Construction of residents' healthy lifestyle cognitive index system in the context of carbon peaking and carbon neutrality / 环境与职业医学

Background Healthy lifestyle is one of the important factors affecting individual health. How to promote residents' cognition of healthy lifestyle has become an urgent practical problem for the whole society. However, there is no residents' healthy lifestyle cognitive indexes available with consideration of carbon peaking and carbon neutrality. Objective To construct a cognitive index system for providing effective assessment on residents' cognition of healthy lifestyle under the background of carbon peaking and carbon neutrality. Methods Based on the health belief model, a preliminary cognitive index system of residents' healthy lifestyle under the background of carbon peaking and carbon neutrality was proposed after literature study and relevant policy review. Then three rounds of indicator importance evaluation and screening by Delphi method were conducted before the index system was finally constructed. The weights of all levels of indicators were determined using analytic hierarchy process. In addition, a self-assessment questionnaire was developed based on the index system. The questionnaire was utilized to conduct a survey among 200 residents by convenience sampling in Shenyang, Liaoning Province from November to December 2021. The survey was used to examine the reliability and validity of the indicator system. Results The effective recovery rates of the three rounds of Delphi method were all 100%. The authority coefficient was 0.84. The Kendall's W consistency test showed good expert consistency (P<0.001). Finally, a cognitive index system of residents' healthy lifestyle under the background of carbon peaking and carbon neutrality was initially constructed, including 4 first-level indicators, 8 second-level indicators, and 35 third-level indicators. Among them, the weights of the first-level indicators were 0.4541 for practice cognition, 0.2248 for benefit and obstacle cognition, 0.1626 for action clue cognition, and 0.1585 for risk cognition, respectively. The correlation coefficients between each indicator were from 0.586 to 0.977 (P<0.01). The overall Cronbach's α coefficient was 0.95, indicating high reliability. Invited experts agreed that the entries were representative and the content validity of the constructed indicator system was good. The factor analysis also showed that the structure validity was good. Conclusion The proposed index system for residents' cognition of healthy lifestyle show good reliability and validity, which can be used as an effective assessment tool for residents' healthy lifestyle cognition under the background of carbon peaking and carbon neutrality. It can provide a scientific and theoretical basis for promoting residents' cognition and practice of healthy lifestyle.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Prediction of Responses of Patients with Hepatocellular Carcinoma to Anti-PD-1 Immunotherapy by T-cell Invigoration to Tumour Burden Ratio / 肿瘤防治研究

Objective To explore the predictive value of T cell activation in peripheral blood of patients with hepatocellular carcinoma(HCC) after anti PD-1 therapy and its ratio to tumor burden on the efficacy of immunotherapy. Methods Serum specimens were obtained before and after treatment from 85 patients with HCC who received anti-PD-1 treatment. Indicators such as cell subpopulations and T cell activation were detected by flow cytometry. Combined with imaging analysis, cutoff value was obtained by X-tile software. Survival analysis was used to evaluate patients' outcomes. Results The maximum fold change of Ki-67+/PD-1+/CD8+ T cells in treatment cycles and the tumor burden determined by imaging were associated with prognoses. The ratio of T cell Ki-67+/PD-1+/CD8+ expression to tumor burden ratio greater than 0.6 at the first cycle of anti-PD-1 immunotherapy was associated with improvements in progression-free survival and overall survival (P < 0.05). Conclusion The ratio of activationa in T cells in peripheral blood after immunotherapy to the tumor burden may be related to the clinical efficacy of anti-PD-1 immunotherapy for HCC.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro.@*METHODS@#The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1.@*RESULTS@#Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01).@*CONCLUSION@#Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction / 中国中药杂志

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Establishment and validation of a nomograph model for prediction of bronchopulmonary dysplasia in very low birth weight infants born earlier than 32 weeks / 中华围产医学杂志

Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

Application of minimally invasive ultrasonic osteotome in robotic-assisted sacral tumor resection / 中华骨科杂志

