Objective:The effect of Xuan Bi Decoction on inhibition of cyclooxygenase-2(COX-2)pathway on inflammation in rats with acute gouty arthritis(GA).Methods:Sixty SD rats randomly allocated into control group,model group,celecoxib group(20 mg/kg),Xuan Bi Decoction low-dose group(5 g/kg),Xuan Bi Decoction medium-dose group(10 g/kg),Xuan Bi Decoction high-dose group(20 g/kg),with 10 rats in each group.The classic method of Coderre was used to establish a rat gout model and observe the general condition of each group of rats;analysis of rat gait scores and joint swelling of rats;the histopathological growth of rat ankle Sy-novial membrane were observed by HE staining;the levels of inflammatory factors IL-1β,TNF-α,PGE2 and LTB4 in rats joint fluid were detected by ELISA;Western blot detection of PGE2 receptor 2(EP2)and LTB receptor 1(BLT1)expressions in rats ankle syno-vial tissue;qRT-PCR to detect the effect of mRNA expression of COX-2 and 5-lipoxygenase(5-LOX).Results:Rats in the model group had swollen joints,lameness,lusterless fur and mental lethargy;the rats in the celecoxib group and Xuan Bi Decoction low,medium and high dose groups showed effective improvement in related symptoms;compared with control group,the gait score,degree of joint swelling,degree of histopathology,IL-1β,TNF-α,PGE2,LTB4,COX-2,5-LOX,EP2 and BLT1 levels of the rats in the model group were significantly higher(P<0.05);compared with the COX-2 inhibitor celecoxib,Xuan Bi Decoction(20 g/kg)showed better anti-arthritic properties in rats treated with MSU crystals,accompanied by reduced expression of IL-1β,TNF-α,PGE2,LTB4,COX-2,5-LOX,EP2 and BLT1.Conclusion:Dual inhibition of COX-2 and 5-LOX by Xuan Bi Decoction in GA rats to improve MSU crystal-induced inflammation and may serve as a novel therapeutic strategy.

Objective To observe the value of CT radiomics for differentiating spinal bone islands(BI)and osteoblastic metastases(OBM).Methods Data of 109 BI lesions in 98 patients and 282 OBM lesions in 158 patients(including 103 OBM in 48 lung cancer cases,86 OBM in 52 breast cancer cases and 93 OBM in 58 prostate cancer cases)from 3 medical institutions were retrospectively analyzed.Data obtained from institution 1 were used as the internal dataset and divided into internal training set and internal validation set at a ratio of 7∶3,from institution 2 and 3 were used as external dataset.All datasets were divided into female data subset(including OBM of female lung cancer and breast cancer)and male data subset(including OBM of male lung cancer and prostate cancer).Radiomics features were extracted and screened to construct 3 different support vector machine(SVM)models,including model1 for distinguishing BI and OBM,model2 for differentiating OBM of female lung cancer and breast cancer,and model3 for differentiating OBM of male lung cancer and prostate cancer.Diagnostic efficacy of model1,CT value alone and 3 physicians(A,B,C)for distinguishing BI and OBM were assessed,as well as differentiating efficacy for different OBM of model2 and model3.Receiver operating characteristic(ROC)curves were drawn,and area under the curves(AUC)were calculated and compared.The differential diagnostic efficacy of model2 and model3 were also assessed with ROC analysis and AUC.Results AUC of model1 for distinguishing spinal OBM from BI in internal training set,internal validation set and external dataset was 0.99,0.98 and 0.86,respectively.In internal training set,model1 had higher AUC for distinguishing BI and OBM than that of physician A(AUC=0.78),B(AUC=0.87)and C(AUC=0.93)as well as that of mean CT value(AUC=0.78,all P＜0.05).AUC in internal training set,internal validation set and external dataset of model2 for identifying female lung cancer and breast cancer OBM was 0.79,0.75 and 0.73,respectively,of model3 for discriminating male lung cancer from prostate cancer OBM was 0.77,0.74 and 0.77,respectively.Conclusion CT radiomics SVM model might reliablely distinguish OBM and BI.

BACKGROUND:As a member of bone morphogenetic proteins,growth differentiation factor-5 shows promising potential in the application of cartilage and bone repair.The affinity of growth differentiation factor-5 onto bone tissue determines protein use efficiency,so it is of great significance to prepare growth differentiation factor-5 with bone targeting capability. OBJECTIVE:To modify growth differentiation factor-5 using bisphosphonates and investigate the effects of modified protein on the growth of preosteoblasts in mice. METHODS:Pamidronate disodium/growth differentiation factor-5 complex was prepared using chemical crosslinking to couple growth differentiation factor-5 with pamidronate disodium.The functional groups and structures of the complex were characterized using Fourier transform infrared spectroscopy and circular dichromatography.To determine the bone targeting in vitro,the binding of the modified growth differentiation factor-5 with calcium phosphate and in vitro release amount of growth differentiation factor-5 were measured with an ELISA kit.Growth differentiation factor-5(control group)and the pamidronate disodium/growth differentiation factor-5 complex(experimental group)were co-cultured with preosteoblasts MC3T3-E1.Individually cultured cells were blank controls.The effect of the complex on cell proliferation and differentiation was evaluated. RESULTS AND CONCLUSION:(1)The infrared spectroscopy and circular dichromatography results indicated that the bisphosphonate/growth differentiation factor-5 complex was successfully prepared without significant changes in the protein secondary structure.In vitro protein adsorption results showed that growth differentiation factor-5 adsorption on calcium phosphate was increased by about one time after coupling with a bisphosphonate.In the presence of cysteine,growth differentiation factor-5 could be released from the bisphosphonate/growth differentiation factor-5 complex.(2)CCK-8 assay results showed that the absorbance value of the experimental group cultured for 4 and 7 days was higher than that of the control group and blank control group(P<0.000 1).After 7 days of culture,the expression of alkaline phosphatase in the experimental group was significantly higher than that in the control group and blank control group(P<0.000 1).After 13 days of culture,the content of calcium nodules in the experimental group was significantly higher than that in the control group and the blank control group(P<0.000 1).The results of qRT-PCR showed that the mRNA expression of alkaline phosphatase,osteocalcin and Runx2 in the experimental group was higher than that in the control group and the blank control group after 7 days of culture(P<0.01,P<0.001,P<0.000 1).(3)These findings exhibit that bisphosphonate modification can enhance the binding capacity of growth differentiation factor-5 to calcium phosphate as well as improve its biological activity.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.

Objective To study the serotype, drug resistance, and molecular typing characteristics of Salmonella enteritidis strains isolated from patients with diarrhea in Xiangyang City. Methods Serotyping, drug sensitivity test, pulsed field gel electrophoresis (PFGE) typing, and whole genome sequencing were carried out on Salmonella enteritidis strains isolated from diarrhea patients from 2019 to 2020. Results From the drug susceptibility test , Salmonella enteritidis in this region showed varying degrees of drug resistance, with 94.7% of Salmonella enteritidis strains being multidrug-resistant. The PFGE electrophoretogram of Salmonella enteritidis showed that 19 strains could be divided into 6 PFGE types by cluster analysis, among which 12 strains belonged to the epidemic dominant type. MLST typing showed that all 15 strains were ST11 type, carrying multiple drug resistance genes (mdsA, mdsB, mdsC, gols, and sdiA) and mdtK gene, and all carried various invasiveness-related virulence genes. However, there were slight differences in virulence genes related to the secretion system of the pathogenic island among the different strains. The phylogenetic tree analysis of the system evolution showed that 15 strains could be divided into 2 different evolutionary branches. Conclusion The situation of multidrug resistance in Salmonella enteritidis in Xiangyang is serious, with dominant PFGE types and ST types, and it carries multiple drug resistance genes and various invasiveness-related virulence genes.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Diabetic lower extremity vascular disease is one of the common chronic complications of diabetes,which has a strong disabling effect,clinically,it is of great significance to actively and effectively control the progression of the disease and improve the quality of life of patients.In Sanxiao Lun,LIU Wansu put forward the theory of"dryness-heat and stagnation"according to the pathogenesis of consumptive thirst,and thought that the dryness-heat and stagnation in the stomach and intestines of sanjiao were too severe,the xuanfu was blocked,and the qi and liquid failed to diffuse,which caused diabetes.Vascular endothelial injury and inflammatory reaction are important factors in the development of vascular disease,the pathogenesis evolution of"dryness-heat and stagnation"conforms to the pathological characteristics of inflammatory reaction in western medicine,and the dryness-heat runs through the diabetic lower extremity vascular disease throughout.In this paper,it is believed that diabetic lower extremity vascular disease belongs to the category of"flaccidity and paralysis"in traditional Chinese medicine,and lung scorched by heat is the cause of flaccidity."Dryness-heat and stagnation"is the source of invading heat(dryness-heat),lung scorched by heat,pulse failure and vein stasis occurred,which causes diabetic lower extremity vascular disease.Treatment should be based on flaccidity,combined with the viewpoint of LIU Wansu's Sanxiao Lun,taking yangming as the top priority,regulating the triple diabetes,solving the problem of dryness-heat and stagnation,combined with the method of purging the south and supplementing the north,so that the invading heat is cleared,lung heat is diminished,and flaccidity disease cannot occur,in order to provide new ideas for the clinical prevention and treatment of diabetic lower extremity vascular disease.

Objective To explore the efficacy and safety of dabigatran etexilate in the treatment of elderly patients with non-valvular atrial fibrillation (NVAF), so as to provide reference for clinical treatment and rational drug use. Methods Eighty elderly patients with NVAF in The Seventh People's Hospital of Shanghai from December 2020 to June 2021, aged 65 to 80 years, were enrolled in a self-controlled study. Dabigatran etexilate 110 mg was given orally, twice a day (one in the morning and one in the evening) for 6 months. During the follow-up visit, the coagulation function indexes including APTT, TT, FIB and D-D were observed in patients taking medicine for 1 month and 6 months. Liver function indexes including ALT, AST and TBIL, renal function indicators including UREA and eGFR, and blood routine indexes including HGB and ESR, also were observed in patients taking medicine for 1 month and 6 months. Results Patients were compared at 1 month and 6 months after treatment with dabigatran and before: the difference of coagulation function indexes as APTT and TT was statistically significant (P<0.05);There was no significant difference in liver function index, renal function index and blood routine index (P>0.05); A total of 25 adverse events occurred, and the incidence rate of adverse reactions was 31.25%, there was no adverse events such as serious hemorrhage，life threatening and organ failure hemorrhage occurred．Conclusion Dabigatran has good efficacy and safety in the treatment of the elderly NVAF.