Clinical and genetic characteristics of congenital hypogonadotropic hypogonadism in boys / 中华实用儿科临床杂志

Objective:To analyze the clinical and genetic characteristics of congenital hypogonadotropic hypogonadism (CHH) in boys.Methods:Cross-sectional study.Clinical data, laboratory data and genetic results of boys who were genetically diagnosed with CHH at the Department of Endocrinology of Shenzhen Children′s Hospital from December 2019 to February 2023 were collected in this retrospective study.Their clinical manifestations, hormone levels and gene mutations were analyzed.The non-normal distribution was represented by the median.The rank sum test was used to compare the non-normal distribution data between the two groups.Results:A total of 27 boys were genetically diagnosed with CHH, with the age at first diagnosis ranging from 0.3 to 16.6 years old.All these children presented with micropenis (100%), of whom 16 were complicated with cryptorchidism (59.3%), 9 with microrchidia (33.3%), 7 with simple micropenis (25.9%), and no had simple cryptorchidism.Three children had cardiovascular dysplasia.The median of basal luteinizing hormone(LH) level was 0.09 IU/L, and 92.5%(25/27) of children had the basal LH level below 1.00 IU/L.The median of peak LH level after gonadotropin-releasing hormone(GnRH) stimulation was 1.42 IU/L, and 96.2%(26/27) of children had the peak LH level below 4.00 IU/L.The median of serum inhibin B was 41.15 μg/L, and the median of serum anti-Müllerian hormone(AMH) was 12.62 mg/L.The serum AMH level of children with cryptorchidism was significantly lower than that of children without cryptorchidism (10.02 mg/L vs.50.50 mg/L, P<0.05). A total of 12 gene mutations were detected in the 27 children, of which 1 was biallelic mutation.The most common gene mutations were in CHD7 and ANOS1 genes (7 children each, both accounting for 51.8%), followed by FGFR1 gene (3 children, 11.1%). After short-term treatment by GnRH pump or subcutaneous injection of recombinant human follicle stimulating hormone in 4 children, the levels of serum inhibin B and AMH increased significantly, and the testicular volume also increased. Conclusions:CHH is a congenital disease with different clinical manifestations at different ages.The main manifestations in childhood are micropenis and cryptorchidism, and some children have microrchidia.Its diagnosis in prepuberty is difficult, but genetic testing is of great significance for early diagnosis.

Sinogram interpolation combined with unsupervised image-to-image translation network for CT metal artifact correction / 南方医科大学学报

OBJECTIVE@#To propose a framework that combines sinogram interpolation with unsupervised image-to-image translation (UNIT) network to correct metal artifacts in CT images.@*METHODS@#The initially corrected CT image and the prior image without artifacts, which were considered as different elements in two different domains, were input into the image transformation network to obtain the corrected image. Verification experiments were carried out to assess the effectiveness of the proposed method using the simulation data, and PSNR and SSIM were calculated for quantitative evaluation of the performance of the method.@*RESULTS@#The experiment using the simulation data showed that the proposed method achieved better results for improving image quality as compared with other methods, and the corrected images preserved more details and structures. Compared with ADN algorithm, the proposed algorithm improved the PSNR and SSIM by 2.4449 and 0.0023 when the metal was small, by 5.9942 and 8.8388 for images with large metals, and by 8.8388 and 0.0130 when both small and large metals were present, respectively.@*CONCLUSION@#The proposed method for metal artifact correction can effectively remove metal artifacts, improve image quality, and preserve more details and structures on CT images.

Research progress on drug resistance of anti-varicella-zoster virus drugs / 中华预防医学杂志

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

Comparison of detection rates of chromosome G-banding karyotype analysis and fluorescence in situ hybridization among children with sex chromosome mosaicisms / 中华医学遗传学杂志

OBJECTIVE@#To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms.@*METHODS@#A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared.@*RESULTS@#The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05).@*CONCLUSION@#No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

Helsmoortel-Van der Aa syndrome due to hotspot mutation of ADNP gene and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis.@*METHODS@#Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed.@*RESULTS@#The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents.@*CONCLUSION@#Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

MYRF gene variant resulted in 46, XY disorders of sex development with aortic coarctation / 中华内分泌代谢杂志

