ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

Dry eye disease(DED)is a multifactorial ocular surface disorder characterized by the loss of tear film homeostasis among which evaporative DED associated with meibomian gland dysfunction(MGD)accounts for up to 86%, and traditional drugs fail to effectively target the core pathological mechanism. As a new type of anhydrous and preservative-free eye drops approved by the FDA, perfluorohexyloctane has a unique amphiphilic structure, which can form an artificial lipid monolayer at the air-liquid interface of the tear film. It exerts its therapeutic effects by inhibiting tear evaporation, stabilizing the tear film, unclogging meibomian gland orifices, and promoting corneal oxygen supply. This drug can not only serve as a first-line treatment option for evaporative DED but also be combined with other drugs for personalized treatment. This review summarizes the mechanism of action, pharmacological properties, clinical efficacy, and safety of perfluorohexyloctane eye drops, and further elaborate on its application value in complex types of DED and patients with other concurrent ocular surface diseases, aiming to provide more evidence support for the precise treatment of DED.

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

OBJECTIVE: To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c.661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. METHODS: A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c.661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 ug/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committee of Handan First Hospital (Ethics No. HDYY-LW-25053). RESULTS: The child was found to harbor a heterozygous c.661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. CONCLUSION The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.
Humans ; HEK293 Cells ; Mutation ; SOXE Transcription Factors/metabolism* ; Waardenburg Syndrome/genetics* ; Child

Objective:To explore the pathogenic mechanism of a child with Waardenburg syndrome type 4C due to a c. 661_664dup (p.P222Lfs*60) variant of SOX10 gene through in vitro experiments. Methods:A child diagnosed at the Handan First Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, trio-whole exome sequencing was carried out. Pathogenicity of candidate variant was determined by bioinformatic analysis and reference to the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was verified by Sanger sequencing. Expression plasmids of wild-type SOX10 and the c. 661_664dup (p.P222Lfs*60) variant were constructed and transiently transfected into 293T cells to determine the expression at the RNA and protein levels. The 293T cells transiently transfected with the wild-type/mutant SOX10 were treated with 10 μg/mL cycloheximide (CHX) for 0, 4, 8, 24 h, respectively, and the degradation rate of target protein was detected by Western blotting assay. This study has been approved by the Ethics Committe of Handan First Hospital(Ethics No.HDYY-LW-25053). Results:The child was found to harbor a heterozygous c. 661_664dup (p.P222Lfs*60) variant of the SOX10 gene, which was unreported previously. The variant did not significantly alter the expression of SOX10 at the mRNA level but the protein level. After the CHX treatment, the degradation of mutant SOX10 protein had slowed down. Conclusion:The mutant SOX10 may affect the expression of downstream genes by affecting the degradation rate of its protein product.

Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L⁻¹ and 0.63 μg·g⁻¹ before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.

