Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.

OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

Hashimoto's thyroiditis(HT)is an autoimmune thyroid disease characterized by diffuse enlargement of thyroid gland and elevated thyroid autoantibodies.HT is closely related to emotional factors,conveyance and dispersion function of the liver,and the qi movement of the five zang organs.This paper explores the approach to the differentiation and treatment of HT based on Professor Yang Shuyu's view of regulation of both mind and body.In the view of regulation of both mind and body,the regulation of mind is to harmonize emotions,and the regulation of body refers to the conveyance and dispersion function of zang-fu organs.Based on the view of regulation of both mind and body,the pathological changes of HT are characterized by the disordered conveyance and dispersion of qi movement,and the stable phase,hyperthyroid phase,and hypothyroid phase of HT correspond to obstructed conveyance and dispersion,excessive conveyance and dispersion,and insufficient conveyance and dispersion,respectively.The emotional disorders caused by the failure of mind regulation exist throughout the disease course.Therefore,the treatment of HT can be conducted by using the therapies of unblocking,suppressing,and tonifying separately for stable phase,hyperthyroid phase,and hypothyroid phase to address the root cause,and then the conveyance and dispersion of visceral qi movement are restored.Besides,the therapeutic method of resolution is used to alleviate symptoms by removing goiter and dissipating nodules.Simultaneously,emotional regulation therapy is incorporated to achieve a comprehensive efficacy for harmonizing physique-spirit and mind-body through the regulation of emotions,conveyance and dispersion of qi movement,and visceral functions.The view of regulation of both mind and body provides new methods and approaches for traditional Chinese medicine management of HT.

Objective To investigate the correlations of CALLY index in early pregnancy with the onset and severity of preeclampsia.Methods A total of 987 pregnant women were prospectively en-rolled as study subjects,with 42 lost during follow-up,resulting in a final inclusion of 945 subjects.Based on the occurrence and severity of preeclampsia during follow-up,the pregnant women were di-vided into preeclampsia group(n=47),severe preeclampsia group(n=49),and normal group(n=849).General information and laboratory test results were collected from all pregnant women,and the CALLY index was calculated.The Pearson correlation analysis was used to explore the correlation be-tween CALLY index and severity of preeclampsia(mean arterial pressure);the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficacy of each indicator for pre-eclampsia;Cox regression analysis was used to explore the influencing factors for the onset of preeclamp-sia.Results The mean arterial pressure and 24-hour urine protein levels were higher in the severe pre-eclampsia group than those in the preeclampsia group and normal group,and higher in the preeclampsia group than those in the normal group(P＜0.05).The CALLY index was lower in the severe preeclamp-sia group than in the preeclampsia group and normal group,and lower in the preeclampsia group than in the normal group(P＜0.05).Pearson correlation analysis showed a negative correlation between CALLY index and mean arterial pressure(r=-0.571,P＜0.001).The ROC curve showed that the area under the curve(AUC)of CALLY index for predicting preeclampsia was 0.941(95％CI,0.900 to 0.981).Multivariate Cox regression analysis showed that an increased CALLY index was an independent protective factor for the onset of preeclampsia(HR=0.185,95％CI,0.092 to 0.374,P＜0.001).Conclusion The CALLY index is negatively correlated with the severity of preeclampsia and is an independent influencing factor for the onset of preeclampsia,which can be used as an auxiliary indicator to assess the onset and severity of preeclampsia in pregnant women.

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

Although great progress has been achieved in the techniques and materials of cardiopulmonary bypass (CPB), cardiac surgery under CPB is still one of the surgeries with the highest complication rate. The systemic inflammatory response is an important cause of complications, mainly characterized by activation of innate immune cells and platelets, and up-regulation of inflammatory cytokines. After activation, a variety of molecules on the membrane surface are up-regulated or down-regulated, which can amplify tissue inflammatory damage by releasing cytoplasmic protease and reactive oxygen species, and activate multiple inflammatory signaling pathways in the cell, ultimately leading to organ dysfunction. Therefore, the expression of these cell membrane activation markers is not only a marker of cell activation, but also plays an important role in the process of vital organ injury after surgery. Identification of these specific activation markers is of great significance to elucidate the mechanisms related to organ injury and to find new prevention and treatment methods. This article will review the relationship between these activated biomarkers in the innate immune cells and vital organ injuries under CPB.

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg^-1）， high-dose JTTP group （7.2 g·kg^-1）， and metformin group （0.2 g·kg^-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

To provide a theoretical basis for different drug decision-making scenarios by conducting a comprehensive clinical evaluation of nusinersen.

Objective:To explore the interaction effects on brain activity between the smoking addiction and weight status by resting-state functional magnetic resonance imaging.Methods:Retrospective analysis of clinical data and resting-state functional magnetic resonance imaging data were analyzed from 99 recruited subjects from January 2019 to December 2021. All participants were divided into four groups: overweight smokers ( n=24), normal-weight smokers ( n=28), overweight non-smokers ( n=19), and normal weight non-smokers ( n=28). Calculate regional homogeneity (ReHo) to reflect the internal brain activity of the subjects. Two-way ANOVA was used to detect the interaction effects between smoking addiction and overweight on ReHo by SPM12 software, correcting for age, years of education and head motion. Results:The interaction effect between smoking addiction and overweight on ReHo was significant in right superior frontal gyrus(x, y, z=15, 9, 60)(GRF corrected, Pvoxel<0.005, Pcluster<0.05). The ReHo value in the right superior frontal gyrus of overweight smokers was significantly higher than that of normal weight smokers ( t=3.768, P<0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight non-smokers were significantly lower than those of normal weight non-smokers ( t=-3.242, P=0.002, Bonferroni corrected). The ReHo values in the right superior frontal gyurs of normal-weight smokers were significantly lower than those of normal weight non-smokers( t=-3.540, P=0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight smokers were significantly higher than those of overweight non-smokers ( t=3.392, P=0.002, Bonferroni corrected). Correlation analyses showed that the strengthen ReHo value in right superior frontal gyrus was positively associated with pack-year in smoking addicts( r=0.387, P=0.007, Bonferroni corrected). Conclusion:Smoking addiction and overweight have an antagonistic effect on brain activity in the right superior frontal gyrus, which may provide potential therapeutic targets for individuals with comorbidity of smoking addiction and overweight.

Objective To develop and validate a prediction model for severe disability or death(SDD)in acute ischemic stroke(AIS)patients who underwent endovascular treatment(EVT).Methods Based on the dataset of ANGEL-ACT study who received EVT for AIS between november 2017 and march 2019,a retrospective analysis was performed on 1 677 patients,including 1 111 males and 566 females,aged ≥ 18 years.Patients were divided into two groups according to whether SDD occurred(mRS 5-6 scores 90 days after surgery):SDD group(n=478)and non-SDD group(n=1 199).Risk factors that might influence SDD after EVT in AIS patients were screened and analyzed by multifactorial analysis,LAS-SO regression,and RF-RFE methods.A nomogram was developed after evaluating the model performance and the execution of internal validation.Results SDD occurred in 380(28.1％)patients in the develop-ment cohort and 98(30.2％)patients in the validation cohort.Combining the three variable screening meth-ods,10 risk factors were selected for inclusion in the final model:age,NIHSS score,whether successful re-canalization,glucose level,hemoglobin,hematocrit,onset to puncture time,systolic blood pressure,AS-PECT score,and whether have treatment-related serious adverse events.A two-stage model means that model 1 contains pre-treatment variables(7 in total)and model 2 contains pre-treatment and post-treatment variables(10 in total).The area under the curve(AUC)of model 1 in the development cohort was 0.705(95％CI 0.674-0.736)and 0.731(95％CI 0.701-0.760)in model 2.Both models had good calibration with aslope of 1.000,and the decision curve analysis showed good clinical applicability.The results of the validation cohort were similar to those of the development cohort.Conclusion Age,admission NIHSS score,whether successful recanalization,admission glucose level,hemoglobin content,erythrocyte pressure volume,onset to puncture time,admission systolic blood pressure,ASPECT score,and whether have treat-ment-related serious adverse events are risk factors for SDD in patients with acute ischemic stroke.The two prediction models based on the above factors were used before and after endovascular treatment to predict SDD occurrence better.