Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg-1）， and low-dose （4.78 g·kg-1·d-1）， middle-dose （9.56 g·kg-1·d-1）， and high-dose （19 g·kg-1·d-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

The Material Basis of Bitter Taste Drugs in Pulmonary Diseases was Analyzed Based on the Research Progress of Bitter Taste Receptors in Respiratory Diseases / 世界科学技术-中医药现代化

Bitter taste is one of the important contents in the theory of"Five tastes"in traditional Chinese medicine(TCM).It has the functions of"releasing,dryness and firmness"and plays an important role in the treatment of respiratory diseases.Bitter taste receptors(T2Rs)is a kind of G-protein-coupled receptors,studies have shown that it can act on human airway smooth muscle,relax smooth muscle and dilate bronchus,and play a vital role in the treatment of bronchial asthma and chronic obstructive pulmonary disease.It can also inhibit the inflammatory reaction and reduce the damage of lung tissue by reducing the release of inflammatory factors and promoting the apoptosis of inflammatory cells.The therapeutic mechanism of bitter Chinese herbs action may depend on the effect of T2Rs,the effects of bitter Chinese herbs such as"lowering qi","releasing heat","eliminating dampness"are quite consistent with the cognitions of western medicine that bitter taste receptors could"relaxe bronchus","reduce airway resistance","inhibits inflammatory factors"and"reduces mucus secretion".Based on the understanding of bitter taste in TCM theory and modern research,this study aims to discuss the effect of bitter Chinese herbs depend on T2Rs as the starting point,so as to provide a new research direction for clinical treatment of pulmonary diseases such as bronchial asthma and chronic obstructive pulmonary disease.

Progress of Research on the Cause of Tobacco Smoke is Based on the Discussion of the Endogenous Mechanism other than"Tobacco Poisoning" / 世界科学技术-中医药现代化

In the past decades,numerous chemical analysis studies have identified numerous compounds in tobacco smoke,and the number is increasing,as of 2013,9582 compounds have been identified in tobacco smoke,including nicotine,tobacco smoke-specific nitrosamines,benzo[alpha]pyrene and other substances,as well as cotinine,4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol and other products that are metabolized in the body.The products of metabolic transformation,such as cotinine and 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol,can target the heart,lungs and other organs,inducing chronic obstructive pulmonary disease,coronary heart disease,lung cancer,esophageal cancer and other types of cancer.Chinese medicine's understanding of"toxicity"originates from the Nei Jing,which believes that"poisonous evil"can be an external pathogenic factor,but can also cause the five organs to lose harmony and produce phlegm and stagnation and other pathological products that accumulate into internal toxicity.The modern medical understanding of tobacco smoke toxic substances and their metabolites is quite consistent with the understanding of"external toxicity"and"internal toxicity"in Chinese medicine,so the author intends to explore the main components and pathogenic mechanisms of tobacco smoke harmful substances and their metabolites.To clarify the etiological characteristics and pathogenic transformation characteristics of"internal"and"external"tobacco smoke toxicity,so as to explore the modernization of"tobacco smoke toxicity"and the combination of tobacco smoke pathogenesis and TCM theory for TCM.Theoretical foundation is laid.

A comparative study between one-stage Hui-Jing procedure and Bracka two-stage procedure for the treatment of severe hypospadias / 中华泌尿外科杂志

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.

Comparison of modified "double flaps" pyeloplasty and traditional pyeloplasty in the treatment of special types of hydronephrosis in children / 中华泌尿外科杂志

