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This study aims to explore the relationship between chronic hepatitis B virus (HBV) infection and the risk of gastrointestinal (GI) cancers including liver, gastric, gallbladder or extrahepatic bile duct, pancreatic, small intestine, esophageal, and colorectal cancer in the Kailuan Cohort study. We prospectively examined the relationship between HBV infection and new-onset GI cancers among 93,402 participants. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset GI cancers. During a median follow-up of 13.02 years, 1,791 incident GI cancer cases were diagnosed. Compared with HBsAg seronegative participants, a significant positive association between HBV infection and GI cancers was observed in the multivariate-adjusted models (HR 5.59, 95% CI: 4.84-6.45). In the site-specific analyses, participants with HBsAg seropositive exhibited an increased risk of liver cancer (HR = 21.56, 95% CI: 17.32-26.85), gallbladder or extrahepatic bile duct cancer (HR = 14.89, 95% CI: 10.36-21.41), colorectal cancer (HR = 1.75, 95% CI: 1.15-2.96), and pancreatic cancer (HR = 1.86, 95% CI: 1.10-3.99). After taking death as the competing risk event, the associations of HBV infection with the risk of these cancers were attenuated but remained significant both in the cause-specific hazards (CS) models, the sub-distribution proportional hazards (SD) models and sensitivity analyses. This study suggests that HBV infection is associated with the elevated risk of liver cancer and extrahepatic cancer including gallbladder or extrahepatic bile duct, pancreatic, and colorectal cancer among adults in Northern China. This article is protected by copyright. All rights reserved.

Background Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. Methods This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group

Background Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil‐to‐lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. Methods This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all‐cause mortality. The association between NLR and all‐cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two‐sided P‐value. Optimal stratification was used to solve threshold points. We also evaluated the cross‐classification of NLR for each variable of survival. Results Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow‐up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%–32.0%), resulting in a rate of 226.07 events per 1000 patient‐years. An increase in NLR had an inverted L‐shaped dose–response association with all‐cause mortality. The optimal cut‐off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33–1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ‐C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. Conclusions The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Background Previous studies have observed a close association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) as well as extrahepatic cancers. However, research concerning the effect of HBV infection on the risk of colorectal cancer (CRC) is rare and inconsistent. This study aims to determine the relationship between HBV infection and new-onset CRC. Methods We prospectively examined the relationship between HBV infection and new-onset CRC among 93,390 participants from Kailuan Cohort study. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset CRC. Results During a median follow-up of 11.28 years, 448 incident CRC cases were identified. The adjusted HR (95%confidence interval (CI)) for the association of HBsAg Seropositive with CRC was 1.85(1.15 ~ 2.96) in the Cox regression. Subgroup analyses showed that the HBsAg seropositive group was associated with increased risk of new-onset CRC among male, middle-aged, normal weight, smokers and non-drinker participants, respectively. A positive association of HBV infection with the risk of CRC was observed in the adjusted sub-distribution proportional hazards (SD) models (HRSD = 1.77, 95% CI:1.11–2.84) and cause-specific hazards (CS) models (HRCS = 1.79, 95% CI: 1.13–2.91). Conclusions Our results have found a significant association between HBV infection and the risk of incident CRC among Chinese participants. Trial registration Kailuan study, ChiCTR–TNRC–11001489. Registered 24 August 2011 - Retrospectively registered, http:// http://www.chictr.org.cn/showprojen.aspx?proj=8050

Backgrounds Hand grip strength (HGS) is one of diagnose criteria factors of sarcopenia and is associated with the survival of patients with cancer. However, few studies have addressed the association of HGS and 1 year mortality of patients with cancer cachexia. Methods This cohort study included 8466 patients with malignant solid tumour from 40 clinical centres throughout China. Cachexia was diagnosed using the 2011 International cancer cachexia consensus. The hazard ratio (HR) of all cancer cachexia mortality was calculated using Cox proportional hazard regression models. Kaplan–Meier curves were generated to evaluate the association between HGS and the 1 year mortality of patients with cancer cachexia. The interaction analysis was used to explore the combined effect of low HGS and other factors on the overall survival of patients with cancer cachexia. Results Among all participants, 1434 (16.9%) patients with cancer were diagnosed with cachexia according to the 2011 International cancer cachexia consensus with a mean (SD) age of 57.75 (12.97) years, among which there were 871 (60.7%) male patients. The HGS optimal cut‐off points of male and female patients were 19.87 and 14.3 kg, respectively. Patients with cancer cachexia had lower HGS than those patients without cachexia (P

