Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

Background Flurochloridone (FLC) can induce apoptosis in Sertoli cells, but the specific mechanism remains unknown. Objective To investigate the testicular cell apoptosis in mice as well as apoptosis and activation of endoplasmic reticulum stress in TM4 cell line induced by FLC through in vivo and in vitro study designs respectively, and study the role of inosital-requiring enzyme 1α (IRE1α)-c-Jun N-terminal kinase (JNK) signaling pathway in the process of FLC-induced apoptosis in TM4 cells through intervention study design. Methods Testicular tissues were collected from male C57BL/6 mice which were treated with 3, 15, 75, and 375 mg·（kg·d）⁻¹ FLC by oral perfusion for 28 d. Apoptosis was observed by TUNEL staining, and the levels of apoptosis-related proteins were detected by Western blotting, including B-cell lymphoma-2 (Bcl-2), Bcl-2 interacting mediator of cell death (Bim), and Bcl-2 associated X protein (Bax). In the in vitro study, TM4 cells were treated with different concentrations of FLC (40, 80, and 160 μmol·L⁻¹) for 6 h, then apoptosis rate was detected by flow cytometry, and the levels of apoptosis-related proteins (Bcl-2, Bim, and Bax) and endoplasmic reticulum stress-related proteins [glucose regulated protein 78 (GRP78), phosphorylated-protein kinase R like endoplasmic reticulum kinase (p-PERK), activating transcription factor 6 (ATF6), phosphorylated-inosital-requiring enzyme 1α (p-IRE1α), and phosphorylated-JNK (p-JNK)] were measured by Western blotting. In the intervention study, TM4 cells were pretreated with IRE1α phosphorylation inhibitor 4μ8C and JNK phosphorylation inhibitor SP600125 for 6 h, then treated with 160 μmol·L⁻¹ FLC for 6 h. The levels of apoptosis-related proteins and endoplasmic reticulum stress-related proteins were measured by Western blotting, and cell viability was detected by cell counting kit-8. Results After the male C57BL/6 mice orally exposed to FLC for 28 d, apoptosis occurred in the seminiferous tubule. The protein expression level of Bcl-2, apoptosis inhibitor, was decreased in the 75 and 375 mg·(kg·d)⁻¹ groups (P<0.05), and the protein expression levels of Bim and Bax, apoptosis promoters, were increased in the 75 and 375 mg·(kg·d)⁻¹ groups respectively (P<0.05). The percentages of apoptotic cells in the 0, 40, 80, and 160 μmol·L⁻¹ FLC groups were 2.7%±0.2%, 4.8%±1.3%, 9.4%±0.3%, and 13.2%±0.2%, respectively, increased significantly compared with the control group (P<0.05). The protein expression level of Bcl-2 also was decreased in the 160 μmol·L⁻¹ FLC group (P<0.05), while the levels of Bim and Bax were increased in both of the 80 and 160 μmol·L⁻¹ groups (P<0.05). The expression levels of endoplasmic reticulum stress-related proteins (GRP78, p-PERK, ATF6, p-IRE1α, and p-JNK) were increased (P<0.05) or showed a rising trend in TM4 cells. Pre-treatment with 4μ8C (25 and 50 μmol·L⁻¹) and SP600125 (10 and 20 μmol·L⁻¹) significantly down-regulated the protein expression levels of GRP78, p-IRE1α, p-JNK, and Bax induced by FLC (P<0.05) or in a downward trend. Both of the inhibitors alleviated the decreased cell viability induced by FLC (P<0.05) or in alleviating fashion. Conclusion FLC could induce apoptosis in mice testis and TM4 cell apoptosis through activating endoplasmic reticulum stress and IRE1α-JNK signaling pathway.

COVID-19/transmission* ; Communicable Disease Control/organization & administration* ; Humans ; Remote Consultation/organization & administration* ; Singapore/epidemiology* ; Videoconferencing/organization & administration*

BACKGROUND: Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. METHODS: Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. RESULTS: A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed. CONCLUSION Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

BACKGROUNDThe role of tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is not clear and is a challenge for anti-tumor immunotherapy. This study aimed to investigate the effects of interleukin (IL)-18 and -12 on cytotoxic functions of TILs.

METHODSTILs from postoperative gastric cancer patients were costimulated with IL-18 and IL-12. SGC-7901 tumor cells were pre-incubated with TILs and subcutaneously injected into BALB/C SCID mice. The function of TILs was evaluated by measuring tumor sizes in tumor-bearing mice, T helper (Th)1 (tumor necrosis factor (TNF)-α, interferon (IFN)-γ) and Th2 cytokine levels (IL-10 and IL-4) in serum and cytotoxicity of mouse natural killer (NK) and CD8(+) T cells.

RESULTSIL-18 and IL-12 synergistically inhibited the growth of SGC-7901 cells in vivo and significantly extended the survival rate of SGC-7901-bearing mice (66.7% vs. 13.7%, P < 0.01). Moreover, TILs could promote the secretion of TNF-α and IFN-γ ((130.34 ± 7.65) vs. (210.63 ± 12.31) pg/ml, P < 0.01; (14.23 ± 1.97) vs. (30.52 ± 2.12) pg/ml, P < 0.01), and downregulate IL-10 and IL-4 secretion ((103.72 ± 11.21) vs. (61.36 ± 5.41) pg/ml, P = 0.021; (49.36 ± 4.67) vs. (28.48 ± 3.86) pg/ml, P = 0.024).