Objective:To compare the efficacy of modified "double flaps" pyeloplasty and traditional dismembered pyeloplasty in the treatment of special types of hydronephrosis with small pelvis and long proximal ureteral stricture in children.Methods:The data of 39 children with special types of hydronephrosis treated in Seventh Medical Center, General Hospital of PLA from June 2018 to June 2019 were retrospectively analyzed. Among them, 33 were boys and 6 were girls. The median age of the patients was 12.0(4.5, 63.5) months. Nine of them had left hydronephrosis and four children had right hydronephrosis. These patients with small pelvis existed the characteristics that the anteroposterior diameter of pelvis was smaller than 2.5 cm and these patients existed the symptom of hematuria, flank pain or recurrent urinary tract infection with the imaging revealing ureteral obstruction. The length of proximal ureteral stenosis ranged from 2.0 to 4.0 cm. Among 39 cases, 19 cases were operated with modified "double flaps" pyeloplasty, which was the modified "double flaps" pyeloplasty group. 20 cases were operated with traditional Anderson-Hynes pyeloplasty, which was traditional pyeloplasty group. The technique of modified "double flaps" pyeloplasty mainly included that the renal pelvis was cut into double flaps, the inferior flap was anastomosed with the spatulated ureter and the superior was covered, so that the length and caliber of the ureter were partial extended. The median age of two groups were 12.0 (6.0, 44.0) months and 12.0 (4.8, 62.8) months respectively, the anterior and posterior diameter of renal pelvis were (2.8±0.8)cm and (2.6±0.6)cm respectively, and split renal function were (36.7±5.1)% and (36.0±6.8)% respectively. There were no statistically significant differences in above parameters between the two groups( P>0.05). The clinical efficacy of the two groups were compared by collecting and comparing the operation related data and postoperative follow-up data. Results:The operation of 39 children in this study was successfully completed without conversion to open surgery.The operation time of "double flap" pyeloplasty group and traditional pyeloplasty group were (142.6±9.6) min and (124.5±8.6) min respectively, and the intraoperative anastomosis time were (56.1±7.2) min and (47.6±4.8) min respectively. There were significant difference in operation time and intraoperative anastomosis time between the two groups( P<0.05). Thirty-nine children were followed up normally without loss. The mean follow-up time was (27.7±2.5) months after surgery. In the "double flaps" pyeloplasty group, 2 cases suffered with fever who were diagnosed as urinary tract infection and improved after antibiotic treatment. In the traditional pyeloplasty group, 2 cases suffered with fever who were diagnosed as urinary tract infection and improved after antibiotic treatment. Two children had flank pain during follow-up to more than one year and the examination revealed that the anteroposterior diameter of the renal pelvis gradually increased. So surgery were performed again and the two children recovered. There were no significant differences in complication rate (2/19 and 4/20) and short-term surgical success rate(19/19 and 18/20) between the two groups ( P>0.05). Conclusions:The operation time and anastomosis time of the modified "double flap" technique for treating hydronephrosis are longer than those of the traditional method. But in the treatment of special types of hydronephrosis with small renal pelvis or long proximal ureteral stricture, it may have application prospects in reducing complications.

Advances in the RNA N6-methyladenine modification in regulating pubertal sexual development / 国际儿科学杂志

N6-methyladenine(m 6A)has been identified as the most abundant, common and conserved internal RNA modification.RNA m 6A can couple different levels of gene regulation and may play an important role in epigenetic regulation(such as RNA splicing, translation, stabilization, and ectopic). Studies have shown that RNA m 6A methylation is an important factor in pubertal sexual development.The abundance of RNA m 6A methylation changed with the progression of pubertal development.The abnormalities of RNA m 6A methylation can lead to dysfunction of hypothalamic gonadotropin-releasing hormone(GnRH)neuronal networks.Those genes affected by RNA m 6A methylation may be critical targets in regulating puberty initiation.The review summarizes the research progress between RNA m 6A methylation and pubertal sexual development to provide the evidence to discover new therapeutic targets and improve the prognosis of the disease.

A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature / 中华儿科杂志

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.

Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

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.

Species Differences of Bakuchiol-induced Liver Injury in Mice Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

Scanning electron microscopic observation of the external morphology of Dermatophagoides farinae at different developmental stages / 中国血吸虫病防治杂志

Objective To investigate the morphological characteristics of Dermatophagoides farinae at different developmental stages. Methods The cultured D. farinae was isolated, and the external morphological features of mites at various developmental stages were observed using scanning electron microscopy (SEM), including egg, larva, nymph and adult stages. Results The D. farinae egg appeared a long oval shape, and the larval mites had three pairs of legs. The nymph had four pairs of legs and underdeveloped genital pores containing genital setae and anal setae, and adult mites appeared long and oval in shape, with decorative patterns on epidermis, and had four pairs of legs. In male adult mites, remarkable thickening of the leg I and thicker and longer leg III than the leg IV were seen, and ventral genital regions were found between the basal segments of legs III and IV; the anus was surrounded by a circular peri-anal ring, with a pair of anal suckers and anal setae within the ring. In the female adult mites, slender legs III and IV with an equal length were seen, and a “λ-shape” genital hole was observed on the ventral surface, with a crescent-like genital plate in the anterior part, and the anus appeared a longitudinal slit. Conclusions An SEM observation of the external morphology of D. farinae provides understandings of the morphological characteristics of D. farinae, which is of great significance for the classification and identification.

Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain.@*METHODS@#A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate.@*RESULTS@#Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%).@*CONCLUSIONS@#Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

A follow-up study on the introduction of vegetables and fruits during infants aged 4-8 months in Beijing and Chenzhou City of Hunan Province / 北京大学学报(医学版)

OBJECTIVE@#To investigate the introduction of vegetables and fruits in 4-8 months old infants, and to describe the maternal and infants' characteristics associated with the introduction of vegetables and fruits.@*METHODS@#Mother-infant dyads (n=228) were recruited from 12 to 16 weeks postpartum and formally entered the study at 4 months of age. Data collected via face to face interview at 4-8 months postpartum, including the timing and types of added vegetables and fruits, as well as a variety of maternal and infant characteristics (n=204). Rank sum test and multiple linear regression were used to analyze the maternal and infant characteristics related to the introduction of vegetables and fruits.@*RESULTS@#The time of introducing vegetables was concentrated at the age of 7 months, and the time of adding fruits was mainly at 6 months. Fruits were added earlier than vegetables (P < 0.001), and the variety of the added fruits was higher than that of vegetables (P=0.045). 48% (n=98) of infants had no more than three types of fruits and vegetables at 8 months. Only 9.8% (n=20) had added more than 10 kinds of fruits and vegetables at 8 months. Green leafy vegetables were the most commonly added vegetable, and apple was the most popular fruit. Compared with women who were 35 years of age or younger, women beyond 35 years old introduced vegetables to their babies 0.6 months later. 4-month-old exclusively breastfed infants had vegetables 0.4 months later than mixed-fed infants. Women with a bachelor's degree or above added 2-3 more types of fruits and vegetables to their babies than those with junior high school education and below.@*CONCLUSION@#The adding time of fruits was earlier than that of vegetable. Apples and green leafy vegetables are commonly added. Women with lower educational backgrounds add fewer types of fruits and vegetables to their babies. Mothers who choose exclusive breastfeeding and those over 35 years of age at childbirth add vegetables to their babies later than others. They should be targeted for health promotion programs that aim to improve the intake of fruits and vegetables among infants.

The incidence of non-thyroidal illness syndrome in children with type 1 diabetes mellitus and correlated factors analysis / 中华实用儿科临床杂志

Objective:To explore the incidence of non-thyroidal illness syndrome (NTIS) in children with type 1 diabetes mellitus (T1DM) and the correlation between triiodothyronine level and the severity of T1DM, thus providing evidence for clinical diagnosis and treatment.Methods:A total of 125 children initially diagnosed as T1DM at the Department of Endocrinology and Genetic Metabolism of Children′s Hospital of Shanghai Jiao Tong University from January 2015 to December 2019 were recruited.The data were retrospectively analyzed.The incidence of NTIS in T1DM children was explored.T1DM children were classified into euthyroid group and NTIS group, two independent sample t-test were used to compare the differences in multiple factors between euthyroid group and NTIS group in children with T1DM, and Spearman correlation analysis was used to further analyze the correlation between the levels of free triiodothyronine (FT3), total triiodothyronine (TT3) and the severity of children with primary T1DM. Results:The incidence of NTIS in 125 T1DM children was 26.4%(33/125 cases). FT3, TT3, total thyroxine (TT4), thyrotropin (TSH), pH value, HCO 3- and high density lipoprotein cholesterol (HDL-C) levels in NTIS group were significantly lower than those of euthyroid group [(3.10±0.45) pmol/L vs.(4.85±0.75) pmol/L, (0.60±0.28) nmol/L vs.(1.05±0.38) nmol/L, (65.77±23.41) nmol/L vs.(89.57±18.23) nmol/L, (0.91±0.89) mIU/L vs.(2.05±0.76) mIU/L, 7.21±0.17 vs.7.31±0.18, (11.49±7.54) mmol/L vs.(16.80±8.38) mmol/L, (1.08±0.49) mmol/L vs.(1.28±0.44) mmol/L]( t=4.56, 5.67, 4.48, 5.61, 2.82, 2.68, and 2.53, all P<0.05). Moreover, the anion gap (AG) level, blood glucose (BG) and triglyceride in NTIS group were significantly higher than those of euthyroid group [(22.53±8.33) mmol/L vs.(16.94±7.52) mmol/L, (24.85±4.71) mmol/L vs.(21.46±6.64) mmol/L, (2.72±2.05) mmol/L vs.(2.33±3.05) mmol/L]( t=3.22, 2.67 and 2.04, all P<0.05). The incidence of diabetic ketoacidosis (DKA) was statistically significant in euthyroid group, NTIS group and abnormal thyroid disease group (33.3% vs.63.6% vs.35.7%)( χ2=8.990, P<0.05). In T1DM children, FT3 was positively correlated with pH value and HCO 3-, and negatively correlated with AG level ( r=0.376 9, 0.439 7 and -0.411 9, all P<0.05). In addition, TT3 was positively correlated with pH value and HCO 3-, and negatively correlated with AG and BG ( r=0.513 2, 0.539 8, -0.482 4 and -0.211 5, all P<0.05). Conclusions:Children with T1DM are prone to have abnormal thyroid hormone levels, and the incidence of NTIS was 26.4%.The incidence of DKA differed in T1DM children with different thyroid functions.FT3 or TT3 level may contribute to evaluate the disease severity of T1DM children.

Potential hepatotoxic compounds and mechanisms of Epimedii Folium based on network toxicology and cell experimental validation / 中国中药杂志

To probe the potential hepatotoxic components of Epimedii Folium and investigate its mechanism based on network toxicology and cell experimental validation. According to the previous results of component measurement and cytotoxicity evaluation, 11 active compounds related to hepatotoxicity in Epimedii Folium were chosen as research object in this study. Through SwissTargetPrediction database and GeneCards database, the potentially hepatotoxic targets of Epimedii Folium were obtained. Subsequently, the protein-target interaction network and active compounds-hepatotoxic targets network were established to analyze the core targets and screen the key hepatotoxic compounds in Epimedii Folium. Meanwhile, the signaling pathways and molecular mechanisms were inferred with GO functional enrichment analysis and KEGG pathway enrichment analysis on the core targets. At last, the effect of icaritin as the chief hepatotoxic compound on the indexes related to hepatotoxicity in HL-7702 cells and HepG2 cells was investigated to validate the hepatotoxicity mechanism of Epimedii Folium. Through the network toxicology analysis, 190 action targets and 991 hepatotoxic targets were collected, then 64 potentially hepatotoxic targets of Epimedii Folium including AKT1, EGFR, MAPK3, TNF and so on were obtained, and icaritin was screened as the key hepatotoxic compound. GO functional enrichment analysis indicated 160 biological process terms such as protein phosphorylation and negative regulation of apoptotic process, 41 molecular function terms such as protein binding and ATP binding, and 32 cellular component terms such as cytosol and cell surface. KEGG pathway enrichment analysis inferred 75 signaling pathways involving PI3 K-Akt and HIF-1. After comprehensive analysis, it was inferred that the hepatotoxicity mechanism of Epimedii Folium was related with regulating oxidative stress and apoptosis. The results of cell biology experiments showed that icaritin could significantly increase the level of aspartate aminotransferase and lactate dehydrogenase, reduce the level of glutathione, improve the quality of reactive oxygen species and reduce mitochondrial membrane potential, indicating that it could cause hepatotoxicity by destroying cell membrane structure, inhibiting antioxidant enzyme activity, activating oxidative stress and inducing apoptosis. These results proved the reliability of results of network pharmacology. This study preliminarily clarified the material base and the mechanism of potential hepatotoxicity of Epimedii Folium, which provided important information for further research and safe application.

Analysis of epidemic characteristics of COVID-19 clusters in Chenzhou， Hunan Province / 上海预防医学

Objective:To analyze the epidemiological characteristics of 8 clusters of coronavirus disease 2019 （COVID-19） in Chenzhou City， and provide scientific basis for epidemic prevention and control. Methods:Descriptive epidemiological analysis was conducted for 8 COVID-19 clusters， comparing and analyzing the differences of infection rates among close contacts within and outside the family， and emphatically describing two typical cases. Results:8 COVID-19 clusters were reported in Chenzhou with a total of 31 cases from January to February， 2020. The main source of infection of the family index cases was Hubei Province. Cough symptoms were observed in 67.74% of the cases， followed by fever （54.84%）. The infection rate of close contacts within the family （55.00%） was higher than that outside the family （2.56%）， and the difference was statistically significant （χ2=28.177， P<0.001）. The infection rate of spouse of the family index cases was 85.71%， higher than that of parents （77.78%）， other family members （44.44%） and children （40.00%）， and the difference was not statistically significant （χ2=6.004， P=0.120）. Two typical cases suggested that both COVID-19 pre-symptomatic and asymptomatic patients have the potential to excrete the virus from the body and become sources of infection. Conclusion:Effective family prevention and control measures and early sampling and screening of people in key epidemic areas are conducive to early detection， early isolation and early treatment of infected people， so as to avoid the occurrence and spread of family clusters.

Exploring Key Genes and Signaling Pathways in Treatment of Bronchial Asthma with Xiao Qinglongtang Based on Network Pharmacology and Bioinformatics / 中国实验方剂学杂志

Objective:This research aims to construct the "disease-gene-target-components-drug" network with the methods of network pharmacology and bioinformatics， and to explore the key genes and signaling pathways of Xiao Qinglongtang in the treatment of bronchial asthma. Method:First，we selected the differentially expressed genes between patients with asthma and healthy people with use of the gene expressing Omnibus（GEO） database，and searched the active ingredients from Xiao Qinglongtang with use of TCMSP database，and then screened disease genes and herb ingredient targets as intersecting genes to construct the protein-protein interactions （PPI） network by using R language and Cytoscape 3.7.2 software. At the same time Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out. Result:Series GSE43696 in GEO database were successfully filtered，which contained 108 pieces of chip data. A total of 820 differentially expressed genes were screened from the chip data. Then we filtered 169 active ingredients and 246 targets of Xiao Qinglongtang from database. Through the above steps，we obtained 25 intersecting genes， and PPI network results showed that 91 potential targets may be involved in the mechanism of Xiao Qinglongtang. A total of 180 gene functions such as response to oxidative stress，inflammatory response，extracellular matrix organization and positive regulation of vascular endothelial growth factor production were showed in GO enrichment analysis results. 39 signaling pathways were showns in the results of KEGG pathway enrichment analysis，such as T helper cell 17（Th17） cell differentiation，interleukin 17（IL-17）signaling pathway，tumor necrosis factor（TNF） signaling pathway，and hypoxia inducible factor-1（HIF-1） signaling pathway. Conclusion:Xiao Qinglongtang fully embodies the characteristics of multi-components，multi-targets and multi-pathways in the intervention of bronchial asthma. The results of the study could provide an important basis for mechanism research of Xiao Qinglongtang in treating asthma.

Regulatory mechanisms of microRNAs involved in pubertal development / 国际儿科学杂志

The regulatory mechanisms of pubertal development are complex and affected by many factors.MicroRNAs, which major participants in epigenetics, are short single-stranded RNAs composed of 21-25 nucleotides.They can regulate the expression or translation of multiple target genes, playing an important role in complex biological phenomena.During pubertal development, microRNAs can regulate the expression of related genes on the hypothalamic-pituitary-gonadal axis(HPGA). Recently, studies have found that the lack or overexpression of some specific microRNAs can cause abnormal pubertal development(premature or delayed)and lead to reproductive disorders, providing a new direction for the diagnosis and treatment of puberty diseases.Here we mainly review the regulatory mechanisms that microRNAs participate in pubertal development.

Clinical features and genetic results of 6 cases with pseudohypoaldosteronism type 1 and literature review / 中华实用儿科临床杂志

Objective:To summarize clinical features, diagnosis, treatment, and follow-up of children with pseudohypoaldosteronism type 1 (PHA1) and review relevant literatures to improve the understanding of the disease and reduce misdiagnosis.Methods:Six children with the main performance of salt losing treated in the Shanghai Children′s Hospital from January 2015 to December 2018, who were diagnosed as PHA1 after relevant auxiliary examinations and genetic tests.They were classified and analyzed for their treatment courses and follow-up prognosis.Results:Six children with PHA1 had varying degrees of salt losing, dehydration and infection.After the examination, 3 cases with urinary system malformations were diagnosed as secondary PHA1.Genetic testing of 2 cases revealed 2 hete-rozygous mutations c. 1439+ 1G>C and c. 875+ 1G>A in the intron region of the SCNN1A gene, and they were diagnosed as multiple target organ defect/systemic PHA1 according to American College of Medical Genetics and Genomics(ACMG) guidelines.The other case failed to be examined by genetic testing due to the refusal of parents, and was finally diagnosed as renal PHA1 according to clinical diagnosis and treatment.Conclusions:PHA1 is a rare cause of infant salt-losing syndrome, renal and secondary PHA1 children can recover quickly after sodium supplementation and the secondary factors are removed; while multiple target organ defect/systemic PHA1 has severe clinical manifestations, electrolyte imbalance is not easy to correct, and fatal arrhythmia is prone to occur, the mortality rate is high.It is easy to be misdiagnosed in clinical practice.Auxiliary examination and genetic testing can help to diagnose and classify PHA1, as well as individualized treatment.

Second-generation Sequencing Analysis of Ph / 中国实验血液学杂志

OBJECTIVE@#To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph@*METHODS@#The WES/RNA-seq examination results of Ph@*RESULTS@#For Ph@*CONCLUSION@#There are obviously abnormal DNA damage repair pathways in children with Ph