Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.

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 investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective:To explore the correlation of serum adiponectin (APN) , D-dimer (D-D) and neutrophil-to-lymphocyte ratio (NLR) levels with disease severity and prognosis in patients with diabetic foot ulcer infection.Methods:92 patients with diabetic foot ulcer infection in the Nantong Third Hospital Affiliated to Nantong University from Feb. 2020 to Feb. 2021 were selected, and they were divided into mild ( n=30) , moderate ( n=44) and severe ( n=18) patients according to the severity of the disease. The serum APN, D-D and NLR levels in patients with different severity were compared, the relationship between serum APN, D-D and NLR levels and disease severity in patients with diabetic foot ulcer infection were analyzed. Patients were followed up for 1 year, and the prognosis of the patients was counted. Factors affecting serum APN, D-D and NLR levels in patients with diabetic foot ulcer infection were analyzed, and the receiver operating curve (ROC) was used to analyze the value of serum APN, D-D and NLR levels in predicting poor prognosis of patients. Results:There were significant differences in serum APN, D-D and NLR levels in patients with different severity ( P<0.05) . APN level in severe patients was 5.35±0.98, in moderate patients was 7.64±1.25, both lower than that of the mild patients 9.19±1.73 ( P<0.05) . Serum APN level in severe patients was lower than that in moderate patients ( P<0.05) . Serum D-D and NLR levels were 3.49±0.72 and 2.86±0.58 in severe patients, respectively; and they were 3.02±0.63 and 2.24±0.46 in moderate patients, higher than that of mild patients 2.43±0.51; 1.71±0.33 ( P<0.05) . The levels of serum D-D and NLR in severe patients were higher than those in moderate patients ( P<0.05) . Spearman correlation analysis showed that the severity of the disease was negatively correlated with serum APN levels ( r=-0.414, P<0.001) , and positively correlated with serum D-D and NLR levels in patients with diabetic foot ulcer infection ( r=0.387, P<0.001; r=0.461, P<0.001) . Univariate analysis showed that the proportion of severe disease, serum fasting blood glucose, glycosylated hemoglobin, fibrinogen, D-D and NLR levels in patients with poor prognosis were higher than those in patients with good prognosis ( P<0.05) , and the APN level in patients with poor prognosis was lower than that in patients with good prognosis ( P<0.05) . Logistic multivariate regression analysis showed that severe disease, serum glycosylated hemoglobin, APN, D-D, and NLR levels were independent risk factors for poor prognosis in patients with diabetic foot ulcer infection ( P<0.05) . ROC analysis showed that the optimal cut-off points of serum APN, D-D and NLR levels for predicting poor prognosis of patients were 5.73 mg/L, 3.06 mg/L, 2.12, the sensitivity was 78.57%, 82.14%, 85.71%, the specificity was 76.56%, 67.19%, 73.44%, the area under the curve (AUC) was 0.793, 0.784, 0.818, the specificity and AUC of the three were 98.44 %, 0.918, respectively. Conclusions:Serum APN, D-D and NLR levels are related to the severity of the disease in patients with diabetic foot ulcer infection. Clinical detection of serum APN, D-D and NLR levels can be used as sensitive indicators to predict poor prognosis.

Objective:To investigate the correlation between serum complement C1q/tumor necrosis factor associated protein 3 (CTRP3) and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).Methods:From January 2018 to December 2019, 111 T2DM patients hospitalized in the Endocrinology Department of Nantong Third People ′s Hospital Affiliated to Nantong University, and 30 healthy physical examiners in the physical examination center of Nantong Third People 's Hospital Affiliated to Nantong University in the same period were selected. Thirty cases of healthy physical examination were the control group, 111 cases of T2DM were divided into 52 cases of T2DM group and 59 cases of T2DM+NAFLD group according to whether they were combined with NAFLD. The cross-sectional study method was used to collect the relevant clinical data of three groups. The comparison data between multiple groups conformed to the normal distribution and the variance was uniform. One way ANOVA was used. SNK- q test was used for pairwise comparison, χ2 test for qualitative data comparison. The correlation between carotid intima-media thickness (IMT) and influencing factors was analyzed by partial correlation analysis, and the influencing factors of carotid IMT were analyzed by multi factor linear regression. Results:In the control group, T2DM group and T2DM+NAFLD group, body mass index (BMI) (23.65±2.81), (25.52±3.12), (24.90±2.94) kg/m 2,systolic blood pressure (119.43±15.81), (130.63±10.20), (139.37±14.11) mmHg, diastolic blood pressure (72.93±9.74), (73.40±9.44), (77.97±10.00) mmHg, and fasting blood glucose (5.12±0.77), (9.78±1.37), (9.24±1.46) mmol/L,glycosylated hemoglobin (HbA1c) (4.87±1.43)%, (7.99±1.10)%, (8.56±1.29)%,homeostasis model assessment of insulin resistance (HOMA-IR)(1.56±0.37),(2.80±1.00), (3.47±0.94), high density lipoprotein cholesterol (HDL-C) (1.52±0.34),(1.23±0.31), (1.22±0.31) mmol/L,low density lipoprotein cholesterol (LDL-C) (2.41±0.53), (2.73±0.61), (2.93±0.59) mmol/L, CTRP3 (292.93±68.54), (241.69±61.01), (150.80±56.67) μg/L, the difference between groups were statistically significant ( F=3.712,23.023,4.074,134.285,90.818,47.105,10.139,7.941,60.035,all P<0.05). Pairwise comparison shows that the systolic blood pressure, diastolic blood pressure, HbA1c and HOMA-IR in T2DM+NAFLD group were higher than those in control group and T2DM group,and CTRP3 was lower than those in control group and T2DM group, the difference was statistically significant (all P<0.05). BMI, fasting blood glucose, HbA1c, HOMA-IR, HDL-C and LDL-C in T2DM group were higher than those in the control group, CTRP3 was lower than that in the control group (all P<0.05). In the control group, T2DM group and T2DM+NAFLD group, IMT were (0.75±0.13), (1.11±0.17) and (1.25±0.15) cm; Crouse scores were (1.28±0.97), (3.22±1.42) and (4.54±1.22); the plaque detection rates 16.7%(5/30), 65.4%(34/52) and 78.0%(46/59), and there were significant differences between the two groups ( F=105.941,67.063, χ2=32.108, all P<0.001). There were significant differences between the two groups (all P<0.05). T2DM+NAFLD group was the highest, followed by T2DM group, and the control group was the lowest. Partial correlation analysis showed that carotid IMT was positively correlated with systolic blood pressure, fasting blood glucose, HbA1c, HOMA-IR, triglyceride and LDL-C ( r=0.356, 0.572, 0.575, 0.620, 0.172, 0.291, all P<0.05), and negatively correlated with HDL-C and CTRP3 ( r=-0.335, -0.675, all P<0.001). Multivariate linear regression analysis showed that HbA1c, HDL-C and ctrp3 were the influencing factors of carotid atherosclerosis ( t=2.621, -3.764, -7.280, all P<0.05) Conclusion:Serum CTRP3 is associated with carotid atherosclerosis in T2DM patients with NAFLD,and may have a protective effect on vascular lesions in T2DM patients with NAFLD.

ABSTRACT OBJECTIVE：To establish a method for simultaneous determination of 8 components in the lyophilized product of Chaihu shugan san decoction. METHODS：UPLC method was adopted to determine the contents of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone in 6 batches of lyophilized product of Chaihu shugan san decoction. The determination was performed on Phenomenex column with mobile phase consisted of 0.1％ formic acid water-acetonitrile at the flow rate of 1 mL/min，the sample volume was 10 μL. The detection wavelength was set at 250 nm，and column temperature was 30 ℃. RESULTS：The linear range of albiflorin，paeoniflorin，ferulic acid，naringin，hesperidin，benzoyl paeoniflorin，glycyrrhizic acid and α-cyperone were 3.606-8.414，23.988-55.972，1.218-2.842，35.964-83.916，12.009-28.021， 1.194-2.786，3.609-8.421，5.294-12.352 μg/mL，respectively（r＝0.999 5-0.999 9）. The limits of quantitation were 0.206，0.178， 0.256，0.168，0.196，0.242，0.268，0.157 μg/mL，respectively. RSDs of precision，stability（12 h）and repeatability tests were all lower than 2％（n＝5 or 6）；the recoveries were 97.93％，98.18％，96.57％，97.61％，98.51％，97.45％，98.14％，96.91％（all RSD＜2％ ）. The average contents of albiflorin， paeoniflorin， ferulic acid， naringin， hesperidin， benzoyl guanosine， and glycyrrhizic acid in 6 batches of samples were 59.258，429.237，23.173，625.847，200.424，15.048，67.620 μg/g，respectively. α-cyperone was not detected because of its volatility. CONCLUSIONS：The method is simple，stable，reliable and accurate. It could provide reference for quality control of the lyophilized product of Chaihu shugan san decoction

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Objective:New Zealand rabbits were immunized with VLPs-MEpS,VLPs-E2S,and the levels of neutralizing antibodies in serum were determined.Methods: New Zealand rabbits were immunized with 10 μg VLPs-MEpS and VLPs-E2S,serum was collected at diffferent time with a two-weeks interval.The neutralizing antibodies were determined by ELISA.HCV(type 1b) had been prepared and mixed with serum from immunized rabbit before infected Huh7.5 cell.The protection of neutralizing antibodies in serum was assessed.Results: Neutralizing antibodies had been induced in rabbit after immunized with VLPs-MEpS and VLPs-E2S.VLPs-MEpS group had higher titer of antibodies than that of VLPs-E2S group(P<0.05),both group had higher titer of antibodies than that of control groups significantly(P<0.01).VLPs-MEpS group had higher neutralization than that of VLPs-E2S group(P<0.05),the highest neutralization rate was 61.49%.Both groups were higher than control group notably(P<0.01).Conclusion: Protective neutralizing antibodies have been induced in New Zealand rabbit after immunized with VLPs-MEpS and VLPs-E2S.It′s the basement for development of neutralizing antibodies vaccine.