ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

[摘 要] 目的：探讨安罗替尼联合免疫检查点抑制剂（ICI）作为一线方案治疗晚期肺鳞状细胞癌（LUSC）的有效性及安全性。方法：采用单中心回顾性队列设计，连续纳入2018年10月至2023年12月福建省福州肺科医院收治的37例初治晚期LUSC患者。所有患者接受安罗替尼（剂量为8、10或12 mg/d，用药2周/停药1周）联合ICI治疗。主要终点为无进展生存期（PFS），次要终点包括客观缓解率（ORR）、疾病控制率（DCR）及治疗相关不良事件（TRAE）。结果：全组患者中位随访15.2个月，ORR达54.1%（20/37），DCR为97.3%（36/37），中位PFS为11.8个月（95%CI：8.3~NA），12个月PFS率为48.6%。探索性亚组分析显示：安罗替尼12 mg剂量组的中位PFS（未达到 vs 7.5个月，HR = 0.09，95%CI：0.01~0.67，P < 0.01）及ORR（100% vs 42.9%，P < 0.01）均显著优于8/10 mg组。分期分层显示ⅢB/ⅢC期患者ORR显著优于Ⅳ期（84.6% vs 41.7%，P = 0.02）。安全性方面，62.2%（23/37）的患者发生TRAE，以1~2级高血压[29.7%（11/37）]、手足综合征[21.6%（8/37）]为主，3例（8.1%）因3级TRAE终止治疗。结论：安罗替尼联合ICI作为晚期LUSC一线治疗方案具有良好的疗效前景和可管理的安全性。其中，12 mg剂量组在探索性分析中显示出更优疗效的潜在信号，早期分期患者ORR更高。该结果值得开展大规模前瞻性研究进行进一步验证。

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the effect of G9a histone methyltransferase inhibitor BIX01294 on the proliferation of vascular smooth muscle cell(VSMC)and its underlying mechanism.Methods Twelve SD rats were divided into the control group and the treatment group,with 6 rats in each group.The rats were anesthetized by intraperitoneal injection with sodium pentobarbital,then exposed the common carotid artery and the internal and external carotid artery after disinfection and skin preparation,ligated the distal end of the internal and external jugular veins,clamped the proximal end of the common carotid artery,cut the external carotid artery,inserted the balloon catheter,blocked the blood flow by compression,and ligated the proximal end of the external carotid artery after withdrawing the balloon.The common carotid artery clamping state of rats in the treatment group was maintained after withdrawing the balloon,then restored the blood flow after perfusion with 100 μmol/L BIX01294 solution for 30 seconds;rats in the control group were restored the blood flow after perfusion with PBS for 30 seconds.VSMC were divided into the normal group and the BIX01294 groups.Cells in the normal group were cultured in low glucose medium containing 2%fetal bovine serum,and cells in the BIX01294 groups were co-treated with 2.5,5.0,7.5 and 10.0 μmol/L BIX01294 on the basis of the normal group,respectively.CCK-8 assay and EDU assay were used to detect the cell activity and proliferative ability respectively,to screen appropriate concentration of BIX01294.The cell apoptosis was detected by TUNEL assay between the normal group and the BIX01294 group,and the control group and the treatment group.Western blot was used to detect the expression levels of autophagy-and apoptosis-related proteins in the normal group and BIX01294 group.Results Compared with 0 μmol/L,the activity and proliferative ability of VSMC decreased in a concentration-dependent manner after treatment with BIX01294 at different concentrations(P<0.05).Compared with the normal group,the apoptosis level of VSMC in the BIX01294 group was increased(P<0.05),the expression of VSMC autophagy-and apoptosis-related proteins of LC3Ⅰ/Ⅱ and Bax were up-regulated(P<0.05),and the expression of Bcl-2 and p62 proteins were down-regulated(P<0.05).In vivo test results showed that BIX01294 local perfusion aggravated the apoptosis of carotid VSMC.Conclusion BIX01294 activates VSMC autophagy and apoptosis and inhibits its proliferation.

Objective To observe the correlation between fat fraction(FF)and T2 value of multifidus muscle and Pfirrmann grade of L4-5 intervertebral disc in patients with lumbar muscle strain.Methods Totally 200 L4_5 intervertebral discs in 200 patients with lumbar muscle strain were retrospectively enrolled,including 6 cases of Pfirrmann grade Ⅰ,61 of grade Ⅱ,52 of grade Ⅲ,56 of grade Ⅳ and 25 cases of grade V.Based on modified DIXON quantification(mDIXON-Quant)and T2 mapping,FF and T2 value of multifidus muscle were calculated and compared among intervertebral discs with different Pfirrmann grades,and the correlations between the above parameters and Pfirrmann grade of intervertebral disc were analyzed.Results Significant differences of left,right and bilateral multifidus muscles FF,as well as of T2 values in left and bilateral multifidus muscles were found among L4-5 intervertebral discs with different Pfirrmann grades.Multifidus muscle FF was moderately positively correlated with Pfirrmann grade of L4-5 intervertebral disc(r=0.538,P＜0.05),while T2 value was weakly positively correlated with Pfirrmann grade of L4-5 intervertebral disc(r=0.202,P＜0.05).Conclusion FF of multifidus muscle was moderately positively correlated with Pfirrmann grade of L4-5 intervertebral disc,while T2 value of multifidus muscle was weakly positively correlated with Pfirrmann grade of L4-5 intervertebral disc in patients with lumbar muscle strain.

Objective:To explore the impact of marital status on the prognosis of adult patients with primary intrahepatic cholangiocarcinoma.Methods:3283 patients with primary intrahepatic single tube carcinoma from 1998 to 2018 were collected.They were divided into married group(n=1999)and unmarried group(n=1284)based on marital status.The clinical data of adult patients with primary intrahepatic cholangiocarcinoma of different marital statuses were compared.Kaplan Meier survival curves were used to analyze the survival status of adult patients with primary intrahepatic cholangiocarcinoma in different marital statuses.Univariate and multivariate Cox regression analysis were used to investigate the factors affecting the survival of adult patients with primary intrahepatic cholangiocarcinoma.Kaplan Meier survival curves were used to analyze the survival status of adult patients with primary intrahepatic cholangiocarcinoma in different marital statuses,including whether they received surgical treatment,radiotherapy treatment,and gender differences.Results:The proportion of male patients,the proportion of white patients,the proportion of patients over 60 years old,the proportion of patients receiving surgical treatment,the proportion of patients receiving radiotherapy,and the proportion of patients receiving chemotherapy in the married group were higher than those in the unmarried group(P＜0.05).Kaplan Meier survival curve analysis results showed that,the 3-month and 5-year survival rates between married and unmarried groups were Log-rank test P＜0.05.Multivariate Cox regression analysis showed that,age over 60 years old,later tumor stage,surgical treatment,radiotherapy,and chemotherapy were risk factors for survival in adult patients with primary intrahepatic cholangiocarcinoma(P＜0.05).Kalplan Meier survival curve results showed that,there was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received surgical treatment(Log-Rank test P=0.381).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received surgical treatment(Log-Rank test P=0.015).There was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received radiotherapy(Log-Rank test P=0.073).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received radiotherapy(Log-Rank test P＜0.001).There was no significant difference in 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who received chemotherapy(Log-Rank test P=0.337).There was a significant difference in the 5-year survival rate between married and unmarried adult patients with primary intrahepatic cholangiocarcinoma who have not received chemotherapy(Log-Rank test P＜0.001).There was no significant difference in the survival status of male patients with primary intrahepatic cholangiocarcinoma in adults of different marital statuses(Log-Rank test P=0.136).There were differences in the survival status of female patients with primary intrahepatic cholangiocarcinoma in adults of different marital statuses(Log-Rank test P＜0.001).Conclusion:Male,white,and over 60 years old are risk factors for the occurrence of primary intrahepatic cholangiocarcinoma in adults.Among them,more than half of the patients did not receive surgery or radiotherapy treatment,and about half of the patients did not receive chemotherapy.Married individuals are more likely than unmarried individuals to undergo anti-tumor treatments such as surgery,radiotherapy and chemotherapy.The staging of intrahepatic cholangiocarcinoma and whether surgery or chemotherapy is received are independent predictors of long-term survival.Marital status is not an independent predictor and can indirectly affect long-term survival.Male marital status has no significant survival benefits for this disease,while female marital status has survival benefits for this disease.The marital status of patients with intrahepatic cholangiocarcinoma who have not undergone radiotherapy,chemotherapy,or surgical intervention has a significant impact on their survival outcomes.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Purpose To explore the diagnostic efficacy of texture analysis in grading multiple ligament injuries of the knee Joint.Materials and Methods MRI images of 203 patients with knee injuries in the Second Affiliated Hospital of Shantou University School of Medicine from June 2018 to September 2020 were retrospectively collected,and then graded the injuries of multiple ligaments.Extraction of texture features and discriminant analysis were accomplished by MaZda software.Spearman correlation analysis and LASSO penalized Logistic regression analysis were used to further explore the differential diagnostic efficacy of each texture parameter for grading knee ligament injuries.Results(1)MaZda software was found to have the highest diagnostic efficacy for patellar ligament injury grading by using different texture feature screening methods in combination with discriminant analysis.Non-linear discriminant analysis had the lowest misclassification rate of 4.43%.(2)The texture parameters that were ultimately included in the analysis of the subjects'work characteristic curves appeared more frequently in the gray level co-occurrence matrix and the run length matrix.(3)The area under the curve of the texture parameters finally included in the analysis were 0.870-0.975,0.772-0.912,0.836-0.929 and 0.766-0.920,respectively in patellar ligament,anterior cruciate ligament,posterior cruciate ligament and lateral collateral ligament for the diagnosis of knee ligament injury grading.The diagnostic efficacy for patellar ligament injury grading was the highest,which was consistent with the lowest misclassification rate for patellar ligament in the discriminant analysis of texture features.And the texture parameters ultimately included in patellar ligament were all highly correlated with its injury grading.Conclusion The texture analysis technique has high diagnostic efficacy for grading knee ligament injuries,and can provide a more accurate diagnostic imaging basis for the clinic.

Purpose To evaluate the long-term efficacy of radiofrequency ablation(RFA)for T1N0M0 papillary thyroid carcinoma(PTC)with rich blood supply and poor blood supply.Materials and Methods Clinical data,ultrasound and contrast-enhanced ultrasound(CEUS)images,RFA parameters,and postoperative follow-up indicators of 375 T1N0M0 PTC patients who received RFA from June 2014 to December 2018 were retrospectively collected.The propensity score matching method was used to match the baseline data of the two groups in a 1:1 ratio,finally a total of 212 patients were included in the study.The RFA parameters,volume,tumor disappearance,and local tumor progression(LTP)were compared between the groups.Besides,the correlation between rich blood supply and LTP was analyzed using multivariate COX regression.Results According to the peak intensity displayed by preoperative CEUS,all lesions were divided into a group with rich blood supply(n=129)and another with poor blood supply(n=246).After a mean follow-up time of(84.48±14.44)months,the tumor disappearance in the rich blood supply group was 87.74%,while in the poor blood supply group it was 88.68%,and there was no statistically significant difference(Z=0.05,P=0.831).There were 10 cases of LTP in the rich blood supply group(6 cases of residual cancer and 4 cases of new cancer),and 6 cases of LTP in the poor blood supply group(2 cases of residual cancer and 4 cases of new cancer).The LTP rates of the two groups were 9.43%and 5.67%,with no statistically significant difference(x2=1.08,P=0.298).The Kaplan-Meier survival curve showed no statistically significant difference in progression free survival between both groups(P=0.265).The adjusted multivariate COX proportional risk model analysis showed that rich blood supply was no association with LTP(HR=1.54,P=0.409).Conclusion RFA for T1N0M0 PTC with rich blood supply can achieve effective ablation,and its long-term efficacy is similar to that of poor blood supply.RFA can serve as an effective alternative treatment for T1N0M0 PTC patients with different blood supply.

Objective:To construct a predictive model for benign and malignant colorectal lesions based on modal ultrasound parameters and clinical indicators,and evaluate the effectiveness of the predictive model.Methods:Clinical data of 198 patients with colorectal lesions treated in Hebei Petro China Central Hospital from March 2020 to March 2024 were recorded.According to pathological diagnosis,they were grouped into a benign lesion group of 102 cases and a malignant lesion group of 96 cases.All patients underwent multimodal ultrasound examination.Multivariate Logistic re-gression analysis was applied to screen the influencing factors of colorectal cancer progression.R software package was applied to build a nomogram prediction model.Hosmer-Lemeshow test,calibration curve,ROC curve,and clinical deci-sion curve were used for validation.Results:There were statistically obvious differences in internal echo,morphology,blood flow signal,rise time(RT),contrast agent of"fast in and fast out",mean Young's modulus(Emean),age,positive fecal occult blood,and polyps between the benign and malignant lesion groups(P＜0.05).Uneven internal echoes,irregu-lar shapes,abundant blood flow signals,contrast agent of"fast in and fast out",age ≥ 60 years,positive fecal occult blood,and polyps ≥ 2 were independent risk factors for colorectal cancer(P＜0.05),while RT is a protective factor for colorectal cancer(P＜0.05).The internal validation results of the nomogram prediction model showed that the Hosmer-Lemeshow test showed x2=3.661 and P=0.886.The calibration curve showed that the actual probability was basically consistent with the predicted probability,and the AUC of the ROC curve was 0.802(95％CI:0.732-0.871),indicating that the calibration and discrimination of the column chart prediction model were good.Within the high-risk threshold range of 0.28-0.98,the decision curve was above the All line and None line,indicating a high net benefit and clinical practicality.Conclusion:Internal echo,morphology,blood flow signal,contrast agent of"fast in and fast out",age,positive fecal occult blood,polyps,and RT are influencing factors for the occurrence of colorectal cancer.The column chart prediction model constructed based on this has good predictive performance and provides reference for early inter-vention by clinical physicians.