Research progress of the impact of payment by disease diagnosis-related group on nursing care / 中国实用护理杂志

The National Medical Insurance Administration launched a national pilot project based on diagnosis-related group (DRG) payment across the country in 2019. It optimizes and reuses limited resources from a clinical perspective, controls hospitalization expenses and medical costs, and reduces average hospital stays based on DRG payment. This article expounds the concept and application of DRG payment, from the perspective of clinical nursing, expounds the research progress of DRG payment at home and abroad, attempts to analyze the relationship between DRG payment and nursing, and further proposes the impact on the development of clinical nursing.

Application and progress of intraoperative neuromonitoring techniques in robotic thyroid surgery / 中华内分泌外科杂志

Robotic surgical systems are gradually being used in minimally invasive surgery with their advantages of high-definition magnified 3D images, stable surgical field and flexible operation. The change of surgical approach and the narrow operating space in robotic thyroid surgery have made it more difficult to identify and protect the laryngeal nerve, and the application of nerve monitoring has been limited. Many researchers have attempted to improve the monitoring equipment and probe placement to make intraoperative neuromonitoring techniques work well in robotic thyroid surgery. In this paper, we seek effective ways to protect the laryngeal nerve in robotic thyroid surgery, and lay the foundation for a more minimally invasive and standardized development of this technology.

Influence of preoperative Naples prognostic score on prognosis of patients with thoracic esophageal squamous cell carcinoma / 国际肿瘤学杂志

Objective:To explore the impact of preoperative Naples prognostic score (NPS) on the survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC).Methods:From December 2014 to December 2020, a total of 134 patients who underwent radical esophagectomy in Department of Thoracic Surgery, Affiliated Taixing People′s Hospital of Yangzhou University were retrospectively analyzed. The NPS was calculated by the median values of preoperative serum albumin, total cholesterol, neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR), and then the enrolled patients were divided into NPS 0 group (20 cases), NPS 1 or 2 group (62 cases) and NPS 3 or 4 group (52 cases). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univa-riate and multivariate Cox models were used to analyze the relationship between NPS and survival prognosis.Results:The 1-, 3- and 5-year progression free survival (PFS) rates were 95.0%, 70.0% and 60.0% in the NPS 0 group, 66.1%, 24.2% and 24.2% in the NPS 1 or 2 group, and 48.1%, 3.8% and 1.9% in the NPS 3 or 4 group respectively, with a statistically significant difference ( χ2=31.27, P<0.001). In the NPS 0 group, the 1-, 3- and 5-year overall survival (OS) rates were 100.0%, 80.0% and 70.0% respectively. In the NPS 1 or 2 group, the 1-, 3- and 5-year OS rates were 96.8%, 36.7% and 32.3% respectively, while in the NPS 3 or 4 group, the 1-, 3- and 5-year OS rates were 90.4%, 32.7% and 5.8% respectively, and there was a statistically significant difference ( χ2=29.70, P<0.001). Univariate analysis found that sex, T stage, N stage, TNM stage and NPS were closely related to PFS and OS of patients with thoracic ESCC (all P<0.05). Furthermore, multivariate Cox regression analysis showed that T stage ( HR=1.46, 95% CI: 1.07-2.00, P=0.019), N stage ( HR=1.34, 95% CI: 1.02-1.76, P=0.037) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.35, 95% CI: 1.58-7.11, P=0.002; NPS 3 or 4 group: HR=6.15, 95% CI: 2.89-13.11, P=0.001) were independent prognostic factors for PFS. Additionally, T stage ( HR=1.67, 95% CI: 1.01-2.77, P=0.046), N stage ( HR=1.44, 95% CI: 1.00-2.20, P=0.048) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.10, 95% CI: 1.31-7.32, P=0.010; NPS 3 or 4 group: HR=5.09, 95% CI: 2.14-12.11, P=0.001) were independent prognostic factors for OS. Conclusion:Preoperative NPS plays an important role in predicting the survival prognosis of patients with thoracic ESCC.

The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Promising natural lysine specific demethylase 1 inhibitors for cancer treatment: advances and outlooks / 中国天然药物

Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.

