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Background Anthracycline‐based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection. Methods We retrospectively analyzed the data of a nation‐wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889). Results In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline‐taxane‐based combinations for neo‐ and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40‐65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease‐free survival (p < 0.001) were more likely to be recommended to ABC. Conclusion Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China., The nation‐wide study revealed that anthracycline‐based chemotherapy (ABC) remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy, and was predominantly used as a combination therapy. The correlation between clinicopathological characteristics and ABC choice varied at different settings, suggesting the preference and different perspectives of medication regarding the use ABC in China. The real‐world data contribute to guide the selection of the appropriate treatment and maximize the benefit of chemotherapy for patients.

The transport mechanism of intestinal α-synuclein to the central nervous system has become a new hot topic in Parkinson's disease (PD) research. It is worth noting that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported to be involved in the pathogenesis of PD. After silencing GAPDH expression by GAPDH siRNA, the normal human intestinal epithelial crypt-like (HIEC) and human SH-SY5Y neuroblastoma cell lines were co-cultured with Escherichia coli cells which were transfected with an α-synuclein overexpression plasmid. The levels of autophagy-related proteins (BECN1, ATG5, LC3A/B and p62) were determined by Western blot analysis. Changes in pro-apoptosis protein levels and flow cytometry analysis were used to assess cell apoptosis and relative intracellular ATP concentration was measured. Oxidative stress was assessed by measuring the levels of reactive oxygen species (ROS) using 2',7'-dichlorofluorescein diacetate (DCFH-DA), thiobarbituric acid-reactive substances (TBARS), and antioxidant capacity was assessed by measuring the glutathione (GSH) levels and superoxide dismutase (SOD) activity. The silencing of the expression of GAPDH pre-knockdown was found to reduce the intracellular levels of ROS and lipid peroxidation, enhance autophagy activity, thereby reducing the cell injury, apoptosis and necrosis induced by exogenous α-synuclein protein in SH-SY5Y cells. This study identifies a new therapeutic target of exogenous α-synuclein protein induced SH-SY5Y cell injury and improves our understanding of the pathophysiological role of GAPDH in vitro.

BACKGROUND AND AIM Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD). METHODS We performed a nested case-control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age-matched, gender-matched, and trial-matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial. RESULTS Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P-trend

Poor oral health, indicated by tooth loss and periodontal disease, may be an important risk factor for various cancers. Prior studies have found inconsistent associations between tooth loss and several cancer types. Here, we examined the relationship between tooth loss and incident cases of multiple cancers in the Linxian General Population Nutrition Intervention Trial cohort. In this large prospective cohort of over 29,000 participants, there were 3101, 1701, 626, 327, 348, and 179 incident esophageal, gastric cardia, gastric noncardia, liver, lung, and colorectal cancer cases, respectively, over 30 years of follow-up. Adjusted Cox proportional hazards regression models with time-varying covariates were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between tooth loss and cancer outcomes during three time intervals: ≤ 5 years (early), > 5 and ≤ 10 years (mid), > 10 years (late). Tooth loss was assessed as quartiles of the number of lost teeth in excess of the loess-smoothed, age-specific median number of teeth lost. For esophageal cancer, the increase in risk associated with the highest quartile of tooth loss was 25% (95% CI: 1.02, 1.52) in the mid time interval, but the association weakened thereafter. For gastric cardia cancer, the increase in risk associated with the highest quartile of tooth loss was 1.34 in both the early (95% CI: 1.06, 1.71) and mid time intervals (95% CI: 1.02, 1.76), with no significant associations in the late interval. Gastric noncardia cancer was only associated with the second quartile of tooth loss in the late time interval (HR = 1.54; 95% CI: 1.16, 2.04). All associations between tooth loss and liver, lung, and colorectal cancers were null. Tooth loss was associated with risk of esophageal and gastric cancers in this updated analysis from the cohort.

Background Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC). Methods We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer. Results Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07–1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P P = 0.13). Conclusions This study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.

Gastric cancer shows a strong male predominance, and sex steroid hormones have been hypothesized to explain this sex disparity. Previous studies examining the associations between sex hormones and sex hormone binding globulin (SHBG) and risk of gastric cancer come primarily from western populations and additional studies in diverse populations will help us better understand the association. We performed a nested case–control study in Linxian Nutrition Intervention Trials cohorts to evaluate the associations among Chinese men, where we had sufficient cases to perform a well-powered study. Using radioimmunoassays and immunoassays, we quantitated androgens, estrogens, and SHBG in baseline serum from 328 men that developed noncardia gastric cancer and matched controls. We used multivariable unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) and explored interactions with body mass index (BMI), age, alcohol drinking, smoking, and follow-up time. Subjects with SHBG in the highest quartile, as compared with those in the lowest quartile, had a significantly increased risk of gastric cancer (OR = 1.87; 95% CI, 1.01–3.44). We found some evidence for associations of sex steroid hormones in men with lower BMI. Our study found a novel association suggesting that higher serum concentrations of SHBG may be associated with risk of gastric cancer in men. We found no overall associations with sex hormones themselves, but future studies should expand the scope of these studies to include women and further explore whether BMI modifies a potential association. Prevention Relevance: It was the first study to investigate the association of gastric cancer with prediagnostic sex steroid hormones and SHBG in an Asian male population. Although there were no overall associations for sex steroid hormone concentrations, higher concentrations of SHBG was associated with increased risk of noncardia gastric cancer.

Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions.

Background:. The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. Methods:. A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. Results:. In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45–1.07; P = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). Conclusions:. As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. Trial registration. chictr.org.cn, No. ChiCTR-TRC-12003513

Background: Accumulating evidence has shown that serum calcium and vitamin D may be associated with or influence various cancer risks. However, no prospective studies have evaluated the independent and joint associations between prediagnostic levels of serum calcium and vitamin D and future risk of incident primary liver cancer. Methods: We used a nested case–control design to evaluate subjects over 22 years of follow-up. Serum calcium, 25-hydroxy vitamin D [25(OH)D], and three markers of hepatitis B virus and hepatitis C virus were measured in baseline serum from 226 incident primary liver cancer cases and 1,061 matched controls. We calculated ORs and 95% confidence intervals (CI) using logistic regression to estimate the associations between calcium, 25(OH)D, and primary liver cancer risk. Results: Multivariable adjusted models showed that subjects with both low (ORLow/Medium = 1.48, 95% CI = 1.01–2.17) or high (ORHigh/Medium = 1.92, 95% CI = 1.34–2.76) calcium had an increased primary liver cancer risk, while those with high 25(OH)D had a decreased risk of primary liver cancer (ORHigh/Medium = 0.54, 95% CI = 0.35–0.82). In joint analyses, when compared with subjects with medium calcium and 25(OH)D, subjects with high calcium and medium 25(OH)D had elevated odds of developing primary liver cancer (OR = 1.89, 95% CI = 1.17–3.05); those with medium calcium and high 25(OH)D had reduced odds of developing primary liver cancer (OR = 0.34, 95% CI = 0.17–0.67); and subjects in other classifications of calcium and serum 25(OH)D levels had no change in the odds of developing primary liver cancer (all P > 0.05). Conclusions: In a nutrient-deficient population, we found that serum calcium and serum 25(OH)D could potentially be modifiable risk or protective factors. Impact: Our findings provide potential targets for primary liver cancer prevention and control.

Background To investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. Methods A total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During the 30‐year follow‐up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long‐term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05–1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11–1.97), females (HR = 1.44, 95% CI: 1.11–1.89), non‐smokers (HR = 1.44, 95% CI: 1.15–1.81), nondrinkers (HR = 1.28, 95% CI: 1.04–1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05–1.79). No associations were observed between OL and risk of GCC and GNCC mortality. Conclusions OL may increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism., OL could increase the long‐term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non‐smokers, and subjects with a family cancer history. The specific etiological mechanism needs to be further explored.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects. Methods: A total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers. Results: ESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects. Conclusions: Our study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists.

Background: Clarithromycin is widely used for infections of helicobacter pylori. Clarithromycin belongs to polymorphic drug. Crystalline state changes of clarithromycin in sustained release tablets were found. Objective: The aim of this study was to find the influential factor of the crystal transition of clarithromycin in preparation process of sustained-release tablets and to investigate the possible interactions between the clarithromycin and pharmaceutical excipients. Methods and Results: The crystal transition of active pharmaceuticals ingredients from form II to form I in portion in clarithromycin sustained release tablets were confirmed by x-ray powder diffraction. The techniques including differential scanning calorimetry and infrared spectroscopy, x-ray powder diffraction were used for assessing the compatibility between clarithromycin and several excipients as magnesium stearate, lactose, sodium carboxymethyl cellulose, polyvinyl-pyrrolidone K-30 and microcrystalline cellulose. All of these methods showed compatibilities between clarithromycin and the selected excipients. Alcohol prescription simulation was also done, which showed incompatibility between clarithromycin and concentration alcohol. Conclusion: It was confirmed that the reason for the incompatibility of clarithromycin with high concentration of alcohol was crystal transition.

Background The objective of this study was to explore the association between fresh fruit consumption and long-term risk of upper gastrointestinal cancer (UGI) in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. Methods A cohort of 3318 subjects with esophageal squamous dysplasia participated in the Linxian Dysplasia NIT in May 1985 and were followed up until 30 September 2015. Demographic characteristics, lifestyle, and history of diseases were collected at the baseline. The primary endpoint was death from esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric noncardia carcinoma (GNCC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. Results In the 30-year follow-up, a total of 541 ESCC, 284 GCC, and 77 GNCC deaths occurred. Relative to those who never or rarely consumed fresh fruit, the risk of ESCC mortality in participants who consumed fresh fruit more than 12 times/year were significantly decreased by 37.3% (HR = 0.63, 95% CI: 0.49-0.81). In the subgroup analyses, significantly protective effects on ESCC mortality were observed especially in females (HR = 0.59, 95% CI: 0.40-0.89), non-smokers (HR = 0.67, 95% CI: 0.48-0.94), and nondrinkers (HR = 0.69, 95% CI: 0.51-0.93). Conclusions Consuming fresh fruit more than 12 times/year may reduce the long-term risk of ESCC mortality in this dysplasia population, particularly in females, non-smokers, and nondrinkers. Future studies are needed to confirm these findings.

To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients. A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI. Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups. Conclusions: Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992]

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p-trend

Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA-192 and -215. In summary, miRNA-192 and -215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.

Background: Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia. Methods: A nested case–control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders. Results: There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24–0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50–1.36) or ESCC (OR = 1.05; 95% CI, 0.58–1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66–8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA. Conclusions: APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population. Impact: APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Omics techniques develop quickly and have made a great contribution to disease study. Omics data are usually complex. How to analyze the data and mine important information has been a key part in omics research. To study the nature of disease mechanisms systematically, we propose a new data analysis method to define the network biomarkers based on horizontal comparison (DNB-HC). DNB-HC performs molecule horizontal relationships to characterize the physiological status and differential network analysis to screen the biomarkers. We applied DNB-HC to analyze a large-scale metabolomics data, which contained 550 samples from a nested case-control hepatocellular carcinoma (HCC) study. A network biomarker was defined, and its areas under curves (AUC) in the receiver-operating characteristic (ROC) analysis for HCC discrimination were larger than those defined by six efficient feature selection methods in most cases. The effectiveness was further corroborated by another nested HCC dataset. Besides, the performance of the defined biomarkers was better than that of α-fetoprotein (AFP), a commonly used clinical biomarker for distinguishing HCC from high-risk population of liver cirrhosis in other two independent metabolomics validation sets. All and 90.3% of the AFP false-negative patients with HCC were correctly diagnosed in these two sets, respectively. The experimental results illustrate that DNB-HC can mine more important information reflecting the nature of the research problems by studying the feature horizontal relationship systematically and identifying effective disease biomarkers in clinical practice. Graphical abstract.

Aim: To compare efficacy between total gastrectomy (TG) and proximal gastrectomy (PG) for upper-third gastric cancer. Materials & methods: PubMed, Embase and Cochrane library were searched to select suitable researches. Stata was used for meta-analysis including 5-year overall survival rate, recurrence rate, complication morbidities and serum nutritional levels. Results: Ten retrospective English researches were contained. Our study showed no significant difference of 5-year overall survival rate, recurrence rate, reflux symptoms and anastomotic leakage. TG experienced longer operation time, more lymph nodes-retrieved number, more estimated blood loss and higher ileus, but less anastomotic stricture. PG showed advantages over TG in terms of serum nutritional levels. Conclusion: PG is more preferable to TG for treatment of upper-third gastric cancer.

