Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Our hospital first used the housing and training information management platform in 2018 in order to improve the management efficiency and teaching quality of standardized resident training in the Department of Otolaryngology-Head and Neck Surgery. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, through continuous optimization and upgrading of system functions and the mobile APP terminal, the integrated development of teaching and management and the maximization of resource sharing have been realized, thus making up for the defects and deficiencies of the traditional resident training management mode. Our practice shows that the new resident training management mode based on informatization mobile platform can not only save time and effort for departments to grasp all aspects of resident training management, but also enable residents to complete the resident training plan step by step and reasonably with improvement in their knowledge, skills, and competence. Therefore, the new resident training management mode has broad application prospects.

Objective:To investigate the effects of dexmedetomidine combined with propofol on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy.Methods:The clinical data of 82 patients who underwent painless gastroenteroscopy in Fuyang Minsheng Hospital from April 2021 to November 2022 were retrospectively collected, and they were divided into the control group and the observation group by anesthesia induction method, each group with 41 cases. The control group was anesthetized with propofol, and the observation group was anesthetized with dexmedetomidine and propofol. The recovery time, orientation recovery time and satisfaction of the two groups were compared; the cognitive function before anesthesia, 1, 12 h after anesthesia and 1, 7 d after anesthesia were compared; the changes of hemodynamics and diaphragm movement before anesthesia induction (T 0), 5 min after anesthesia induction (T 1) and at awakening (T 2) and adverse reactions were compared. Results:The recovery time, orientation recovery time in the observation group were shorter than those in the control group: (9.87 ± 1.52) min vs. (11.92 ± 1.74) min, (15.87 ± 2.31) min vs.(18.79 ± 2.54) min; the dosage of propofol was less than that in the control group: (200.21 ± 50.46) mg vs. (300.23 ± 60.29) mg; the satisfaction scores was higher than that in the control group: (9.54 ± 0.32) scores vs. (8.81 ± 0.47) scores, there were statistical differences ( P<0.05). The scores of Mini-Mental State Examination (MMSE) at 1 h after anesthesia and 12 h after anesthesia in the observation group were higher than those in the control group: (23.12 ± 1.86) scores vs. (20.31 ± 1.65) scores, (26.21 ± 1.43) scores vs. (24.12 ± 1.57) scores, there were statistical differences ( P<0.05). The scores of MMSE at 1, 7 d after anesthesia had no statistical differences between the two groups ( P>0.05). The levels of mean arterial pressure (MAP) and heart rate (HR) at T 1 and T 2 were decreased and the levels of MAP and HR at T 1 and T 2 in the observation group were higher than those in the control group: (76.48 ± 4.01) mmHg (1 mmHg = 0.133 kPa) vs. (72.31 ± 3.26) mmHg, (82.31 ± 3.27) mmHg vs. (77.97 ± 3.64) mmHg; (78.72 ± 2.17) bpm vs. (76.23 ± 2.35) bpm, (82.19 ± 3.08) bpm vs. (79.63 ± 2.56) bpm, there were statistical differences( P<0.05). The diaphragm thickness fraction (DTF) and diaphragmatic motion amplitude (DM) at T 1 and T 2 were decreased and the levels of DTF and DM at T 1 and T 2 in the observation group were higher than those in the control group: 0.21 ± 0.02 vs. 0.17 ± 0.03, 0.26 ± 0.03 vs. (0.22 ± 0.04); (15.67 ± 0.81) mm vs. (14.21 ± 0.77) mm, (16.72 ± 0.68) mm vs. (15.46 ± 0.82) mm, there were statistical differences ( P<0.05). The adverse reactions in the two groups had no significant difference ( P>0.05). Conclusions:The combination of dexmedetomidine and propofol has little effect on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy, which can accelerate the recovery of patients and improve patient satisfaction.

ObjectiveTo explore the mechanism of Tibetan medicine Ershiwuwei Guijiuwan against osteoporosis in ovariectomized rats through the classical Wnt/β-catenin signaling pathway. MethodForty-eight 3-month-old SD female rats were randomized into model group （equivalent volume of normal saline）， sham operation group （equivalent volume of normal saline）， estradiol group （0.1 mg·kg^-1 estradiol valerate）， and high-， medium-， low-dose Ershiwuwei Guijiuwan groups （800， 400， 200 mg·kg^-1， respectively）. For the modeling， some adipose tissue near the ovaries was removed in the sham operation group， and ovaries were excised in other groups. Administration （ig， once a day） started two weeks after the operation and lasted 12 weeks. After sampling， based on hematoxylin and eosin （HE） staining， the morphological changes of the right femur and lumbar spine of the rats were observed. The enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum levels of rat tartrate-resistant acid phosphatase 5b （TRAP5b）， collagen type Ⅰ C-terminal peptide （CTX-Ⅰ）， bone alkaline phosphatase （BALP）， amino-terminal propeptide of type Ⅰ procollagen （PINP）， and bone Gla-protein （BGP）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to examine the mRNA expression of β-catenin and Runt-related transcription factor 2 （Runx2） in femur， and Western blot to detect the protein expression of β-catenin， Runx2， and low-density lipoprotein receptor-related protein-5 （Lrp-5）. ResultCompared with the sham operation group， the model group showed disordered and sparse bone trabecula with fewer connections， decrease in serum levels of BALP， BGP， and PINP （P<0.01）， increase in levels of CTX-Ⅰ and TRAP5b （P<0.01）， reduction in mRNA expression of β-catenin and Runx2 in femoral tissue （P<0.01） and protein expression of Lrp-5， β-catenin， and Runx2 （P<0.01）. Compared with the model group， estradiol and each dose of Ershiwuwei Guijiuwan increased the volume of bone trabecula， made thebone trabecula closely arranged， reduced the loss of the trabecular meshwork， raised the serum levels of BALP and BGP （P<0.01）， and lowered TRAP5b level （P<0.01）. PINP level was significantly increased in the high-dose Ershiwuwei Guijiuwan group and estradiol group （P<0.01） and CTX-Ⅰ level was significantly decreased in the high-dose Erwenwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. The mRNA expression of β-catenin in femoral tissue and protein expression of Lrp-5 and β-catenin in estradiol group and three Ershiwuwei Guijiuwan groups were significantly increased （P<0.05， P<0.01）， and the levels of Runx2 mRNA and protein were significantly increased in the high-dose Ershiwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. ConclusionTibetan medicine Ershiwuwei Guijiuwan is effective for the osteoporosis in ovariectomized rats， which may be related to the classic Wnt/β-catenin signaling pathway. It affects bone metabolism by up-regulating the expression of osteogenesis-related genes in the signaling pathway.

Objective:To explore the effect of nursing interventions based on systematic concept in elderly patients with type 2 diabetes.Methods:From May 2018 to August 2019, 120 elderly patients with type 2 diabetes in Hangzhou Red Cross Hospital were selected by convenience sampling. The patients were randomly divided into observation group and control group with 60 cases each. Patients in each group were given nursing interventions based on systematic concept and routine nursing respectively. The anxiety, depression, benefit finding and coping modes of the two groups were compared before and after the intervention.Results:Before the intervention, there was no statistical difference between the two groups in the scores of anxiety, depression, benefit finding and behavior pattern ( P>0.05) . After intervention, the scores of anxiety and depression in the two groups decreased, and the scores in the observation group were lower than those in the control group, with statistically significant differences ( P<0.05) . After the intervention, the scores of benefit finding of the two groups increased, and that of the observation group was higher than that of the control group, and the differences were statistically significant ( P<0.05) . After intervention, the scores of confronting of the two groups increased, and that of observation group was higher than that of the control group, and the differences were statistically significant ( P<0.05) . After intervention, the scores of avoidance and resignation in the two groups decreased, and the scores in the observation group were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:Systematic concept nursing can reduce the anxiety and depression of elderly patients with type 2 diabetes, improve the benefit finding, increase the sense of benefit, and urge patients to adopt a positive coping style to deal with the disease.

OBJECTIVE：To establish characteristic chromatogram of Cornus officinalis and its different wine-processedproducts，investigate the differences of chromaticity values，and analyze them with chemical pattern recognition technology.METHODS：UPLC method was adopted. Using loganin as reference，UPLC characteristic chromatograms were drawn for 10batches of C. officinalis and 20 batches of different wine-processed products （stewing with wine，steaming with wine）. TCMFingerprint Similarity Evaluation System（2012A edition）was used for similarity evaluation，and common peaks were confirmed.The chromaticity values [lightness（L），red and green tone value（a），yellow and blue tone value（b），color difference value（ΔE）]were determined by spectrophotometer. SPSS 20.0 and SIMCA 14.0 software were used for cluster analysis，principal componentanalysis and partial least squares-discriminant analysis；taking the area of characteristic peak and chromaticity value as indexes，andthe variable importance projection greater than 1 as the standard，the difference markers affecting its quality were screened.RESULTS：There were 6 common peaks in the chromatograms for decoction piece of C. officinalis，7 common peaks forwine-processed C. officinalis（stewing with wine）and wine-processed C. officinalis（steaming with wine）. Four components wereidentified as gallic acid，5-hydroxymethylfurfural，morroniside，loganin. 5-hydroxymethylfurfural was produced after processing.The similarity between C. officinalis and different wine-processed products （stewing and steaming with wine） was low（0.869-0.937，0.845-0.944），but the similarity between different wine-processed products was higher than 0.99. ΔL，Δa，Δb and ΔEof C. officinalis decoction pieces and wine-processed C. officinalis decoction pieces（stewing in wine）were －9.42-－3.58，－24.92- －15.00，－11.33- －7.00 and 17.01-28.12，respectively. ΔL，Δa，Δb and ΔE of C. officinalis decoction pieces and wine-processed C. officinalis（steaming in wine）decoction pieces were －8.58-－2.42，－25.08-－13.83，－10.92-－6.08，15.58-28.67. ΔL，Δa，Δb and ΔE of wine-processed C. officinalis decoction pieces（stewing and steaming with wine）were －2.17-3.00，－0.75-2.50， 0.25-1.42 and 1.25-3.83，respectively. Results of cluster analysis showed that 30 batches of sample were clustered into two categories，S1-S10 were clustered into one category，and S11-S30 were clustered into other category. Principal component analysis showed that cumulative contribution rate of former two main components was 83.147％. Results of partial least squares-discriminant analysis showed that morroniside，No.5 peak and chromaticity values（L，a，b）were the difference markers affecting its quality. CONCLUSIONS：Established UPLC characteristic chromatogram is stable and feasible，and can be used to rapidly identify C. officinalis and its different wine-processed products. Established chemical mode can be used to identify different wine-processed products.

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.

Objective: To investigate the diagnostic value of multimodal magnetic resonance imaging (MRI) in primary central nervous system lymphoma (PCNSL). Methods: The multimodal MRI findings of 16 patients with PCNSL confirmed by histopathology from January 2016 to December 2018 in Affiliated Hospital of North Sichuan Medical College were retrospectively analyzed. Routine MRI plain scan, enhancement, diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) examination were performed in all cases. Results: All 16 patients were diagnosed with diffuse large B cell non-Hodgkin lymphoma. There were 7 cases with solitary lesions and 9 cases with multiple lesions. A total of 36 lesions were detected, with 30 above and 6 below the curtain. Sixteen lesions were located in the deep white matter near the ventricle (among which 2 lesions involved the corpus callosum), 5 lesions in the superficial cerebral hemisphere, 7 lesions in basal ganglia, 2 lesions in thalamus, 3 lesions in cerebellum, and 3 lesions were in brainstem. T₁WI showed equal or slightly low signal, and T₂WI showed equal or slightly high signal. There was different degree of edema around the lesions. 32 lesions were mild to moderate, and 4 lesions were severe. On enhancement scanning, 31 lesions showed patchy, nodular or lumpy uniform enhancement; 5 lesions showed irregular annular enhancement. "Incision" was found in 12 lesions, and "angular" was found in 7 lesions. Obvious enhancement of adjacent meninges or ependymal membranes occurred in 1 case each. DWI showed 29 high signals in the focal areas and 7 equal or slightly high signals, and all apparent dispersion coefficient (ADC) values were reduced. MRS showed that choline peak increased, and N-acetyl aspartate (NAA) peak and creatine peak decreased in all cases. highly elevated lipid peak was observed in 8 cases, inverted lactic acid peak in 3 cases, and both lipid peak and lactic acid peak were observed in 2 cases. Conclusions Multimodal MRI can reflect the characteristics of PCNSL from different aspects, which is of great value in improving the diagnostic accuracy of PCNSL.