AZD9291 suppresses proliferation and migration of nasopharyngeal carcinoma cells by inhibiting the PI3K-AKT-mTOR pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of AZD9291 on the proliferation and migration of nasopharyngeal carcinoma cells.@*METHODS@#Nasopharyngeal carcinoma HNE1 and CNE2Z cells were treated with AZD9291 at the doses of 0.5, 1, 2, 4, and 8 μmol/L and at the doses of 1, 2, 4, 8, and 16 μmol/L, respectively. Cell survival was measured using CCK8 assay, and proliferation inhibition of the cells after AZD9291 treatment was examined with colony-forming assay; the cell repair and migration abilities were determined using scratch assay and Transwell experiment. The expressions of EGFR-related signaling proteins and migration-related proteins were detected using Western blotting.@*RESULTS@#The results of CCK8 assay and colonyforming assay showed that AZD9291 significantly inhibited the viability and proliferation of both HNE1 and CNE2Z cells (P < 0.01). AZD9291 treatment also attenuated the migration ability of HNE1 and CNE2Z cells (P < 0.01). Western blotting showed that, as the concentration of AZD9291 increased, the expression levels of the proteins involved in the PI3K-AKT-mTOR signaling pathway were lowered progressively (P < 0.01), resulting in inhibition of migration of HNE1 and CNE2Z cells (P < 0.01).@*CONCLUSION@#AZD9291 suppresses proliferation and attenuates repair and migration capacities of nasopharyngeal carcinoma cells by inhibiting the EGFR/PI3K/AKT/mTOR signaling pathway, suggesting the potential value of AZD9291 in the treatment of nasopharyngeal carcinoma.

Research advances on the role and mechanism of epidermal stem cells in skin wound repair / 中华烧伤杂志

Epidermal stem cells play an pivotal role in skin self-renewal, wound repair, and re-epithelialization process. The emergence of new technologies and concepts such as single-cell sequencing and gene knockout further revealed a new mechanism of epidermal stem cells in epidermal self-renewal and wound repair, providing new ideas for wound repair. In this review, the mechanisms of proliferation, differentiation, and migration of epidermal stem cells are discussed. Combined with the analysis of researches on stem cell heterogeneity and cell plasticity, the physiological function of epidermal stem cells can be further understood. The application advances of epidermal stem cells in wound repair is also summarized, which would provide some advice for workers engaged in clinical and basic research on wound repair.

Associations between internet addiction, screen time and depressive symptoms / 中华流行病学杂志

Objective: To understand the associations between internet addiction, screen time (computer/mobile devices use and television watching time) and depressive symptoms in adults. Methods: A total of 6 932 adults aged <60 years from the Tianjin Chronic Low-grade Sgstemic Inflammation and Health (TCLSIH) Cohort of 2013-2019 were surveyed. The information about their computer/mobile devices use and television watching time were collected by using a self-reported questionnaire. The depressive symptoms were assessed using the self-rating depression scale (SDS). The adults surveyed were divided into two groups: non-depressive symptom group (SDS score <45) and depressive symptom group (SDS score ≥45). The associations between internet addiction, screen time and depressive symptoms were estimated using Cox proportional hazard regression models, with adjusting for multiple confounders. Results: After adjusting for confounding factors, the hazard ratios (HRs) of depressive symptom in the adults who had internet addiction before, had light internet addiction and had moderate or severe internet addiction were 0.83 (95%CI: 0.56-1.23) , 1.20 (95%CI: 1.03-1.41) for light and 1.48 (95%CI: 1.16-1.89), respectively, compared with those without internet addiction. The linear trend test results of the association between internet addiction and depressive symptoms was significant (trend P<0.001). Compared with the adults who used computer/mobile devices for <1 hour/day, the HRs of depressive symptoms in those who used computer/mobile devices for >1 hour, >3 hours, >5 hours and >10 hours were 0.59 (95%CI: 0.40-0.88), 0.58 (95%CI: 0.40-0.85), 0.52 (95%CI: 0.36-0.76) and 0.69 (95%CI: 0.45-1.05) respectively, a U-shaped association was found between computer/mobile devices use time and depressive symptoms (trend P<0.001). Compared with the adults who never watch TV, the HR of depressive symptoms was 1.36 (95%CI:1.09-1.69) for those watching TV for ≥3 hours/day in crude model and 1.34 (95%CI: 1.07-1.68) for those watching TV for ≥3 hours/day in adjusted model (trend P<0.001). Conclusion: Our findings suggested that internet addiction and television watching time were associated with an increased risk of depressive symptoms, while computer/mobile device use time was associated with a reduced risk of depressive symptoms.

Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-‍κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β‍-‍catenin (P‍-‍β‍-‍catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P‍-‍β‍-‍catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.

