ObjectiveBased on the conjoint analysis of transcriptome and metabolome， the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored， which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem， leaves， and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and weighted correlation network analysis （WGCNA）， and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study， 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism， nine key differential metabolites and four key genes related to them were finally discovered. Among them， cinnamic acid， 5-O-caffeoylshikimic acid，sinapyl alcohol， and chlorogenic acid were higher in flowers， and the content of the iconic effective component， namely chlorogenic acid，decreased sharply during the withering period. Caffeic acid，ferulic acid， 5-hydroxyconiferaldehyde，p-coumaryl alcohol， and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase （CAD） family， 4-coumaric acid： Coenzyme A （4CL） family， hydroxycinnamyl transferase （HCT） family， and L-phenylalanine ammonlyase （PAL） family genes. ConclusionAmong the four key genes excavated from L. macranthoides， TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid，ferulic acid，and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA， and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Thromboembolic disease seriously affects people's health, and even endangers life. Nattokinase(NK) is an alkaline serine protease with strong thrombolytic activity and low toxicity. However, when NK passes through the stomach, it is degraded by gastric acid and pepsin, and subsequently loses its thrombolytic activity. The application of preparation technology can form a protective layer and improve the high bioavailability of NK. This article briefly introduced the pharmacological properties of NK, and discussed the characteristic of different dosage forms. The development of NK preparation was prospected in order to promote its research and application.

Objective To investigate the correlation between the total load of cerebral small vessel disease(CSVD)and the early prognosis of patients with acute cerebral infarction(ACI).Methods A total of 150 patients with ACI admitted to the Department of Neurology,the First Hospital of Jiaxing from October 2020 to June 2022 were included,according to modified Rankin scale(mRs)score,patients were classified good prognosis group(mRs≤2 points)and poor prognosis group(mRs≥3 points),baseline data and clinical characteristics were compared between the 2 groups,and total CSVD load was assessed by cranial MRI,single factor and multi-factor analysis were performed with Logistic model.The relativity of CSVD load and early prognosis was analyzed with Pearson method.Results Age,length of stay,National Institute of Health stroke scale(NIHSS),hypersensitivity C-reactive protein,triglyceride and homocysteine were significantly higher in poor prognosis group than those in good prognosis group,the difference was significant(P<0.05).The scores of lacunar,cerebral microhemorrhage,white matter hyperintensity and CSVD in poor prognosis group were significantly higher than those in good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that length of stay(OR=1.278,95％CI=1.054-1.548,P=0.012),admission NIHSS score(OR=1.354,95％CI=1.113-1.647,P=0.002),CSVD total load(OR=2.494,95％CI=1.666-3.735,P<0.001)were independent risk factors for poor early prognosis in patients with acute cerebral infarction.Conclusion CSVD load is associated with poor prognosis in patients with acute cerebral infarction.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective Polysaccharide is a major active component in Lycium barbarum.the structure and content of polysaccharide are different among different producing districts.At present,most of the quality control methods of Lycium barbarum polysaccharide construct fingerprint from the aspect of monosaccharide composition,but the quality control of Lycium barbarum polysaccharide only by analyzing monosaccharide composition can not fully explain the relationship between structure and Lycium barbarum polysaccharide.Therefore,we established the Needs methylation method of Lycium barbarum polysaccharide fingerprint to achieve quality control of Lycium barbarum from different places by determining the sugar residue linkage mode of Lycium barbarum polysaccharide on the basis of monosaccharide composition.Methods Lycium barbarum polysaccharide was extracted through water extraction followed by alcohol precipitation,and the Needs methylation,complete acid hydrolysis,reduction by NaBH4,acetylation and other methods combined with GC-MS to determine the sugar residue linkage motif of Lycium barbarum polysaccharide.Result The chromatograms of 18 batches of Lycium barbarum polysaccharides were imported into the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2004 edition),combined with chemometrics to evaluate the differences of Lycium barbarum polysaccharide from different origin.The result of similarity showed that the similarity of three batches of Lycium barbarum polysaccharide from Tibet ranged from 0.551 to 0.569,others were more than 0.929.16 common peaks were marked in chromatogram of sugar residue linkage mode,and 10 of them was identified,they are T-Arap,T-Araf,T-Xylp,1,2-Arap,1,3-Rhap,1,5-Araf,T-Glcp,T-Galp,1,4-Glcp,1,6-Galp.The results of HCA,PCA and PLS-DA analysis divided 18 bathes of Lycium barbarum polysaccharide were divided into three categories,and three signature components were screened,which were T-Araf,1,5-Araf and T-Glcp,to judge the differences of Lycium barbarum polysaccharides from different places.Conclusion The Needs methylation fingerprint of 18 batches of Lycium barbarum polysaccharide was established for the first time.The establishment of the fingerprint can provide experimental data reference for the quality control of Lycium barbarum polysaccharide,and further prove the role of polysaccharide in the quality control of Traditional Chinese Medicine.

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.

Objective:To study the reliability modeling method of rehabilitation diagnosis and treatment equipment based on non-homogeneous Poisson process,and to improve the reliability analysis effect of rehabilitation diagnosis and treatment equipment.Methods:Statistics and analysis of the total running time of rehabilitation diagnosis and treatment equipment in a specific period of time were performed,and the trend test of its operation data was conducted.The bathtub curve was used as the trend of rehabilitation diagnosis and treatment equipment failure,under the condition of bathtub curve change trend,a reliability model of non-homogeneous Poisson process of rehabilitation diagnosis and treatment equipment was established.The least squares estimation method was used to estimate the non-homogeneous Poisson process reliability model parameters of rehabilitation diagnosis and treatment equipment,determine the reliability index of rehabilitation diagnosis and treatment equipment,and complete the reliability modeling of rehabilitation diagnosis and treatment equipment.A total of 17 rehabilitation diagnosis and treatment equipment in clinical use in the Second Medical Center of PLA General Hospital from April to October 2022 were selected,including 6 pulse short-wave therapy instruments,5 interference electrical therapy instruments,3 swallowing disorder treatment instruments,and 3 air wave pressure therapy instruments.In July 2022,the reliability modeling method of rehabilitation diagnosis and treatment equipment based on non-homogeneous Poisson process was applied to the management of rehabilitation diagnosis and treatment equipment.The failure rate of rehabilitation diagnosis and treatment equipment before and after the application of the reliability modeling method based on non-homogeneous Poisson process was compared.Results:The average failure rate of 17 rehabilitation diagnosis and treatment equipment was 64.71%(11/17)before application and decreased to 23.53%(4/17)after application,of which the failure rate of 6 pulse shortwave therapy devices decreased from 66.7%(4/6)before application to 16.7%(1/6),the failure rate of 5 interference electrotherapy devices decreased from 60.0%(3/5)before application to 20.0%(1/5),and the failure rate of 3 dysphagia treatment instruments decreased from 66.7%(2/3)to 33.3%before application(1/3),the failure rate of the 3 air wave pressure therapy devices decreased from 66.7%(2/3)before application to 33.3%(1/3).Conclusion:The reliability modeling method for rehabilitation diagnosis and treatment equipment based on non-homogeneous Poisson process can accurately calculate the failure intensity function and cumulative failure intensity function of rehabilitation diagnosis and treatment equipment,reduce the failure rate of rehabilitation diagnosis and treatment equipment,and improve the quality of use of rehabilitation diagnosis and treatment equipment.

Based on analyzing the connotation and essence of the Westward Relocation Spirit and its unique expression and value in the medical field,through strengthening the professional identity and sense of honor of medical staff,this research optimizes the working environment and treatment of medical staff,enhances the training of their professional literacy and skills,boosts measures including the mental health and care of medical staff,so as to develop the sense of gain of medical staff to enable them to better perform their duties,and make contribution to the improvement of people's health and sharing of good doctor-patient relations.