Currently,the diagnosis of malignant pheochromocytoma still faces a big challenge.Neither biochemical nor histological features can be reliably used to distinguish malignancy from benign tumors.Numerous efforts have been applied to identify novel molecular markers to predict malignancy.

4"-O-isovaleryltransferase gene (ist) was regulated by positive regulatory genes of midecamycin 4"-O-propionyltransferase gene (mpt) in Streptomyces lividans TK24. A BamH I ~8.0 kb fragment from Streptomyces mycarofaciens 1748 was proved that it contained mpt gene and linked with two positive regulatory genes, orf27 and orf28. Orf of mpt was replaced by orf of ist and linked with two regulatory genes or orf27 single, and individually cloned into the vectors pKC1139 or pWHM3 (high copy number), and then transformed into S. lividans TK24. The levels of mpt and ist expression were evaluated by the bio-tramsformation efficacy of spiramycin into 4"-O-acylspiramycins in these transformants. The results showed that 4"-O-isovalerylspiramycins could be detected only in the transformants containing the plasmids constructed with pWHM3. The efficacy of bio-transformation of the transformants containing two regulatory genes was higher than that of orf27 single. So, the positive regulatory genes system of mpt gene could enhance ist gene expression.
Acyltransferases ; genetics ; metabolism ; Bacterial Proteins ; genetics ; metabolism ; Gene Expression ; Genetic Vectors ; Plasmids ; Spiramycin ; analogs & derivatives ; biosynthesis ; Streptomyces ; enzymology ; genetics ; Streptomyces lividans ; metabolism ; Transformation, Genetic

Objective To study the anti-oxidation properties of Zn2+-quercetin complexes .Methods The binding stoi-chiometric ratios and the binding constant of Zn2+ to quercetin were measured with UV-Vis spectroscopy .The binding sites on quercetin were determined via1 H NMR spectroscopy .The antioxidant activities of Zn2+-quercetin complexes were compared to quercetin by scavenging DPPH radical method .The binding ratio of Zn2+ to quercetin depends on neutralization of phenol groups of quercetin .Results The binding ratio of Zn2+ to quercetin is 1:2 when less than two OH groups were deprotonated . The binding ratio is 1:1 when more than three OH groups were deprotonated .The apparent binding constant is 2 .42 × 106 M -1 for the 1:1 Zn2+-quercetin complex .The 3′-OH and 4′-OH of quercetin are involved in the Zn2+ binding .The scavenging DPPH radical activity of Zn2+-quercetin complex is 2 .3 times of quercetin .Conclusion These results provide a new insight to expand applications of this traditional Chinese medicine .

OBJECTIVETo investigate the major influence factors of child neglect among rural areas children aged 3-6 years in China.

METHODSAccording to multi-stage stratified cluster sampling, distribution characteristics and the level of economic development, we randomly sampled 10 provinces, 26 cities (8 capital cities, 16 prefecture-level cities and 2 municipalities) using lottery method. Depending on the different level of economic and cultural, we sampled one medium county from each city (municipalities sampled two counties), a total of 28 counties. All towns were divided into high, medium and low three levels in accordance with economic and cultural, each level sampled one town, each conty sampled three towns, a total of 84 towns were sampled. Each town sampled 40 children, including 20 boys and 20 girls (including each 10 children aged 3 to 6, half and half boys and girls). 4 096 rural children aged 3-6 years old were sampled and surveyed of China. Based on "the Neglect Norms for Children Aged 3 to 6 Years Old in Rural Areas of China" explored the risk factors of child neglect. SPSS 18. 0 for windows was employed for statistics analysis. Multifactorial analysis was conducted through multivariate Logistic Regression.