Sacral tumors are surgically challenging and at a high risk of complications. In recent years, robotic-assisted resection has been gradually applied in sacral tumors, but it is difficult to remove bone tissue by present robotic instruments, which limits the application of surgical robot in sacral tumor. The present study aimed to explore the application range and therapeutic effect of minimally invasive ultrasonic osteotome in robotic-assisted sacral tumor resection. Eighteen patients underwent robotic-assisted sacral tumor resection in the First Affiliated Hospital of Sun Yat-Sen University from May 2015 to March 2021 by the Da Vinci robotic surgical system. Among them three patients who underwent osteotomy with minimally invasive ultrasonic osteotome were enrolled. There were 2 males and 1 female, aged 24, 32, 71 years, respectively. The tumors included 2 schwannomas and 1 ganglioneuroma. The operation time, bleeding volume and postoperative hospitalization days were recorded. The recurrence and complications were evaluated during follow-up. The operative time of the 3 patients was 80, 240 and 300 minutes, and the intraoperative bleeding volume was 30, 30 and 100 ml. Complete resection was performed in 2 cases and intralesional resection in 1 case. The postoperative hospital stay was 5, 3 and 7 days respectively. The follow-up time was 58, 17 and 31 months respectively. No tumor recurrence was found during the follow-up. As regards complications, only one patient had left foot pain after operation, and there were no other intraoperative or postoperative complications. The therapeutic advantages of ultrasonic osteotome combined with the Da Vinci robotic surgical system can achieve precise osteotomy, reduce intraoperative bleeding and accelerate postoperative recovery for certain patients with sacral tumors.

Long-term prognostic analysis of different treatment strategies for T 3-T 4 nasal sinus adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognosis and influencing factors of different treatment strategies in T 3-T 4 nasal sinus adenocarcinoma. Methods:The data of 93 cases of T 3-T 4 stage nasal sinus adenocarcinoma diagnosed from 2006 to 2018 were retrospectively analyzed. All patients were divided into combined operation group and non-operation group. The survival status and failure mode after corresponding treatment were analyzed. The enumeration data were analyzed by Chi-square test or Fisher's exact test. Survival analysis was performed by Kaplan-Meier method. Univariate analysis was conducted by log-rank test. Multivariate prognostic analysis was performed by Cox model. Results:The average follow-up time in the whole cohort was 81.3 months (18-156 months). By the end of follow-up, a total of 38.7% (36/93) of patients had local recurrence, 14.0% (13/93) had distant metastasis, 17.2% (16/93) had local recurrence complicated with distant metastasis, and 28.0% (26/93) were stable. The overall 2-, 5-, and 10-year overall survival (OS) and progression free survival (PFS) rates were 83.5%, 59.3%, 31.8% and 73.6%, 40.7% and 25.3%, respectively. In univariate analysis, the PFS and OS of patients aged 46-64 years old (all P<0.001), male ( P=0.022, P=0.001), patients with lesions located in the maxillary sinus ( P=0.001, P<0.001), adenoid cystic carcinoma ( P=0.001, P<0.001), non-invasion of orbital / clivus ( P=0.041, P<0.001), GTV P dose>64 Gy ( P=0.003, P=0.006) and N 1 stage ( P=0.014, P=0.014) were statistically different among different treatment modes. Multivariate analysis showed that age ≥65 years old ( P=0.012, P=0.005), orbital / clival invasion ( P<0.001, P=0.005), and GTV p dose ≤64 Gy ( P<0.001, P=0.011) were the independent adverse prognostic factors affecting PFS and OS in T 3-T 4 stage nasal sinus adenocarcinoma. Conclusions:The local failure rate of T 3-T 4 stage nasal sinus adenocarcinoma is high after treatment. Age, orbital / clival invasion, and GTV p dosage are the independent adverse prognostic factors. Surgery based intervention is superior to other treatment strategies.

