Objective:To investigate the ultrasonographic features and genetic etiology of complex talipes equinovarus (TE) in fetuses.Methods:This retrospective study enrolled 95 cases of complex TE (TE complicated by other abnormalities) who were diagnosed by prenatal ultrasound in the Third Affiliated Hospital of Zhengzhou University from March 2018 to December 2022. Chromosome karyotype analysis and/or chromosomal microarray analysis (CMA) [or copy number variation-sequencing (CNV-seq)] were performed on all cases for prenatal genetic diagnosis and those with normal results were further tested by whole exome sequencing (WES). Prenatal ultrasonographic and genetic features of complex TE in fetuses were summarized. Complicated abnormalities in the fetuses were classified into nine categories according to the involved system or site and based on each category these subjects were divided into with or without the corresponding complicated abnormalities groups. Besides, these cases were also divided into single-system and multi-system abnormality groups based on the number of involved systems or sites of complicated abnormalities. The detection rates of WES abnormality (pathogenic or likely pathogenic variants) and the overall detection rate of genetic abnormality [karyotype abnormality detected by chromosome karyotype analysis, pathogenic or likely pathogenic copy number variations (CNVs) detected by CMA (or CNV-seq), and pathogenic or likely pathogenic variation detected by WES] were compared between different groups using Chi-square test or Fisher's exact test. Results:Abnormal chromosome karyotypes were identified in 10 (24.4%) of 41 cases receiving chromosome karyotype analysis, pathogenic and likely pathogenic CNVs were found in seven (7.6%) of 92 cases by CMA (or CNV-seq). WES was performed on 37 cases with negative results of chromosomal karyotype analysis and CMA (or CNV-seq) and the detection rate of pathogenic and likely pathogenic variants was 43.2% (16/37). The detection rate of WES abnormality was higher in the fetuses with musculoskeletal abnormalities than in those without the abnormalities [71.4% (15/21) vs. 1/16, Fisher's exact test, P<0.001], while in those with other postural abnormalities was higher than that in the group without other postural abnormalities [12/16 vs. 19.0% (4/21), Fisher's exact test, P=0.001]. The genetic causes of complex TE were identified in 34.7% (33/95) of the fetuses by the sequential genetic diagnosis using chromosome karyotype analysis, CMA (or CNV-seq), and WES. The overall detection rate of genetic abnormality was higher in the group with multi-system abnormality than in the group with single-system abnormality [48.9% (22/45) vs. 22.0% (11/50), χ2=7.55, P=0.006], in the group with musculoskeletal system abnormalities and without [46.8% (22/47) vs. 22.9% (11/48), χ2=5.98, P=0.014], and in the group with other postural abnormality and without [47.2% (17/36) vs. 27.1% (16/59), χ2=3.99, P=0.046]. Nine cases that were considered isolated TE on initial ultrasound were corrected to a complex diagnosis on subsequent ultrasound examinations. Of all the involved system or site, the neurologic abnormalities were the most diverse (13 kinds) and had a diversity of ultrasound presentations. Conclusions:Genetic diagnosis should be performed when prenatal ultrasound suggests fetal complex TE. WES is conducive to improving the prenatal detection rate of monogenic diseases, especially in fetuses complicated by musculoskeletal abnormalities. Isolated TE fetuses require serial ultrasound examinations to correct the diagnosis in time and genetic testing should be performed if necessary. Additional attention should be paid to the TE fetus for comorbid neurologic abnormalities at the time of ultrasonography to rule out TE as an intrauterine harbinger of neuromuscular disease.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Acute respiratory tract infection is the most common infectious disease in children, which seriously threatens children′s health.Rapid and accurate etiological diagnosis is of great significance for the clinical treatment and control of these diseases.Pathogen nucleic acid test was applied and became the main method of respiratory tract infection diagnosis for its high sensitivity and specificity.To regulate the application of pathogen nucleic acid amplification test in respiratory tract infection in children, improve the diagnosis level, expert consensus on nucleic acid amplification test of respiratory pathogens in children was prepared to guide the application and promote pathogens diagnosis ability.

This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing (Trio-WES). Prenatal diagnosis was performed because the ultrasound at 24 +4 gestational weeks revealed the fetus presenting with eclabium, flattened nose, short mandible, small auricle and abnormal posture of the toes. Copy number variation sequencing (CNV-seq) showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples. Trio-WES showed that the fetus carried two heterozygous mutations, c.2593-1G>A and c.7444C>T in ABCA12. Sanger sequencing confirmed that c.2593-1G>A, a previously unreported variant, was paternally inherited and c.7444C>T was maternally inherited. Both parents had normal phenotype. The fetus was finally diagnosed with harlequin ichthyosis. After prenatal counseling, the parents made an informed choice to terminate the pregnancy at 28 +4 gestational weeks. The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.

Radiotherapy and/or chemotherapy-induced oral mucositis is a common oral complication in tumor patients undergoing radiotherapy and/or chemotherapy, which seriously compromises patients’ quality of life and even affects anti-tumor treatment. Biomarkers are signal indicators that appear at different biological levels before or during disease. A comprehensive understanding of the biomarkers associated with oral mucositis contributes to the early identification of high-risk patients with oral mucositis and aids in the screening of patients prone to develop severe oral mucositis, guiding the prevention and treatment of oral mucositis. This article reviews the existing biomarkers associated with oral mucositis. The literature review results showed that the biomarkers associated with oral mucositis included growth factors, inflammatory cytokines, genes, plasma antioxidants, and pro-apoptotic proteins/inhibitor of apoptosis proteins. These biomarkers can be used to predict the risk of oral mucositis or facilitate early discrimination of patients prone to exhibit severe radiotherapy and/or chemotherapy-induced oral mucositis. EGF, TNF-α, IL-6, IL-1β and CRP can be used to predict and evaluate the risk and development of oral mucositis, whereas genes such as excision repair cross complementing 1(ERCC1), X-ray repair cross complementing 1(XRCC1), methylenetetrahydrofolate reductase (MTHFR) and tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) have been focus of research in recent years. The genotypes and expression levels of some of these genes exhibit variable capacities to predict the risk and severity of oral mucositis. However, no biomarkers have been used in clinical practice, and more studies are needed in the future to verify the reliability and accuracy of these biomarkers, to provide a reference for the early accurate prevention and treatment of radiation and chemotherapy oral mucositis.

Antibiotic-associated diarrhea(AAD) is a frequent adverse effect of antibiotic in children.AAD is associated with longer hospitalization, higher healthcare cost and even lead to death.Pediatricians usually do not pay enough attention to AAD.Domestic experts from pulmonary medicine, infection and gastroenterology are organized to develop the consensus, to improve the diagnosis, treatment and prevention of AAD, and contribute the children health in future.

This study was aimed to evaluate the clinical effect and safety of Qing-Fei Tong-Luo (QFTL) ointment for treating children with pneumonia.Randomized controlled trial (RCT) was conducted among 460 cases of children with pneumonia.The observation group was given QFTL ointment combined with basic treatment.And the control group was only treated by basic treatment.Evaluation was given on the total clinical efficacy,disappeared time of fever,cough,expectoration,shortness of breath,and medication safety.The incidence of respiratory diseases was followed up on the 30th days after drug withdrawal.The results showed that in the aspect of clinical efficacy between two groups,the cure rate of the observation group was 98.26％,and that of the control group was 93.89％,with statistic significance (P ＜ 0.05).The cure rate of the observation group was better than that of the control group.There was statistical difference on expectoration disappeared time (P ＜ 0.05).There was no statistical difference on disappeared time of fever,cough and shortness of breath (P ＞ 0.05).There was statistical difference on the incidence of respiratory diseases on the 30th days followed-up after drug withdrawal (P ＜ 0.05).There was no statistical difference on the incidence of upper respiratory tract infection,pneumonia and asthma (P ＞ 0.05).No adverse reactions occurred in the observation group.It was concluded that QFTL ointment combined with basic therapy on the treatment of pneumonia in children was significantly better than the control group in the aspect of clinical efficacy,expectoration disappeared time and the incidence of bronchitis.It is safe and effective.The prognosis is good and worthy of promotion in the clinical practice.

Objective To explore the morphological characteristics of intraepidermal nerve fibers in healthy Chinese by skin biopsy,to provide reference basis for the early diagnosis of peripheral neuropathy.Methods Skin biopsies samples were obtained from 192 healthy volunteers (half male and half female,collected in our hospital from June 2009 to August 2013),and these samples were divided into 6 groups according to different anatomic sites (far-end of the upper arm,far-end of the forearm,opisthenar,near-end of thigh,far-end of crus and acrotarsium) and 4 groups according to age (patients of younger than 20,patients of 21-40 years old,patients of 41-60 years old and patients of older than 61).Morphological observation of the intraepidermal nerve fibers was performed by skin biopsy and immunohistochemical technique.Results Various branch models emerged at each location:non-branching,branching at the epidermis-dermis junction,branching near the epidermis-dermis junction,branching at faraway side of epidermis-dermis junction,and branching near the cuticle.Branch models showed no significant diferences among patients of different ages.The above branch models appeared in far-end of the upper arm,far-end of the forearm,opisthenar,near-end of thigh,far-end of crus and acrotarsium,and as body based site famess,skin nerve fibers usually had more branches,and more axon expansion and varicose.Conclusions The age and lanatomic sites do not affect the branching pattems of intraepidermal nerve fibers.The closer to the extremities,the more branches of the intraepidermal nerve fiber.