ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Objective To investigate the clinical effect of Sansheng Decoction combined with Chinese herbal medicine fumigation on patients with lumbar disc herniation after percutaneous endoscopic lumbar discectomy(PELD).Methods Sixty-six patients with lumbar disc herniation of liver and kidney deficiency complicated with blood-stasis syndrome who were planning to take PELD were randomly divided into control group and treatment group,33 cases in each group.Both groups were treated with PELD.After PELD,the control group was routinely treated with anti-inflammatory,analgesic,neurotrophic and anti-infective treatment.On the basis of treatment for the control group,the treatment group was treated with modified Sansheng Decoction(composed of Eucommiae Cortex,Atractylodis Macrocephalae Rhizoma,Corni Fructus,Notoginseng Radix et Rhizoma,Acanthopanacis Cortex,etc.)orally combined with Chinese herbal medicine fumigation(consists of Achyranthis Bidentatae Radix,Angelicae Sinensis Radix,Spatholobi Caulis,Taxilli Herba,Kadsurae Coccineae Radix,etc.).Before and after treatment,the changes of Visual Analogue Scale(VAS)score of lumbar pain,Japanese Orthopedic Association(JOA)score and Oswestry Disability Index(ODI)score of lumbar function in the two groups were observed.Moreover,the postoperative complications and recurrence in the two groups were compared.Results(1)After 1 month,3 months and 6 months of treatment,except that there was no significant difference between the post-6-month VAS scores and the post-3-month VAS scores in the control group(P＞0.05),the VAS scores of lumbar pain in the two groups were all significantly lowered compared with those at the previous observation time point(P＜0.05),and the decrease in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.05 or P＜0.01).(2)After 1 month,3 months and 6 months of treatment,except that the JOA scores of lumbar function in the control group after 6 months of treatment did not differ from those after 3 months of treatment(P＞0.05),the JOA scores of the two groups were all significantly increased compared with those at the previous observation time point(P＜0.05),and the increase in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.01).(3)After 1 month,3 months and 6 months of treatment,the ODI score of lumbar function in the two groups were all significantly decreased compared with those at the previous observation time point(P＜0.05),and the decrease in the treatment group after 1 month,3 months and 6 months of treatment was significantly superior to that in the control group(P＜0.01).(4)In terms of the complications,no injury of nerve root and dura mater or other adverse reactions occurred in the two groups after operation.(5)During the trial,there was one patient lost from each group,and the remaining patients were followed up for 3 years.Within the 3 years,4 patients in the control group relapsed,and one patient in the treatment group relapsed,and all of the relapsed patients did not receive reoperation.Conclusion Sansheng Decoction combined with Chinese herbal medicine fumigation exerts certain effect in the treatment of patients with liver and kidney deficiency complicated with blood-stasis syndrome after PELD for lumbar disc herniation.The therapy can effectively relieve postoperative pain and promote the recovery of postoperative lumbar function.

As essential concepts of the traditional Chinese medicine theory,"deficiency"and"toxin"have been enriched and developed continuously since Huangdi Neijing.By tracing back and combing"deficiency"and"toxin",this paper sums up their relationship,analyzes and explains their basic connotation,and discusses their extension.The"deficiency-toxin"theory has two meanings:it covers the pathological state of the human body with deficiency of vital qi and excess of pathogenic toxin,and it also refers to the pathological evolutionary process in which"deficiency"and"toxin"promote each other.Based on the connotation and dynamic pathogenesis of the"deficiency-toxin"theory,it is pointed out that this theory can be applied to the prevention and treatment of infectious diseases and chronic debilitating diseases,including the"inflammation-cancer transformation"of inflammatory bowel disease.Taking inflammatory bowel disease as an example and combining its Western medical background,this paper expounds on the pathogenesis and treatment of the"inflammation-cancer transformation"of inflammatory bowel disease,and provides a paradigm of"deficiency-toxin"theory guiding clinical research.

Jaundice is one of the common clinical symptoms,which is characterized by eyes stained yellow especially.The classification and prescription of jaundice are improved continuously.This consensus describes the history of jaundice,etiology and pathogenesis,common symptoms,clinical treatment,evaluation of therapeutic effect,preventive regimen and regression follow-up,highlighting its clinical practicality and reflecting the latest research progress.

Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.

Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.

[Abstract] Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma. Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay. Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022). Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.

[摘 要] 目的：本研究旨在评估白蛋白紫杉醇+卡铂联合抗血管生成药物（nab-paclitaxel, carboplatin, antiangiogenic drug, NCA）方案用于既往治疗失败的晚期黑色素瘤患者的疗效和安全性。方法：收集2012年4月1日至2019年5月31日在北京大学肿瘤医院肾癌黑色素瘤科住院的黑色素瘤患者，回顾性分析NCA方案在既往治疗失败后的不可切除Ⅲ c期和Ⅳ期黑色素瘤患者中的疗效和安全性。主要终点指标为无进展生存期（PFS），次要指标为客观缓解率（ORR）、总生存期（OS）、疾病控制率（DCR）和不良反应。根据使用的抗血管药物分为恩度治疗组（n=73）和贝伐珠单抗治疗组（n=103），采用倾向性评分匹配以均衡不同抗血管生成药物组间基线变量的差异。结果：共计176例患者被纳入本项分析中。所有患者中位年龄51岁（范围为18~78岁）。Ⅳ期患者占97%，50%的患者LDH水平高于正常值，28%的患者存在肝转移。既往治疗线数占比分别为1线57%、2线33%、3~4线10%。所有患者的中位PFS为3.8个月（95%CI：3.0~4.6），中位OS为10.5个月（95%CI： 8.9~12.1）。2例患者获得完全缓解，9例患者获得部分缓解，全组的ORR为6%，DCR达70%。恩度治疗组和贝伐珠单抗治疗组的中位PFS分别为4.7个月（95%CI：3.5~5.9）和3.4个月（95%CI：3.0~4.6），两组中位OS分别为12.2个月（95% CI：11.1~13.2）和9.1个月（95%CI： 7.8~10.4）。对所有患者的年龄、性别、既往治疗线数和LDH水平进行倾向性评分匹配，贝伐珠单抗和恩度治疗组间PFS和OS差异无统计学意义。常见的不良反应包括脱发、周围神经病变、中性粒细胞减少、疲劳和恶心。26名（15%）患者由于不良反应停止了治疗。结论：白蛋白紫杉醇+卡铂联合抗血管生成药物对既往治疗失败的晚期黑色素瘤患者具有一定的疗效，不良反应可耐受。