Astrocytes are heavily activated in Alzheimer's disease,engulfing damaged synapses,Aβ proteins,Tau proteins,apoptotic cells and other substrates.However,these substrates are difficult to degrade,accumulate as the disease progresses,and impair the phagocytosis of astrocytes.During phagocytosis,astrocytes recognize different substrates through a variety of phagocytosis receptors and partially degrade the substrates through degrad-ing enzymes and lysosomal pathways.The accumulation of Aβ and Tau proteins in astrocytes caused astrocyte im-mune and metabolic disorders,and Aβ toxicity changed after phagocytosis.In addition,astrocytes and microglia form a complementary pattern and cooperate to complete phagocytosis through interaction.Regulating the pathway of astrocyte phagocytosis and degradation is believed to be a potential novo therapeutic for clinical treatment of Alzheimer's disease.

ObjectiveTo explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia （FD） based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 2 （ROCK2）/Myosin phosphatase target Subunit 1 （MYPT1） pathway. MethodSixty male SD suckling rats in SPF grades were randomly divided into blank group （n=10） and model group （n=50）. The comprehensive modeling method （gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety） was used to replicate the rat model of FD. After successful replication of the model， the rats in the model group were randomly divided into model group， mosapride group， and high， middle， and low-dose Xiangsha Liujunzi Tang groups， with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg^-1·d^-1 normal saline， those in the mosapride group were given 1.35 mg·kg^-1·d^-1 mosapride， and those in the high， middle， and low-dose Xiangsha Liujunzi Tang groups were given 12， 6， and 3 g·kg^-1·d^-1 Xiangsha Liujunzi Tang， respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration， and the 3-hour food intake and body mass of rats were measured. After intervention， the intestinal propulsion rate of rats was measured， and the pathological changes in the gastric tissue were observed by hematoxylin-eosin （HE） staining. The content of choline acetyl transferase （ChAT） and vasoactive intestinal peptide （VIP） in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay （ELISA）， the distribution of adenosine triphosphate （ATP） enzyme in gastric antrum smooth muscle was observed by frozen section staining， and the protein expression levels of RhoA， ROCK2， and phosphorylated-myosin phosphatase target subunit 1 （p-MYPT1） in the gastric tissue were detected by Western blot. ResultCompared with the blank group， the model group had withered hair， lazy movement， slow action， poor general living condition， lower 3-hour food intake， body mass， and lower intestinal propulsion rate （P<0.05）， whereas no obvious abnormality in gastric histopathology. In the model group， the content of ChAT in the medulla oblongata and gastric tissue decreased， the content of VIP in gastric tissue increased， the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue decreased significantly （P<0.05）. As compared with the model group， the general living condition of rats in each intervention group was significantly improved， and the 3-hour food intake， body mass， and intestinal propulsion rate were significantly increased （P<0.05）. There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly， the content of VIP in the gastric tissue decreased， the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue increased significantly （P<0.05）. The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent. ConclusionXiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD， and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective To evaluate the influence of stress distributions on bone-anchored maxillary protraction at different protraction sites, so as to guide patients to choose an optimal protraction site in clinic. Methods A three-dimensional (3D) finite element model of child head with implant anchorages was establised. Four protraction sites were set according to the position of implant installation. Working condition 1: the alveolar bone at the intersection of distal 2 mm of primary lateral incisor crown distal surface and gingival cervical margin to 5 mm. Working condition 2: the alveolar bone at the intersection of mesial 2 mm of maxillary first primary molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 3: the alveolar bone at the intersection of mesial 2 mm of maxillary first molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 4: the alveolar bone at the intersection of distal 2 mm of maxillary first molar crown distal surface and gingival cervical margin to 5 mm. The finite element models were loaded with 500 g protraction force at each side with 30° forward direction to the occlusal plane. Stress distributions on each suture were analysed. Results The maximum stress of frontomaxillary suture was in working condition 2 (1 477-28 190 Pa). The maximum stress of nasomaxillary suture was in working condition 1 (5.296-924 Pa). The maximum stress of zygomaticomaxillary suture was in working condition 4(394.7-13 130 Pa). The maximum stress of zygomaticofrontalis suture was in working condition 4 (495.2-31 690 Pa). The maximum stress of zygomaticotemporal suture was in working condition 3 (1 148-15 870 Pa). The maximum stress of medianpalatine suture was in working condition I (6.479-730 Pa). Conclusions When the protraction sites are set in distal maxillary primary lateral incisor and mesial maxillary first primary molar, it is of positive significance to improve the concave profile, especially in nose root. When the protraction sites are set in mesial or distal maxillary first molar, it is of positive significance to improve the concave profile, especially in maxillary basal bone of the midface.

Objective To investigate the effect of Kunxian capsule combined with candesartan axetil on blood pressure, renal function, blood lipids and inflammatory factors in patients with chronic glomerulonephritis complicated with hypertension. Methods 101 patients with chronic glomerulonephritis who were admitted to our hospital from November 2017 to December 2019 were selected and randomly divided into observation group (51 cases) and control group (50 cases). The control group was treated with candesartan cilexetil on the basis of conventional treatment, and the observation group was treated with Kunxian capsule on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the blood pressure, renal function indexes (24 h Upro, BUN, Scr), blood lipid indexes (TG, TC, LDL-C), and inflammatory factors of the two groups (IL-6, hs-CRP) significantly decreased, and the observation group was significantly lower than the control group (P<0.05). After treatment, the blood lipid index HDL-C of the two groups increased significantly, and the blood lipid index HDL-C of the observation group was significantly higher than that of the control group (P<0.05). Conclusion Kunxian capsule combined with candesartan axetil can enhance the clinical efficacy, improve renal function, regulate blood lipids and reduce inflammation in patients with chronic glomerulonephritis complicated with hypertension.

Cutinase can degrade aliphatic and aromatic polyesters, as well as polyethylene terephthalate. Lack of commercially available cutinase calls for development of cost-effective production of efficient cutinase. In this study, eight cutinase genes were cloned from Sclerotinia sclerotiorum. The most active gene SsCut-52 was obtained by PCR combined with RT-PCR, expressed in Escherichia coli BL21 and purified by Ni-NTA affinity chromatography to study its characteristics and pathogenicity. Sscut-52 had a total length of 768 bp and 17 signal peptides at the N terminals. Phylogenetic analysis showed that its amino acid sequence had the highest homology with Botrytis keratinase cutinase and was closely related to Rutstroemia cutinase. Sscut-52 was highly expressed during the process of infecting plants by Sclerotinia sclerotiorum. Moreover, the expression level of Sscut-52 was higher than those of other cutinase genes in the process of sclerotia formation from mycelium. The heterologously expressed cutinase existed in the form of inclusion body. The renatured SsCut-52 was active at pH 4.0-10.0, and mostly active at pH 6.0, with a specific activity of 3.45 U/mg achieved. The optimum temperature of SsCut-52 was 20-30 ℃, and less than 60% of the activity could be retained at temperatures higher than 50 ℃. Plant leaf infection showed that SsCut-52 may promote the infection of Banlangen leaves by Sclerotinia sclerotiorum.
Ascomycota/genetics* ; Carboxylic Ester Hydrolases ; Cloning, Molecular ; Phylogeny

Objective:To investigate the colonscopy screening interval among patients with negative colonscopy.Methods:We selected 14 606 participants who completed the baseline and 3-year or 5-year colonoscopy examinations in the American Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset as the target population. Sociodemographic characteristics (i.e., sex, age, marital status, race, and smoking), lifestyle, family history of cancer, and family history of colorectal cancer were collected. Cochran-Armitage trend analysis was used to examine whether the rate of positive cases (colorectal cancer, advanced adenoma, adenoma, and hyperplastic polyp) was increased with the length of screening interval. We compared the differences in number of detected cases, positive rates, and proportions of 3-year and 5-year screening interval strategies using internal standardization method.Results:The age of the population was （61.9±5.2） years and over half of them were males (54.4%) and 46.2% had family cancer history. The mean screening interval between the first and second endoscopies was （1 639.1±320.9） days. A total of 1 716 cases had positive endoscopic findings. With the screening interval extended, rate of the screened positive cases was also increased ( P for trend<0.001). After standardized by the internal standardized population (14 606), 17.99 and 11.57 colorectal cancer cases and 177.37 and 240.35 advanced adenoma cases were detected by 3-year and 5-year screening interval strategies, respectively. Conclusion:Based on the initial screening negative population of colonoscopy in the United States, the 3-year screening interval strategy could detect a relatively large number of colorectal cancer cases, but its health and economic evaluation needs to be further explored.

