Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Objective:To investigate the value of an MRI and digital pathology images based omics nomogram for the prediction of recurrence risk in soft tissue sarcoma (STS).Methods:This was a retrospective cohort study. From January 2016 to March 2021, 192 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled, among which 112 patients in the Laoshan campus were enrolled as training set, and 80 patients in the Shinan campus were enrolled as validation set. The patients were divided into recurrence group ( n=87) and no recurrence group ( n=105) during follow-up. The clinical and MRI features of patients were collected. The radiomics features based on fat saturated T 2WI images and pathomics features based on digital pathology images of the lesions were extracted respectively. The clinical model, radiomics model, pathomics model, radiomics-pathomics combined model, and omics nomogram which combined the optimal prediction model and the clinical model were established by multivariate Cox regression analysis. The concordance index (C index) and time-dependent area under the receiver operating characteristic curve (t-AUC) were used to evaluate the performance of each model in predicting STS postoperative recurrence. The DeLong test was used for comparison of t-AUC between every two models. The X-tile software was used to determine the cut-off value of the omics nomogram, then the patients were divided into low risk ( n=106), medium risk ( n=64), and high risk ( n=22) groups. Three groups′ cumulative recurrence-free survival (RFS) rates were calculated and compared by the Kaplan-Meier survival curve and log-rank test. Results:The performance of the radiomics-pathomics combined model was superior to the radiomics model and pathomics model, with C index of 0.727 (95% CI 0.632-0.823) and medium t-AUC value of 0.737 (95% CI0.584-0.891) in the validation set. The omics nomogram was established by combining the clinical model and the radiomics-pathomics combined model, with C index of 0.763 (95% CI 0.685-0.842) and medium t-AUC value of 0.783 (95% CI0.639-0.927) in the validation set. The t-AUC value of omics nomogram was significantly higher than that of clinical model, TNM model, radiomics model, and pathomics model in the validation set ( Z=3.33, 2.18, 2.08, 2.72, P=0.001, 0.029, 0.037, 0.007). There was no statistical difference in t-AUC between the omics nomogram and radiomics-pathomics combined model ( Z=0.70, P=0.487). In the validation set, the 1-year RFS rates of STS patients in the low, medium, and high recurrence risk groups were 92.0% (95% CI 81.5%-100%), 55.9% (95% CI 40.8%-76.6%), and 37.5% (95% CI 15.3%-91.7%). In the training and validation sets, there were statistically significant in cumulative RFS rates among the low, medium, and high groups of STS patients (training set χ2=73.90, P<0.001; validation set χ2=18.70, P<0.001). Conclusion:The omics nomogram based on MRI and digital pathology images has favorable performance for the prediction of STS recurrence risk.

Cassiae Semen is a substance with both edible and medicinal uses approved by the National Health Administration， and it is widely used in health food products in China. In this study， an information database of Cassiae Semen-based health food products was constructed， and the common patterns of functional claims， major raw materials， and dosage forms were analyzed. The Apriori algorithm and network method were used to analyze the association rules of high-frequency ingredients with the three major functional claims： Maintaining blood lipid （cholesterol/triglyceride） level， controlling fat， and relaxing bowel. Secondly， based on the positioning and regulatory requirements of health food and the recent research progress in Cassiae Semen， this paper analyzed the problems in technology review and product development from safety， function claim， and quality controllability. Finally， suggestions were put forward to promote the inheritance and carry forward China's traditional healthcare culture and the achievement of the Healthy China Initiative. These suggestions included classifying and optimizing the access management of health food， innovating the traditional healthcare function claims， and strengthening the quality system construction and information disclosure of post-marketing evaluation.

A 72-year-old male patient with right lung squamous cell carcinoma treated with 1 cycle of pembrolizumab combination chemotherapy and pembrolizumab 200 mg monotherapy.After 20 days of treatment,a small amount of erythema appeared around the mouth,head,neck,chest and back,accompanied by itching.Then the lesions aggravated progressively,spreading to the head,limbs,buttocks and perianal area,with blisters and epidermal detachment and necrosis,and the lesions involved＞70％of the body surface area,and the pain was obvious.After multidisciplinary consultation,toxic epidermal necrolysis(TEN)was considered.The patient's lesions gradually improved and regressed after treatment with hormones,adjunctive therapy with intravenous immunoglobulin,wound care,infection prevention and nutritional support.TEN adverse reactions were highly likely to be associated with pembrolizumab.This paper reviewed the literature on the cases of TEN induced by pembrolizumab.It analyzed the clinical characteristics and drug treatment strategies of TEN induced by pembrolizumab,to improve clinical staff's ability to recognize and manage immunosuppressant-related skin toxicity and improve the prognosis of tumor patients.

ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer （TNBC） cells based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor A （VEGFA） signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group， capecitabine group （0.2 mg·kg^-1）， Chaihu Guizhitang low-dose group， medium-dose group， and high-dose group （10.62， 21.23， 42.46 g·kg^-1）， with 10 mice in each group. After 21 days of medication， the content of tumor necrosis factor-α （TNF-α） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （real-time PCR）. Immunohistochemistry （IHC） was employed to detect the expression of HIF-1α， TNF-α， and VEGFA in tumor tissues， and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density （MVD） was calculated， and the protein expression of HIF-1α， VEGFA， and epidermal growth factor receptor （EGFR） in tumor tissues was measured by Western blot. ResultCompared with the model group， the rest four groups showed low levels of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， VEGFA， and CD34 in cells， and MVD （P<0.05， P<0.01）， and low protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. Compared with capecitabine group， medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， and VEGFA in cells （P<0.01）， CD34 expression， MVD， and protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway， thus exerting anti-tumor effect.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To discuss the medication law in prescriptions of Professor Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on data mining.Methods:Medical cases of kidney deficiency and bone marrow loss in senile dementia in the Geriatric Hospital of Shandong University of Traditional Chinese Medicine from 1st Jan. 2014 to 31st Oct, 2019 were collected. Through hospital electronic medical records system prescription statistics, using ancient and modern medical case cloud platform (V1.2.4), medication frequency, property ans taste, efficacy analysis, correlation rule analysis, clustering analysis and complex network analysis were performed.Results:Totally 110 cases were included in medical cases, involving 238 kinds of Chinese materia medica. The top 10 Chinese materia medica with use frequency were Poria, Acori Tatarinowii Rhizoma, Corni Fructus, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Alpiniae Oxyphyllae Fructus, Rehmanniae Radix, Astragali Radix, Chuanxiong Rhizoma, Atractylodis Macrocephalae Rhizoma; the properties were mainly mild, warm slight cold, and cold; the tastes were mainly sweet, bitter, pungent, and light; the meridians were mainly spleen, liver, lung and kidney meridians; the efficacy was clearing dampness and promoting diuresis, clearing heat and promoting blood circulation, calming mind, clearing heat and detoxification, reducing dampness and promote appetizing, tonifying spleen; the association analysis found 15 groups of drug combinations used more than 25 times, they were: Corni Fructus and Poria, Corni Fructus and Dioscoreae Rhizoma, Dioscoreae Rhizoma and Corni Fructus, Rehmanniae Radix Praeparata and Corni Fructus, Dioscoreae Rhizoma and Poria, Astragali Radix and Poria, Alismatis Rhizoma and Poria, Moutan Cortex and Poria, Rehmanniae Radix Praeparata and Poria, Rehmanniae Radix and Poria, Polygalae Radix and Acori Tatarinowii Rhizoma, Moutan Cortex and Corni Fructus, Moutan Cortex and Dioscoreae Rhizoma, Alismatis Rhizoma and Corni Fructus, Alismatis Rhizoma and Dioscoreae Rhizoma; clustering analysis identified four groups of new prescriptions, the first group: Poria, Rehmanniae Radix, Rehmanniae Radix Praeparata, Alismatis Rhizoma, Moutan Cortex, Corni Fructus, Dioscoreae Rhizoma; the second group: Acori Tatarinowii Rhizoma, Cistanches Herba, Morindae Officinalis Radix; the third group: Alpiniae Oxyphyllae Fructus, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle; the fourth group: Atractylodis Macrocephalae Rhizoma, Codonopsis Radix, Astragali Radix, Angelicae Sinensis Radix; the results of complex network analysis showed that the core prescription was modified Liuwei Dihuang Pills. Conclusion:This study found that in view of kidney deficiency and bone marrow loss in senile dementia, Professor Shao pays attention to strengthening the healthy qi, and focuses on tonifying deficiency, taking into account the methods of clearing dampness, clearing heat, detoxification, removing blood stasis and restoring consciousness. The four new prescriptions found in the study can provide a reference for modified medication for syndrome differentiation.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective To verify the molecular mechanism of Qiangxin Decoction in treating CHF,which was created by Professor Lu Jianqi,a famous old Chinese medicine and Qihuang scholar in Guangxi,based on network pharmacological methods,molecular docking technology and animal experiments.Methods Firstly,TCMSP database and related literatures were searched to find the important compounds of Qiangxin decoction;Through TCMSP database and STITCH database,find the target of Qiangxin Tang;Get the main target points of CHF with the help of GeneCards,DisGeNET,OMIM and other databases;The Venny platform was selected to obtain the intersection target of the two;Using STRING platform and Cytoscape 3.6.1,build a"component target"network and a PPI network of Qiangxin Tang target CHF target;The DAVID 6.8 database was used for GO enrichment analysis and KEGG pathway enrichment analysis;Use AutoDock Vina software for molecular docking.Finally,the model of CHF after AMI was established by ligating the anterior descending branch of left coronary artery in rats,and the expression of core target protein was detected by Western blot.Results 185 important active components including quercetin,kaempferol,luteolin,tanshinone iia and naringenin were obtained from the analysis of network pharmacological results.The core targets were signal transduction and transcription activation factor 3(STAT3),mycobacterium tuberculosis regulatory protein(RELA),phosphorylated protein kinase 1(AKT1)100 therapeutic targets,such as mitogen activated protein kinase 1(MAPK1)and interleukin-6(IL-6),preliminarily indicate that Qiangxin decoction may regulate cytokine mediated signal pathway,positive regulation of gene expression,response to hypoxia The reaction to lipopolysaccharide,drug and other biological processes play a role in the treatment of CHF.The results of molecular docking showed that the important compounds of Qiangxin Tang had strong binding ability to the core target;The results of animal experiments showed that the components of Qiangxin decoction could significantly reduce the phosphorylation expression level of STAT3 protein and MAPK1 protein and the expression level of IL6 protein(P<0.05).The high dose group of Qiangxin Decoction was slightly better than the low dose group.Conclusion This study preliminarily clarified that Qiangxin decoction can play a role in treating CHF by reducing the phosphorylation of STAT3 protein and MAPK1 protein and the expression level of IL6 protein,and also verified that Qiangxin decoction has the characteristics of multiple components,multiple targets,and multiple ways of synergistic effect in treating CHF.Animal experiments provide experimental theoretical basis for clinical doctors to treat CHF and further research.

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.