OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-β(TGF-β), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1β in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-β, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-β/Smad4 signaling pathway.
Mice ; Male ; Animals ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Olive Oil/therapeutic use* ; Carbon Tetrachloride/metabolism* ; Liver Cirrhosis/metabolism* ; Liver ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/metabolism*

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans ; Practice Guidelines as Topic

Objective:To acquire the differences in health and healthcare utilization among different regions with various economic development in China,so as to provide references for improving health inequalities related to economic development.Methods:Decomposing the health and healthcare utilization among different income groups.Results:Inequalities in health and healthcare utilization were captured,whereas the gaps among groups were enlarging over time in terms of low birth weight newborns and healthcare utilization.Conclusion:In order to promote the equality in newborns,more attention should be paid to high income regions.In order to improve the equality in healthcare utilization,more attention should be drawn to low income regions and rural areas.

OBJECTIVETo investigate the difference in the vulnerability of carotid atherosclerotic plaques in patients with unilateral and bilateral intraplaque hemorrhage (IPH).

METHODSA retrospective analysis was conducted among 44 patients with unilateral IPH (30 cases) or bilateral IPH (14 cases) in the carotid plaques detected by magnetic resonance imaging (MRI) in our hospital between December, 2009 and December, 2012. The age, maximum wall thickness and incidence of fibrous cap rupture were compared between the two groups.

RESULTSCompared with those with unilateral IPH, the patients with bilateral IPHs had a significantly younger age (66.6∓9.4 years vs 73.7∓9.0 years, P=0.027), a significantly greater maximum plaque thickness (6.3∓1.9 mm vs 5.0∓1.3 mm, P=0.035) and a higher incidence of ulcers (50% vs 13.3%, P=0.025). Logistic regression analysis revealed a significant association between bilateral IPHs and the occurrence of ulcer with an odd ratio (OR) of 6.5 (95% confidence interval [CI]: 1.5-28.7, P=0.014). After adjustment for gender in Model 1, bilateral IPHs were still significantly associated with presence of ulcer (OR=5.7, 95%CI: 1.1-29.2, P=0.036). But after adjustment for age (P=0.131) or maximum plaque thickness (P=0.139) in model 2, no significant correlation was found between bilateral IPHs and the presence of ulcer.

CONCLUSIONCompared with patients with unilateral IPH, those with bilateral IPHs are at a younger age and have a greater plaque burden and a higher incidence of fibrous cap rupture, suggesting a greater vulnerability of the carotid plaques in patients with bilateral IPHs.

Aged ; Carotid Arteries ; diagnostic imaging ; Carotid Stenosis ; diagnostic imaging ; physiopathology ; Fibrosis ; Hemorrhage ; diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Odds Ratio ; Plaque, Atherosclerotic ; diagnostic imaging ; Retrospective Studies

OBJECTIVETo investigate the influence of exposure to different concentrations of ethanol on neural progenitor cells and the differentiation of neurons and glial cells in zebrafish embryos.

METHODSZebrafish embryos were exposed to 1%, 2%, and 2.5% (V/V) ethanol at 5 hpf by adding ethanol to the egg water. In situ hybridization and real-time PCR were used to detect the changes in the mRNA expression profiles of the markers of different cells to examine the effects of alcohol on neural development.

RESULTSThe number of neural precursor cells, neurons and mature glial cells was significantly reduced in the zebrafish embryos following ethanol exposure, and this reduction became more prominent as the ethanol concentration increased. The expression of the early glial marker slc1a3a was down-regulated in the spinal cord but increased in the brain after exposure to increased ethanol concentrations. The expression of the mature glial markers was significantly lowered in response to exposure to increasing ethanol concentrations.

CONCLUSIONSEthanol can reduce neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.

Animals ; Brain ; Cell Differentiation ; drug effects ; Embryo, Nonmammalian ; drug effects ; Ethanol ; adverse effects ; Neural Stem Cells ; drug effects ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; Neurons ; drug effects ; Spinal Cord ; Zebrafish ; embryology

OBJECTIVEThe main purpose of this work was to give the evidence of reasonable and feasible dust control measures which will be taken in the future by analyzing the trend of dust concentration from 1991 to 2010 and identifying working faces with the severe dust contamination in one underground iron mine.

METHODSThe data was from routine monitoring between the years 1991 and 2010, which enclosed the total dust concentrations and silica contents. China National Standard of Occupational exposure limits for hazardous agents in the workplace used to judge whether the dust concentration exceeded the National Standard.

RESULTSThe general trend of total dust concentration from 1991 to 2010 was decreased, especially maximum and average levels. The highest exceeding rate was 43.16% in 1993 and the best years were 2009 and 2010, but the exceeding rates were still over 30%. The dust exposure levels varied with different work faces. The mining and supporting were the most severe dust pollution faces which the highest ultra exceeding rates were 51.61% and 51.48% and the maximum exceeding times were 64.6 and 16.4 respectively. The next was constructing face with 40.23% exceeding rate and 24.6 times more than standard.

CONCLUSIONThe trend of total dust concentration from 1991 to 2010 was decreased, but the dust exceeding rate was still high. The strong measures should be taken to control the dust pollution in this iron mine, especially mining and supporting faces.

Air Pollutants, Occupational ; analysis ; Dust ; analysis ; Environmental Monitoring ; Iron ; analysis ; Mining ; Occupational Exposure ; analysis

OBJECTIVETo observe serum TGF-beta1 and TNF-alpha in silicosis patients and workers exposed to silica dust to study the role of TGF-beta1 and TNF-alpha in the development of silicosis.

METHODSOne hundred non-exposed workers were selected as control group, 200 workers exposed to silica dust for more than 1 year as exposed group, 32 suspected silicosis patients (originally diagnosed as 0+) as observing group, 130 silicosis patients were as silicosis group. Serum TGF-beta1 and TNF-alpha in each group were determined with ELISA.

RESULTSSerum TNF-alpha in exposed group [(47.86 +/- 16.52) pg/ml], observing group [(109.11 +/- 31.08) pg/ml], silicosis group [(216.35 +/- 51.03) pg/ml] were significantly higher than that in control group [(6.90 +/- 2.24) pg/ml] (P < 0.01); Silicosis group and observing group were also higher than exposed group (P < 0.01, P < 0.05). Compared with control group [(23.28 +/- 12.24) pg/ml] and exposed group [(29.31 +/- 14.52) pg/ml], serum TGF-beta1 in silicosis group was much higher (P < 0.01).

CONCLUSIONTGF-beta1, and TNF-alpha were essential in the development of silicosis, so the detection of TGF-beta1 and TNF-alpha in peripheral blood was very useful for occupational health surveillance and early diagnosis of silicosis.

Adult ; Case-Control Studies ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Silicosis ; blood ; diagnosis ; Transforming Growth Factor beta1 ; blood ; Tumor Necrosis Factor-alpha ; blood