Objective:To investigate the colonscopy screening interval among patients with negative colonscopy.Methods:We selected 14 606 participants who completed the baseline and 3-year or 5-year colonoscopy examinations in the American Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset as the target population. Sociodemographic characteristics (i.e., sex, age, marital status, race, and smoking), lifestyle, family history of cancer, and family history of colorectal cancer were collected. Cochran-Armitage trend analysis was used to examine whether the rate of positive cases (colorectal cancer, advanced adenoma, adenoma, and hyperplastic polyp) was increased with the length of screening interval. We compared the differences in number of detected cases, positive rates, and proportions of 3-year and 5-year screening interval strategies using internal standardization method.Results:The age of the population was （61.9±5.2） years and over half of them were males (54.4%) and 46.2% had family cancer history. The mean screening interval between the first and second endoscopies was （1 639.1±320.9） days. A total of 1 716 cases had positive endoscopic findings. With the screening interval extended, rate of the screened positive cases was also increased ( P for trend<0.001). After standardized by the internal standardized population (14 606), 17.99 and 11.57 colorectal cancer cases and 177.37 and 240.35 advanced adenoma cases were detected by 3-year and 5-year screening interval strategies, respectively. Conclusion:Based on the initial screening negative population of colonoscopy in the United States, the 3-year screening interval strategy could detect a relatively large number of colorectal cancer cases, but its health and economic evaluation needs to be further explored.

Objective:To observe the application effect of single disease nursing pathway intervention in patients with maintenance hemodialysis.Methods:Using the convenient sampling method, a total of 128 patients who underwent MHD treatment in Beijing Friendship Hospital of Capital Medical University from June 2018 to June 2019 were selected. They were divided into the single disease nursing group and routine nursing group by random number table method, with 64 cases in each group. The routine nursing group was given routine MHD nursing intervention. On the basis of routine nursing intervention and based on clinical nursing pathway, the single-disease nursing intervention group formulated the single-disease nursing pathway for the first-time dialysis patients, interdialytic patients and maintenance dialysis patients for nursing intervention. After 6 months of intervention, mastery of dialysis knowledge, complication rate and dialysis tolerance were compared between two groups.Results:The scores of five aspects of diet principles, functional exercise, medication principles, acute and chronic complications, internal fistulas and venous catheterization in the single-disease nursing group and the total score of dialysis knowledge were all higher than those of the routine nursing group. The incidence of bleeding, thrombosis and overall complications in the single-disease nursing group were lower than those in the routine nursing group. The scores of kidney disease-targeted assessment, quality of life assessment and total score of dialysis quality of life questionnaire for patients in the single-disease nursing group were higher than those of the routine nursing group. All differences were statistically significant ( P<0.05) . Conclusions:Single-disease nursing pathway intervention can improve the knowledge of dialysis in MHD patients, reduce the incidence of complications and improve the tolerance of patients with dialysis.

Three hundred and nine patients with thyroid nodules detected by physical examination in Harrison International Peace Hospital from October 2013 to October 2017 were divided into intervention group (155 cases) and control group (154 cases). Patients in intervention group received oral levothyroxine sodium 25 g / d for 12 months and those in control group had no treatment, patients were followed up every 3 months to 12 months. After treatment, the maximum diameter and thyroid nodule volume of the intervention group were (31.87±3.84) mm and (17.32±0.94) cm3, which were significantly smaller than those of the control group [(34.01±3.72) mm and (24.25±1.21)cm3, P<0.05]. TSH in intervention group was lower than that in control group [(2.24±0.41) vs. (2.52±0.58) mIU/L, P<0.05] and free T4 (FT4) was higher than that in control group [(25.64 ± 3.85) vs. (16.39 ± 3.28) pmol/ L, P<0.05]. TC, TG and LDL?C in intervention group, were lower than those in the control group .The HDL?C level in intervention group was higher than that in control group (all P<0.05). After treatment, there were no malignant changes in the intervention group, while the malignant change rate in control group was 2.6％ (4/154). It is suggested that levothyroxine treatment can reduce TSH level in patients with benign thyroid nodules, inhibit the growth of thyroid nodules.