Objective·To investigate the therapeutic effect of combined vitamin D and docosahexaenoic acid(DHA)supplementation on preschool children with attention deficit hyperactivity disorder(ADHD).Methods·From April 2021 to May 2021,a total of 1 412 children aged 4 to 6 years from eight kindergartens in Pudong New Area of Shanghai,including Tangqiao Street,Chuansha Town,and Heqing Town,were randomly selected by stratified cluster random sampling method.Attention and hyperactivity symptom assessment was performed using the Conner's Scale,Diagnosis and Statistical Manual of Mental Disorders(fifth edition,DSM-Ⅴ),and Swanson,Nolan,and Pelham(version Ⅳ,SNAP-Ⅳ)Scale,and other neurodevelopmental disorders were excluded using the Wechsler Intelligence Scale.A total of 82 preschool children with ADHD were enrolled,and after fully informing them of the intervention measures,they were divided into an intervention group(n=64)and a control group(n=18)based on their parents' choice.The control group received routine health education.In addition to routine health education,the intervention group received daily supplementation of Vitamin D(800 IU)and DHA(400 mg).Venous blood samples were collected from both groups at baseline,3 months,and 12 months for the measurement of serum 25 hydroxy vitamin D[25(OH)D]and DHA levels.ADHD symptoms were evaluated using Conner's Scale,SNAP-Ⅳ Scale,and DSM-Ⅴ.Results·After 3 and 12 months of intervention in the intervention group,serum 25(OH)D levels and DHA levels were significantly higher(P<0.05),the ADHD symptom scores,including impulsivity-hyperactivity and hyperactivity index scores in Conner's Scale,the attention and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale,and the attention and hyperactivity/impulsivity scores in DSM-Ⅴ,were significantly reduced compared with the scores before the intervention(P<0.05).There was no significant difference in serum 25(OH)D and DHA levels,or ADHD symptom scores,at the 3-and 12-month follow-ups compared to baseline.After 3 months of nutritional intervention in the intervention group,the hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ were significantly improved compared to the control group(P<0.05).After 12 months of intervention,conduct problems,impulsive-hyperactivity and hyperactivity index scores in Conner's Scale,and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ showed significant improvement compared to the control group(P<0.05).Conclusion·Combined supplementation with vitamin D and DHA significantly improves serum 25(OH)D and DHA levels and alleviates ADHD symptoms in preschool children.

Objective:To construct and validate a predictive model and application program for stone recurrence after endoscopic retrograde cholangiopancreatography (ERCP) based on machine learning algorithms in patients with common bile duct stones (CBDS).Methods:A multicenter retrospective cohort study was conducted, 862 CBDS patients underwent ERCP from June 2020 to September 2023 in Changshu First People′s Hospital (data set 1, 759 cases, including a training set of 588 cases and a validation set of 171 cases) and Changshu Hospital of Traditional Chinese Medicine (data set 2, 103 cases, used as a test set). The demographics, medical history, ERCP procedural records and laboratory indices were collected. All patients were followed up for 1 year, and the stone recurrence was recorded. In training set, the feature selection was conducted by the least absolute shrinkage and selection operator (LASSO) algorithm, and a conventional Logistic regression model was constructed based on selected features. The 3 machine learning algorithms (gradient boosting machine model, extreme gradient boosting model and random forest model) and a conventional Logistic regression model (LASSO model) were trained to fit predictive models. The model performance was assessed by area under curve (AUC) of receiver operating characteristic curve. The model interpretability was analyzed by feature importance evaluation, Shapley additive explanations (SHAP) and force plots. The best-performing model was deployed as an online application by Streamlit framework (V1.36.0).Results:Among the 862 patients, 158 patients (18.33%) developed stone recurrence after ERCP. There were no statistical difference in demographics, medical history, ERCP procedural records and laboratory indices between training set and a validation set ( P>0.05). LASSO regression analysis result showed that 6 key variables (in descending order of significance: endoscopic sphincterotomy, common bile duct angulation, stone diameter, stone count, common bile duct diameter, and periampullary diverticulum) influencing stone recurrence. ROC curve analysis result showed that the random forest model exhibited the highest predictive performance (it had the largest AUC of 0.900). SHAP analysis result showed that common bile duct angulation, common bile duct diameter, stone diameter, endoscopic sphincterotomy and stone count were the top 5 contributing factors in the random forest model. Using Python, the random forest model was implemented into a Streamlit-based application with a user-friendly visual interface, providing predictive outcomes, confidence levels, SHAP force diagram and health recommendations. In the test set, the application program achieved an accuracy of 84.5% (87/103), sensitivity of 82.6% (19/23), and specificity of 85.0% (68/80). SHAP plots and force diagram intuitively illustrated the impact of key features on stone recurrence prediction, offering a clear visualization of each variable′s role within the model. Conclusions:The predictive model and application program based on the random forest machine learning algorithms demonstrate excellent predictive performance and practical usability in predicting stone recurrence after ERCP in patients with CBDS.

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.