ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.

Drug delivery technologies are crucial components in drug development, greatly enhancing drug bioavailability and therapeutic efficacy and reducing toxic side effects. Cell membrane-based biomimetic carriers have attracted considerable interest owing to their intrinsic biointeractive capability derived from source cells in vivo. This review summarizes the fundamental properties and functional attributes of cell membrane–based biomimetic carriers from different cellular sources and discusses their advancements in tumor-targeted drug delivery and role in the activation of antitumor immunity. Ultimately, the discussion focuses on the prospects and potential challenges in employing cell membrane-based biomimetic carriers for antitumor treatment.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Bioengineering majors require students to acquire excellent abilities of thinking and analyzing complex problems and have high requirements for students' comprehensive practical skills. Because of the professional characteristics, it is necessary to develop students' abilities to solve complex problems via the teaching of a series of experiments. Therefore, it is particularly important to reform the traditional experiment teaching for students majoring in bioengineering to improve the teaching quality, which have great significance for the cultivation of comprehensive talents. In this study, with the advantages of geographical location and resources to cultivate application-oriented innovative talents, the course group of Comprehensive Experiment of Bioengineering has designed the course based on virtual simulation technology in Binzhou University. Taking the experiment of extraction and bioactivity analysis of Suaeda salsa (growing in the Yellow River Delta) polysaccharide in fermentation as a case, we studied the course design idea, experimental process, teaching method and result analysis, and have improved the teaching performance. This case analysis provides new ideas and content reference for the teaching reform of similar courses.
Bioengineering/education* ; Biomedical Engineering/education* ; Humans ; Students ; Technology ; Universities

Objective:To explore the prognostic factors predicting the recovery of elderly patients with hospital-acquired pneumonia(HAP).Methods:Data of HAP inpatients aged over 60 years in the First Affiliated Hospital of Nanjing Medical University between October 2015 and October 2020 were collected.Body mass index(BMI), neutrophil/lymphocyte rate(NLR), Charlson Comorbidity Index(CCI), Combined Comorbidity Score(CCS)and other data were retrospectively analyzed.The predictive value of the related factors was evaluated by using the Student's t test, the Logistic regression model and the receiver operating characteristic curve(ROC). Results:A total of 200 cases were enrolled in this study, and grouped into survival group(n=158)and death group(n=42). There were significant differences between the death group and the survival group in length of age, BMI hospital stay, state of consciousness, swallowing function, indwelling gastric tube, the use of proton pump inhibitors, leukocyte count, lymphocyte count, neutrophil count, hemoglobin, NLR, albumin, alanine aminotransferase, aspartate aminotransferase, D-dimer, C-reaction protein, procalcitonin(all P<0.05). Scores of CCI and CCS were higher in the death group than in the survival group[(6.79±2.86) vs.(3.42±1.98), (6.21±3.08) vs.(1.66±1.94), t=-7.193, -9.116, both P<0.001]. Multivariate Logistic analysis showed that age>86 years( OR=1.155, 95% CI: 1.014-1.316), BMI<21.77 kg/m 2( OR=0.651, 95% CI: 0.480-0.883), neutrophil count>10.10×10 9/L( OR=1.208, 95% CI: 1.025-1.422), C-reaction protein>59.32 mg/L( OR=1.055, 95% CI: 1.018-1.093), CCS>6.21 scores( OR=2.859, 95% CI: 1.559-5.244)were risk factors for death inpatients aged 60 years and older with HAP.Area under the ROC curve showed that CCS could better predict the mortality of elderly patients than CCI, and the areas under the ROC curve were 0.831(95% CI: 0.753-0.909)and 0.898(95% CI: 0.850-0.946)respectively(both P< 0.001). Conclusions:The elderly patients with HAP are inclined to multiplecomplications and high mortality rates.Combined application of multiple assessment systems and clinical indicators can improve the ability to predict the outcome of HAP.