Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

Objective:To investigate the predictive value of differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on the therapeutic response to 131I treatment in patients with papillary thyroid cancer (PTC). Methods:A retrospective study was conducted on 46 PTC patients (16 males, 30 females, age 20-77 years) who underwent total thyroidectomy and received 131I treatment between January 2021 and August 2021 in First Hospital of Shanxi Medical University. Peripheral blood lymphocyte subsets (T, B, CD4 + T, CD8 + T, natural killer (NK), helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells) were measured 1-2 d before and 30 d after 131I treatment. Based on serological and imaging evidence, therapeutic response at 6-12 months post- 131I therapy was categorized as either excellent response (ER) or non-excellent response (NER). Differences of preablative stimulated thyroglobulin (psTg) and clinical baseline characteristics between two groups were assessed by using independent-sample t test, paired t test, or Mann-Whitney U test. Predictive value of lymphocyte subsets before and after 131I treatment for therapeutic response was assessed through logistic regression analysis, ROC curve analysis, and decision curve analysis (DCA). Results:In ER group ( n=33) and NER group ( n=13), most lymphocyte subsets showed different degrees of reduction 30 d after 131I treatment compared to before 131I treatment, such as T, B, CD4 + T and Th1 cells in ER group, as well as T, B, CD4 + T, Th1, Th2, Th17, and Treg cells in NER group ( t values: 2.41-9.57, all P<0.05). Before 131I treatment, NER group had significantly higher levels of psTg, Th2, Th17, and Treg cells compared to the ER group ( t values: from -3.32 to -2.48, U=29.00, all P<0.05). After 131I treatment, most of lymphocyte subsets in NER group (T, B, CD4 + T, CD8 + T, Th1 and Treg cells) showed higher trend than those in ER group but without statistical significances ( t values: from -1.12 to -0.06, all P>0.05). Th2 cells before 131I treatment (odds ratio ( OR)=25.00, 95% CI: 1.36-459.10, P=0.030) was identified as a risk factor for NER. ROC curve analysis indicated that AUCs of psTg and Th2 cells for predicting therapeutic response were 0.932 and 0.790, respectively, which was 0.958 for the combined psTg and Th2 cells. DCA showed that within the threshold probability range of 10%-60%, the curves for psTg, Th2 cells, and the combined psTg and Th2 cells were all higher than the extreme curve, suggesting good effect. Conclusions:Most lymphocyte subsets decrease to varying degrees, and NER group shows a significant decrease 30 d after 131I treatment. Th2 cells may be a risk factor for poor response to 131I treatment, providing a certain value in predicting the therapeutic response to 131I treatment.

Humans ; Mesothelioma/pathology* ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis* ; Pleural Effusion, Malignant ; Pleural Effusion/pathology*

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

Animals ; Cardiomegaly ; Constriction ; Heart ; Mice

Objective: To investigate the efficacy and safety of Rivaroxaban for elderly patients with thrombotic diseases. Methods: This was a retrospective study.A total of 301 elderly patients taking Rivaroxaban from October 2012 to November 2017 at the Second Medical Center of the Chinese PLA General Hospital were consecutively selected.The ages ranged from 60 to 102 years, with an average age of(86.5±8.4)years.Anticoagulation regimens were developed based on comprehensive evaluation of indications, creatinine clearance, ischemia and bleeding risk.Patients were divided into a Rivaroxaban 2.5-5.0 mg/d group(n=72), a 10.0 mg/d group(n=205), and a 15.0-20.0 mg/d group(n=24). Hepatic function, renal function, and coagulation indexes were measured before and after the administration of Rivaroxaban.Fatal bleeding, cardiovascular deaths, all-cause deaths, non-fatal bleeding and thromboembolic events were recorded during the follow-up period. Results: The average dose of Rivaroxaban was(9.3±3.0)mg/d, and the minimum dose was 2.5 mg/d.The average follow-up time was(14.9± 13.9)months and the longest follow-up time was 48 months.One patient had intracranial bleeding.Twenty patients(6.6%)died with a cumulative incidence of 25.2%, three(1.0%)died of cardiac events, and 55.0% died of pneumonia and multiple organ failure.Forty patients(13.3%)had non-fatal hemorrhagic events with a cumulative incidence of 42.4%.Seven patients(2.3%)had thromboembolic events with a cumulative incidence of 16.0%, including 2 cases of non-fatal myocardial infarction, 3 cases of cerebral infarction and 2 cases of deep vein thrombosis.After treatment, levels of prothrombin time and fibrinogen significantly increased while levels of D-dimer significantly deceased(P<0.05). Conclusions Compared with previous reports, low-dose Rivaroxaban is safe and effective for elderly patients with thrombotic diseases.However, the risk of bleeding and ischemia should be comprehensively evaluated, and appropriate doses of Rivaroxaban should be selected individually.