To summarize the clinical manifestations of a case with 46, XY sex development disorder caused by myelin regulatory factor(MYRF) gene mutation and review the literature to deepen the specialists′ understanding of the clinical disease spectrum resulting from MYRF gene variations. The child had a female phenotype with mild masculinity, chromosome 46, XY, sex-determining region of Y gene(SRY gene) positive, laboratory tests were consistent with primary hypogonadism, ultrasound did not detect the gonads, but the residual reproductive tract was visible, and echocardiography suggested coarctation of the aorta, MYRF gene c. 2518C>T(p.R840*) heterozygous variant. The father did not carry this variant. The mother was untraceable, and genetic testing had not been completed. It was analyzed as pathogenic variation according to American College of Medical Genetics and Genomics(ACMG) guidelines. Sixteen cases of disorders of sex development caused by MYRF gene variation reported from 2018 to 2021 were reviewed, MYRF gene variants, 46, XY, and 46, XX individuals can be pathogenic, can affect the gonad and reproductive tract at the same time, and can also affect multiple systems. In this case, the patient presents with 46, XY sex development disorder due to MYRF gene mutation, accompanied by rare cardiovascular complications. When encountering 46, XY primary hypogonadism without well-developed Müllerian duct structures, this condition should be considered. Following confirmation, a comprehensive assessment of multi-organ function is necessary.

Analysis on epidemiological characteristics of dengue fever and E gene evolution of dengue virus in Guangzhou, 2020 / 中华流行病学杂志

Objective: To assess the incidence of dengue fever and E gene evolution of dengue virus in Guangzhou in 2020 and understand the local epidemiological characteristics of dengue fever and spreading of dengue virus. Methods: The information of dengue fever cases in Guangzhou in 2020 was collected from Notifiable Infectious Disease System of Chinese Center for Disease Control and Prevention Information System. Serum samples from the cases were detected by real-time PCR. The E gene was sequenced and analyzed. Maximum likelihood phylogenetic trees were constructed using software MEGA 5.05. The statistical analysis was conducted using software SPSS 20.0. Results: A total of 33 dengue fever cases were reported in Guangzhou in 2020, including 31 (93.94%) imported cases and 2 (6.06%) local cases. Compared with the data during 2016 to 2019, the number of cases, overall incidence and local incidence all decreased with statistically significant differences (all P<0.05). The imported cases from Southeast Asia constituted 90.32% (28/31) of imported cases. The E gene sequences and the phylogenetic trees of imported and local cases demonstrated close relationship with the virus sequences from Southeast Asian, and they were less homologous with the sequences of dengue virus isolated in Guangzhou in previous years. Conclusions: The incidence of dengue in Guangzhou in 2020 was significantly affected by the imported cases, especially those from Southeast Asian countries. The study result demonstrated that dengue fever was not endemic in Guangzhou and it was caused by imported ones.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Thyroid hormone metabolism defect caused by SECISBP2 gene mutation: a case report and literatures review / 中华内分泌代谢杂志

We reported the first case of a boy with selenocysteine insertion sequence binding protein 2 (SECISBP2) compound heterozygous mutation in China and provide a review of literatures to improve clinicians′ understanding of the thyroid hormone metabolism defect. Clinically, for children with growth retardation and delayed motor development, thyroid hormone metabolism deficiency should be considered if the thyroid function test shows normal or slightly elevated TSH, elevated T 4 and decreased T 3.

Changes and significance of CD8 + CD28 - regulatory T cells in acute phase of Kawasaki disease / 中华微生物学和免疫学杂志

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

DHX37 gene heterozygous variant—a frequent cause of embryonic testicular regression syndrome / 中华内分泌代谢杂志

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

Gender difference in clinical manifestations of KBG syndrome due to variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore gender difference in the clinical manifestations of two children with Keishi-Bukuryo-Gan syndrome (KBGS).@*METHODS@#Clinical manifestations of the two children were reviewed. Genetic testing was carried out through next generation sequencing (NGS). Treatment was summarized, and the prognosis was followed up.@*RESULTS@#Both children showed particular appearance including megatooth, abnormal hair distribution, hands' abnormality and language development delay. NGS revealed that both children have carried pathogenic variants of the ANKRD11 gene (c.1903_1907del and c.4911delT), which resulted in shifting of amino acid sequences starting from the Lysine and Proline at positions 635 and 1638, respectively. The female patient exhibited central precocious puberty. Her height has increased by 13 cm, and sex characteristics has retracted after treatment with leuprorelin for 23 months and recombinant human growth hormone for 1 month.@*CONCLUSION@#Comparison of the two cases with different genders and summary of previously reported cases found that male KBGS patients have more obvious dysmorphisms such as triangular face, synophrys, ocular hypertelorism and vertebral body abnormality, with higher morbidity of epilepsy, mental retardation, autism, congenital heart disease, immune thrombocytopenia and other complications. KBGS is an autosomal dominant disease featuring more evident peculiar appearance and global development delay. Male patients often have multi-system involvement, and multidisciplinary cooperation is required for early recognition of particular features in order to improve the prognosis.

