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 examine the clinical characteristics and abnormal reflux branches of primary isolated chylopericardium.Methods:Totally 43 patients with primary isolated chylopericardium at Department of Lymphatic Surgery, Affiliated Beijing Shijitan Hospital,Capital Medical University from June 2007 to January 2018 were recruited in this study. There were 21 males and 22 females, aging (23.0±15.9) years (range: 2 to 57 years). The levels of triglyceride, total cholesterol, total protein and albumin in pericardial effusion and blood were compared by paired- t test, and the characteristics of lymphatic system in direct lymphangiography and postoperative CT were analyzed. Results:Pericardial effusion was mainly milky white and monocytes, and 95.3%(41/43) were positive for Rivalta test. The level of triglyceride in pericardial effusion was significantly higher than that of blood ((9.67±5.11) mmol/L vs. (1.28±0.89) mmol/L, t=10.557, P<0.01), and the levels of total cholesterol ((2.19±0.52) mmol/L vs. (4.12±1.06) mmol/L, t=-3.732, P<0.01), total protein ((61.25±16.17) g/L vs. (68.26±8.30) g/L, t=-2.958, P=0.005) and albumin ((36.63±7.06) g/L vs. (42.32±4.73) g/L, t=-5.747, P<0.01) were significantly lower than that of blood. In the direct lymphangiography, the imaging of iliac and retroperitoneal lymphatics showed dilated or tortuous in 90.7% (39/43), the thoracoabdominal segment of thoracic duct showed dilation in 46.5% (20/43), and cervical thoracic duct imaging showed dilation in 44.2% (19/43) and stenosis in 55.8% (24/43). The image of lipiodol flowing into the vein showed obstruction at the venous angle. There were 60.5%(26/43) of the patients with lipiodol reflux through the bronchomediastinal trunk (type Ⅰ), 11.6%(5/43) with lipiodol diffusion to the pericardium through the abnormal pathway from the thoracic segment of the thoracic duct (type Ⅱ), while no communication pathway between the thoracic duct and the pericardial cavity (type Ⅲ) found in 27.9%(12/43). CT images obtained after the direct lymphangiography showed 34.9%(15/43) had abnormal distribution of lipiodol in pericardium, mediastinal lymph nodes and lung hilar lymph nodes, 46.5%(20/43) in mediastinal lymph nodes and lung hilar lymph nodes, 14.0%(6/43) only mediastinal lymph nodes, 4.6%(2/43) had no lipiodol in the above areas. Conclusions:Pericardial effusion compared with same period blood, has higher triglyceride, lower total cholesterol, total protein and albumin. The obstruction of the cervical segment of the thoracic duct and the formation of abnormal reflux branches would be corelative to primary isolated chylopericardium.

Objective:To examine the clinical characteristics and abnormal reflux branches of primary isolated chylopericardium.Methods:Totally 43 patients with primary isolated chylopericardium at Department of Lymphatic Surgery, Affiliated Beijing Shijitan Hospital,Capital Medical University from June 2007 to January 2018 were recruited in this study. There were 21 males and 22 females, aging (23.0±15.9) years (range: 2 to 57 years). The levels of triglyceride, total cholesterol, total protein and albumin in pericardial effusion and blood were compared by paired- t test, and the characteristics of lymphatic system in direct lymphangiography and postoperative CT were analyzed. Results:Pericardial effusion was mainly milky white and monocytes, and 95.3%(41/43) were positive for Rivalta test. The level of triglyceride in pericardial effusion was significantly higher than that of blood ((9.67±5.11) mmol/L vs. (1.28±0.89) mmol/L, t=10.557, P<0.01), and the levels of total cholesterol ((2.19±0.52) mmol/L vs. (4.12±1.06) mmol/L, t=-3.732, P<0.01), total protein ((61.25±16.17) g/L vs. (68.26±8.30) g/L, t=-2.958, P=0.005) and albumin ((36.63±7.06) g/L vs. (42.32±4.73) g/L, t=-5.747, P<0.01) were significantly lower than that of blood. In the direct lymphangiography, the imaging of iliac and retroperitoneal lymphatics showed dilated or tortuous in 90.7% (39/43), the thoracoabdominal segment of thoracic duct showed dilation in 46.5% (20/43), and cervical thoracic duct imaging showed dilation in 44.2% (19/43) and stenosis in 55.8% (24/43). The image of lipiodol flowing into the vein showed obstruction at the venous angle. There were 60.5%(26/43) of the patients with lipiodol reflux through the bronchomediastinal trunk (type Ⅰ), 11.6%(5/43) with lipiodol diffusion to the pericardium through the abnormal pathway from the thoracic segment of the thoracic duct (type Ⅱ), while no communication pathway between the thoracic duct and the pericardial cavity (type Ⅲ) found in 27.9%(12/43). CT images obtained after the direct lymphangiography showed 34.9%(15/43) had abnormal distribution of lipiodol in pericardium, mediastinal lymph nodes and lung hilar lymph nodes, 46.5%(20/43) in mediastinal lymph nodes and lung hilar lymph nodes, 14.0%(6/43) only mediastinal lymph nodes, 4.6%(2/43) had no lipiodol in the above areas. Conclusions:Pericardial effusion compared with same period blood, has higher triglyceride, lower total cholesterol, total protein and albumin. The obstruction of the cervical segment of the thoracic duct and the formation of abnormal reflux branches would be corelative to primary isolated chylopericardium.

Objective:To investigate the characteristics, diagnosis and therapeutic effect of acquired lymphangiectasia of the vulva (ALV).Methods:A retrospective analysis of clinicopathological and follow-up data was conducted on the patients treated in Capital Medical University Affiliated Beijing Shijitan Hospital due to female ALV from July 2009 to July 2023. The patients who completed the staged operations [partial labiectomy and reconstruction + thoracic ductplasty and (or) perineal lymphovenous anastomosis] were included in the study and followed up. The improvement of perineal swelling, blister range, fluid leakage volume and frequency were evaluated through outpatient visits by the symptom rating scale of ALV (hereinafter referred to as the symptom rating scale) before and after surgery.Results:A total of 48 patients were treated due to ALV from July 2009 to July 2023, of which 98% (47/48) were postoperative pelvic malignant tumors and 94% (45/48) had a history of radiotherapy. A total of 10 patients with ALV who completed the staged operations were included in this study. (1) Clinical characteristics and diagnosis: 10 patients had a median age of 60 years old (50, 63 years old ). The median duration from cervical cancer surgery and radiation therapy to vulvar swelling was 1.5 years (0.0, 2.0 years), and the median duration from vulvar swelling to blister formation and leakage was 0.0 years (0.0, 4.8 years). Seven patients (7/10) had a history of recurrent erysipelas; 7 patients (7/10) had the most severe symptom (widespread blisters, persistent fluid leakage, and large amount of fluid leakage); noncontrast magnetic resonance lymphography (NCMRL) showed edema signals in the perineal region of all the patients, and increase of agent in the perineal region was observed in lymphoscintigram (LS). (2) Surgical treatment and postoperative pathological examination: of the 10 ALV patients who completed staged surgical treatment, 6 cases (6/10) were diagnosed with thoracic duct outlet obstruction and underwent thoracic ductplasty and partial labiectomy and reconstruction. Perineal lymphovenous anastomosis and partial labiectomy and reconstruction were performed in 4 cases (4/10) without thoracic duct outlet obstruction. Postoperative routine pathological examination of 10 patients (10/10) showed dermal papilla lymphangiectasia. Immunohistochemical tests were performed on 5 patients, all of which were positive for D2-40 and negative for CD 34. (3) Efficacy: 8 patients completed the postoperative follow-up, and the median follow-up time was 31.0 months (17.5, 78.3 months). The perineal swelling and the blister fluid leakage were all significantly improved after the staged operations. All indexes of the symptom rating scale, including the degree of perineal swelling, blister range, fluid leakage volume and frequency, were significantly improved in 8 follow-up patients, and 3 (3/8) of them were cured; the median symptom score decreased significantly from 11.0 before surgery to 3.0 after surgery ( P<0.001). The incidence of erysipelas was significantly reduced from 7/10 before surgery to 2/8 after surgery ( P=0.035). Conclusions:The main causes of female ALV are pelvic tumor surgery and radiotherapy. The clinical diagnosis is made from relevant medical history, clinical manifestations, LS and magnetic resonance imaging. The diagnosis is confirmed by histopathological findings. Pathological results show lymphangiectasia in the dermal papilla, and immunohistochemical staining show positive for D2-40 and negative for CD 34. The effect of staged surgery on ALV is remarkable and even cured, and could effectively reduce the incidence of erysipelas.