Effect of Guiqi Baizhu Prescription Combined with Oxaliplatin on Expression of EGFR and VEGFR2 and Angiogenesis in Gastric Cancer-bearing Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Guiqi Baizhu prescription （GQBZ） combined with oxaliplatin on the expression of epidermal growth factor receptor （EGFR） and vascular endothelial growth factor receptor-2 （VEGFR2） and angiogenesis in gastric cancer-bearing mice. MethodThe tumor-bearing model of gastric cancer was induced in Kunming mice. The mice were randomly divided into blank group， model group， oxaliplatin group （10 mg·kg-1）， and high- （17.68 g·kg-1）， medium- （8.84 g·kg-1）， and low-dose （4.42 g·kg-1） combination groups （GQBZ combined with oxaliplatin）. After the last administration， the transplanted tumor was collected and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of tumor tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum content of epidermal growth factor （EGF）， interleukin-8 （IL-8）， and vascular endothelial growth factor （VEGF）. Western blot and immunohistochemistry （IHC） were used to detect the expression of EGFR， phosphorylated EGFR （p-EGFR）， VEGFR2， phosphorylated VEGFR2 （p-VEGFR2）， and platelet-endothelial cell adhesion molecule （CD31）. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of EGFR and VEGFR2. ResultThe tumor weight in the drug intervention groups was significantly lower than that in the model group （P<0.01）. Compared with the oxaliplatin group， the high- and medium-dose combination groups showed reduced tumor weight （P<0.05， P<0.01）. The tumor cells in the model groups were high in cell density and regular in shape， and no clear tissue necrosis was seen. The tumor cell density in the drug intervention groups was reduced， and clear tissue necrosis and large-scale inflammatory cells were visible. Compared with the blank group， the model group and the drug intervention groups showed increased serum levels of EGF， VEGF， and IL-8 （P<0.05， P<0.01）. Compared with the model group， the drug intervention groups showed decreased serum levels of EGF， VEGF， and IL-8 （P<0.01）， reduced protein expression of EGFR， p-EGFR， VEGFR2， p-VEGFR2， and CD31， and declining mRNA expression of EGFR and VEGFR （P<0.01）. Compared with the oxaliplatin group， the high- and medium-dose combination groups showed decreased serum levels of EGF， VEGF， and IL-8 （P<0.05， P<0.01）， reduced protein expression of EGFR， p-EGFR， VEGFR2， p-VEGFR2， and CD31， and dwindled mRNA expression of EGFR and VEGFR2 （P<0.05， P<0.01）. The low-dose combination group showed decreased serum levels of EGF， VEGF， and IL-8， reduced protein expression of EGFR， p-EGFR， VEGFR2， p-VEGFR2， and CD31， and dwindled mRNA expression of EGFR and VEGFR2， but the difference was not statistically significant. ConclusionGQBZ combined with oxaliplatin can inhibit the growth and angiogenesis of tumor tissues in gastric cancer-bearing mice by affecting the expression of EGFR and VEGFR2.

Expression and Clinical Significance of CAS in Acute Myeloid Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the expression of cellular apoptosis susceptibility protein （CAS） in acute myeloid leukemia （AML） and its correlation with clinical characteristics.@*METHODS@#The expression of CAS in bone marrow tissue of 54 patients with AML and 24 patients with non-hematological malignant diseases was detected by Western blot and immune-histochemical method, and compared between AML group and control group. Also the relationship of CAS expression in AML and sex, age, WBC count, Hb, platelet count, bone marrow blast cell ratio, ki-67 index, cytogenetic and molecular biological prognostic risk stratification, extramedullary infiltration and other clinical characteristics was analyzed.@*RESULTS@#Western blot showed that the expression of CAS protein in bone marrow biopsies of AML patients was significantly higher than that in control group (P<0.05). Immune-histochemical method revealed that CAS was mainly located in the cytoplasm in both AML group and control group. Among 54 AML patients, 14 patients (25.9%) showed high expression of CAS, while all the 24 patients in the control group showed low expression of CAS. The high expression rate of CAS in AML patients was significantly higher than that in the control group (P<0.05). There were statistically significant differences in prognostic risk stratification and the remission rate of the first chemotherapy between CAS high expression group and CAS low expression group in AML (P<0.05). The proportion of high risk patients and unremission patients after the first chemotherapy in CAS high expression group were significantly higher than those in CAS low expression group (57.1% vs 27.5%, 30.8% vs 7.9%), while the proportion of low risk patients and complete remission patients after the first chemotherapy were significantly lower than those in CAS low expression group (14.3% vs 37.5%, 53.8% vs 84.2%). In AML patients, the ki-67 index of bone marrow tissue in CAS high expression group was higher than that in CAS low expression group (60% vs 50%) (P<0.05).@*CONCLUSION@#CAS is localized in cytoplasm in both AML and non-hematological malignant diseases, and its expression increases in AML. CAS is related to the risk stratification of cytogenetics and molecular biology, the remission rate after the first chemotherapy and ki-67 index in AML, which suggests that CAS may be involved in the occurrence and development of AML.

Effects of Tingli Dazao Xiefei Decoction on the immune inflammation and intestinal flora in asthmatic rats / 药学学报

The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.

Characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion based on consolidating the root and cultivating the primary / 中国针灸

Based on the theory of consolidating the root and cultivating the primary, the paper collates and reviews the theoretical evidences and the characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion so as to provide the ideas for further research. Xin'an medical masters thoroughly acquainted with the theory of consolidating the root and cultivating the primary in treatment of bi syndrome with acupuncture and moxibustion, emphasizing the regulation of qi and blood, yin and yang, the nutrient qi and the defensive qi; and replenishing the middle jiao (spleen and stomach) and the lower jiao (kidney). The acupoint selection was distinctive, in which, the acupoints were selected and stimulated in terms of the etiology and the pathogenesis of diseases, as well as the properties of special points. The remarkable therapeutic effect on bi syndrome was ensured through specially selecting he-sea points, ashi points and "yin-yang opposite" points; effectively using the penetrating needling technique and moxibustion method and combining acupuncture with herbal medication.

Tongdu Xingshen acupuncture and moxibustion combined with cognitive training in treatment of post-stroke mild cognitive impairment: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of Tongdu Xingshen (promoting the governor vessel and regaining consciousness) acupuncture and moxibustion combined with cognitive training and the simple cognitive training for post-stroke mild cognitive impairment (PSMCI).@*METHODS@#Eighty-four patients with PSMCI were randomly divided into an observation group and a control group, with 42 cases in each group (3 cases in the observation group and 2 cases in the control group dropped off). The observation group was treated by Tongdu Xingshen acupuncture and moxibustion combined with cognitive training, acupuncture was given at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), etc., and moxibustion was given at Shenting (GV 24) , Baihui (GV 20), Shendao (GV 11), Fengfu (GV 16) and Xinshu (BL 15). The control group was only given cognitive training. All the above treatment was given once a day, 5 times a week, for 4 consecutive weeks. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living (ADL) and stroke-specific quality of life (SS-QOL) were compared between the two groups before treatment, after treatment, 4 weeks and 12 weeks after treatment.@*RESULTS@#After treatment, 4 weeks and 12 weeks after treatment, the MoCA, MMSE and SS-QOL scores of the two groups were all higher than those before treatment (P<0.05), and the ADL scores were lower than those before treatment (P<0.05). In the observation group, the MoCA and MMSE scores were higher than those of the control group after treatment, 4 weeks and 12 weeks after treatment (P<0.05), and the SS-QOL score was higher than that of the control group 12 weeks after treatment (P<0.05).@*CONCLUSION@#Both Tongdu Xingshen acupuncture and moxibustion combined with cognitive training and simple cognitive training can improve cognitive function, daily living ability and quality of life in patients with PSMCI, and the combined therapy is superior to simple cognitive training in improving cognitive function and long-term quality of life in patients with PSMCI.

Brain Metabolic Network Redistribution in Patients with White Matter Hyperintensities on MRI Analyzed with an Individualized Index Derived from 18F-FDG-PET/MRI

Objective@#Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. @*Materials and Methods@#This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent 18F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called “individual contribution index” were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUVmean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. @*Results@#The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) x 10-3 and (0.0967 ± 0.0545) x 10-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785–0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUVmean of the limbic network (p < 0.001). @*Conclusion@#The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Identification and quality evaluation of germplasm resources of commercial Scutellaria baicalensis based on DNA barcode and HPLC / 中国中药杂志

Scutellaria baicalensis is a commonly used Chinese medicinal herb. In this study, we identified the germplasm resources of commercial S. baicalensis samples based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences according to the available chloroplast genome sequencing results, and measured the content of baicalin by HPLC. Through the above means we determined the best DNA barcode that can be used to detect the germplasm resources and evaluate the quality of commercial S. baicalensis samples. A total of 104 samples were collected from 24 provinces, from which DNA was extracted for PCR amplification. The amplification efficiencies of trnH-psbA, petA-psbJ, and ycf4-cemA sequences were 100%, 59.62%, and 25.96%, respectively. The results of sequence analysis showed that 5, 4, and 2 haplotypes were identified based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences, respectively. However, the sequences of haplotypes in commercial samples were different from that of the wild type, and the joint analysis of three fragments of S. baicalensis only identified 6 haplotypes. Furthermore, the phylogenetic analysis and genetic distance analysis indicated that trnH-psbA could be used to identify S. baicalensis from adulterants. The above analysis showed that trnH-psbA was the best fragment for identifying the germplasm resources of commercial S. baicalensis samples. We then analyzed the haplotypes(THap1-THap5) of commercial S. baicalensis samples based on trnH-psbA and found that THap2 was the main circulating haplotype of the commercial samples, accounting for 86.55% of the total samples, which indicated the scarce germplasm resources of commercial S. baicalensis samples. The content of baicalin in all the collected commercial S. baicalensis samples exceeded the standard in Chinese Pharmacopoeia and had significant differences(maximum of 12.21%) among samples, suggesting that the quality of commercial S. baicalensis samples varied considerably. However, there was no significant difference in baicalin content between different provinces or between different haplotypes. This study facilitates the establishment of the standard identification system for S. baicalensis, and can guide the commercial circulation and reasonable medication of S. baicalensis.

