Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

The construction of health enterprises practice the concept of big health. It is an important solution to protect the overall health of occupational groups in the new era, which is of great significance to promoting a healthy city and helping to build a healthy China. This paper clarifies the connotation of healthy enterprises in the new era, discusses the key points of healthy enterprise construction around the "four in one" construction content, "PDCA" construction procedures, and evaluation methods of healthy enterprises. It focuses on the progress of healthy enterprise construction, analyzes the problems faced by the construction of health enterprises in China, and puts forward suggestions to improve the construction efficiency, with a view to providing ideas for further promoting the construction of health enterprises in China.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.
Calibration ; Ginkgo biloba ; Least-Squares Analysis ; Medicine, Chinese Traditional ; Plant Leaves ; Quality Control ; Spectroscopy, Near-Infrared ; Tablets

Objective: To investigate the prognosis and postoperative complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A descriptive case series study was carried out. Patient inclusion criteria: (1) patients who underwent local excision by transanal endoscopic microsurgery (TEM) after nCRT; (2) magnetic resonance evaluated tumor regression grade (mrTRG) as 1, 2 after nCRT;(3) American Society of Anesthesiologists class I to III. Patient exclusion criteria: (1) with multiple primary colorectal cancers; (2) with other malignant tumors within five years; (3) with emergency surgicery indications like digestive tract obstruction, perforation or bleeding. Clinicopathological and follow-up data of rectal cancer patients with obvious tumor regression after nCRT who underwent local excision in Peking Union Medical College Hospital from January 2010 to August 2019 were retrospectively collected. Outcome measures included disease-free survival (DFS), short-term postoperative complications, and at postoperative 1-year during follow up, gas continence, fecal continence, and quality of life (using the EORTC QLQ-CR29 scale, higher score indicated worse quality of life) at postoperative 1-year. Results: A total of 40 patients were included in this study. There were 27 males and 13 females with an average age of (66.7±12.3) years. Preoperative rectal ultrasound and other imaging examinations indicated that the tumor was located in the anterior wall in 16 cases, the lateral wall in 12 cases, and the posterior wall in 12 cases. The distance between the lower margin of the tumor and the anal verge was (4.3±1.2) cm before nCRT and (5.1±0.9) cm after nCRT. According to mrTRG, 31 cases were assessed as mrTRG 1 and 9 cases as mrTRG 2. All the patients received local extended excision of rectal cancer using TEM platform. A total of 19 cases(47.5%) suffered from complications within one month postoperatively. Clavien-Dindo grade I complications happened in 14 cases, grade II in 3 patients, and grade III in 2 cases, who all were healed by conservative treatment. Except that 2 patient presented severe low anterior resection syndrome (LARS) at 1 year postoperatively, no severe anal dysfunction was found in this cohort patients. EORTC QLQ CR29 scale results for quality of life showed that at 1 year after TEM excision, except taste (Z=-1.968, P=0.049), anxiety (Z=-3.624, P<0.001) and skin irritation (Z=-2.420, P=0.023) were worse than the situation before neoadjuvant therapy, there were no statistically significant differences in other assessment results between pre-operation and post-operation (all P>0.05). Postoperative pathological results indicated complete tumor regression (pTRG0) in 17 cases, moderate remission (pTRG1) in 13, and mild remission (pTRG2) in 10. During the follow-up of (49.1±29.6) months, 3 patients had local recurrence and 4 had distant metastasis (3 patients with liver metastasis and 1 patient with lung metastasis followed by liver metastasis). No death was found and the 5-year disease-free survival (DFS) was 84.3%. Conclusions: Local excision through TEM following nCRT not only can be adopted as an important means to accurately determine complete clinical remission (cCR), but also has high therapeutic value for rectal cancer patients presenting cCR or near cCR, with little impact on defecatory function and quality of life. However, the morbidity of complication of TEM excision after nCRT is relatively high and there is a risk of recurrence and metastasis. Therefore, it is still necessary to strictly select the indications of local excision.
Aged ; Chemoradiotherapy ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Postoperative Complications ; Prognosis ; Quality of Life ; Rectal Neoplasms/therapy* ; Retrospective Studies ; Syndrome ; Treatment Outcome

Objective: To investigate whether protective colostomy and protective ileostomy have different impact on anastomotic leak for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) and radical surgery. Methods: A retrospectively cohort study was conducted. Inclusion criteria: (1) Standard neoadjuvant therapy before operation; (2) Laparoscopic rectal cancer radical resection was performed; (3) During the operation, the protective enterostomy was performed including transverse colostomy and ileostomy; (4) The patients were followed up regularly; (5) Clinical data was complete. Exclusion criteria: (1) Colostomy and radical resection of rectal cancer were not performed at the same time; (2) Intestinal anastomosis is not included in the operation, such as abdominoperineal resection; (3) Rectal cancer had distant metastasis or multiple primary colorectal cancer. Finally 208 patients were included in this study. They suffered from rectal cancer and underwent protective stoma in radical surgery after nCRT at our hospital from January 2014 to December 2018. There were 148 males and 60 females with age of (60.5±11.1) years. They were divided into protective transverse colostomy group (n=148) and protective ileostomy group (n=60). The main follow up information included whether the patient has anastomotic leak and the type of leak according to ISREC Grading standard. Besides, stoma opening time, stoma flow, postoperative hospital stay, stoma related complications and postoperative intestinal flora were also collected. Results: A total of 28 cases(13.5%) suffered from anastomotic leak and 26 (92.9%) of them happened in the early stage after surgery (less than 30 days) . As for these early-stage leak, ISREC Grade A happened in 11 cases(42.3%), grade B in 15 cases(57.7%) and no grade C occurred. There was no significant difference in the incidence [12.8% (19/148) vs. 15.0% (9/60) , χ(2)=0.171, P=0.679] or type [Grade A: 5.4%(8/147) vs. 5.1%(3/59); Grade B: 6.8%(10/147) vs. 8.5%(5/59), Z=0.019, P=1.000] of anastomotic leak between the transverse colostomy group and ileostomy group (P>0.05), as well as operation time, postoperative hospital stay, drainage tube removal time or stoma reduction time (P>0.05). There were 10 cases (6.8%) and 24 cases (40.0%) suffering from intestinal flora imbalance in protective transverse colostomy and protective ileostomy group, respectively (χ(2)=34.503, P<0.001). Five cases (8.3%) suffered from renal function injury in the protective ileostomy group, while protective colostomy had no such concern (P=0.002). The incidence of peristomal dermatitis in the protective colostomy group was significantly lower than that in the protective ileostomy group [12.8% (9/148) vs. 33.3%(20/60), χ(2)=11.722, P=0.001]. Conclusions: It is equally feasible and effective for rectal cancer patients after nCRT to carry out protective transverse colostomy or ileostomy in radical surgery. However, we should pay more attention to protective ileostomy patients, as they are at high risk of intestinal flora imbalance, renal function injury and peristomal dermatitis.
Aged ; Anastomosis, Surgical ; Anastomotic Leak/prevention & control* ; Cohort Studies ; Colostomy ; Female ; Humans ; Ileostomy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective::To investigate the effect of serum containing Yanghetang (YHT) on the apoptosis of MCF-7 cells in breast cancer based on the mitogen-activated protein kinase (p38)/signal transduction and transcriptional activator 3 (STAT3) signal pathway. Method::YHT liquid with crude drug 1 g·mL^-1 was prepared. Female SD rats were randomly divided into control group (distilled water), and high, medium and low-dose YHT groups (24, 12, 6 g·kg^-1). YHT-medicated serum was prepared, and 10%medicated serum was used to intervene MCF-7 cells. Cell proliferation and cytotoxicity assay (CCK-8) was used to detect the effect of serum containing YHT on MCF-7 cell proliferation, apoptosis of MCF-7 cells was detected by flow cytometry protein expressions of p38 and STAT3 were detected by Western blot, Quantitative Real-time PCR (Real-time PCR) was used to detect the expressions of B-cell lymphoma/leukemia-xl(Bcl-xl) and Survivin mRNA. Result::CCK-8 assay showed that YHT serum inhibited the proliferation of MCF-7 cells in a time and dose-dependent manner compared with the blank group. The inhibitory effect was most obvious in the high-dose group, with the inhibition rates of 38%, 45%and 54%at different time points (P<0.01). Flow cytometry showed that, compared with the blank group, the apoptosis rate in the medium and high-dose groups increased significantly in a dose-dependent manner, with the apoptosis rates at 11.6%and 16.5%respectively (P<0.05, P<0.01). Western blot analysis showed that, compared with the blank group, the expressions of p38 and STAT3 protein was decreased in high, medium-dose YHT groups (P<0.01) in a dose-dependent manner. Compared with the blank group, the expressions of Bcl-xl and Survivin mRNA were decreased in high, medium-dose YHT groups (P<0.05, P<0.01) in a dose-dependent manner. Conclusion::YHT serum can promote the apoptosis of MCF-7 cells in breast cancer, which may be related to the p38/ STAT3 signaling pathway.