DMRT1 gene variant/haploinsufficiency and 46, XY disorders of sex development / 中华内分泌代谢杂志

Objective:To summarize the clinical manifestations of four patients with 46, XY disorders of sex development(46, XY DSD)due to doublesex and mab-3 related transcription factor 1(DMRT1)gene variant/haploinsufficiency, and to improve the understanding of clinicians for this disease.Methods:The medical history, physical examination, endocrine function assessment, gonadal pathology, and genetic data of 4 patients with 46, XY DSD were retrospectively collected.Results:A heterozygous new missense mutation in DMRT1 was found in one child. The chief complain was primary amenorrhoea at the age of 15 years, with the external masculinisation score(EMS)0. The DMRT1 haploinsufficiency was found in 3 cases, 1.2 Mb, 5.1 Mb, and 6.0 Mb fragments were deleted at the 9p, and one of 3 cases had 33.3 Mb repeats in the 5p. All patients visited doctor under 1 year. Two patients were raised as females, and one was raised as male. All chief complains were external genital abnormalities, EMS of them were 1, 0, and 5 respectively. Endocrine evaluation of 2 out of 4 children showed varying degrees of primary hypogonadism, and presented with complete gonadal dysgenesis. One patient showed a well function of Leydig cells and poorly function of Sertoil cells, and presented with mixed gonadal dysgenesis. One of 3 cases was diagnosed with gonadoblastoma at the age of 18 months. Patient No.4 didn′t agree with the gonadal biopsy. The chromosome karyotypes of 4 children were 46, XY.Conclusions:The visiting ages of 46, XY DSD patients caused by DMRT1 variation were older than those of patients caused by DMRT1 haploinsufficiency. The clinical manifestations are complex, and gonadal function can vary from normal to complete gonadal dysgenesis. Such patients are at high risk of gonadoblastoma and young onset. Gonadal biopsy should be performed as early as possible.

Factors affecting skeletal maturation / 国际儿科学杂志

Skeletal maturation is a complex process involving the appearance of ossification centers, the width and capping of the epiphysis, and the fusion of the epiphysis.Bone age is considered to be a valuable tool in assessing children′s skeletal maturity and evaluating growth.Many factors influence the progress of skeletal maturation, which are mainly devided into endocrine and non-endocrine ones.The former include estrogen, adrenal hormone, growth hormone, and thyroid hormone.The latter contain nutrition, chronic disease, environment or diet, genetics, etc.But there is not a scientific system that has been established.Whether some factors are responsible for skeletal maturation is still controversial, such as insulin-like growth factor-1, leptin, sex hormone binding globulin, insulin and so on.This review focuses on the factors affecting skeletal maturation.It is expected to develop individualized programs in the clinical evaluation and management of children with growth and related diseases, and to provide references for further research.

A review of studies on health status of migrant children / 国际儿科学杂志

Since the reform and opening up, a large number of migrant population have appeared in our country, which has created a special social group of migrant children; and there is no concept of migrant children based on household registration system abroad.However, there are immigrant and refugee children, and the health of migrant children is influenced by the living and/or learning environment as well as factors such as diet, guardianship and health care conditions.According to current studies at home and abroad, the health status of migrant children is lower than that of non-migrant children, so more attention and supports are needed in the areas of psychological status, social support, disease occurrence, nutrition intake, height growth, health care services, etc.Targeted measures have been formulated in the areas of psychological care, public health and medical security to improve the health status of migrant children.

Case report of fetal alcohol syndrome / 中华实用儿科临床杂志

The clinical characteristics of a case of fetal alcohol syndrome (FAS) diagnosed by Shenzhen Children′s Hospital were summarized.The patient was 6 years and 4 months old, and admitted to the hospital because of her " slow growth of height for more than 6 years" . There was a history of alcohol exposure in the fetus.The infant was born with low body mass, and grew slowly in height and body mass after birth.She was diagnosed with FAS due to typical facial features of FAS, microcephalia, poor memory and narrative ability.The effect of alcohol exposure during pregnancy on fetus is permanent, and abstinence is the only way to prevent FAS.In this paper, the clinical characteristics of FAS were summarized and the literature was reviewed in order to improve the clinical understanding of the disease.

Growth profile of children with common type disorders of sex development / 中华实用儿科临床杂志

With the advancement of genetic testing technology, more and more patients were diagnosed with disorders of sex development (DSD) at an increasingly earlier stage.How to better improve the quality of life in patients with DSD has become an urgent problem for medical workers.The growth of children with DSD is an important factor affecting their treatment and quality of life, so it should also be concerned by the majority of medical workers.The factors affecting the growth of children with DSD and the characteristics of the growth patterns of children with common type DSD were described in this review.