Cloning and subcellular location of the PnMYB1R1 gene from Panax notoginseng and expression analysis with different stresses / 药学学报

MYB transcription factors, one of the largest transcription factor families in plants, play an important role in signal transduction, plant growth and plant resistance. In this study a full-length cDNA of the PnMYB1R1 gene was cloned from Panax notoginseng. Sequence analysis, prokaryotic expression and purification, subcellular location, transcriptional activity analysis, tissue-specific analysis and expression analysis under different abiotic stresses was performed. The open reading frame (ORF) of PnMYB1R gene was 738 bp, encoding a protein of 245 amino acids with a predicted molecular mass (MW) of 27.0 kD. The sequence analysis and polygenetic analysis indicated that the PnMYB1R1 protein contains a conserved R3 domain, belonging to TRF-like protein in 1R-MYB-type transcription factors. The recombinant PnMYB1R1 protein was expressed in Escherichia coli BL21(DE3) cells using the prokaryotic expression vector pET28a-PnMYB1R1 and was purified. Subcellular localization analysis showed that PnMYB1R1 was localized in the nucleus. Transcriptional activity analysis indicated that the PnMYB1R1 transcription factor has transcriptional activation activity. Expression analysis indicated that PnMYB1R1 was primarily expressed in roots, followed by stems and leaves, and then rootlets. The expression level of PnMYB1R1 in root, stems, leaves and rootlets was influenced by salt, low temperature and drought treatment, while the abundance of PnMYB1R1 was significantly induced by salt stress in these tissues. These results provide valuable insights into the role of 1R-MYB transcription factors in plant defense.

Molecular identification and quality analysis of Rhei Rhizoma based on chloroplast matK gene and UPLC / 药学学报

Rhei Rhizoma is commonly used as a traditional Chinese medicine with multiple botanical origins. Different botanical sources may have different pharmacological activities. The germplasm resources of commercial Rhei Rhizoma were determined based on the chloroplast gene matK, and the anthraquinone and free anthraquinone content was determined by UPLC to analyze quality of commercial Rhei Rhizoma. Eighty-nine commercial Rhei Rhizoma samples were collected from 40 cities in 27 provinces. DNA was extracted and the matK gene was amplified by PCR. Results indicated that the collected samples were from the same botanical origin, Rheum palmatum, and 8 genotypes were identified, including Rp1, Rp2, Rp3, Rp4, Rp5, Rp6, Rp10 and Rp12. Rp4 and Rp6, cultivated in Gansu, Sichuan and Yunnan provinces were the main circulating genotypes, representing 40.45% and 37.08% of the total samples, respectively. Phylogenetic tree analysis showed that the eight genotypes were mainly divided into two branches, of which the main genotypes Rp4 and Rp6 were in one branch. Genetic distance analysis indicated that the genetic separation of the eight genotypes was between 0.001 and 0.010. UPLC analysis indicated that 93.26% of the samples met the Pharmacopoeia standards. There were significant differences in the content of total anthraquinone and free anthraquinone among the samples, in which the difference in free anthraquinone was 1.01% and the difference in total anthraquinone content was 3.79%, indicating that the quality of commercial Rhei Rhizoma samples varies considerably. There was no significant difference in the content of total anthraquinone and free anthraquinone in commercial Rhei Rhizoma among different collection provinces and genotypes. This study will help guide the circulation of Rhei Rhizoma in the market and provides valuable insights for molecular identification and quality analysis of other traditional Chinese medicines.

Tracing PRX1+ cells during molar formation and periodontal ligament reconstruction / 国际口腔科学杂志·英文版

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1+ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1+ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1+ cells in PDL cells. The behavior of PRX1+ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1+ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1+ cells; during transplanted teeth PDL reconstruction, PRX1+ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1+ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.