Background This prospective study investigated the association between tooth loss and upper gastrointestinal (UGI) cancer mortality in the Linxian Dysplasia Nutrition Intervention Trial Cohort. Methods Subjects were categorized into three groups according to age at baseline. No missing teeth and less or greater than median tooth loss in each group was defined as none, moderate, and severe, respectively. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. Results Through 30 September 2015, 541 esophageal squamous cell carcinoma (ESCC), 284 gastric cardia carcinoma (GCC), and 77 gastric non‐cardia carcinoma (GNCC) deaths occurred. In the six‐year follow‐up, severe tooth loss was associated with an increased risk of GCC mortality (HR 1.55, 95% CI 1.06–2.18). In the 15‐year follow‐up, moderate tooth loss increased the ESCC mortality risk by 58% (HR 1.58, 95% CI 1.06–2.35), while severe loss increased the GCC mortality risk by 30% (HR 1.30, 95% CI 1.03–1.64). In the 30‐year follow‐up, moderate tooth loss increased the risk of ESCC mortality (HR 1.34, 95% CI 1.01–1.76). In subjects aged < 55 at baseline and men, moderate tooth loss had 53% and 52% higher risks of ESCC mortality (HR

Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined.Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting.Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1.Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

BACKGROUND: Breast cancer is currently the most common female malignancy in China. However, the clinical features and overall prognosis of young women diagnosed with this malignancy remain unclear. This study aimed to describe the clinicopathological characteristics of young patients (≤34 years of age) with breast cancer and explore the current treatment approaches used in China. METHODS: This was a hospital-based, multicenter, retrospective study of women with breast cancer across seven Chinese hospitals from 1999 to 2008. A total of 295 young (≤34 years of age) patients (research group) and 2,119 women aged 35 to 49 years (control group) were included in the study. Patient epidemiology, pre-operative examinations, clinical pathology, and treatment were analyzed. RESULTS: The percentage of young patients with breast cancer in the study group was 7.01%. These young women had a lower body mass index (BMI), a higher level of education, a lower number of previous births, and a lower history of breastfeeding than the control group (P

BackgroundClinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.MethodsUsing data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.ResultsA total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.ConclusionsLess than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.

Objective. To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. Methods. This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. Results. A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II–IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall’s correlation coefficient = 0.3, P < 0.0001 ), while no prohibitive variables among clinical characteristics were detected. Conclusion. Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

ObjectiveThe objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models.ResultsThere were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HRESCC = 1.45, 95%CI: 1.35–1.56; HRGCC = 1.27, 95%CI: 1.15–1.40; Mortality: HRESCC = 1.40, 95%CI: 1.30–1.52; HRGCC = 1.27, 95%CI: 1.14–1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HRESCC = 1.65, 95%CI: 1.40–1.95; HRGCC = 1.42, 95%CI: 1.12–1.81) and deaths (HRESCC = 1.65, 95%CI: 1.38–1.97; HRGCC = 1.42, 95%CI: 1.09–1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17–1.47; Mortality: HR = 1.33, 95%CI: 1.17–1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results.ConclusionOur data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.

BACKGROUND Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Dry-type hollow reactor is widely used in power system, its operating environment is bad, the annual sun and rain also accelerate the aging of its insulation, it is easy to cause the dry reactor inter-turn insulation damage and burn down. At present, the main methods of live detection of dry reactor are infrared thermal imaging technology. DC resistance and insulation resistance are required in blackout test. These tests can not detect the inter-turn insulation of dry reactor. In this paper, the magnetic field and impedance characteristics of the interturn insulation damage of dry reactor are studied. The magnetic field changes and impedance characteristics of dry reactor are simulated by using ANSYS analysis software when the interturn magnetic field occurs in the end and middle of the reactor, respectively. A fault simulation platform for dry reactor is established, and a new method for interturn insulation detection is proposed.

Background Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Methods This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. Results At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. Conclusions LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. Trial registration ClinicalTrials.gov, NCT03090659; Registered on March 27, 2017, retrospectively registered Electronic supplementary material The online version of this article (10.1186/s13045-018-0681-6) contains supplementary material, which is available to authorized users.

BackgroundVitamin C insufficiency occurs across many countries and has been hypothesised to increase risk of various diseases. Few prospective studies with measured circulating vitamin C have related deficiency to disease mortality, particularly in low-income and middle-income countries.MethodsWe randomly selected 948 subjects (473 males and 475 females) aged 53–84 years from a Chinese cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in plasma samples collected in 1999–2000. A total of 551 deaths were accrued from sample collection through 2016, including 141 from cancer, 170 from stroke and 174 from heart diseases. Vitamin C was analysed using season-specific quartiles, as a continuous variable and as a dichotomous variable based on sufficiency status (normal >28 µmol/L vs low ≤28 µmol/L). HRs and 95% CIs were estimated using Cox proportional hazards models.ResultsWe found significant inverse associations between higher plasma vitamin C concentrations and total mortality in quartile (HRQ4 vs Q10.75, 95% CI 0.59 to 0.95), continuous (HRq20umol/L0.90, 95% CI 0.82 to 0.99) and dichotomous analyses (HRnormal-vs-low0.77, 95% CI 0.63 to 0.95). We observed significant lower risks of heart disease (ptrend-by-quantile=0.03) and cancer deaths (pglobal-across-quantile=0.04) for higher vitamin C, whereas the association was attenuated for stroke in adjusted models. Similar inverse associations were found when comparing normal versus low vitamin C for heart disease (HRnormal-vs-low0.62, 95% CI 0.42 to 0.89).ConclusionIn this long-term prospective Chinese cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health.

Background This study was conducted to explore the association between oral leukoplakia (OL) and the risk of upper gastrointestinal cancer death in the Linxian General Population Trial Cohort. Methods A prospective cohort study of the Linxian General Population Trial Cohort was performed. Participants with OL were treated as an exposed group, and the remainder was selected as a control group. All subjects were followed monthly by village health workers and reviewed quarterly by the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence interval (CIs) were evaluated using proportional hazard and proportional subdistribution hazard models, respectively. Results Over a median of 27 years of observation, 29 476 subjects were followed-up. A total of 17 473 deaths occurred, including 2345 esophageal squamous cell carcinoma (ESCC), 1139 gastric cardia carcinoma, and 506 gastric non-cardia carcinoma deaths. Significant increased ESCC mortality was observed in subjects with OL (exposed 9.66% vs. unexposed 7.39%; P

Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P −5 in the stage-1 meta-analysis of NCI and Henan GWAS data. In stage-2, the association for rs79747906 (located at 18p11.31, P = 5.79 × 10−6 in discovery) was replicated (P = 0.006), with a pooled-OR of 1.59 (95%CI: 1.11-2.28). We identified potential genetic variants associated with FH of UGI cancer. Our findings may provide important insights into new low-penetrance susceptibility regions involved in the susceptibility of families with multiple UGI cancer cases.

Although a number of previous studies have noted either positive or no association for body mass index (BMI) and gastric cancer risk, little evidence exists in the Chinese population. We prospectively examined the associations of BMI with risk of gastric cancer in the Linxian General Population Trial cohort, with 29 584 healthy adults enrolled in 1985 and followed through to the end of 2014. Body weight and height were measured during physical examination at baseline and BMI was calculated as weight in kilograms divided by height in meters squared. Body mass index from 138 subjects was missing, and a total of 29 446 participants were included in the final analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. During 30 years of follow‐up, we confirmed 1716 newly diagnosed gastric cardia adenocarcinoma (GCA) cases and 626 new gastric non‐cardia adenocarcinoma (GNCA) cases. Overall, compared to the lowest quartile (BMI

// Jin-Hu Fan 1, * , Yu-Qing Zhang 1, * , Su-Sheng Shi 2 , Yuan-Jia Chen 3 , Xing-Hua Yuan 4 , Li-Ming Jiang 5 , Shao-Ming Wang 1 , Li Ma 6 , Yu-Tong He 7 , Chang-Yan Feng 8 , Xi-Bin Sun 9 , Qing Liu 10 , Katrina Deloso 11 , Yihebali Chi 12 and You-Lin Qiao 1 1 Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College 2 Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College 3 Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences 4 Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College 5 Department of Radiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College 6 Department of Epidemiology, Dalian Medical University 7 Hebei Cancer Registry, the Fourth hospital of Hebei medical university 8 Department of Nutrition, Chongqing Cancer Hospital & Institute & Cancer Center 9 Department of Cancer Epidemiology, Henan Cancer Hospital/Institute 10 Department of Cancer Prevention, Sun Yat-sen University Cancer Center 11 Division of Biological Sciences, the University of Chicago 12 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College * These authors have contributed equally to this work Correspondence to: You-Lin Qiao, email: Qiaoy@cicams.ac.cn Yihebali Chi, email: yihebalichi@hotmail.com Keywords: neuroendocrine tumors, digestive system, epidemiology, retrospective study multicenter study Received: October 20, 2016 Accepted: April 11, 2017 Published: May 03, 2017 ABSTRACT Background: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients. Methods: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients’ information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared. Results: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger ( P

// Jian Zhang 1 , Xiao Li 1 , Rong Huang 2,3 , Wei-Liang Feng 4 , Ya-Nan Kong 5 , Feng Xu 6 , Lin Zhao 7 , Qing-Kun Song 2 , Jing Li 2 , Bao-Ning Zhang 8 , Jin-Hu Fan 2 , You-Lin Qiao 2 , Xiao-Ming Xie 5 , Shan Zheng 9 , Jian-Jun He 1 and Ke Wang 1 1 Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China 2 Department of Cancer Epidemiology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China 3 Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, P.R. China 4 Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, P.R. China 5 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China 6 Department of Breast-thyroid Surgery, Xiangya Second Hospital, Central South University, Changsha, P.R. China 7 Department of Breast Surgery, Liaoning Cancer Hospital, Shenyang, P.R. China 8 Center of Breast Disease, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China 9 Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China Correspondence to: Ke Wang, email: // Jian-Jun He, email: // Keywords : breast cancer, axillary lymph node metastasis, prediction model, nomogram Received : June 21, 2016 Accepted : October 26, 2016 Published : November 12, 2016 Abstract Axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) alone may lead to postoperative complications. Among patients with positive ALN in the preoperative examination, approximately 40% patients do not have SLN metastasis. Herein, we aimed to develop a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. We retrospectively analyzed the clinicopathological features of 4211 female patients with breast cancer who were diagnosed in seven breast cancer centers representing entire China, over 10 years (1999-2008). The patients were randomly categorized into a training cohort or validation cohort (3:1 ratio). Multivariate logistic regression analysis was performed for 1869 patients with complete information on the study variables. Age at diagnosis, tumor size, tumor quadrant, clinical nodal status, local invasion status, pathological type, and molecular subtypes were the independent predictors of ALN metastasis. The nomogram was then developed using the seven variables. Further, it was subsequently validated in 642 patients with complete data on variables in the validation cohort. Coefficient of determination (R²) and the area under the receiver-operating characteristic (ROC) curve (AUC) were calculated to be 0.979 and 0.7007, showing good calibration and discrimination of the model, respectively. The false-negative rates of the nomogram were 0 and 6.9% for the predicted risk cut-off values of 14.03% and 20%, respectively. Therefore, when the predicted risk is less than 20%, SLNB may be avoided. After further validation in various patient populations, this model may support increasingly limited axillary surgery in breast cancer.

To explore the optimal cutoff score for initial detection of Alzheimer’s Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas.

Background: Extramedullary disease (EMD) is characterized as the presence of myeloma cells invasion outside the bone marrow in a patient with multiple myeloma (MM), it may be found 6%~8% in de novo patients, and 10% to 30% in relapsed or refractory (R/R) MM patients across the overall disease course (Joan Blade et al. 2011, Matthew Weinstock et al. 2013 and 2015, Cyrille Touzeau et al. 2015). EMD was considered as high-risk group of myeloma and is associated with adverse prognosis and the management is particularly challenging. Here we discuss and improve the understanding of the clinical characters and prognoses of the R/R MM with EMD in the treatment of CAR T therapy, illustrate our experience in a single institution. Methods: LCAR-B38M is a Chimeric antigen receptor (CAR) T cell therapy with 4-1BB as the co-stimulator, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen (BCMA) epitopes. In total of 57 patients were treated in China from The Second Affiliated Hospital of Xi'an Jiaotong University (LEGEND-2, NCT03090659), 17 patients with R/R MM with EMD were included and received the CAR T treatment. The study was initiated on March 30, 2016, and the analysis reported here is from a data cutoff date of July 31, 2019, the detailed treatment schema was presented in the former paper (Zhao et al, 2018). Results: Overall, 17 (29.8%) of 57 treated patients with EMD were included in our CAR T treatment. The median age of R/R MM patients with EMD (EMD group) and without EMD (non-EMD group) were 55 (range, 27-72) and 53.3 (range, 42-73) years old respectively, and the median number of prior therapy lines were 3 (range, 1-6 and 1-9) in both groups. There were no statistical difference in the proportion of male and female patients, median time from initial diagnosis and ISS stage in EMD group and non-EMD group. The Eastern Cooperative Oncology Group (ECOG) scores of patients receiving CAR T treatment were 0-2 points, the proportion of ECOG 1-2 points in EMD group were higher than non-EMD group (P < 0.05, R=0.1474, 95% CI, 0.03 to 0.73). IgG and IgA subtype were the main types in the non-EMD patients while the light chain type was more frequently seen in EMD group (P = 0.014, OR=0.1886, 95% CI, 0.05 to 0.66). The overall response rates (ORR) in the EMD group and non-EMM group were 82.4% and 90% respectively (Fig 1 A), and there were no significant difference in the median time to the first response and the best response between the EMD group and non-EMD group(P > 0.05). At cutoff, the median follow-up was 25 months, the median progression-free survival (PFS) in EMD group and non-EMD group were 8.1 months and 25 months (P < 0.001, R=0.32, 95% CI, -0.19 to 0.84), and the median overall survival (OS) were 13.9 months and not reached (P = 0.0019, R=4.833, 95% CI, 1.91 to 12.22), survival curves were shown in Fig 1 B, C . Conclusions: LCAR-B38M is a highly effective therapy in R/R MM patients with EMD and without EMD, and both groups had similar response time and reached a high ORR rate. R/R MM patients with EMD demonstrated a poor prognosis and they may lost their best response in a relatively shorter time compared with the patients without EMD. With a median follow-up of 25 months, LCARB38M manifested a relatively durable therapeutic effect in this high-risk R/R MM patients with EMD. Disclosures No relevant conflicts of interest to declare.

Background The concordance rate of human epidermal growth factor receptor 2 (HER2) status between core needle biopsy (CNB) and subsequent excisional biopsies of the same tumor varies from 81 to 96%, which may cause inappropriate neoadjuvant therapy that impair the potential benefit from HER2 targeted therapy for patients. This study aimed to establish a nomogram to predict the HER2 status pre-operatively as an auxiliary diagnosis to CNB assessment. Methods Among 4211 breast cancer patients cataloged in the Nation-wide Multicenter 10-year Retrospective Clinical Epidemiological Study of Breast Cancer in China, 2291 patients with complete relevant information were included in this study, which were further randomized 3:1 and divided into a training set and a validation set. The nomogram was established based on independent predictors of HER2 positivity recognized by logistic regression analysis and further validated internally and externally. Results The multivariate logistic regression analysis showed that T-stage, N-stage, estrogen receptor (ER) status, progesterone receptor (PR) status were independent predictors for HER2 status. The nomogram was thereby constructed by those independent predictors as well as histology type. The areas under the receiver operating characteristic curve (AUC) of the training set and the validation set were 0.636 and 0.681, respectively. The calibration plots demonstrated good fitness of the nomogram for HER2 status prediction. With the optimal cutoff value, the nomogram yielded 80.0% sensitivity, 43.1% specificity in the training set and 81.1% sensitivity, 49.8% specificity in the validation set. Conclusions The present nomogram can provide valuable information on HER2 status and combined with standard CNB assessment, clinicians could make more appropriate decision on neoadjuvant therapy of breast cancer. Electronic supplementary material The online version of this article (10.1186/s13000-019-0806-4) contains supplementary material, which is available to authorized users.