Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary , the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.
Aneuploidy ; Female ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis/methods* ; Sex Chromosome Aberrations ; Sex Chromosomes/genetics*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

N6-methyladenosine (m6A) is one of the most abundant modifications on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex (MTC) containing a key factor methyltransferase-like 3 (Mettl3). How-ever, the functions of Mettl3 and m6A modification in hepatic lipid and glucose metabolism remain unclear. Here, we showed that both Mettl3 expression and m6A level increased in the livers of mice with high fat diet (HFD)-induced metabolic disorders. Overexpression of Mettl3 aggravated HFD-induced liver metabolic disorders and insulin resistance. In contrast, hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain, reducing lipid accumulation, and improving insulin sensitivity. Mechanistically, Mettl3 depletion-mediated m6A loss caused extended RNA half-lives of metabolism-related genes, which consequently pro-tected mice against HFD-induced metabolic syndrome. Our findings reveal a critical role of Mettl3-mediated m6A in HFD-induced metabolic disorders and hepatogenous diabetes.

Objective To evaluate the clinical efficacy and safety of dimemorfan phosphate in the treatment of dry cough.Methods Three hundred seventy -eight patients with dry cough were randomly divided into experimental group ( n=216 ) , positive control ( n=108 ) and place-bo group ( n=54 ).Experimental group was taken dimemorfan phosphate 20 mg, orally, tid, 5 -7 d.Positive control group was taken dextro-methorphan 30 mg, orally, tid, 5 -7 d.Placebo group was taken dimemorfan phosphate simulation tablets 20 mg or dextromethorphan simulation tablets 30 mg, tid, 5-7 d.Comparison of the clinical effica-cy, change of the total cough score after 5-7 d treatment, and the inci-dence of adverse drug reactions between the three groups.Results The clinical effectiveness of cough symptom after treatment , experimental group and positive control group and placebo group were 81.02%, 84.26%and 38.89%, respectively.The difference between experimen-tal group with placebo group was statistically significant ( P <0.01 ) , there was no statistically significant difference between experimental group with positive control group ( P>0.05 ).The average decrease of total cough score after treatment in the experimental group , the positive control group and the placebo group were (2.34 ±1.42), (2.43 ±1.55) and (1.39 ±1.20), respectively.The decrease in the total cough score of experimen-tal group was superior to that of placebo group ( P<0.01 ) , the decrease in the total cough score of experimental group was not inferior to positive control group ( P>0.05 ).The incidence of adverse events were 4.21% in experimental group , 12.04%in positive control group and 5.66%in placebo group , respectively.Among these , the incidence of adverse events associated with drug were 1.87%, 10.19%, 5.66%, respectively.Conclusion Dimemorfan phos-phate has exact antitussive efficacy in the treatment of dry cough , has the same antitussive efficacy and similar side effect in the treatment of dry cough compared with the dextromethorphan.

BACKGROUNDSrc homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed its roles in various disease, however, whether SHP-2 involves in renal fibrosis remains unclear. The aim of this study was to explore the roles of myeloid cells SHP-2 in renal interstitial fibrosis.

METHODSMyeloid cells SHP-2 gene was conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The total collagen deposition in the renal interstitium was assessed using picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage infiltration in renal tubular interstitium. Quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to analyze the production of cytokines in the kidney. Transferase-mediated dUTP nick-end labeling stain was used to assess the apoptotic renal tubular epithelial cells.

RESULTSSrc homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO in myeloid cells significantly reduced collagen deposition in the renal interstitium after UUO. Macrophage infiltration was evidently decreased in renal tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro-inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However, no significant difference was observed in the number of apoptotic renal tubular epithelial cells between wild-type and SHP-2 CKO mice.

CONCLUSIONSOur observations suggested that SHP-2 in myeloid cells plays a pivotal role in the pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells may protect renal from inflammatory damage and prevent renal fibrosis after renal injury.

Animals ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrosis ; enzymology ; pathology ; Immunohistochemistry ; Kidney Diseases ; enzymology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells ; metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; genetics ; metabolism ; Ureteral Obstruction ; enzymology ; pathology

BACKGROUNDTransurethral resection of the bladder tumor (TURBT) remains the gold standard for non-muscle-invasive bladder cancer (NMIBC). Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor (HoLRBT) vs. TURBT.

METHODSA systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated.

RESULTSFive studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups (weighted mean difference (WMD) 1.01, 95% confidential interval (95% CI) -3.52 - 5.54, P = 0.66). The significant difference in the obturator nerve reflex (OR 0.05, 95% CI 0.01 - 0.04, P = 0.004), bladder perforation (OR 0.14, 95% CI 0.03 - 0.61, P = 0.009), bladder irrigation (OR 0.13, 95% CI 0.04 - 0.45, P = 0.001), catheterization time (WMD -0.96, 95% CI -1.11 to -0.82, P < 0.00001), and hospital stay (WMD -1.46, 95% CI -1.65 to -1.27, P < 0.00001) showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group (OR 1.46, 95% CI 1.02 - 2.11, P = 0.04).

CONCLUSIONSAs a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.

Aged ; Female ; Follow-Up Studies ; Humans ; Lasers, Solid-State ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Urethra ; Urinary Bladder Neoplasms ; surgery

Aged ; Humans ; Male ; Urinary Diversion ; adverse effects ; Urinary Fistula ; diagnosis ; etiology

BACKGROUNDAlthough many midterm oncologic data have been reported for extraperitoneal laparoscopic radical prostatectomy (ELRP) in western countries, few oncologic data of the extraperitoneal procedure was published in China. The aim of the study was to evaluate the oncologic outcomes of patients treated with ELRP in China.

METHODSFrom January 2005 to March 2010, a total of 152 consecutive patients diagnosed with clinically localized prostate cancer were included in this study and treated with ELRP. The patients were staged according to the TNM (tumor, nodes, metastases) system. Median and mean postoperative follow-up were 28.1 months and 27.0 months, respectively. The patients were retrospectively analyzed for progression-free survival.

RESULTSOne hundred and twelve cases (73.7%) were postoperatively diagnosed as pT2 in, and 40 cases (26.3%) as pT3. Positive lymph nodes were shown in 5 patients (3.3%). Gleason score was < 7 in 49 men (32.2%), 7 in 69 men (45.4%), and > 7 in 34 men (22.4%). Positive surgical margins (PSM) were observed in 15 patients (9.9%), which included 32.0% of all pT3a cases and 46.7% of all pT3b cases, respectively. The overall prostate-specific antigen recurrence-free survival rate was 86% in all patients. The recurrence-free survival rates were 91.8% and 62.2% in pT2N0 patients and pT3N0 patients, respectively. Preoperative prostate-specific antigen, surgical margins, tumor stage, and lymph nodal status were identified as independent predictors of biochemical recurrence-free survival using multivariate Cox proportional hazard model.

CONCLUSIONSELRP is a precise, safe and effective procedure at this particular Chinese institution. The prognostic power of prostate-specific antigen relapse after ELRP is not identical to that described previously with transperitoneal or open retropubic approaches.

Aged ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Prostate ; surgery ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery ; Treatment Outcome

BACKGROUNDEfficient cell adhesion and proliferation is a central issue in cell-based tissue engineering, which offers great promise for repair of urethral defects or strictures. This study evaluated the adhesion and growth of rabbit uroepithelium on a surface-modified three-dimensional poly-L-lactic acid (PLLA) scaffold.

METHODSUrethral mucosa were harvested from male New Zealand rabbits and the urothelium were dissociated and then cultured. Immunocytochemistry on cultured uroepithelium for pancytokeratin and uroplakin II and TE-7 confirmed pure populations. After in vitro proliferation, cells were seeded onto a surface-modified urethral scaffold with non-knitted filaments. The morphology and viability of the cells were examined by immunohistochemical and fluorescence staining. Inverted and scanning microscopes were used to document cell growth and adhesion.

RESULTSThree to five days after primary culture, the uroepithelial cells gradually became confluent, assuming a cobblestone pattern. The filaments of the urethral scaffold had excellent biocompatibility and allowed growth of the uroepithelium, without affecting viability. The uroepithelial cells adhered to and grew well on the scaffold. After 3 - 7 days, the cells grew vigorously and meshes of the scaffold were full of uroepitheliums.

CONCLUSIONSThe surface-modified urethral scaffold with non-knitted filaments allows the growth of uroepithelium and can serve as a carrier for the tissue engineering of urethra.

Absorbable Implants ; Animals ; Cells, Cultured ; Epithelial Cells ; physiology ; Lactic Acid ; Male ; Polyesters ; Polymers ; Rabbits ; Tissue Engineering ; methods ; Urethra ; cytology