The influence of acceptance and commitment therapy on the psychological flexibility, self-compassion, anxiety and depression of the primary caregivers of patients with primary liver cancer / 中国实用护理杂志

Objective:To explore the intervention effect of acceptance and commitment therapy on the psychological flexibility, self-compassion, anxiety and depression of the primary caregivers of patients with primary liver cancer, so as to provide reference for the clinical care of the primary caregivers of cancer patients.Methods:This was a prospective study. A total of 80 primary caregivers of patients with primary liver cancer treated in Tianyou Hospital Affiliated to Wuhan University of Science and Technology from July to December 2021 were selected as the observation objects, and they were randomly divided into the control group and the intervention group according to the random drawing method, with 40 cases in each group. The control group was given routine nursing measures, while the intervention group was given acceptance and commitment therapy on the basis of routine nursing. The intervention effect was evaluated by the Acceptance and Action Questionnaire-2nd Edition (AAQ-Ⅱ), Self-Compassion Scale Short-Form (SCS-SF) and Hospital Anxiety and Depression Scale (HADS) before the intervention, on the day of discharge, and one month after discharge.Results:Finally, 71 primary caregivers completed the intervention and follow-up, 36 in the control group and 35 in the intervention group. Before the intervention, there was no statistically significant difference in the scores of AAQ-Ⅱ, SCS-SF, Anxiety subscale of HADS(HADS-A) and Depression subscale of HADS(HADS-D) between the two groups ( P>0.05). The AAQ-Ⅱscores of the intervention group on the day of discharge and one month after discharge were (19.63±2.59), (19.12 ± 2.20) points, which were significantly lower than those of the control group (23.14 ± 2.49), (22.56 ± 2.40) points. The differences were statistically significant ( t=5.83, 6.25, both P<0.01). The SCS-SF scores of the intervention group on the day of discharge and one month after discharge were (39.34 ± 2.68), (39.89 ± 2.81) points, which were significantly higher than those of the control group (36.69 ± 3.08), (37.72 ± 2.41) points, the differences were statistically significant ( t=-3.86, -3.49, both P<0.01). The HADS-A/HADS-D scores of the intervention group on the day of discharge and one month after discharge were (9.31 ± 1.95), (9.09 ± 1.60) points and (8.80 ± 2.15), (8.54 ± 1.75) points,which were significantly lower than those of the control group(11.42 ± 1.50), (11.03 ± 1.70) points and (10.11 ± 1.92), (10.03 ± 1.84) points, the differences were statistically significant( t values were 2.71-5.10, all P<0.01). The scores of AAQ-Ⅱ, SCS-SF, HADS-A and HADS-D of the two groups were analyzed by repeated measures analysis of variance, and there were significant differences in time effect, inter-group effect and interaction effect ( F vaules were 3.42-37.90, all P<0.05). Conclusions:Acceptance and commitment therapy can improve the self-compassion and psychological flexibility, reduce anxiety and depression of the primary caregivers of patients with primary liver cancer.

Effects of lentinan on dendritic cell metabolism / 中国药理学通报

Aim To study the effects of lentinan(LNT)on the metabolism of dendritic cells(DCs)by metabonomics, and uncover the potential mechanism of its regulation of DC function. Methods DC2.4 cells were co-incubated with LNT for 24 h, and the activity of the cells was detected by thiazolyl blue tetrazolium bromide(MTT)assay. The contents of interleukin-6(IL-6), tumor necrosis factorα(TNF-α)and interleukin-12(IL-12)in supernatant were detected by enzyme-linked immunosorbent assay(ELISA). The metabolic general changes of DC2.4 cells were detected by Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS), and the differential metabolites were analyzed by multi-distance covariates and bioinformatics, partial least squares-discriminant analysis(PLS-DA). Finally, metabolic pathway analysis was performed by MetaboAnalyst 5.0. Results LNT did not significantly inhibit the activity of DC2.4 cells at the dose of 25100 mg·L-1. LNT(100 mg·L-1)could significantly stimulate the secretion of IL-6, TNF-α and IL-12 in DC2.4 cells. 20 differential metabolites were identified in DC2.4 cells after being stimulated by LNT(100 mg·L-1), which involved 25 metabolic pathways including urea cycle, arginine and proline metabolism. Conclusion The regulation of LNT on DC function involves a variety of amino acid metabolism.