CONCLUSIONIL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.

Adult ; Aged ; Animals ; CD8-Positive T-Lymphocytes ; immunology ; metabolism ; Cell Line, Tumor ; Female ; Humans ; In Vitro Techniques ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; pharmacology ; Interleukin-18 ; pharmacology ; Interleukin-4 ; metabolism ; Lymphocytes, Tumor-Infiltrating ; drug effects ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Stomach Neoplasms ; immunology ; Tumor Necrosis Factor-alpha ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo analyze clinical characteristics of children with 45, X/46, XY mosaicism and explore effective managements for them.

METHODFive children with 45, X/46, XY mosaicism were all in puberty period, of whom, three were female and two male. The standing height, weight and sexual development were measured. The levels of sex hormones, other endocrine parameters were also determined, and imaging examinations were performed.

RESULTAll the patients had disorders of sex development, of whom, 4 had short stature, and the HtSDs was -2.8 ± 1.1. The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism, with the average level of LH (13.5 ± 5.8) IU/L and FSH (56.8 ± 37.4) IU/L. Imaging examinations revealed that 2 cases had cryptorchidism, 1 had immature uterus, 1 had testicular dysgenesis and 1 had normal testis. Three patients received rhGH treatment and 1 took gender assignment into account.

CONCLUSIONPatients with mosaic 45, X/46, XY karyotypes had a wide range of phenotypic manifestations, and disorders of sex development and short stature were the main clinical features. However, the disorders of sex development varied among these patients. And the management for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.

Adolescent ; Child ; Chimerism ; Developmental Disabilities ; complications ; Female ; Gonadal Dysgenesis, 46,XY ; complications ; Humans ; Male ; Sex Chromosome Aberrations ; Sexual Development ; Turner Syndrome ; complications

OBJECTIVETo explore the potential anti-inflammatory and analgesic activities of carboxyamidotriazole (CAI).

METHODSA variety of animal models, including the croton oil-induced ear edema, the cotton-induced granuloma, the rat adjuvant-induced arthritis, were used to evaluate anti-inflammatory effect of CAI. Vascular endothelial growth factor (VEGF)--or histamine-stimulated local vascular permeability in mouse modulated by CAI was also determined. In addition, we assessed the effect of CAI on the levels of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-beta) at the site of inflammation and in sera. Moreover, antinociceptive effect of CAI on inflammatory pain was assessed using acetic acid-induced writhing model and the formalin test.

RESULTSCAI significantly inhibited acute and chronic phases of inflammation, reduced VEGF or histamine-induced vascular permeability, and showed marked inhibition of proinflammatory cytokines such as TNF-alpha and IL-1 beta. CAI also showed potential therapeutic effect on peripheral inflammatory pain.

CONCLUSIONCAI is a promising anti-inflammatory and analgesic agent.

Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Drug Evaluation, Preclinical ; Female ; Male ; Mice ; Mice, Inbred ICR ; Rats ; Rats, Wistar ; Triazoles ; pharmacology

x, which might reduce entry of Ca2+ into cells during ischemia and reperfusion, and at the same time, restore concentration of intracellular calcium [Ca2+]. All this might account for the therapeutic effect of HBO on cerebral ischemia.

x, which might reduce entry of Ca2+ into cells during ischemia and reperfusion, and at the same time, restore concentration of intracellular calcium [Ca2+]. All this might account for the therapeutic effect of HBO on cerebral ischemia.

OBJECTIVEThis study attempted to explore the value of combining serum hepatic fibrosis-related markers and ultrasound parameters together on diagnosis of hepatic fibrosis.

METHODSSix serum markers and 8 ultrasound parameters were measured from 100 patients with chronic hepatitis B or cirrhosis. The results of the serum hepatic fibrosis-related markers and ultrasound in disease group were analyzed and compared with the findings of hepatic pathology.

RESULTSBy filtrating,the group of platelet derived growth factor-BB (PDGF-BB) plus hyaluronic acid (HA) plus echo characteristics of liver parenchyma (LPEC) plus length of spleen (SL) had the highest Se and Spe, which were 90.7% and 85.4% respectively.

CONCLUSIONThe advantageous combination of serum markers and ultrasound parameters can significantly improve Se and Spe, which is superior to any single serum index or ultrasound parameter. And it was a better non-invasive method for diagnosing hepatic fibrosis.

Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Biomarkers ; blood ; Collagen Type III ; blood ; Female ; Hepatitis B, Chronic ; blood ; diagnosis ; diagnostic imaging ; Humans ; Hyaluronic Acid ; blood ; Liver Cirrhosis ; blood ; diagnosis ; diagnostic imaging ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; analysis ; Proto-Oncogene Proteins c-sis ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Transforming Growth Factor beta ; blood ; Ultrasonography, Doppler, Color ; methods ; Young Adult