Despite the known association between muscle mass/function and malnutrition-related mortality in upper gastrointestinal (UGI) cancer, no comprehensive study to determine the impact of muscle mass-dominant nutritional status on cancer prognosis has been conducted. The present study aimed to investigate the prognostic significance of integrated muscle mass and function in UGI cancer.Between July 2013 and March 2018, we enrolled 2546 cancer patients with risks of malnutrition (Nutrition Risk Screening 2002, ≥3 points) from a multicenter cohort study and split 527 patients with primary UGI cancer into an internal validation group. We prospectively performed instant nutritional assessment and recorded all general clinical characteristics of the participants, such as weight loss, body mass index, anthropometric measurements of muscle mass and function, dietary intake conditions, and disease burden and/or inflammation status based on the validated tools. Prognostic analyses were performed with post-assessment overall survival (OS).According to the entire set, UGI cancer was identified as the dominant risk factor for disease burden and inflammation criteria (hazard ratio (HR), 2.08, 95% confidence interval (Cl), 1.81-2.39, P 0.001). Integrated muscle mass/function analysis with validated cutoff values showed that hand grip strength/weight followed by triceps skinfold thickness and maximum calf circumference are the most potent predictors. Univariate and multivariate analyses revealed that reduced muscle mass/function (74.8%) and dietary intake (66.2%) independently affect OS of patients with UGI cancer. Significant associations were found between the reduced muscle mass/reduced dietary intake and the shortest OS (HR, 4.48; 95% Cl, 3.07-6.53; P 0.001). Appending subgroups of muscle mass/function and dietary intake to the pre-existing risk model increased the efficiency of the time-dependent receiver operating characteristic curve analysis for OS in UGI cancer, particularly within 2 years of instant nutritional assessment.Impaired muscle mass/function adversely affects the near-term prognosis in patients with UGI cancer. Along with a comprehensive evaluation of dietary intake conditions, the timely nutritional assessment might be useful for risk stratification of UGI cancers with potential for enteral and parenteral nutrition interventions.ChiCTR1800020329.

Xiao-Yue Liu,1– 4,&ast; Xi Zhang,1– 3,5,&ast; Guo-Tian Ruan,1– 3 Kang-Ping Zhang,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Meng-Meng Song,1– 3 Xiao-Wei Zhang,1– 3 Yi-Zhong Ge,1– 3 Ming Yang,1– 3 Hong-Xia Xu,6 Chun-Hua Song,7 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Oncology, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4School of Clinical Medicine, Hebei University, Baoding, 071000, People’s Republic of China; 5Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 6Department of Clinical Nutrition, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 7Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaEmail shihp@ccmu.edu.cnPurpose: Serum albumin can indicate the onset of cancer cachexia, provide information about a patient’s nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia.Patients and Methods: We conducted a nested case–control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for < 1 year and 266 patients who survived for ≥ 1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates.Results: Logistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia.Conclusion: Serum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia.Keywords: nutrition, survival, death, cachectic patients

Objective: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet–lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC).Methods: A total of 1131 patients with GC (811 men and 320 women, average age: 59.45 years) were evaluated. Receiver operating characteristic curves were used to determine the best cut-off values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. Results: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.06; 95% CI: 0.95-1.18; adjusted P = 0.271). In patients with SII >1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI: 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score, the worse the OS (PConclusion: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A Higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

Guo-Tian Ruan,1– 3,&ast; Ming Yang,1– 3,&ast; Xiao-Wei Zhang,1– 3,&ast; Meng-Meng Song,1– 3 Chun-Lei Hu,1– 3 Yi-Zhong Ge,1– 3 Hai-Lun Xie,1– 3 Tong Liu,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Xi Zhang,1– 3 Kang-Ping Zhang,1– 3 Xiang-Rui Li,1– 3 Qin-Qin Li,1– 3 Yong-Bing Chen,1– 3 Kai-Ying Yu,1– 3 Ming-Hua Cong,4 Kun-Hua Wang,5 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, People’s Republic of China; 5Department of Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery and Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, People’s Republic of ChinaTel +86-10- 6392 6985Fax +86-10 -6392 6325Email shihp@ccmu.edu.cnBackground: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality.Patients and Methods: This multicenter cohort study included 746 EPCC (age > 65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria.Results: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (< 25.03) had a worse overall survival (OS) than patients with high ALI (≥ 25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590– 2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups.Conclusion: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.Keywords: ALI, systemic inflammation, cancer cachexia, elderly, overall survival

BackgroundRecently, albumin–globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia.ObjectivesThis study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis.MethodsWe recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan–Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools.ResultsThe optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose–response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia.ConclusionAGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.

Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI.Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model.Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P < 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss (P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P < 0.001).Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.

OBJECTIVES To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

Objective Malnutrition is common and related to negative prognosis in patients with gastric cancer (GC). The Global Leadership Initiative on Malnutrition (GLIM), a novel consensus for the diagnosis of malnutrition, was proposed recently. However, the roles of GLIM in diagnosing malnutrition and predicting overall survival (OS) in patients with GC have been unclear. Method We conducted a multicenter, observational cohort study including 877 hospitalized patients with GC 2013 through 2018. Different anthropometric measurements were compared to assess reduced muscle mass. Kaplan-Meier curves and multivariate Cox regression were used to analyze the relationship between GLIM-defined malnutrition and the OS of patients with GC. Independent prognostic variables were incorporated to develop a nomogram for individualized survival prediction. The calibration curve was used to determine the predictive accuracy and discriminatory capacity of the nomogram. In addition, 219 patients with GC were enrolled for external validation. Results A total of 464 (53%) patients with GC were diagnosed with malnutrition. Patients diagnosed with severe malnutrition based on either midarm circumference or body weight–standardized hand grip strength had a shorter median survival time (16.7 mo; interquartile range, 8.4–32.7 mo) and a higher hazard ratio (HR, 1.49; 95% CI, 1.15–1.92; P = 0.002). Severe malnutrition was an independent risk factor for OS (HR, 1.32; 95% CI, 1.02–1.71; P = 0.038). The GLIM nomogram showed good performance in predicting 3-y survival in patients with GC. Conclusions Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in patients with GC.

Background Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients.Patients and Methods 8,749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and Decision Curve Analysis. Kaplan-Meier survival curves were used to compare the survival rate.Results Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score Ps < 0.001).Conclusion Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, validated and shown a better predictive validity for the overall survival of cancer patients.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe3O4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe3O4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe3O4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe3O4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe3O4, Lf@GO@Fe3O4@DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe3O4 nanocomposites for therapeutic application in the treatment of gliomas.

INTRODUCTION For patients with refractory secondary hyperparathyroidism (SHPT), parathyroidectomy (PTX) has received increasing attention. However, evidence-based medicine shows that there is still controversy regarding surgical methods, efficacy, and safety. We retrospectively analyzed the process of diagnosis and treatment in one patient with severe SHPT and long-term chronic renal failure (CRF), so as to further improve the therapeutic effect. CASE PRESENTATION A 61-year-old female with SHPT and CRF manifested as no urine for 18 years, underwent PTX 4 times since September 2010, with satisfactory final recovery. The first operation involved resection of 3 parathyroid glands in the normal position; the second operation involved removal of an ectopic parathyroid gland, combined with parathyroid gland autotransplantation; the third operation was performed to resect suspected recurrent parathyroid gland; the fourth operation involved partial excision of the autotransplanted parathyroid glands. CONCLUSION Accurate preoperative localized diagnosis and optimal surgical approach play key roles in the prevention and treatment of SHPT; postoperative recurrence of SHPT caused by ectopic or autotransplanted parathyroid gland should receive more attention.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.