HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

Prevalence of occupational injury and its associated factors among emergency department physicians in China: A large sample, cross-sectional study.

BACKGROUND: Medical personnel, particularly emergency department (ED) physicians, face a variety of occupational hazards. However, the current state of occupational injuries among ED physicians remains unknown. This study aimed to assess the occupational injury of Chinese ED physicians and to identify its associated factors. METHODS: From July to August 2018, a cross-sectional survey was conducted in Chinese emergency departments. A structured questionnaire covering sociodemographic characteristics, individual health behaviours, and work-related characteristics was completed by 10,457 ED physicians. Binary logistic regression was used to analyse the factors associated with occupational injuries. RESULTS: In this study, 81.13% of ED physicians reported occupational injuries in the previous 12 months. All participants who had experienced occupational injuries had suffered verbal violence. Among physicians who experienced at least one injury, 76.57% and 71.30% reported injuries sustained while moving patients and from falls, slips, and sprains during office visits, respectively. Occupational injuries were significantly associated with gender, education level, drinking behaviour, sleep quality, the frequency of night shifts per month, self-perceived physician shortage, and work-family conflict. Physicians who experienced effort-reward imbalance were at a higher risk of occupational injury. CONCLUSION: In China, occupational injuries are common among ED physicians. Individual factors as well as work-related factors are independently linked to occupational injuries. To reduce the rate of occupational injuries among ED physicians, health policymakers and healthcare facility managers should consider multi-injury interventions.

The clinicopathological significance and relapse predictive role of tumor microenvironment of intrahepatic cholangiocarcinoma after radical surgery.

BACKGROUND: This study attempts to detect the expression of FoxP3, CD68, CD8α, and PD-L1 in the tumor microenvironment (TME) of intrahepatic cholangiocarcinoma (ICC), and analyze the relationship between the corresponding cells and clinicopathological characteristics as well as prognosis of ICC. METHODS: RNA sequencing (RNA-seq) provided the general landscape of the TME in ICC. A total of 99 ICC patients and the corresponding specimens were used for multiplex immunofluorescence and relapse-free survival (RFS) was analyzed. Flow cytometry further validated the effect of regulatory T (Treg) cells on ICC relapse. RESULTS: RNA-seq data showed that the infiltration of Treg cells, CD8+ T cells, and macrophages were likely associated with ICC relapse. The survival analysis based on multiplex immunofluorescence showed that the high FoxP3(+) Treg cells ratio and low CD68(+) macrophages ratio in mesenchyme were associated with higher RFS rate, respectively. Low FoxP3(+) Τreg cells ratio was associated with more perineural invasion, and high CD68(+) macrophages ratio was correlated with more lymph node metastasis. Cox regression analysis revealed that FoxP3(+) Treg cells ratio was an independent predictive factor for ICC relapse. Flow cytometry showed that TregIII was the predominant Treg cell subtype in both tumor tissue and peripheral blood of ICC patients, and high TregIII abundance in peripheral blood was significantly associated with longer RFS of ICC patients. CONCLUSION: High FoxP3(+) Treg cells ratio in the mesenchyme of ICC tumor tissue predicted longer RFS and was an independent favorable prognostic factor for ICC patients. Among all Treg cell subtypes, TregIII in peripheral blood was correlated with the RFS of ICC patients.

Noninvasive urinary protein signatures combined clinical information associated with microvascular invasion risk in HCC patients.

BACKGROUND: Microvascular invasion (MVI) is the main factor affecting the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify accurate diagnostic biomarkers from urinary protein signatures for preoperative prediction. METHODS: We conducted label-free quantitative proteomic studies on urine samples of 91 HCC patients and 22 healthy controls. We identified candidate biomarkers capable of predicting MVI status and combined them with patient clinical information to perform a preoperative nomogram for predicting MVI status in the training cohort. Then, the nomogram was validated in the testing cohort (n = 23). Expression levels of biomarkers were further confirmed by enzyme-linked immunosorbent assay (ELISA) in an independent validation HCC cohort (n = 57). RESULTS: Urinary proteomic features of healthy controls are mainly characterized by active metabolic processes. Cell adhesion and cell proliferation-related pathways were highly defined in the HCC group, such as extracellular matrix organization, cell-cell adhesion, and cell-cell junction organization, which confirms the malignant phenotype of HCC patients. Based on the expression levels of four proteins: CETP, HGFL, L1CAM, and LAIR2, combined with tumor diameter, serum AFP, and GGT concentrations to establish a preoperative MVI status prediction model for HCC patients. The nomogram achieved good concordance indexes of 0.809 and 0.783 in predicting MVI in the training and testing cohorts. CONCLUSIONS: The four-protein-related nomogram in urine samples is a promising preoperative prediction model for the MVI status of HCC patients. Using the model, the risk for an individual patient to harbor MVI can be determined.

Rates of perceived medical errors and its correlation with work-related factors and personal distress among emergency physicians in China: a national cross-sectional study.

PURPOSE: Medical errors are a global concern, and specifically, EDs are at considerable risk for medical errors. Few studies focus on the healthcare provider's self-perceived medical errors in hospitals, let alone the ED. Hence, this study explored perceived medical errors and their correlation with work-related factors and personal distress among physicians in EDs in China. METHODS: From July 2018 to August 2018, a national web-based cross-sectional study was conducted. The link to the web-based questionnaire was posted on the emergency physicians' working platform, inviting Chinese licensed emergency physicians to participate anonymously in this survey. Our outcome of interest, medical errors, was investigated using self-reporting methods. Occupational stress was assessed using the Chinese version of the Effort-Reward Imbalance scale. The Patient Health Questionnaire, the subscale of the 10-item Positive and Negative Affect Schedule, the subscale of the validated Leiden Quality of Work Questionnaire and the 10-item Generalised Self-efficacy Scale were used to assess personal distress. Logistic regression analysis was used to determine factors significantly associated with perceived medical errors. RESULTS: A sample of 10 457 emergency physicians completed the survey. Almost half (43.63%) of physicians reported self-perceived medical errors during the previous 3 months. The rate of workplace verbal aggression, effort-reward imbalance and depressive symptoms were 81.81%, 78.39% and 35.71%, respectively. Medical errors were more likely to be reported among chief physicians, and those who reported the department was short-staffed for physicians, and who experienced workplace verbal aggression and intense work stress. Medical errors were significantly associated with negative affect and lower self-efficacy. CONCLUSION: Self-perceived medical errors are prevalent among physicians working in EDs and are associated with their workplace environment and personal distress. Targeted interventions are required to reduce physicians' workload and improve their working environment. Accounting for healthcare providers' distress is imperative for reducing the incidence of medical errors and improving their health.

Occurrence of self-perceived medical errors and its related influencing factors among emergency department nurses.

AIMS AND OBJECTIVES: To determine the prevalence and the associated factors of self-perceived medical errors among Chinese emergency department nurses. BACKGROUND: The emergency department is a place with a high incidence of medical errors. Studies about the occurrence and related influencing factors of medical errors among emergency nurses in China are very insufficient. DESIGN: A nationwide cross-sectional study. METHODS: A nationwide cross-sectional study was conducted from July 2018-August 2018. A total of 17,582 emergency department nurses from 31 provinces across China were eventually included in the analysis. Logistic regression is applied to examine the association of the independent variables with the perceived medical errors. The reporting of this study was compliant with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies. RESULTS: Of 17,582 participating nurses, 4445 (25.28%) reported self-perceived medical errors in the past 3 months. Nurses who were serving as nurses-in-charge; who reported fair or bad physical health; who reported staff shortage; who were exposed to more verbal abuse at work; who experienced effort-reward imbalance; who reported more over-commitment; or who had depressive symptoms were more likely to report medical errors. Older age and female gender were protective factors. CONCLUSIONS: In this study, a quarter of the emergency nurses reported that they had made medical errors in the past 3 months. Self-perceived medical errors are associated with multiple domains of work-related factors and personal distress. Feasible measures should be taken to reduce nurses' workload, improve their working environment, monitor and minimise the occurrence of medical errors among emergency department nurses. RELEVANCE TO CLINICAL PRACTICE: Emergency nurses, who are the most frequently in contact with patients, play an important role in identifying risk factors and preventing medical errors. Identifying risk factors that may lead to medical errors in the medical environment from both internal and external aspects will help nursing practitioners, hospital administrators and policy makers to take timely preventive measures to reduce the occurrence of medical errors and reduce harm to patients.

Factors related to turnover intention among emergency department nurses in China: A nationwide cross-sectional study.

BACKGROUND: Turnover intention among nurses is high, especially in the emergency department. However, factors that are associated with Chinese emergency department nurses' turnover intention have been scarcely studied. AIMS: The present study examined relationships between turnover intention and demographic characteristics, job-related factors, depressive symptoms, and organizational commitment among emergency department nurses. STUDY DESIGN: A cross-sectional study of emergency department nurses was conducted in China between July and August 2018. The questionnaire included demographic characteristics (age, gender, level of education, and self-rated health status), job-related factors (qualification title, job seniority, night shifts, and workplace violence), depressive symptoms, organizational commitment, and turnover intention. A hierarchical linear regression model was used to identify factors that are associated with turnover intention among emergency department nurses. RESULTS: A total of 17 582 emergency department nurses participated in the study. The response rate was 68.9%. The findings indicated that poor self-rated health status (ß = 0.25, p < .001), working more than 11 night shifts per month (ß = 0.14, p < .01), experiencing workplace violence in the past year (ß = 0.08, p < .05), and higher depressive symptom scores (ß = 0.07, p < .001) positively correlated with turnover intention. More years of service (ß = -0.38, p < .001) and higher organizational commitment scores (ß = -0.45, p < .001) negatively correlated with turnover intention. CONCLUSIONS: Health status, job seniority, night shift frequency per month, workplace violence, depressive symptoms, and organizational commitment were significantly associated with emergency department nurses' turnover intention. RELEVANCE TO CLINICAL PRACTICE: To reduce turnover intention in the emergency department nurses, hospital administrators and managers should implement measures to improve their physical and mental health, increase organizational commitment, develop staff acceptable shift schedules, and reduce incidences of workplace violence.

Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC.

BACKGROUND AND AIMS: Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy. APPROACH AND RESULTS: We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted. CONCLUSIONS: Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.

Prevalence of inappropriate use behaviors of antibiotics and related factors among chinese antibiotic users: an online cross-sectional survey.

BACKGROUND: Inappropriate use of antibiotics could have a profound negative impact on individual and community. This study aimed to assess the prevalence of inappropriate use behaviors of antibiotics in Chinese antibiotic users and explored their related factors. METHODS: A cross-sectional survey was conducted from July 1, 2018 to September 30, 2018. A structured questionnaire was widely distributed on the online survey platform (Questionnaire Star, https://www.wjx.cn ) and was used to collect data from respondents in China on demographic and sociological characteristics, antibiotic use and related knowledge. Main outcomes included self-medication with antibiotics (SMA), self-storage with antibiotics (SSA), and non-adherence to antibiotic treatment (NAAT). Logistic regression was used to identify the related factors of above inappropriate use behaviors of antibiotics. RESULTS: Of the 15,526 participants, 37.1% reported SMA in the past 6 months, 67.9% reported SSA in the past 6 months, and 48.3%, 15.2%, 25.5% and 78.0% of respondents said that they had missed antibiotics, increased antibiotic dosage, decreased antibiotic dosage, and discontinued antibiotics once symptoms disappear, respectively. Overall, 53.3% reported NAAT during this period. After adjusting for other variables, multivariate logistic regression analyses showed that those aged 30-44 years old, with higher levels of education, poorer status of self-perceived health, or lower levels of antibiotic knowledge were more likely to have these inappropriate use behaviors of SMA, SSA, and NAAT (P < 0.05). CONCLUSIONS: The prevalence of SMA, SSA, and NAAT is high in China. Developing a nationwide action plan for the rational use of antibiotics among publics, including national media publicity, online and offline health education, and medication guidance from general practitioners, is urgently needed.

Risk factors for inpatient malnutrition and length of stay assessed by 'NutritionDay' in China.

BACKGROUND AND OBJECTIVES: NutritionDay is a yearly global point-prevalence study of malnutrition or nutritional risk in hospitals. We aimed to provide a comprehensive nutritional survey of hospitalized patients and analyze the risk factors of malnutrition and prolonged hospitalization in Chinese inpatients. METHODS AND STUDY DESIGN: The international daylong cross-sectional survey was performed on November 07th, 2019. Ten hospitals were invited to participate in this NutritionDay survey. Nutritional risk was identified by nutritional risk screening 2002, and malnutrition was identified by the ESPEN criteria. We measured the incidence of malnutrition and nutritional risk. And we analysed risk factors for malnutrition and length of stay in Chinese hospitalized patients. RESULTS: 875 hospitalized patients from 6 departments were included in the analysis. The malnutrition rate was 11.6% and the incidence of nutritional risk was 17.8%. It was analyzed that tumor load, end-stage disease, motility, self-rated health, types of oral medicine, and food intake during the past week were independent risk factors for malnutrition or nutritional risk. 56.2% (118/210) of patients at nutritional risk or malnutrition received extra nutritional support, whereas 22.5% (88/391) well-nourished patients did. Moreover, nutrition status, ever stayed in ICU and self-rated health were associated with prolonged length of stay. CONCLUSIONS: In a word, the prevalence of malnutrition or nutritional risk was about 29.4%. Patients with malnutrition or nutritional risk had a higher transfer rate, lower rehabilitation rate and longer hospital stays. The attention to malnutrition patients needs to be further strengthened.

Establishment, validation and evaluation of predictive model for early relapse after R0 resection in hepatocellular carcinoma patients with microvascular invasion.

BACKGROUNDS: This is the first study to build and evaluate a predictive model for early relapse after R0 resection in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). METHODS: The consecutive HCC patients with MVI who underwent hepatectomy in Cancer Hospital of Chinese Academy of Medical Science from Jan 2014 to June 2019 were retrospectively enrolled and randomly allocated into a derivation (N = 286) and validation cohort (N = 120) in a ratio of 7:3. Cox regression and Logistic regression analyses were performed and a predictive model for postoperative early-relapse were developed. RESULTS: A total of 406 HCC patients with MVI were included in our work. Preoperative blood alpha-fetoprotein (AFP) level, hepatitis B e antigen (HBeAg) status, MVI classification, largest tumor diameter, the status of serosal invasion, number of tumors, and the status of satellite nodules were incorporated to construct a model. The concordance index (C-index) was 0.737 and 0.736 in the derivation and validation cohort, respectively. The calibration curves showed a good agreement between actual observation and nomogram prediction. The C-index of the nomogram was obviously higher than those of the two traditional HCC staging systems. CONCLUSION: We have developed and validated a prediction model for postoperative early-relapse in HCC patient with MVI after R0 resection.

PD-1 mRNA expression in peripheral blood mononuclear cells as a biomarker for different stages of primary gouty arthritis.

There is currently a lack of biomarkers to assist the diagnosis and prediction of primary gouty arthritis (PG). Therefore, we evaluated the clinical value of programmed cell death protein 1 (PD-1) mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with PG. This study included 36 patients with acute phase PG (APPG), 48 with non-acute phase PG (NAPPG), 42 with asymptomatic hyperuricemia (AH) and 79 normal controls (NCs). PD-1 mRNA expression levels were detected by qRT-PCR. PD-1 mRNA expression was statistically analysed by ANOVA or t tests, while correlations between PD-1 mRNA and clinical variables were assessed using Pearson correlation tests. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic value of PD-1 in different PG stages. PD-1 mRNA expression was significantly lower in patients with APPG than that in NAPPG, AH and NCs (P < 0.01). Correlation analysis revealed that PD-1 mRNA levels correlated negatively with T-score (r = -0.209, P < 0.01). ROC curve analysis showed that serum uric acid (SUA), PD-1 mRNA and both combined displayed higher diagnostic value in patients with PG, NAPPG and APPG compared to that in NCs and patients with non-PG arthritis (NPG). Moreover, ROC curve analysis showed that SUA and PD-1 mRNA had good diagnostic value in APPG, with the greatest diagnostic power when combined. PD-1 mRNA could be a clinical auxiliary diagnostic biomarker for APPG, and the combined use of PD-1 mRNA and SUA is better than that of SUA alone.

Postoperative adjuvant treatment strategy for hepatocellular carcinoma with microvascular invasion: a non-randomized interventional clinical study.

BACKGROUND: Microvascular invasion (MVI) is considered to be one of the important prognostic factors that affect postoperative recurrence in patients with hepatocellular carcinoma (HCC) with variable results across their treatment options. This study was carried out to investigate efficacy of postoperative adjuvant RT in HCC patients with MVI. METHODS: This was single center, prospective study carried out in HCC patients with MVI, aged 35-72 years. All patients were non-randomly allocated to receive standard postoperative treatment of HBV/HCV and nutritional therapy or RT in addition to standard postoperative treatment (1:1). The primary endpoints assessed were relapse-free survival and overall survival. The prognostic factors associated with survival outcomes were also analyzed. The safety events were graded according to NCI-CTCAE v4.03 criteria. RESULTS: Of the 115 patients eligible for study, 59 patients were included in analysis. Univariate analysis revealed that MVI classification (P = 0.009), post-operative treatment strategies (P = 0.009) were prognostic factors for worst RFS; tumor size (P = 0.011), MVI classification (P = 0.005) and post-operative treatment (P = 0.015) were associated for OS. The 1-, 2-, 3-year RFS rates were 86.2, 70.5 and 63.4% for patients in RT group, and 46.4, 36.1, and 36.1% in control group. For OS, corresponding rates were 96.6, 80.7, and 80.7% for patients in RT group and 79.7, 58.3, and 50.0% in control group. Subgroup classification of HCC patients according to low risk MVI showed significantly longer RFS (P = 0.035) and OS (P = 0.004) in RT group than control group, while for high risk MVI, RT depicted longer OS than control group with no significance (P = 0.106). Toxicities were usually observed in acute stage with no grade 4 toxicities. CONCLUSION: Postoperative adjuvant RT following hepatectomy offers better RFS for HCC patients with MVI than with standard postoperative therapy. Also, it will be useful to control microscopic lesions in both M1 (low risk) and M2 (high risk) subgroups of HCC patients with MVI. TRIAL REGISTRATION: Trial Registration number: ChiCTR1800017371 . Date of Registration: 2018-07-26. Registration Status: Retrospectively registered.

Prognostic value of the controlling nutritional status (CONUT) score in intrahepatic cholangiocarcinoma patients especially who had long-time alcohol consumption.

Our study is to investigate the preoperative prognostic value of the Controlling Nutritional Status score in intrahepatic cholangiocarcinoma patients after curative resection. One hundred and sixty-seven patients admitted to our hospital between January 2012 and December 2018 were included retrospectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of the Controlling Nutritional Status score to predict recurrence and survival. Patients with high Controlling Nutritional Status score (≥3) had significantly poorer RFS compared to those with low Controlling Nutritional Status score (low: <3) (p = 0.000) in Kaplan-Meier survival curve. Multivariate analyses identified Controlling Nutritional Status score, lymph node metastasis, tumor numbers and preoperative CEA as independent prognostic factors for RFS. Lymph node metastasis was the independent risk factor of OS. The Cox regression model with Controlling Nutritional Status score had better prognostic value for recurrence than the Cox regression model without Controlling Nutritional Status score in long-time alcohol consumption intrahepatic cholangiocarcinoma patients (AUC: 0.760 vs 0.706, p = 0.036). CONUT score may be a more powerful prognostic biomarker, which is tightly associated with other tumor characteristics, to predict recurrence but not survival, especially in long-time alcohol consumption intrahepatic cholangiocarcinoma patients after curative-intent surgery.

[HPLC fingerprint of famous traditional formula Sanpian Decoction and quality value transmitting of Chuanxiong Rhizoma].

Famous traditional formula Sanpian Decoction(SPD)comes from Dialectical Records of Chen Shiduo of the Qing Dynasty,and ranks among 100 classic prescriptions of Classic Famous Traditional Formula catalogue(the First Batch). SPD was prepared according to Management Standards for Traditional Chinese Medicine Decoction Room in Medical Institutions. According to the polarity of different components in SPD,two HPLC fingerprints were established, in which six herbs, namely Chuanxiong Rhizoma, Paeoniae Randix Alba, Sinapis Semen, Glycyrrhizae Radix et Rhizoma, Pruni Semen, Angelicae Dahuricae Radix,are all reflected in the fingerprints; The dry extract rate, transfer rate and similarities of fingerprints were used as indicators to study the relationship between the quality value transmitting of medicinal herbs-decoction pieces-whole decoction of Chuanxiong Rhizoma. Experiment result shows that,the transfer rate of ferulic acid from medicinal herbs to decoction pieces is between 72.00% and 108.36%; the transfer rate of ferulic acid from decoction pieces to SPD is between 31.76% and 64.09%; the dry extract rate of the whole decoction is between 14.69% and 20.16%;The similarity range of fingerprint 1 of 15 batches of SPD is between 0.971 and 0.998, and the similarity range of fingerprint 2 is between 0.980 and 0.996. The established fingerprint has rich information,and the established quality evaluation method is suitable for the quality control of medicinal herbs-decoction pieces-whole decoction of Chuanxiong Rhizoma, which can provide a certain reference for developing the quality control evaluation method for formulated granules, famous formulae and other terminal products derived from traditional Chinese medicine decoction.

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy: A 10-year real-world evidence.

OBJECTIVE: A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy. METHODS: Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated. RESULTS: The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05). CONCLUSIONS: Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

High Beclin-1 and ARID1A expression corelates with poor survival and high recurrence in intrahepatic cholangiocarcinoma: a histopathological retrospective study.

BACKGROUND: Although surgical resection provides a cure for patients with intrahepatic cholangiocarcinoma (ICC), the risk of mortality and recurrence remains high. Several biomarkers are reported to be associated with the prognosis of ICC, including Beclin-1, ARID1A, carbonic anhydrase IX (CA9) and isocitrate dehydrogenase 1 (IDH1), but results are inconsistent. Therefore, a histopathological retrospective study was performed to simultaneously investigate the relationship of these four potential biomarkers with clinicopathological parameters and their prognostic values in patients with ICC. METHODS: A total of 113 patients with ICC were enrolled from Cancer Hospital of Chinese Academy of Medical Sciences between January 1999 and June 2015. The expression of Beclin-1, ARID1A, IDH1 and CA9 were determined by immunohistochemical staining. The prognostic values of the four biomarkers were analyzed by Cox regression and the Kaplan-Meier method. RESULTS: Beclin-1, ARID1A, CA9 and IDH1 were highly expressed in ICC tumor tissues. Higher mortality was positively associated with Beclin-1 expression (HR = 2.39, 95% CI = 1.09-5.24) and higher recurrence was positively associated with ARID1A expression (HR = 1.71, 95% CI = 1.06-2.78). Neither CA9 nor IDH1 expression was significantly associated with mortality or disease recurrence. Kaplan-Meier survival curves showed that ICC patients with higher Beclin-1 and ARID1A expression had a lower survival rate and a worse recurrence rate than patients with low Beclin-1 and ARID1A expression (p < 0.05). CONCLUSIONS: High Beclin-1 and ARIDIA expression are strongly associated with poor prognosis in ICC patients, and thus Beclin-1 and ARID1A should be simultaneously considered as potential prognostic biomarkers for ICC patients.

Glycyrrhizin ameliorates inflammatory pain by inhibiting microglial activation-mediated inflammatory response via blockage of the HMGB1-TLR4-NF-kB pathway.

Chronic inflammatory pain is a severe clinical problem that greatly affects patients' quality of life and causes huge economic burden. Microglia-mediated neuroinflammation exerts critical roles in the pathogenic progression of inflammatory pain. Recent evidence corroborates the anti-inflammatory and neuroprotective efficacy of glycyrrhizin; however, its function in inflammatory pain remains poorly elucidated. In the present study, glycyrrhizin suppressed LPS-induced activation of microglial cell BV2 by inhibiting NO production and expression of microglial marker IBA-1. Intriguingly, LPS-induced high expression and generation of inflammatory cytokines (i.e., IL-6, TNF-α and IL-1ß) was notably reversed by glycyrrhizin pre-treatment. Mechanistic analysis confirmed that high expression of high-mobility group box 1 (HMGB1) in LPS-activated microglia was inhibited following glycyrrhizin. More importantly, restoring HMGB1 expression by recombinant adenovirus vector of Ad-HMGB1 counteracted glycyrrhizin-restrained inflammatory response in microglia upon LPS stimulation. Furthermore, glycyrrhizin dampened the activation of subsequent TLR4-NF-κB pathway in LPS-stimulated microglia, which was abrogated by HMGB1 elevation. Furthermore, blocking this pathway by si-TLR4 transfection reversed the effects of HMGB1 overexpression on the inhibitor roles of glycyrrhizin in microglia-triggered inflammation. Additionally, glycyrrhizin administration also alleviated CFA-evoked mechanical allodynia and thermal hyperalgesia in inflammatory pain model of mice, concomitant with suppression in inflammatory response and microglial activation. Simultaneously, elevation of HMGB1, TLR4 and p65-NF-κB protein expression induced by CFA injection was also abrogated after glycyrrhizin. Accordingly, this study reveal that glycyrrhizin may act as a promising therapeutic avenue for the treatment of inflammatory pain.

Surgical outcomes of hand-assisted laparoscopic liver resection vs. open liver resection: A retrospective propensity score-matched cohort study.

OBJECTIVE: Hand-assisted laparoscopic liver resection has the advantages of open and laparoscopic surgeries. There is still lack of comparison of surgical outcomes between hand-assistied laparoscopic liver resection (HALLR) and open liver resection (OLR). This study compared the surgical outcomes of the two approaches between well-matched patient cohorts. METHODS: Patients who received liver resection during January 2014 and October 2017 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were included in this retrospective study. Propensity score matching (PSM) was performed to reduce selection bias between the two groups. Operation and short-term surgical outcomes were compared between the well matched groups. RESULTS: During this period, 232 patients with a median age of 55.1 years old received OLR, while 49 patients with a median age of 54.7 years old received HALLR. Compared with HALLR group, OLR group has a higher proportion in male patients (190/232, 81.9% vs. 34/49, 69.4%, P=0.048) and lower albumin (43.2±4.5 vs. 44.8±3.7, P=0.020). After PSM, 49 patients from each group were included in the following analysis. Two groups were well balanced in their baseline characteristics, liver functions, preoperative treatments, abdominal surgery history, and surgical difficulty. None perioperative mortality was observed in both groups. Operation time and postoperative complications were similar in two groups (P=0.935, P=0.056). The HALLR group showed less bleeding amount (177.8±217.1 mL vs. 283.1±225.0 mL, P=0.003) and shorter postoperative stay period (6.9±2.2 d vs. 9.0±3.5 d, P=0.001). CONCLUSIONS: We demonstrated that hand-assisted laparoscopic surgery is feasible and safe for liver resection, including some difficult cases. HALLR can provide better bleeding control and faster recovery after surgery.

[Analysis of prognostic factors in patients with hepatocellular carcinoma (≤5 cm) underwent hepatectomy].

OBJECTIVE: To explore the clinical and pathological factors influencing the prognosis of patients with hepatocellular carcinoma (HCC)(≤5 cm) after hepatectomy. METHODS: Two hundreds and nineteen cases with HCC(≤5 cm) undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 and July 2013 were collected. The alpha fetoprotein (AFP) level, tumor number, tumor size (diameter), liver cirrhosis, vascular invasion, capsular invasion, differentiation, surgical methods, resection margin, the way of treatments, the situation of recurrence and time to recurrence were analyzed. Log-rank test and the stepwise Cox proportional-hazards models were used to compare the prognosis, respectively. RESULTS: The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3% respectively in all patients.Single factor analysis indicated that vascular invasion, capsular invasion, tumor size, hepatic vascular occult, liver cirrhosis, tumor differentiation, AFP, the way of treatments, the situation of recurrence and time to recurrence can affect the prognosis significantly (all P<0.05). The multifactor analysis showed that AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence were independent prognostic factors (all P<0.05). CONCLUSION: The prognosis of patients with HCC(≤5 cm) underwent hepatectomy are affected by multi-factors, such as AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence.