Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 &mu;m/year in women and 5.8 &mu;m/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Humans ; Mitral Valve/surgery* ; Heart Valve Prosthesis ; Cardiac Surgical Procedures

Humans ; Mitral Valve/surgery* ; Heart Valve Prosthesis ; Cardiac Surgical Procedures

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.
Antineoplastic Agents/pharmacology* ; Asclepias/chemistry* ; Cardenolides/pharmacology* ; Glycosides/pharmacology* ; Humans ; Seeds

Objective: To investigate the clinicopathological characteristics of reactive epithelial hyperplasia and dysplasia in the stomach, as well as the clinical value of mucin special staining and proliferating cell nuclear antigen (Ki-67) in distinguishing the two gastric lesions. Methods: The clinical pathological data of 63 patients with gastric reactive epithelial hyperplasia, 54 patients with low-grade dysplasia, and 63 patients with high-grade dysplasia diagnosed from May 2018 to May 2021 in Beijing Chaoyang Hospital, Capital Medical University, Beijing, China were analyzed. Alcian blue periodic acid Schiff (AB-PAS) and Ki-67 staining were performed to examine the mucin staining pattern, number of Ki-67 positive cells, Ki-67 staining patterns in the three groups of lesions, and histopathologic characteristics. Results: The positive rates of AB-PAS in the reactive epithelial hyperplasia and gastric dysplasia groups were 87.3%(55/63) and 10.3%(12/117), respectively. The expression of AB-PAS in the reactive epithelial hyperplasia was gradually increased from the base to the surface of the epithelium. In low-grade dysplasia and high-grade dysplasia, there was no mucin present in the dysplasia epithelium. The difference between the two groups was statistically significant (P<0.01). The positive rate of Ki-67 in the epithelial reactive hyperplasia (>10%) was 81.0% (51/63), and the positive cells were mainly located in the neck and middle parts of the mucosal glands (58/63, 92.1%). In the low-grade dysplasia group, the positive rate of Ki-67 (>10%) was 90.7%(49/54); the positive cells were mainly located in the upper mucosa (33/54, 61.1%), showing a banded distribution pattern; in the high-grade dysplasia group, the positive rate (>10%) was 95.2%(60/63), and the positive cells were mainly located in the whole mucosa (49/63, 77.8%), showing a diffuse/diffuse scattered distribution pattern. The three groups had statistically different rates and distribution patterns of Ki-67 expression (P<0.01). Conclusion: The gastric epithelial reactive hyperplasia and dysplasia can be differentiated using clinicopathological features, AB-PAS staining and Ki-67 expression pattern.
Alcian Blue ; Humans ; Hyperplasia ; Ki-67 Antigen/metabolism* ; Periodic Acid ; Staining and Labeling ; Stomach Neoplasms/diagnosis*

Objective To establish a rapid nucleic acid detection technique for identification of Echinococcus multilocularis based on the recombinase aided isothermal amplification assay (RAA) and assess its diagnostic efficiency. Methods The mitochondrial gene sequence of E. multilocularis (GenBank accession number: AB018440) was used as a target sequence. The primers were designed according to the RAA reaction principle and synthesized, and RAA was performed using the generated primers. E. multilocularis genomic DNA at various concentrations and the pMD19-T (Simple) vector containing various copies of the target gene fragment were amplified using RAA to evaluate its sensitivity for detection of E. multilocularis, and RAA was em- ployed to detect the genomic DNA of E. granulosus G1 genotype, Taenia saginata, T. asiatica, T. multiceps, Dipylidium caninum, Toxocara canis, Trichuris trichiura, Giardia lamblia, Fasciola hepatica, Paragonimus westermani, Fasciola gigantica and Clonorchis sinensis to evaluate its specificity. In addition, the optimized RAA was employed to detect nine tissue specimens of E. granulosus-infected animals, 3 fecal samples from E. granulosus-infected dogs and 2 fecal samples from field infected dogs to examine its reliability and feasibility. Results The established RAA was able to detect the specific target gene fragment of E. multilocularis within 40 min. The lowest detect limit of RAA was 10 pg if E. multilocularis genomic DNA served as a template. If the re- combinant plasmid was used as a template, the minimally detectable copy number of RAA was 104. In addition, RAA was nega- tive for the genomic DNA of E. granulosus G1 genotype, T. saginata, T. asiatica, T. multiceps, D. caninum, T. canis, T. trichiura, G. lamblia, F. hepatica, P. westermani, F. gigantica and C. sinensis. The established RAA was positive for detection of the tissue specimens of infected animals, and simulated and field dog stool samples. Conclusion A rapid, sensitive and specific RAA is established, which shows promising values in identification of E. multilocularis and gene diagnosis of alveolar echinococcosis.

