Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

The pricing and reimbursement of orphan drugs are related to the accessibility of patients,and are of great significance to the prevention and guarantee of rare diseases.European countries have formed special standards and paths for health technology evaluation,and established special payment funds and diversified risk-sharing agreements,which have effectively improved the accessibility of orphan drugs.Based on this,it selected typical European countries to compare the orphan drug pricing and reimbursement methods.Then,it put forward some suggestions"building orphan drug health technology evaluation accelerated program,exploring the health of orphan drug classification security mechanism,and attaining supply incentives and development incentives through orphan drug pricing and adjustment",to optimize the basis for the orphan drug market access mechanism to provide reference.

Objective To investigate the main dietary patterns of children in urban areas of Maanshan City, and to explore the association between dietary patterns and subthreshold autism trait (SAT), attention-deficit/hyperactivity disorder (ADHD) symptoms and comorbid behaviors in 3-year-old children. Methods Based on the birth cohort of Maanshan Maternal and Infant Health from June 2015 to June 2016，regular physical examinations were conducted from 4 to 2 to 1, and follow-up was conducted until the age of 3. A semi-quantitative food frequency questionnaire was employed to assess dietary intakes. SAT and ADHD symptoms were assessed by Clancy autism behavior scale (CABS) and the 10-item Chinese version of the Conners Abbreviated Symptom Questionnaire (C-ASQ). Social-demographic information was also collected. Results The detection rates of SAT, ADHD symptoms, and comorbidity were 11.03%, 5.28%, and 2.71%, respectively. The older the father, the higher the mother's education level, and the higher the per capita monthly income of the family, the lower the SAT detection rate (P<0.05). The higher the father's educational level, the lower the detection rate of ADHD symptoms (P<0.05). The older the mother and the higher the education level, the lower the detection rate of comorbid behavior in their children (P <0.05). After adjusting for demographic influencing factors, the low intake level was used as a reference. The vegetarian type with moderate intake level was negatively correlated with SAT, while the processed food type with high intake level was positively correlated with SAT. The vegetarian type with high intake level was negatively correlated with ADHD symptoms, while the snack type with high intake level was positively correlated with ADHD symptoms. The vegetarian type with high intake level was negatively correlated with comorbidity. Conclusion Unhealthy dietary patterns are related to children's SAT and ADHD symptoms. Correcting children's unhealthy eating patterns may help reduce children's behavior problems.

Objective To compare the early predictive value of different scoring systems for the severity,organ failure and complications of acute pancreatitis(AP)in elderly patients under the newly revised Atlanta criteria.Methods Patients with acute pancreatitis treated was collected.After admission,complete the computed tomography severity index(CTSI),the bedside index of severity in acute pancreatitis(BISAP),the pancreatis 3(PANC-3)and the harmlessness acute pancreatitis score(HAPS).The area under receiver operating characteristic(ROC)curve(AUC),sensitivity,specificity and Yordan's index of four scores for predicting SAP,local pancreatic complications and multiple organ failure were compared.Results The areas under the ROC curve predicted by the CTSI,BISAP,PANC-3 and HAPS scoring systems for SAP were 0.76,0.91,0.48 and 0.55;sensitivities of 75.87％,89.61％,61.18％and 78.38％;specificity of 80.29％,74.72％,67.48％and 69.69％;Yordan's index of 0.56,0.64,0.29 and 0.48,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting local pancreatic complications were 0.94,0.82,0.59 and 0.64;sensitivity of 74.59％,68.23％,71.11％and 69.28％;specificity of 93.88％,83.01％,78.59％and 76.46％;Yordan's index were 0.68,0.51,0.50 and 0.46,respectively.The AUC of CTSI,BISAP,PANC-3 and HAPS scoring systems for predicting multiple organ failure were 0.60,0.84,0.64 and 0.80,sensitivities were 54.18％,74.82％,58.59％and 65.67％,specificity were 76.11％,77.20％,72.68％and 89.36％,Jordan's indices were 0.30,0.52,0.31 and 0.55,respectively.Conclusion BISAP score is higher than CTSI,HAPS and PANC-3 scoring system in predicting the accuracy of sap and the risk of multiple organ failure.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.

AIM To evaluate the quality of Changmaile Capsules(Ⅰ).METHODS The analysis was performed on a 35℃ thermostatic Thermo Scientific AccucoreTM XL C18 column(4.6 mm×250 mm,4 μm),with the mobile phase comprising of methanol-acetonitrile-0.5% phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.The contents of gastrodin,danshensu,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,3′-hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin,rosmarinic acid,lithospermic acid,ononin,daidzein,salvianolic acid B,calycosin,paeoniflorin and isoquercitrin were determined,after which HPLC fingerprints were established,along with the calculation of similarities.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 87.4%-103.9% with the RSDs of 0.54%-3.10% .At 230 nm,the fingerprints of ten batches of samples demonstrated similarities of 0.954-0.999,which displayed obvious differences at 280 nm.3′-Hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin and daidzein were main differential constituents,paeoniflorin and isoquercitrin exhibited stable contents in various batches of samples.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Changmaile Capsules(Ⅰ).

Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.