To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

OBJECTIVETo assess the effectiveness and safety of intratympanic versus systemic steroid therapy in the initial treatment of idiopathic sudden hearing loss.

METHODSAn extensive search of the literature was performed in Pubmed and other available database from January, 1980 to November, 2011. After filtering by the criteria of Cochrane Collaboration, a meta-analysis was conducted.

RESULTSNine studies met the criteria for meta-analysis, for idiopathic sudden hearing loss patients without diabetes received intratympanic steroid therapy, the improvement rate (RR = 1.11,95% CI = 0.96-1.28, P = 0.15) did not show any significance when compared with the patients received systemic therapy. While a significant difference of improvement rate occurred between intratympanic and systemic steroid therapy in the idiopathic sudden hearing loss patients with diabetes (RR = 1.24, 95% CI = 1.02-1.50, P = 0.03).

CONCLUSIONFor the initial therapy of idiopathic sudden hearing loss patients without diabetes, systemic steroid treatment still remains the first choice, but for the idiopathic sudden hearing loss patients with diabetes, intratympanic steroid treatment should be used for the initial treatment.

Administration, Oral ; Audiometry, Pure-Tone ; Dexamethasone ; administration & dosage ; therapeutic use ; Hearing Loss, Sensorineural ; drug therapy ; Hearing Loss, Sudden ; drug therapy ; Humans ; Methylprednisolone ; Steroids ; administration & dosage ; therapeutic use ; Treatment Outcome ; Tympanic Membrane

OBJECTIVETo analyze the causes of death in patients with heart failure.

METHODSA total of 133 heart failure patients died during hospitalization in our hospital between January 2005 and December 2008 were enrolled in this study. Patients were divided to two groups: sudden death (group A, n = 73, 54.9%), chronic end-stage pump failure (group B, n = 55, 41.4%). The remaining 5 cases died of other causes were excluded from the final analysis. Clinical data (medical history, blood pressure, clinical manifestation, NYHA cardiac function class, left ventricular diameter of diastole, left ventricular ejection fraction, ventricular arrhythmias, drug therapy) of group A and B were analyzed.

RESULTSThere were no significant differences in terms of medical history (including hypertension and diabetes), blood pressure, heart rate and the incidence of ventricular arrhythmia between the two groups. In group A, the NYHA functional class was mostly II or III grade, and LVEF value was significantly higher than that of group B. The incidence of angina pectoris was significantly higher in group A compared to group B. beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use was also significantly higher in group A than in group B, however, the treatment dose was significantly lower and therapy duration was significantly shorter in group A than in group B. There were significantly less patients received statins and anti-platelet aggregation drugs in group A compared to group B.

CONCLUSIONIn our patient cohort, sudden cardiac death often occurred in heart failure patients with NYHA cardiac function II to III grade, angina pectoris, probably due to the unstable coronary plaque and less statins and anti-platelet drug use in these patients.

Adult ; Aged ; Cause of Death ; Death, Sudden, Cardiac ; epidemiology ; Female ; Heart Failure ; mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Treatment Outcome

OBJECTIVETo explore the health related quality of life (QOL) status of patients with peripheral facial paralysis.

METHODSBy introducing, translating and adjusting of the FaCE (Facial Clinimetric Evaluation) scale, a Chinese version came into being. The scale was further strictly tested in eighty-one patients with peripheral facial paralysis and thirty healthy volunteers.

RESULTSThe feasibility, reliability, validity and responsibility of Chinese version of FaCE scale all passed the test. The split-half reliability, Cronbach's alpha and intraclass correlation coefficient were 0.79, 0.88 and 0.87, respectively. The criteria validity calculated between FaCE and SF-36 was 0.41 (P < 0.05). Factor analysis of the construct validity showed that the 15 items were classified into six domains, which were in accordance with the original version. Every domain was sensitive and effective to discriminate between patient population and healthy population (P < 0.05). Chinese version of FaCE scale showed significant correlation with HBGS and SBGS scores (r = -0.40 and 0.42, P < 0.05).

CONCLUSIONChinese version of the FaCE scale can effectively assess QOL status of patients with facial paralysis in China.

Adolescent ; Adult ; Aged ; Facial Paralysis ; Humans ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo explore the correlation of males'age with sperm apoptosis, sperm DNA integrity and other seminal parameters.

METHODSWe collected 104 semen samples and divided them into three groups according to the males' age: <35 yr (n = 43), 35 -39 yr (n = 31), and > or = 40 yr (n = 30). Based on the WHO Laboratory Manual (4th ed), we detected the seminal parameters, calculated the percentage of apoptotic sperm by flow cytometry (FCM), determined sperm DNA integrity by Acridine orange staining, and compared the results among the three groups.

RESULTSThere were no statistically significant differences among the < 35 yr, 35 -39 yr and > or = 40 yr groups in semen volume ([2.87 +/- 0.89] ml vs [2.98 +/- 1.09] ml vs [2.65 +/- 0.95] ml), sperm concentration ([60.40 +/- 25.43] x 10(6)/ml vs [69.74 +/- 28.33] x 10(6)/ml vs [55.97 +/- 27.22] x 10(6)/ml) (P>0.05). The percentage of progressively motile sperm was significantly lower in the > or = 40 yr ([39.00 +/- 8.35 %) than in the <35 and 35 -39 yr groups ([48.73 +/- 9.89]% and [45.65 +/- 10.55]%) (P<.0.1), and so was the percentage of morphologically normal sperm in the > or = 40 yr than in the < 35 yr group ([11.11 +/- 8.26]% vs [16.43 +/- 8.75 ]%, P<0.01). The percentage of apoptotic sperm was markedly higher in the > or = 40 yr than in the <35 yr group ([11.82 +/- 5.77]% vs [7.04 +/- 3.50]%, P<0.01), while the sperm DNA integrity significantly reduced in the > or = 40 yr group ([75.52 +/- 10.60]%) as compared with the <35 yr ([86.55 +/- 5.60])% and 35 -39 yr group ( [81.39 +/- 8.94]%) (P<0.01). The males' age was correlated positively with the rate of sperm apoptosis (P<0.01), and negatively with sperm DNA integrity and the percentage of progressively motile sperm (P<0.01).

CONCLUSIONThe advance in males' age increases sperm apoptosis and reduces sperm progressive motility, normal morphology and DNA integrity.

Adult ; Age Factors ; Apoptosis ; genetics ; DNA ; Flow Cytometry ; Humans ; Infertility, Male ; genetics ; Male ; Sperm Count ; Sperm Motility ; Spermatozoa ; cytology

OBJECTIVETo study the influence of male age on the outcome of conventional IVF-ET.

METHODSBased on male age, 170 couples undergoing conventional IVF-ET were divided into three groups: <35 yr (n = 60), 35 -39 yr (n = 77) and > or = 40 yr (n = 33). We observed the rates of fertilization, cleavage, good quality embryo, implantation, clinical pregnancy and abortion in different groups.

RESULTSThere were no significant differences among the three groups in semen volume ([3.10 +/- 1.22] ml vs [2.84 +/- 1.05] ml vs [2.80 +/- 0.79] ml), sperm concentration ([54.23 +/- 26.07] x 10(6)/ml vs [60.27 +/- 24.80] x 10(6)/ml vs [60.21 +/- 27.42] x 10(6)/ml) and sperm viability ([53.93 +/- 13.25]% vs [56.10 +/- 16.58]% vs [51.82 +/- 15.45]%) (P>0.05). The men of the > or = 40 yr group showed a significantly lower percentage of grade a + b sperm ([40.97 +/- 11.91]%) than those of the <35 and 35 - 39 yr groups ([48.47 +/- 11.78]% and [46.84 +/- 13.51]%) (P<0.05), and morphologically normal sperm ([11.76 +/- 5.97]%) than those of the <35 yr group ([15.25 +/- 6.94]% (P<0.05). The rates of fertilization, cleavage, good quality embryo, implantation, clinical pregnancy were 81.52%, 82.61%, 52.33%, 18.06% and 33.33% in the > or = 40 yr group, with no significant differences from those of the <35 yr group (83.18%, 82.68%, 56.99%, 22.40% and 40.00%) and the 35 - 39 yr group (78.78%, 80.66%, 55.01%, 21.74% and 38.96%) (P>0.05), while the abortion rate was markedly increased in the > or = 40 yr group as compared with the <35 yr group (36.36% vs 8.33%, P>0.05).

CONCLUSIONIncreasing male age is related with decreasing percentages of progressively motile sperm and morphologically normal sperm, but not obviously with the rates of fertilization, good quality embryo, implantation, pregnancy and abortion.

Adult ; Age Factors ; Female ; Fertilization in Vitro ; Humans ; Male ; Middle Aged ; Paternal Age ; Pregnancy ; Pregnancy Outcome

OBJECTIVEThis study was designed to evaluate the role of interleukin (IL)-1β in the development of fibrosis in mice exposed to silica.

METHODSThe total of 96 Male C57BL/6 mice were divided into four groups. (1) blank control group, (2) PBS group in which mice were instilled with PBS only, (3) silica + IL-1β mAb group in which mice were instilled with 2.5 mg silica dust and 40 µg anti-IL-1β mAb, (4) silica group in which mice were instilled with 2.5 mg silica dust and 40 µg IgG. The final volume of suspension or PBS instilled into the mouse was 50 µl. At 7, 28 and 84 days after treatment, 8 mice were sacrificed in each group. Then BALF was collected for the count of inflammatory cells and cytokines determination. The lung tissues were collected for the detecting of mRNA levels of fibrogenic molecules.

RESULTSThe collagen deposition induced by silica in the lung tissues was partly inhibited by anti-IL-1β. A intensely pulmonary cytokines such as IL-1β, TNF-α, MCP-1 were induced by crystalline silica exposure, and partly inhibited by anti-IL-1β. The levels of TGF-β and fibronectin in silica exposed mice were significantly elevated than those in control mice at days 28 and 84 after treatment (P < 0.01). And the mRNA levels of TGF-β, collagen I and fibronectin were significantly decreased in silica+IL-1β mAb group when compared with those in silica group at days 7, 28 and 84 (P < 0.01). There was a significant decrease of the ratios of IFN-γ/IL-4 in both silica+anti-IL-1β mAb and silica groups when compared with those in control mice at the above three time points (P < 0.01). However, the IFN-γ/IL-4 ratios in silica+anti-IL-1β group were significantly higher than those in silica group at 7, 28 and 84 days (P < 0.05 or P < 0.01).

CONCLUSIONIL-1β may promote the pulmonary fibrosis in mice exposed to silica.

Animals ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Collagen Type I ; metabolism ; Disease Models, Animal ; Fibronectins ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; physiology ; Interleukin-4 ; metabolism ; Lung ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Silicon Dioxide ; toxicity ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo evaluate the effect of clustering of cardiovascular risk factors (CVRFs) on type 2 diabetes mellitus (T2DM) incidence and identify some high predictive clusters in the Inner Mongolian population in China.

METHODSA total of 1,884 Mongolian individuals aged 20 years or above were followed up from 2002 to 2013 and included in the final analysis. We categorized the participants into two subgroups according to the study outcome event. A Cox proportional hazards model was used to evaluate the effect of clustering of CVRFs on the incidence of T2DM. Areas under the curve were used to compare the effect of every cluster on T2DM and identify those having higher predictive value.

RESULTSWe found 203 persons with T2DM. Subjects with incident T2DM tended to be older, had a higher prevalence of drinking, had higher systolic and diastolic pressures; total cholesterol, triglyceride, low-density lipoprotein cholesterol, and C-reactive protein levels; waist circumference; body mass index; and heart rate and lower HDL-C level than did those without T2DM. The multivariable adjusted hazard ratio (95% confidence interval) of T2DM was calculated based on comparisons with subjects with 0 CVRFs; in participants with 2 and ⪖ 3 factors, the adjusted hazard ratios were 2.257 (1.448, 3.518) and 3.316 (2.119, 5.188), respectively.

CONCLUSIONThe clustering of CVRFs increased the risk of T2DM. On the basis of fast heart rate, the cluster of abdominal obesity and other CVRFs had higher predictive value for T2DM than the other three CVRF clusters.

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑ^wsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β^{-88 C>G}/β^N). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.
Female ; Humans ; Male ; alpha-Thalassemia/genetics* ; beta-Globins/genetics* ; beta-Thalassemia/diagnosis* ; China ; Cohort Studies ; Genotype ; Molecular Biology ; Mutation

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ² test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism* ; Child ; Child, Preschool ; Copper/metabolism* ; Copper-Transporting ATPases/genetics* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies