incidence of AEs between the observation group （15.91%） and the control group （17.50%， P＞0.05）. CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults， which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile， LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults， and its impact on the patient’s blood lipid is smaller than CAR.

Objective To investigate the relationship between serum tumor necrosis factor α stimulated gene 6(TSG-6)and collagen ⅩⅥ(col-16)levels and severity of the illness and clinical outcome in patients with active ulcerative colitis(UC).Methods A total of 79 patients with active UC admitted to the department of gastroenterology in the hospital from January 2020 to January 2023 were selected as the active UC group,56 patients with UC in remission who were similar in gender and age to the active UC group were selected as the remission UC group,and 60 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.Patients with active UC were divided into mild group(n=25),moderate group(n=34)and severe group(n=20)according to the modified Mayo score.Patients with active UC were divided into good prognosis group(n=58)and poor prognosis group(n=21)according to colonoscopy results after 2 months of treatment.Serum TSG-6 and col-16 levels in each group were detected by enzyme-linked immunosorbent assay,Spearman rank correlation analysis was used to analyze the relation-ship between serum TSG-6 and col-16 levels and severity of the illness,and the influence of serum TSG-6 and col-16 levels on clinical outcome was analyzed by multivariate Logistic regression.Receiver operating charac-teristic(ROC)curve was used to evaluate the predictive value of serum TSG-6 and col-16 for poor prognosis in patients with active UC.Results The serum TSG-6 and col-16 levels in active UC group and remission UC group were higher than those in control group,and the serum TSG-6 and col-16 levels in active UC group were higher than those in remission UC group,the difference was statistically significant(P＜0.05).Serum TSG-6 and col-16 levels in severe group and moderate group were higher than those in mild group,and serum TSG-6 and col-16 levels in severe group were higher than those in moderate group,with statistical significance(P＜0.05).By Spearman rank correlation analysis,serum TSG-6 and col-16 in active UC patients were positively correlated with modified Mayo scores(rs=0.695、0.627,P＜0.05).Multivariate Logistic regression analysis showed that compared with＜159.32 ng/mL,patients with serum TSG-6 interquartile interval of 289.15-413.55 ng/mL and＞413.55 ng/mL had a higher risk of poor prognosis.ROC curve analysis results showed that the area under the curve of TG-6 and col-16 in predicting poor prognosis was 0.776 and 0.764,respective-ly.The predictive value of serum TG-6 and col-16 combined detection was better than that of single index(Z=3.392,4.218,P＜0.05).Conclusion The serum TSG-6 and col-16 levels in active UC patients are ab-normally elevated,which is closely related to severity of the illness and clinical outcome.The levels of serum TSG-6 and col-16 can be used as potential biochemical indicators to judge the disease and predict the clinical outcome.

Zuoguiyin， which first recorded in Jingyue Quanshu written by ZHANG Jiebin in the Ming dynasty， was included in the Catalogue of Ancient Famous Classical Formulas（The Second Batch）. This study followed the Principles of Textual Research on Key Information of Ancient Famous Classical Formulas to determine the key information of Zuoguiyin in ancient and modern literature， such as the formula origin， the composition of the formula and the origin of the drugs. It was found that the composition， dosage， preparation and processing methods of Zuoguiyin were basically the same as the original formula. The original dosage of this formula is 41.03 g of Rehmanniae Radix Praeparata（the fresh or dried tuberous roots of Rehmannia glutinosa， processed by wine stewing or wine steaming）， 7.46 g of Dioscoreae Rhizoma（the dried rhizomes of Dioscorea opposita）， 7.46 g of Lycii Fructus（the dried mature fruit of Lycium barbarum）， 3.73 g of Glycyrrhizae Radix et Rhizoma Praeparata cum Melle（the dried roots and rhizomes of Glycyrrhiza uralensis， processed by honey-roasted method）， 5.595 g of Poria（the sclerotium of Poria cocos）， 5.595 g of Corni Fructus（the dried mature fruit pulp of Cornus officinalis）. The method of administration is to add 600 mL of water to all the herbs， decoct to 140 mL and take before meals. The function of Zuoguiyin is to nourish Yin and tonify the kidney， and it is often used in the treatment of lumbar soreness and ejaculation， night sweating， dry mouth and throat， thirst and desire to drink， glossy red tongue， thin and rapid pulse， etc. Since ancient times， Zuoguiyin has been used to treat a variety of internal and gynaecological diseases as well as diseases of the nervous， circulatory and reproductive systems that are predominantly caused by kidney Yin deficiency. However， there is not much research on the modern application and therapeutic mechanism of this formula， and there is no standardized preparation in the market， so the degree of development and utilization is not high， and there is still a lot of room for research.

Microplastics pollution has attracted worldwide attention. Compared with the status quo of microplastics pollution in marine environment and other major rivers and lakes, the relevant data of the Yellow River basin is relatively inadequate. The abundance, types, and spatial distribution characteristics of microplastic pollution in the sediments and surface water of the Yellow River basin were reviewed. Meanwhile, the status of microplastic pollution in the national central city and Yellow River Delta wetland was discussed, and the corresponding prevention and control measures were put forward. The results showed that the spatial distribution of microplastics pollution in sediments and surface water of the Yellow River basin increased from upstream to downstream, especially in the Yellow River Delta wetland. There are obvious differences between the types of microplastics in sediment and surface water in the Yellow River basin, which is mainly related to the materials of microplastics. Compared with similar regions in China, the microplastics pollution levels in national key cities and national wetland parks in the Yellow River basin are in the medium to high degree, which should be taken seriously. Plastics exposure through various ways will cause serious impact on aquaculture and human health in the Yellow River beach area. To control microplastic pollution in the Yellow River basin, it is necessary to improve the relevant production standards, laws and regulations, and improve the capacity of biodegradable microplastics and the degradation capacity of plastic wastes.
Humans ; Microplastics ; Plastics ; Water Pollutants, Chemical/analysis* ; Environmental Monitoring/methods* ; Water ; China

Aiming at the problems of missing important features, inconspicuous details and unclear textures in the fusion of multimodal medical images, this paper proposes a method of computed tomography (CT) image and magnetic resonance imaging (MRI) image fusion using generative adversarial network (GAN) and convolutional neural network (CNN) under image enhancement. The generator aimed at high-frequency feature images and used double discriminators to target the fusion images after inverse transform; Then high-frequency feature images were fused by trained GAN model, and low-frequency feature images were fused by CNN pre-training model based on transfer learning. Experimental results showed that, compared with the current advanced fusion algorithm, the proposed method had more abundant texture details and clearer contour edge information in subjective representation. In the evaluation of objective indicators, Q ^AB/F, information entropy (IE), spatial frequency (SF), structural similarity (SSIM), mutual information (MI) and visual information fidelity for fusion (VIFF) were 2.0%, 6.3%, 7.0%, 5.5%, 9.0% and 3.3% higher than the best test results, respectively. The fused image can be effectively applied to medical diagnosis to further improve the diagnostic efficiency.
Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging/methods* ; Algorithms

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O₂ and H₂O₂ after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O₂ and H₂O₂ released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.
Rats ; Animals ; Osteogenesis ; Core Binding Factor Alpha 1 Subunit ; Rats, Sprague-Dawley ; Hydrogen Peroxide/pharmacology* ; Cell Differentiation ; Oxygen ; Hypoxia ; Cells, Cultured

This study deeply analyzes the common problems of three military medical universities in the management of undergraduate extracurricular scientific research, such as lack of communication means, limited online resources, backward laboratory opening and low utilization rate of equipment. We have built a cloud platform management system for undergraduate extracurricular scientific research. This system firstly sets up a teaching resources storage module including videos, PPTs, documents, pictures, electronic materials, question bank, etc. Then four subsystems for different roles of students, mentors, experimental teaching staff and administrators are constructed. Finally, this system realizes independent experiments by students, real-time evaluation by mentors, instrument sharing and efficient management through the seamless connection with the user terminal equipment. And the study also makes evaluation on the present usage.

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.