【Objective】 To study the mechanisms and therapeutic effects of human olfactory mucosa-derived mesenchymal stem cells（OMSC）on experimental autoimmune encephalomyelitis（EAE）in mice.【Methods】Under local anesthesia by using nasal endoscopy，olfactory epithelia of healthy donors were obtained，digested and cultured up to the 5th passage. OMSC were identified，differentiated and stained. EAE models were induced in C57 female mice by myelin oligodendrocyte glycoprotein（MOG35- 55）and pertussis toxin（PT）. Neurological function was documented daily. On day 16 after immunization（peak of incidence），the mice were divided randomly into two groups and treated with OMSC and PBS via tail vein injection respectively. On day 24 after immunization ，blood was collected from angular vein and levels of IL-10，IL-17，IFN-γ and IL-6 were determined by cytometric beads array（CBA）. The size of the spinal cord lesion in mice was observed and measured by using HE and LFB staining. Peripheral blood lymphocytes（PBL）of healthy donors were obtained and then co-cultured with OMSC. The proportions of CD4+ T cells secreting IFN- γ（Th1 cells）in lymphocyte group and co-culture group were compared after 2 days of cultivation. Adding IDO or COX pathway inhibitor to co- culture group and cultivating for 2 days，we observed and compared the proportions of Th1 cells in lymphocyte group，co-culture group and inhibitor treatment group respectively.【Results】OMSC exhibited certain mesenchymal stem cell-like characteristics with respect to expression of stem cell surface markers and multilineage differentiation potentials. After induced by MOG35- 55 and PT，EAE models showed different levels of neurological damage. Compared with those in PBS treatment group，in OMSC treatment group，the severity of neural dysfunction in mice was significantly reduced（P =0.002），the level of IFN-γ in serum was lower（P = 0.032），but no significant differences in the levels of IL-10，IL-17 and IL-6 were found between two groups. HE and LFB staining revealed that the inflammatory infiltration and demyelinating areas in OMSC treatment group were less than those in PBS treatment group. The proportion of Th1 cells was lower in co-culture group than that in lymphocyte group（P = 0.001），higher in IDO inhibitor group than that in co-culture group（P = 0.01），but no significant difference was found between IDO inhibitor group and lymphocyte group or between COX inhibitor group and co-culture group.【Conclusions】OMSC may regulate the proportion of Th1 lymphocytes through IDO pathway so as to inhibit the demyelinating injuries of EAE in mice. This study provides a new idea for the clinical treatment of multiple sclerosis.

【Objective】To study the effect of mesenchymal stem cells（MSC）on proliferation and immunomodulation of B cells in vitro.【Methods】Bone marrow 30 mL from healthy donors was isolated by density gradient centrifugation. Isolated MSC were cultivated adherently with L- DMEM medium containing 10% fetal bovine serum（FBS）. Phenotype and differentiation capacity of MSC was detected after the sixth passage. Peripheral blood mononuclear cells（PBMC）of healthy donors were also obtained by density gradient centrifugation. CD19+ B cells were sorted by fluorescence activated and co-cultured with MSC（CD19+ B∶MSC = 5∶1）group. Stimulated by CpG+ CD40L，the proliferation of B cells of two groups were checked 96 hours after co-culture respectively. The CD19+CD5+ B cells percentage and its secretion of IL-10 were detected by FACS. The effects of CD19+ B cells on the proliferation of CD4+ T cells and the secretion of IFN-γ were continually observed. Anti-IL-10 was used to confirm the effect of B cells on proliferation and IFN-γ secretion of CD4+ T cells.【Results】MSC collected from healthy donors remained differentiation capacity. MSC derived from bone marrow expressed CD29，CD44，CD73，CD90，CD105，and CD166，but did not express CD45 and CD34. Compared with control group，the proportion of CD19+ B cells proliferation in co-cultured group was significantly increased after 3 days，meanwhile，the level of IFN-γ，which secreted by CD4+ T cells was significantly restrained. To make a further analysis of the subsets of CD19+ B cells，the percentage of CD5+ B cells in co-cultured group increased from（21.31±1.22）% to（31.27±0.92）%（P=0.014），and its IL-10 secretion increased from（1.09±0.08）% to（2.44±0.06）%（P<0.001）compared with control group. After anti-IL-10 was used，the B cells co-cultured with MSC showed a decreased capacity of inhibiting the proliferation and IFN-γ secretion of CD4+ T cells.【Conclusions】MSC could promote the proliferation of CD19+ B cells to inhibit the secretion of IFN-γ by CD4+ T cells，which may be related to the increasing expression of IL-10 by CD19+CD5+B cells.