Aim To explore the effect of ZLY18 on angiotensin II-induced cardiac fibrosis and the underlying mechanism. Methods Ang II was used to induce cardiac fibrosis in vitro and in vivo. Cardiac fibroblasts were divided into blank control group, model group and medicine group. The medicine group was subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 1, 2, 5 μmol·L-1 respectively. C57BL/6 mice were randomly divided into control group, model group and medicine group. The medicine group were subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 10,20 and 50 mg·kg-1 respectively. Both the model group and the medicine group were given with Ang II to induce cardiac fibrosis. The changes of protein levels were detected by Western blot and immunofluorescence. The changes of cardiac function indexes in C57BL/6 mice were detected by small animal echocardiography. The morphology, cell arrangement and collagen fibers of cardiac fibroblasts were observed by tissue section staining and other methods. Results The model of Ang II-induced myocardial fibrosis was successfully established at the cell and animal levels, and ZLY18 treatment improved the elevated fibrosis-related protein caused by Ang II and abnormal cardiac function in mice. Moreover, ZLY18 was able to inhibit the increased phosphorylation of TGF-1 and Smad3 caused by Ang II and increased Smad2/3 nuclear entry, suggesting that the antifibrotic effect of ZLY18 might be related to the activation of TGF-1/Smads signaling pathway. Conclusions ZLY18 has a protective effect on Ang II-induced cardiac fibrosis. ZLY18 may inhibit TGF-β/Smads signaling pathway activation to exert anti-fibrotic effects.

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
Carbohydrates ; Glycosides ; Oligosaccharides ; Oxidation-Reduction ; Polysaccharides/chemistry*

This study reports the diagnosis and treatment of 2 children with isolated testicular recurrence (ITR) of acute B lymphoblastic leukemia (B-ALL) treated with CD 19 targeted chimeric antigen receptor T (CD 19 CAR-T) cells in May and December 2019 in the Department of Hematology and Oncology, Children′s Hospital of Soochow University, and explores the efficacy of CD 19 CAR-T cells therapy versus conventional radiotherapy and chemotherapy through literature review.Both cases were diagnosed as B-ALL by the morphologic, immunologic, cytogenetic and molecular biology methods.ITR was diagnosed by testicular biopsy at 60 months and 38 months after initial diagnosis in 2 cases, respectively.After infusion of CD 19 CAR-T cells at 7.0×10 6/kg and 1.5×10 7/kg, respectively for 7-10 days, testicular leukemia cell infiltration disappeared and complete remission was obtained.Among them, case 2 developed cytokine release syndrome and immune effector cell-related neurotoxicity syndrome after treatment, which was improved after drug intervention.It is suggested that CD 19 CAR-T cells are effective in the treatment of ITR in children, which may be an alternative to orchiectomy or local radiotherapy for ITR in children with B-ALL.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.
Bacterial Infections ; Humans ; Polysaccharides/chemistry* ; Structure-Activity Relationship

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

OBJECTIVETo develop the mechanism of improving protection function of prepared Cornus officinalis for liver and kidney and the biological activity of 5-hydroxymethylfurfural (5-HMF).

METHODPharmacological and chemical studies were used to choose active part. A compound from active part was separated and appraised. To investigate his biological functions, pharmacological experiment was actualized.

RESULTA component was separated and identified. His is 5-HMF. 5-HMF can protect human vein epidermal cell against H2O2 and glucose and inprove acute liver injury in mice.

CONCLUSION5-HMF is the active component in prepared Cornus officinalis and substance basis for protecting liver and kidney.

Animals ; Cells, Cultured ; Cornus ; chemistry ; Endothelial Cells ; drug effects ; Female ; Furaldehyde ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology ; Liver ; drug effects ; Male ; Mice ; Random Allocation

OBJECTIVETo explore the risk factors for irritable bowel syndrome (IBS) among school adolescents in China.

METHODA stratified, randomized study by cluster sampling was conducted, which recruited 51,956 students from high and primary schools in Chinese cities. All students were requested to fill in a questionnaire.

RESULT(1) Factors including class (odds ratio 1.12), excessive intake of pepper (odds ratio 1.17), fried (odds ratio 1.08) and starch-based foods (odds ratio 1.06), gastrointestinal tract infection (odds ratio 2.66), abuse of analgesic (odds ratio 1.49), inheritance (odds ratio 1.83), fatigue (odds ratio 1.32) and repression (odds ratio 1.45) were significantly associated with the presence of IBS (P < 0.05). High protein food (odds ratio 0.90) was a protective factor.

CONCLUSIONDifferent food intake, gastrointestinal tract infection, abuse of analgesic, inheritance and psychological factors might be related to development of IBS in the students of the cities involved in this study.

Adolescent ; Child ; China ; epidemiology ; Humans ; Irritable Bowel Syndrome ; epidemiology ; etiology ; Risk Factors ; Sampling Studies ; Students ; Surveys and Questionnaires

OBJECTIVETo investigate the synergistic effects of a biotic elicitor yeast extract and different abiotic elicitors (Ag+, Co2+ and alpha-amino isobutyric acid) on the production of tanshinones in Salvia miltiorrhiza hairy root.

METHODDifferent elicitors and their combinations were added to S. miltiorrhiza hairy root culture and the contents of three major tanshinones (crypotanshinone, tanshinone I and tanshinone II A) were analyzed by HPLC.

RESULTThe combinations of yeast extract with different abiotic elicitors had notable synergistic effects on the tanshinone I and tanshinone II A production but not on crypotanshinone. The combination of yeast extract and Ag+ (300 micromol x L(-1)) yielded the highest tanshinone I content, which was nearly 14-fold of the control, and the synergistic elicitation coefficient was 3.0. The combination of yeast extract and Co2+ (100 micromol L(-1)) led to the highest tanshinone IIA content, which was about 14.5-fold of the control, and the synergistic elicitation coefficient was 2.1. Only yeast extract combined with alpha-amino isobutyric acid (200 micromol x L(-1)) increased the crypotanshinone content more effectively than single elicitors. The highest crypotanshinone content was 1.28 mg x g(-1), about 30-fold of the control with a synergistic elicitation coefficient of 1.3.

CONCLUSIONThe elicitation by the combination of a biotic elicitor and an abiotic elicitor can generate a synergistic effect, which is more effective than single elicitors to promote secondary metabolite production in plant tissue cultures.

Aminoisobutyric Acids ; pharmacology ; Bioreactors ; Cobalt ; pharmacology ; Culture Media ; Culture Techniques ; Diterpenes, Abietane ; Drug Synergism ; Phenanthrenes ; metabolism ; Plant Roots ; growth & development ; metabolism ; Plants, Medicinal ; growth & development ; metabolism ; Saccharomyces cerevisiae ; chemistry ; Salvia miltiorrhiza ; growth & development ; metabolism ; Silver ; pharmacology

OBJECTIVETo evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.

METHODThis is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study.

RESULTS(1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.

CONCLUSIONThis study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; administration & dosage ; China ; Double-Blind Method ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Imidazoles ; adverse effects ; therapeutic use ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Olmesartan Medoxomil ; Tetrazoles ; adverse effects ; therapeutic use