To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

OBJECTIVE To construct the drug utilization evaluation criteria for Dezocine injection， so as to provide reference for the rational drug use in medical institutions. METHODS On the basis of evidence methodology， relevant guidelines/expert consensus， systematic reviews/meta-analysis were consulted； the evaluation criteria framework for Dezocine injection was established after screening evidence. Delphi method was employed， whereby 28 clinicians and clinical pharmacists from secondary and above-level medical institutions across eight provinces， including Tianjin， Beijing and Shandong， were selected to participate in two rounds of questionnaire surveys. The final indicators were determined based on the experts’ enthusiasm coefficient， authority coefficient， and degree of coordination. RESULTS The effective recovery rate of questionnaire was 100% in the first round and 92.86% in the second round； expert authority coefficient was 0.82 in the first round and 0.81 in the second round； the coordination degree of experts in the first round was 0.29， and in the second round was 0.31 （P＜0.001）. Drug utilization evaluation standard system for Dezocine injection was formed finally， including three dimensions of medication indications， medication process and medication results， with a total of 11 first-level indicators （such as indications， usage and dosage） and 33 second-level indicators （such as labor analgesia and the management of severe pain following major or moderate surgeries combined with other analgesic drugs）. The average importance scores for each indicator ranged from 4.08 to 5.00 points， with an overall average score of 4.61 points and coefficient of variation ranging from 0 to 0.19. CONCLUSIONS The drug utilization evaluation criteria for Dezocine injection established based on evidence-based methodology and Delphi method is authoritative and scientific， which provides a reference for subsequent evaluation of the rationality of clinical medication.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

ObjectiveTo explore the effect and possible molecular mechanism of Qinghua Yichang Formula （清化益肠方， QYF） in treating acute radiation-induced intestinal injury mice via NOD-like receptor thermal protein domain associated protein 3 （NLRP3）. MethodsSixty C57BL/6J mice were randomly divided into control group， model group， pre-modeling medication group， post-modeling medication group， inhibitor group， and QYF plus inhibitor group， with 10 mice in each group.Except for the control group， the other five groups were irradiated with a single full dose to establish the acute radiation-induced intestinal injury mice model. The pre-modeling medication group and the QYF plus inhibitor group were continuously given 4 g/ml of QYF decoction by gavage before modeling， 0.2 ml each time， once a day for 7 days. The post-modeling medication group， pre-modeling medication group and QYF plus inhibitor group were given 4 g/ml of QYF decoction for 14 days after modeling. The control group， model group and inhibitor group were given 0.2 ml of normal saline once a day for 14 consecutive days. Two hours after irradiation， the inhibitor group and the QYF plus inhibitor group were given an intraperitoneal injection of 0.2 ml of the NLRP3 inhibitor MCC950 （concentration： 10 mg/kg）， once every two days. To observe the pathological changes in intestinal tissues， hematoxylin-eosin （HE） staining was used. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of NLRP3 in intestinal tissues. Immunohistochemistry was used to detect the expression level of NLRP3， Caspase-1 and GSDMD in intestinal tissues. The proportion of CD4⁺ and CD8⁺ T cells in the spleens of mice were detected by flow cytometry. ELISA was used to determine the levels of IFN-γ， IL-18， and IL-1β in mice serum. ResultsHE staining showed no lesions in the intestinal tissue of mice in the control group. The mice in the model group had shortened intestinal villi， thinned mucosal layers， multifocal mucosal necrosis in the lamina propria， and local neutrophil infiltration. The pathological damage of intestinal tissue of mice in each medication group was improved to varied degrees， among which the QYF plus inhibitor group showed most obvious improvement. Compared to those in the control group， the protein and mRNA expression levels of NLRP3 in the intestinal tissue of mice in the model group significantly increased， with higher NLRP3， Caspase-1， and GSDMD protein expression in the intestinal tissue， increased proportion of CD4⁺ T cells in spleen， decreased proportion of CD8⁺ T cells， and increased levels of IFN-γ， IL-18 and IL-1β in serum （P＜0.05）. Compared to those in the model group， the above indicators in the other medication groups were all improved （P＜0.05）.The NLRP3， Caspase-1， and GSDMD proteins in the pre-modeling medication group were lower than those in the post-modeling medication group （P＜0.05）； and the NLRP3 mRNA level in the QYF plus inhibitor group was lower than that in the inhibitor group （P＜0.05）. ConclusionQYF may play a role in preventing and treating acute radiation-induced intestinal injury by inhibiting the expression of NLRP3.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.