Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

OBJECTIVETo study the effects of Tianwang Buxinwan decoction on the contents of amino acids neurotransmitters in corpus striatum of rats to implicate the mechanism of Tianwang Buxinwan promoting and Improving sleeping.

METHODContents of two amino acids neurotransmitters in corpus striatum of rats were prepared by microdialysis technology and were determined by HPLC which involved pre-column derivation with orthophthaladehyde, recersed-phase gradient elution and fluorescence detection.

RESULTIn the experimental separation condition, Tianwang Buxinwan seemed do not influence three kinds of contents of amino acids neurotransmiters (glutamic acid, glycin, aspartic acid), but TBW seemed increase the content of gamma-GABA in corpus striatum of rats.

CONCLUSIONThe effects of Tianwang Buxinwan to relieve uneasiness may relate with the inhibitory amino acids gamma-GABA. Tianwang Buxinwan may promote increasing the content of gamma-GABA. This discovery may be helpful for the deep study of related mechanism of Tianwang Buxinwan.

Animals ; Brain ; drug effects ; metabolism ; Brain Chemistry ; Drugs, Chinese Herbal ; administration & dosage ; Male ; Microdialysis ; Neurotransmitter Agents ; antagonists & inhibitors ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To analyze related factors affecting the prognosis of patients with Acinetobacter baumannii (A.baumannii)bloodstream infection(BSI),guide clinical prevention and treatment.Methods A case-control study was conducted to retrospectively analyze patients with A.baumannii BSI in Peking University Third Hospital from January 2012 to December 2016.According to prognosis,patients were dividedinto poor prognosis group and good prognosis group. Univariate analysis and logistic regression analysis were used to analyze the risk factors of poor prognosis in patients with A.baumannii BSI.Results There were 58 confirmed cases of A.baumannii BSI,including 31 patients with poor prognosis and 27 with good prognosis. Univariate analysis revealed that risk factors for poor prognosis of A.baumannii BSI were antimicrobial use and at least two kinds of antimicrobial agent use three months before admission,at least two kinds of antimicrobial use,and carbapenems use before infection after admission,increase of white blood cell(WBC)count after infection(P<0.05). After 3-day anti-infective treat-ment,examination results of WBC count and X-ray chest film in good prognosis group were all better than poor prognosis group(P<0.05). Logistic multivariate regression analysis showed that independent risk factors for poor prognosis of A.bau m annii BSI were antimicrobial use three months before admission,at least three kinds of antimicrobial use and carbapenem use before infection after admission,increase of WBC count and WBC count>12×109/L after infec-tion,as well as increase of WBC count and WBC count>15×109/L after 3-day anti-infective treatment(P<0.05). Conclusion The probability of poor prognosis is high in patients with A.baumannii infection. For patients receiv-ing≥2 kinds of antimicrobial agents three months before admission,patients receiving≥3 kinds of antimicrobial agents as well as patients receiving carbapenems before infection after admission,the likelihood of A.baumannii BSI should be paid attention.For patients with WBC count>12×109/L after infection and WBC count>15×109/L after 3-day treatment,poor prognosis should be alerted,treatment plan needs to be adjusted in time to reduce the mortality.

Objective:To retrospectively compare the clinical efficacy of two PDE3 inhibitors, oplinone and Milrinone, in order to evaluate which drug has better effects on the improvement of cardiac function, protection of renal function and adverse effects of arrhythmia.Methods:A total of 41 neonates with congenital heart disease after biventricular treatment under cardiopulmonary bypass in the Department of Cardiothoracic Surgery at Soochow University Children's Hospital during 2018-2022 were collected. The experimental group was divided into two groups: Oprilinone(25 cases) and Milinone(16 cases). A retrospective study was conducted on the incidence of renal function, cardiac function improvement and arrhythmia in the children.Results:On the first day after operation, EF in both groups decreased significantly compared with that before operation( P<0.01); On day 4 after surgery, EF in the oprilinone group was significantly higher than that on day 1 after surgery( P<0.01), Milrinone group was slightly higher than that on day 1 after surgery( P<0.05), and EF in oprilinone group was significantly higher than that in Milinone group during the same period( P<0.01); EF in Milinone group continued to increase on day 7 compared with day 4( P<0.01), but there was no significant difference between the two groups. Long-term follow-up showed that there was no significant difference in EF value in the oprilinone intervention group on day 7 after surgery( P<0.05), and the long-term EF in Milinone group was higher than that at 7 days after surgery( P<0.05). The creatinine level in the oprinone intervention group continued to decrease on the 4th and 7th day after surgery( P<0.01; P<0.05); The creatinine level of Milinone group on day 4 after surgery was significantly lower than that on day 1 after surgery( P<0.01), the decrease was not significant on the 7th day after surgery compared with the 4th day after surgery; The creatinine level in the oprilinone group was lower than that in the Milrinone group on day 7 after surgery( P<0.05). The rate of arrhythmia in children was slightly decreased in the intervention group of olplinone. There was no change in the Milinone group. Conclusion:Oplinone improved cardiac function better than Milrinone, and the recovery time to normal cardiac function was shorter. In terms of renal function protection, oplinone was stronger than Milrinone, and the protective effect of oplinone on kidney lasted longer. No significant abnormalities were found with respect to adverse reactions, such as the incidence of arrhythmia.

Objective: To investigate the imaging features and etiology of lymphatic trunk in primary facial lymphedema. Methods: 26 patients with primary facial lymphedema patients (F/M, 13/13, ages 21.8 ± 13.9 years old) were recruited from January 2015 to October 2017 in this study, with 32 sides facial lymphedema reported, including 6 right facial lymphedema, 14 left facial lymphedema, and 6 bilateral facial lymphedema. And all the patient data and imaging were retrospective analysis to summarize the MR imaging features of thoracic duct and right lymphatic duct, meanwhile compared with surgical results. Results: For all 26 patients, MR imaging result in thoracic duct manifests 32 lymphatic duct, including 20 thoracic duct and 12 right lymphatic duct. The imaging features demonstrate two typical findings: dilated(13 cases) and slim(7 cases) demonstrations. While for right lymphatic duct, the MR result included three types: dilated(6 cases), slim(4 cases) and no sign of manifestations(2 cases). In surgery, the thoracic duct in cervical segment demonstrated abnormal structures, including capsulated by fibrous tissues in peripheral area(30 sides), surrounded by internal jugular vein sheath(11 sides), external pressed by venae cervicalis transversa(5 sides) and lymphatic trunk dysplasia(2 sides). Conclusions MR thoracic duct and right lymphatic duct imaging can be used as an effective diagnostic imaging method for primary facial lymphedema, and the structural anomaly of the upper cervical catheter and the right lymphatic catheter may be one of the pathogenic factors of primary facial lymphedema.

Objective To evaluate the relationship between the changes of diffusion tensor imaging(DTI)and the clinical stages in patients with cerebral infarction. Methods One hundred and seven patients with cerebral infarction were chosen to perform conventional MRI and DTI,respectively.With double-blind method,the signal intensity of fractional anisotropy(FA)and isotropic apparent diffusion coefficient(ADCiso)in responsible to infraction regions was observed and based on their results,the relationships between the changes of DTI and the clinical stages were analyzed. Results In 29 cases of cerebral infarction in acute stage,10 were manifested as type I(hypointensity on ADCiso map,hyperintensity on FA map)and type Ⅱ(hypointensity on ADCiso map and FA map with hyper intensive circumference)on DTI;3 were manifested as type Ⅲ on DTI(iso-/Paypo-intensity on ADCiso map and FA map with normal circumference);6 were manifested as type Ⅳ on DTI(hyperintensity on ADCiso map,hypointensity on FA map).In 34 cases of cerebral infarction in sub-acute stage,2 were manifested astype Ⅰ on DTI;20 were manifested astype Ⅱ;8 were manifested as type Ⅲ and 4 were manifested as type IV.In 44 cases of cerebral infarction chronic stage.1 Was manifested as type Ⅱ on DTI;2 were manifested as type Ⅲ and 41 were manifested as type IV.Positive correlation was found between changes of DTI and clinical stages(r=0.693,P=0.000). Conclusion The intensity of infraction on DTI can directly demonstrate the clinical stages,providing precise evidence for classifying the stages of cerebral infarction.

OBJECTIVETo investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC).

METHODSA total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared.

RESULTSFor prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC.

CONCLUSIONIPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.

Adult ; Aged ; Chemotherapy, Cancer, Regional Perfusion ; methods ; Female ; Follow-Up Studies ; Humans ; Hyperthermia, Induced ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Peritoneal Neoplasms ; drug therapy ; secondary ; Prognosis ; Stomach Neoplasms ; drug therapy ; mortality ; pathology ; Survival Rate ; Treatment Outcome

BACKGROUNDChronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.

METHODSA multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed.

RESULTSAmong the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients.

CONCLUSIONSThis large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; epidemiology ; Risk Factors ; Smoking ; Spirometry ; Surveys and Questionnaires