Objective:To evaluate the outcomes of immediate rehabilitation of the edentulous and potential edentulous jaws with implant-supported full-arch prostheses and analyse the risk factors of the complications.Methods:This retrospective study included 273 patients treated with immediate rehabilitation of the edentulous and potential edentulous jaws with implant-supported full-arch prostheses from April 2008 to December 2018 in Department of Implantology, Peking University School and Hospital of Stomatology. The patients′ sex, age, place of residence, jaw position, opposing dentition, number of implants, diameter and length of implants, abutment height and abutment angle were recorded. The survival rate of implants and marginal bone loss were calculated and analyzed. Cox proportional hazards ratio model was adopted to analyze the potential risk factors of prosthetic complications.Results:A total of 225 patients (288 jaws) and 1 260 implants were included, with 126 males and 99 females, aged (57.3±11.0) years, with a following time of (5.04±3.08) years. The 1-year cumulative survival rate of implants was 98.0% (1 235/1 260). Forty-eight implants were lost during the follow-up, with 39 implants in the maxillae and 9 implants in the mandible. The risk of implant failure of the maxillae ［7.2% （39/541）］ is significantly higher than that of the mandible ［1.3% （9/719）］ ( P<0.01). Average marginal bone loss at 1 and 5 years was (0.7±0.2） mm and （1.1±0.3） mm. One hundred and twenty patients experienced prosthetic complications including screw/abutment loosening (44 cases), screw/abutment fracture (2 cases) and artificial tooth/denture base fracture (99 cases). The possibility of immediate prosthesis fracture within 6-8 months was high but declined over the following years with the final prosthesis delivered. Cox regression analysis showed that the use of 17° abutments in the anterior region was significantly related to the prosthetic complications （hazard ratio=1.797, P=0.002）. Conclusions:Immediate rehabilitation of the edentulous jaws with implant-supported full-arch prostheses can be a predictable technique. The immediate prosthetic mechanical complication prevalence was high. The use of 17° abutments in the anterior region may increase the risk of screw/abutment loosening. It is necessary to review in time.

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.

OBJECTIVETo determine the genetic etiology and clinical characteristics of 2 boys featuring development delay (DD).

METHODSRoutine chromosomal banding was performed to analyze the karyotypes of the patients and their parents. Single nucleotide polymorphism array (SNP array) analysis was employed to identify pathogenic deletion/duplication of chromosomes, and quantitative real-time PCR (qPCR) was performed to confirm the results.

RESULTSPatient 1 showed a global developmental delay, especially impaired language development, seizures, behavioral problems belonging to the autism spectrum and mild facial dysmorphism. Patient 2 mainly presented with severely delayed speech and moderate intellectual disability, but did not have obvious facial dysmorphism and autistic-like behavior. The diagnosis of 22q13 syndrome was established based on identification of a heterozygous microdeletion at chromosome 22q13.33 in both patients (69 kb and 587 kb, respectively) by the SNP array analysis. Both patients had deletions of SHANK3 and ACR, which are located at the end of 22q. Quantitative real-time PCR verified that the deletion of SHANK3 gene in both patients were de novo in origin.

CONCLUSIONTwo cases of 22q13 deletion syndrome have been diagnosed by SNP array analysis. Deletion of SHANK3 gene may be the major contributor to the clinical manifestations of the patients. SNP array analysis can facilitate discovery of microdeletions, which has played an important role in the diagnosis and genetic counseling for the family.