Comparison of molecular characteristics between infective and colonizing strains in children with invasive Staphylococcus aureus infection / 中华实用儿科临床杂志

Objective:To study the molecular biological characteristics of isolates from the infection site and isolates colonizing in anterior nares of children with invasive Staphylococcus aureus (SA) infection, and to analyze the concordance between the two types of strains from different sources. Methods:A total of 45 strains were collected from children with invasive SA infection treated in the Pediatric Ward of Sichuan Provincial Maternal and Child Health Care Hospital from January 2019 to August 2019, and 28 colonization isolates were obtained from the anterior nares of these patients.The susceptibility test was carried out by broth dilution method.The drug resistance genes mecA and blaZ and the virulence gene panton-valentine leucocidin( pvl) were detected by PCR.The homology of infective and colonizing isolates was detected by pulsed-field gel electrophoresis(PFGE)typing technique. Results:Colonization of SA was found in the nasal vestibule of 62.2% (28/45 cases) of patients with invasive SA infection.A total of 40.0% (18/45 strains) of the infective isolates and 32.1% (9/28 strains) of the colonizing isolates were Methicillin-resistant SA (MRSA), and the difference was not statistically significant( P>0.05). The resistance of infective isolates to Clindamycin, Azithromycin and Erythromycin was stronger than that of colonizing isolates, the difference of drug resistance rate was statistically significant( χ2=7.114, 7.820, 5.359, all P<0.05). There were no differences in the carrying rates of the drug resistance gene blaZ and the virulence gene pvl between the infective and colonizing bacteria( P>0.05). Phenotypically, Methicillin-susceptible SA (MSSA)was more susceptible to concordant colonization than MRSA[16.7%(3/18 cases) vs.48.1%(13/27 cases), χ2=4.671, P<0.05]. PFGE indicated that patients with invasive MSSA infection were significantly more likely to have a concordant MSSA colonization isolate in their anterior nares, compared with patients with invasive MRSA infection[59.3%(16/27 strains) vs.27.8%(5/18 strains), χ2=4.301, P<0.05]. Conclusions:The infective and colonizing strains of invasive SA show no difference in their resistance to some anti-biotics, but they carry almost the same number of drug resistance and virulence genes.Compared with those with MRSA infection, patients with MSSA infection are more likely to have concordant colonizing isolates.It is of potential clinical significance to screen the colonizing SA strains in patients with invasive SA infection.

Quality evaluation and specification research of Cervus and Cucumis polypeptide injection / 中国药科大学学报

@#To investigate the freshness, high molecular weight substances, the determination of polypeptide, haemolysis and agglomeration, biological activity of Cervus and Cucumis polypeptide injection; to provide the direction for improving the quality of products for enterprises; furthermore, to provide reference for the revision of the quality standards of Cervus and Cucumis polypeptide injection. Firstly, we investigated the factors affecting the freshness of the injection, including biogenic amines, aflatoxins, the acid value and peroxide value of the melon seeds. The method of dansyl chloride pre-column derivatization-HPLC was used to determine the content of 8 biogenic amines in Cervus and Cucumis polypeptide injection. The method validation results showed good specificity, precision, linearity and recovery rates, which was suitable for the determination of biogenic amines in Cervus and Cucumis polypeptide injection. The results of sample determination showed that relatively higher concentrations of cadaverine were detected in the products from company B. The results of aflatoxins, acid value and peroxide value showed that the melon seeds from some companies had rancidity, mildew and other problems, indicating that the quality standards of multi-component biochemical drugs containing animal- and plant-derived components should be controlled in terms of freshness. Secondly, the methods for the determination of high molecular weight substances and polypeptides in the quality standard were improved. Tricine-SDS-PAGE electrophoresis was used instead of gel chromatography to determine the high molecular weight substances, which improved the accuracy of determination. The kits were used instead of folin-phenol for the determination of peptide content, which is easy to operate, specific and suitable for high-throughput sample determination. Finally, the haemolysis, agglomeration, and biological activity of Cervus and Cucumis polypeptide injection were studied. The results showed that no haemolysis and agglomeration were found in all samples, and the inhibitory effect of samples on THP-1 proliferation in vitro from different companies was different to some extent. In conclusion, the optimized quality standard is more suitable for the detection of Cervus and Cucumis polypeptide injection, and can lay the foundation for improving the safety of multi-component biochemical drugs.