The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Humans ; Nutrition Surveys ; Diabetes Mellitus, Type 2/chemically induced* ; Environmental Exposure/analysis* ; Environmental Monitoring ; Phthalic Acids/toxicity* ; Environmental Pollutants/toxicity*

In the clinical practice of rheumatic immune diseases in traditional Chinese medicine （TCM），it`s still unclear about the dominant diseases and breakthrough points. It`s urgent missions to formulate TCM diagnosis and treatment guidelines widely recognized and integrated by traditional Chinese medicine and Western medicine. In order to clarify the dominant diseases and breakthrough points in rheumatism，China association of Chinese medicine initiated a research group covering experts in the field of rheumatism of traditional Chinese medicine and Western medicine. Based on questionnaire survey and on-site discussion，experts had reached the following consensus. Evidence-based medicine research using modern medical methods and scientific methods should be carried out to provide objective clinical evidences. "Four mutuality" were put forward as the basis for the work of integrated traditional Chinese and Western medicine，that is the mutual communication using the exchangeable context，the mutual explanation using common theories，the mutual certification using common standards，and the mutual integration using common means. Key works should focus on solving refractory rheumatism in the future. In terms of dominant diseases and breakthrough points，this paper introduces 21 breakthrough points in 6 dominant diseases，including rheumatoid arthritis，ankylosing spondylitis，Sjogren's syndrome，hyperuricemia and gout，systemic lupus erythematosus and fibromyalgia syndrome. Advice on this discussion can provide valuable references for developing the treatment scheme of rheumatism with TCM and integrated Chinese and Western medicine and clinical practice and scientific research.

ObjectiveThis study aimed to assess the circulating bilirubin profile ［total bilirubin （TBIL）， conjugated bilirubin （DBIL）， unconjugated bilirubin （IBIL）］ and their associations with nonproliferative diabetic retinopathy （NPDR）. MethodsA case-control study which enrolled 312 type 2 diabetic mellitus （T2DM） patients （78 newly diagnosed NPDR 1：3 matched with 234 T2DM without diabetic retinopathy） was conducted. Diabetic retinopathy was screened by artificial intelligence fundus camera and further confirmed by the ophthalmologist， and demographic and clinical information were collected. Serum bilirubin and related biochemical indicators were assessed. ResultsPatients with NPDR had significantly lower serum TBIL， DBIL and IBIL concentrations （P values were 0.003， 0.001 and 0.006）， which were not associated with glycated hemoglobin （HbA1c） concentration （all P values >0.05）. The association persisted after adjustment for traditional risk factors including gender， diabetes duration， HbA1c and systolic blood pressure. Moreover， low IBIL had a higher risk of NPDR with odds ratio （OR） 95%CI of 3.44 （1.04， 11.38） in well glycemic controlled T2DM patients （HbA1c ≤7%） or of 2.53 （1.10， 5.82） in T2DM patients without microalbuminuria ［urine albumin creatine ratio （UACR） ≤30mg/g］； low DBIL had a higher risk of NPDR with OR 95%CI of 2.05 （1.09， 3.86） in poor glycemic controlled T2DM patients （HbA1c>7%） or of 2.40 （1.14， 5.02） in T2DM patients with microalbuminuria （UACR >30mg/g）. ConclusionOur results suggested that circulating bilirubin level is inversely and independently associated with NPDR which might be an early clinical biomarker for predicting and preventing diabetic retinopathy.

Dickkopf-3 (DKK3) , as a critical inhibitor of the Wnt/p-catenin signaling pathway, may he involved in melanogenesis.In the current study, we investigated the effects of DKK3 on melanogenesis in melanocytes of alpaca.Overexpression of DKK3 in alpaca melanocytes, the expression of Wntl, Lefl , Myc and the major target genes termed microphthalmia-associated transcription factor (M1TF) and its downstream genes, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and tyrosinase- related protein 2 (TYRP2) were significantly decreased at both mRNA and protein levels (P<0.05); total alkali melanin, pheomelanin and eumelanin were decreased by 80.30%, 72.17% and 64.60% (P <0.05), respectively.In contrast, in the melanocytes transfected with siRNA-DKK3 (a small interference RNA targeting DKK3) , the expression of Wntl, Lefl, Myc, MITF, TYR, TYRPl and TYRP2 were significantly increased at both mRNA and protein levels (P<0.05) ; total alkali melanin, pheomelanin and eumelanin were significantly increased by 1.65 folds, 1.25 folds and 1.21 folds (P< 0.05) , respectively.These results indicate that DKK3 regulates melanogenesis in alpaca melanocytes via the Wnt/p-catenin signaling pathway and down-regulates MITF.

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg
Animals ; Drugs, Chinese Herbal ; Metabolome ; Quality of Life ; Rats ; Stomatitis ; Tablets ; Transcriptome

Objective:To study the effect of Gegen Qinliantang （GQT） on the structure of intestinal flora in dysbacterial diarrhea rats by 16S rRNA sequencing. Method:Sixty healthy SD rats were randomly and equally divided into a control group， a model group， high-， medium-， and low-dose GQT groups， and a Bifidobiogen group. The rat model was induced in the five groups except the control group by administration of mixed antibiotics （178.6 mg·kg^-1 cefradine and 31.25 mg·kg^-1 gentamicin sulfate） according to the dose. Drug intervention was carried out in each group （7.02， 3.51， and 1.755 g·kg^-1 GQT for the high-， medium-， and low-dose GQT groups， 0.125 g·kg^-1 bifidobacterium capsules for the Bifidobiogen group， and sterile distilled water for the control and model groups） with a volume of 10 mL·kg^-1 for seven days. Colon contents of rats were obtained under anesthesia. The extracted fecal DNA underwent 16S rRNA high-throughput sequencing and the results were analyzed. Result:GQT was proved capable of adjusting the species number and Alpha and Beta diversity， improving the biological richness and diversity of the flora， and positively regulating three differential phyla （Firmicutes， Proteobacteria， and Bacteroidetes） and 14 differential genera （Bacteroides， Parabacteroides， Blautia， etc.） in rat model of dysbacterial diarrhea. Conclusion:The present study confirmed the regulatory effect of GQT on intestinal flora of dysbacterial diarrhea rats， and revealed the physiological and pathological mechanism between intestinal flora and dysbacterial diarrhea.