The hippocampal proteomics mechanism of thalidomide in Alzheimer's disease model mice induced by Aβ / 中国药理学通报

Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ

Dorsal root ganglion receptor subtype P2X3R mediates postoperative-hyperalgesic priming in mice / 中国药理学通报

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

Effect of Taohong Siwu Decoction on apoptosis and EMT of pulmonary fibrosis model rats by JAK2/STAT3 signaling pathway / 中国药理学通报

Aim To explore the effect of Taohong Siwu Decoction on apoptosis and EMT of pulmonary fibrosis model rats by JAK2/STAT3 signaling pathway. Methods Forty SD rats were randomly divided into control group, model group, methylprednisolone group, Taohong Siwu Decoction low-concentration, high-concentration group respectively, with eight cases in each group. The intratracheal injection of bleomycin was applied to induce IPF rat models. HE and Masson staining were performed to observe the pathological changes of lung tissues in each group. ELISA was used to detect the contents of TNF-α, MMP-7 and TGFβ-l in serum of rats. Immunohistochemistry and Western blot were applied to detect the protein expression of JAK2, pJAK2, STAT3, p-STAT3, E-cadherin, α-SMA in lung tissues. RT-PCR was applied to detect the expression of JAK2, STAT3, Bcl2 and Bax genes in lung tissues. Results Compared with control group, the degree of alveolar inflammation and fibrosis degree, the contents of TNF-α, MMP-7 and TGFβ-1 in serum, the levels of JAK2, p-JAK2, STAT3, p-STAT3, α-SMA protein expression, JAK2, STAT3, Bax gene expression were up-regulated, and the levels of Bcl-2 gene and E-cadherin protein expression were down-regulated in lung tissues. Compared with model group, the degree of alveolar inflammation and fibrosis, the contents of TNF-α, MMP-7 and TGFβ-1 in serum, the levels of JAK2, p-JAK2, STAT3, p-STAT3, α-SMA protein expression, JAK2, STAT3 and Bax gene expression were reduced, while the levels of Bcl-2 gene and E-cadherin protein expression were elevated in Taohong Siwu Decoction high-concentration group. Conclusions Taohong Siwu Decoction may regulate JAK2/STAT3 signaling pathway, down-regulate Bax, α-SMA and up-regulate Bcl-2, E-cadherin expression to induce apoptosis and EMT in rat model of pulmonary fibrosis, thus playing an anti-pulmonary fibrosis role.

Bear bile powder alleviates Parkinson's disease-like behavior in mice by inhibiting astrocyte-mediated neuroinflammation / 中国天然药物

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg-1) for five days, followed by BBP (50, 100, and 200 mg·kg-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.

Early changes of retinal and choroidal microvascular structure in hypertensive patients / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the feasibility of swept source optical coherence tomography angiography(SS-OCTA)in evaluating early retinal and choroidal microcirculation changes in patients with hypertension.METHODS:Prospective clinical study. A total of 27 patients with grade 2 or 3 essential hypertension(hypertension group)diagnosed in the Department of Cardiology of Xi'an First Hospital from July to November 2022 were included in the study. There were 14 males and 13 females. The mean age was(57.11±3.36)years. During the same period, 27 age- and sex-matched normal people without a history of hypertension were selected as the control group, including 12 males and 15 females. The average age was(55.74±2.95)years old. All patients underwent BCVA(LogMAR), intraocular pressure, axial length, slit lamp examination, fundus color photography and SS-OCTA examination. SS-OCTA was used to scan the macular area of the right eye in the range of 6×6 mm. The retina and choroid were divided into three concentric circles with diameters of 0-1 mm, 1-3 mm and 3-6 mm around the fovea according to ETDRS. Macular vessel density(VD), perfusion area(PA), retinal thickness(CMT), choroidal thickness(CT), choroidal vessel volume(CVV)and choroidal vasculr index(CVI)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular area of 0-1 mm, 1-3 mm and 3-6 mm were analyzed and recorded. The changes in VD, PA, CMT, CT, CVV and CVI were compared between the two groups. Independent sample t-test was used to compare VD, PA, CMT and CVI between the two groups; CT, CVV and LogMAR visual acuity were analyzed by Wilcoxon signed rank test of independent samples.RESULTS:Compared with the control group, the hypertensive group had significantly lower VD in the macular area 0-3 mm(0-1 mm, t=-3.144; 1-3 mm, t=-3.611, P&#x003C;0.05). VD in the area of 3-6 mm showed a tendency to increase compared with the control group(t=1.715, P&#x003E;0.05). The CMT in the 0-1mm area of the macular area in the hypertension group was lower than that in the control group(t=-2.624, P&#x003C;0.05). There was no significant difference in CT, CVV and CVI between the two groups(P&#x003E;0.05).CONCLUSION:The VD of DCP in the 0-3 mm area and the CMT in the 0-1 mm area are decreased in hypertensive patients. There were no significant differences in CT, CVV and CVI between the two groups. VD and CMT in macular DCP may be used as indicators to evaluate the early changes of retinal and choroidal microcirculation in hypertensive patients.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR / 中华心血管病杂志

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease / 中华心血管病杂志

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China / 中华心血管病杂志

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

Mechanism of Polyphyllin Ⅰ Extract in Activating Hippo Signal to Induce Apoptosis and Autophagy of Colorectal Cancer Cells / 中国实验方剂学杂志

ObjectiveTo study the inhibitory effect of polyphyllin Ⅰ （PPI） on the growth of colorectal cancer cells and its molecular mechanism. MethodRKO cells were cultured and divided into a blank group and PPI treatment groups with concentrations of 0.6， 0.8， 1.0 μmol·L-1， respectively. HRT18 cells were cultured and divided into a blank group and PPI treatment groups with concentrations of 1.2， 1.4， 1.6 μmol·L-1， respectively. The effects of PPI on the proliferation and morphology of colorectal cancer were detected by cell proliferation toxicity assay， trypan blue exclusion assay， plate clone formation assay， and confocal high-intension cell imaging analysis system. Flow cytometry was used to detect the apoptosis rate of colorectal cancer cells. The pQCXIP-GFP-LC3 plasmid transfection assay was used to detect the formation of autophagosomes in colorectal cancer cells after PPI treatment. Western blot was used to detect the expression of apoptosis-related proteins Caspase-3， Caspase-8， and poly ADP ribose polymerase （PARP）， the expression of autophagy related protein LC3Ⅱ， and the expression and phosphorylation of Hippo signaling pathway proteins LATS1 and YAP. In the plvx-Flag-YAP plasmid transfection assay， YAP was overexpressed and treated with PPI， and the proliferation of colorectal cancer cells was detected by cytotoxicity assay. The expression of LC3Ⅱ and PARP in colorectal cancer cells was detected by Western blot. SwissADME predicted pharmacokinetic parameters of PPI. ResultAs compared with the blank group， the survival rate and clone formation ability of colorectal cancer cells in the PPI group were significantly decreased （P<0.01）， the cell area of colorectal cancer cells in the PPI group was significantly decreased， and the roundness of colorectal cancer cells was significantly increased （P<0.01）. As compared with the blank group， the apoptosis rate of colorectal cancer cells in PPI treatment groupw was significantly increased （P<0.01）， the expression of apoptotic proteins Caspase-3 and Caspase-8 protein precursor in PPI treatment groups was decreased， and the cleavage of PARP was increased （P<0.01）. As compared with the blank group， the expression level of autophagy-related protein LC3Ⅱ in colorectal cancer cells in PPI treatment groups was significantly increased， and the formation of autophagosomes was promoted （P<0.01）. As compared with the blank group， the expression of YAP protein in colorectal cancer cells in PPI treatment groups was significantly decreased， and the expressions of phosphorylated LATS1 and YAP were significantly increased （P<0.01）. As compared with the blank group， overexpression of YAP could significantly antagonize the effect of PPI on apoptosis， autophagy activation， and proliferation inhibition of colorectal cancer cells. SwissADME simulation results showed that PPI had good drug like activity. ConclusionPPI can induce apoptosis and autophagy of colorectal cancer cells through targeted activation of Hippo signaling pathway， thereby inhibiting their proliferation.