RESULTSThe total neglected rate of the rural children aged 3 to 6 was 53.7% (2,047/3,810), and the total neglected degree was 44.42±7.57. The multivariate logistic regression analysis showed that, neglected risk of the boys was higher than the girls (OR=1.30, 95% CI: 1.13-1.49), neglected risk of children were higher, when their mothers were migrant workers (OR=2.18, 95% CI: 1.59-3.00); the lower educational level of mothers, the higher neglected risk of children, the children in families that mothers only received primary education or was uneducated were most likely to be neglected (OR=2.92, 95% CI: 1.91-4.47), the second was the families that mothers received primary education (OR=1.86, 95% CI: 1.29-2.69); the lower the household income, the easier to be neglected the children, the easiest one was the household income less than 5000 RMB (OR=2.85, 95% CI: 2.14-3.79), the second was 5000-9,999 RMB (OR=1.76, 95% CI: 1.40-2.20); the relationship between children and mothers was distanced, neglect risk of children was higher (OR=3.88, 95% CI: 1.31-11.52); left behind children were easier to be neglected (OR=1.30, 95% CI: 1.09-1.54).

CONCLUSIONThe influence factors among children aged 3-6 years in the rural areas of China were boys, mother's occupation, maternal education level, the relationship between children and mothers, household income and left-behind children.

Child Abuse ; Child, Preschool ; China ; Demography ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mothers ; Risk Factors ; Rural Population ; Surveys and Questionnaires ; Transients and Migrants

OBJECTIVETo develop a standard Neglect Evaluation Scale which is suitable for rural primary school students in China.

METHODSAccording to the principle of multi-stage stratified cluster sampling, a field investigation was conducted among primary school students in 28 counties from 7 provinces and 2 municipalities. The questionnaires were self-designed, and determined by multiple rounds of pilots and revisions. Among 5 862 students, 2 792 (6-8 years' old) and 3 070 (9-11 years' old) were investigated by using two kinds of Neglect Evaluation questionnaires, respectively. After project analysis, factor analysis, reliability and validity analysis, the reliability and stability of the scale were tested. Then percentile method was used to determine the evaluation standard to develop and finalize the formal scale.

RESULTSThe numbers of the remaining items for 6-8 year-old group and 9-11 year-old group is 69 and 58, respectively, both of which contain six levels of neglect, including body, emotion, health care, education, security, and society. 4 times of factor analysis were conducted in both of the two groups. The factor loadings in these two groups were 0.290-0.700 and 0.276-0.729 respectively. Reliability test results showed that the two kinds of scales' Cronbach alpha coefficient were 0.924 and 0.929 respectively, split-half reliability were 0.891 and 0.904 respectively, the retest reliability were 0.559 and 0.892 respectively, the differences were statistically significant (P < 0.05). The retest reliability among 6-8 year-old group in medical neglect level had no statistical significance, but was close to the cut-off point (P = 0.054). The test results of external validity indicated that both of the two scales could reflect the neglect status of the subjects (P < 0.05), but the subjective and objective evaluation towards neglect were not consistent. The cut-off points for judging whether the children were neglected or not among 6-8 year-old and 9-11 year-old groups were 159 and 137 respectively; and the adjusted values were 160 and 135 respectively.

CONCLUSIONThe two norm scales developed by this study showed good discriminability, reliability, validity, and stability. The norms developed on the basis of the scales was suitable for the situation of rural students in primary schools in China.

Child ; Child Abuse ; China ; Factor Analysis, Statistical ; Humans ; Reproducibility of Results ; Rural Population ; Schools ; Students ; Surveys and Questionnaires

OBJECTIVETo analyze pupils' neglect status aged 6-11 years in China's rural.

METHODSAccording to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect.

RESULTSThe total neglect rate of China's rural pupils aged 6-8 and 9-11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (χ2=3.59, P=0.058); the total neglect degree was 46.04±8.87 and 44.78±10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28±8.76) and female (39.0% (601/1,543) and 45.78±8.97) of aged 6-8 were all no statistical significant (χ2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53±10.11) were higher than female (38.7% (682/1,763) and 44.06±10.69) in the group of aged 9-11, which differences were all statistical significant (χ2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09±9.70) were higher than female (9.4% (155/1,648) and 47.37±9.89), which differences were all statistical significance (χ2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (χ2=8.92, P=0.003).

CONCLUSIONThe neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures.

Child ; Child Abuse ; China ; Female ; Humans ; Male ; Physical Examination ; Pupil ; Risk Factors ; Rural Population ; Schools ; Surveys and Questionnaires

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone