Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To examine the impact of returned migration experience on the prevalence of non-sui-cidal self-injury(NSSI)and its associations with childhood emotional maltreatment(EM),social support and sleep quality.Methods:A total of 3 901 middle school students in Guizhou Province were investigated with the Adoles-cent NSSI behavior Questionnaire,Childhood Trauma Questionnaire-short Form(CTQ-SF),Adolescent Social Sup-port Scale,and Pittsburgh Sleep Quality Index(PSQI).Results:The prevalence of NSSI among middle school students in Guizhou province was 22.8％,with the rate of 27.3％among returned migrant middle school students.Social support and sleep quality partially mediate the relationship between childhood EM and NSSI in mid-dle school students,with effect sizes of 0.06.The EM scores of returned migrant middle school students(β=-0.62)and non-returned migrant middle school students(β=-0.50)were negatively correlated with social sup-port scores in childhood.The sleep quality scores of returned migrant students(β=0.22)and non-returned migrant students(β=0.14)were positively correlated with NSSI scores.Conclusion:The prevalence of NSSI in returned migrant students is higher.Social support and sleep quality play an important role in the relationship between child-hood EM and NSSI in middle school students.The relationship between childhood EM and social support,sleep quality and NSSI in returned migrant middle school students is stronger than that in non-returned migrant middle school students.

Objective:To examine the impact of returned migration experience on the prevalence of non-sui-cidal self-injury(NSSI)and its associations with childhood emotional maltreatment(EM),social support and sleep quality.Methods:A total of 3 901 middle school students in Guizhou Province were investigated with the Adoles-cent NSSI behavior Questionnaire,Childhood Trauma Questionnaire-short Form(CTQ-SF),Adolescent Social Sup-port Scale,and Pittsburgh Sleep Quality Index(PSQI).Results:The prevalence of NSSI among middle school students in Guizhou province was 22.8％,with the rate of 27.3％among returned migrant middle school students.Social support and sleep quality partially mediate the relationship between childhood EM and NSSI in mid-dle school students,with effect sizes of 0.06.The EM scores of returned migrant middle school students(β=-0.62)and non-returned migrant middle school students(β=-0.50)were negatively correlated with social sup-port scores in childhood.The sleep quality scores of returned migrant students(β=0.22)and non-returned migrant students(β=0.14)were positively correlated with NSSI scores.Conclusion:The prevalence of NSSI in returned migrant students is higher.Social support and sleep quality play an important role in the relationship between child-hood EM and NSSI in middle school students.The relationship between childhood EM and social support,sleep quality and NSSI in returned migrant middle school students is stronger than that in non-returned migrant middle school students.

Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To compare and explore the diagnostic performance of adding value of transabdominal and transvaginal contrast-enhanced ultrasound (CEUS) to Ovarian-Adnexal Reporting and Data System (O-RADS US) risk stratification and management system in differential diagnosis of adnexal masses.Methods:A total of 180 adnexal masses with solid components in 175 women were enrolled retrospectively between September 2021 and November 2022. All patients underwent routine Doppler ultrasound examinations and CEUS examinations. Among these masses, 107 masses underwent with transabdominal CEUS, 58 masses underwent with transvaginal CEUS, and 15 masses underwent both transvaginal and transabdominal CEUS. All patients were scheduled for surgery and pathological results served as the reference standard. Routine Doppler ultrasound and CEUS images and video were reviewed by a subspecialty radiologist using Vuebox software. The O-RADS US was downgraded or upgraded according to the CEUS characteristics of the masses. The diagnostic accuracy was assessed using ROC curve analysis. The area under the ROC curve (AUC) was calculated to compare the diagnostic performance of adding value of transabdominal and transvaginal CEUS to O-RADS US.Results:The diagnostic performance of adding transabdominal and transvaginal CEUS to O-RADS US were both significantly higher than of O-RADS US alone (transabdominal CEUS: AUC 0.83 vs 0.76, P=0.018; transvaginal CEUS: AUC 0.92 vs 0.81, P=0.013). Combination of transvaginal CEUS and O-RADS US was superior to that of combination of transabdominal and O-RADS US in the differential diagnosis of adnexal masses ( P=0.047). When the maximal diameter of adnexal masses ≤40 mm, transabdominal combined with O-RADS US presented the lowest diagnostic performance, with an AUC of 0.73. Conclusions:Combination of transvaginal CEUS and O-RADS US was superior to that of combination of transabdominal and O-RADS US in assessing adnexal masses with solid components. When the maximal diameter of adnexal masses ≤40 mm, transvaginal CEUS examination was recommended.

Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.

AIM: Previous studies have suggested that big stick design (BSD) method can only be used in clinical trials of two treatments with equal proportion, which has good statistical performance and has become the recommended choice of randomized methods. This study expands BSD method, so that it can be applied to three groups, and provides more randomized methods for clinical trials. METHODS: On the basis of BSD method used in two treatments with equal proportion, the derivation conditional allocation probability of BSD method used in three treatments with equal proportion was carried out. BSD method was compared with simple randomization (SR) method, permuted block design (PBD) method and block urn design (BUD) method by Monte-Carlo simulation in balance and randomness. RESULTS: In terms of balance, PBD method was the best, followed by BUD method, BSD method, and SR method was the worst. In terms of randomness, SR method was the best, followed by BSD method, BUD method and PBD method. The comprehensive performance showed that BSD method was better than BUD method, PBD method and SR method. CONCLUSION: The expanded BSD method used in three treatments with equal proportion has good comprehensive performance, and it can be the recommended randomization method for clinical trials of three treatments with equal proportion.

As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.

Shear wave elastography (SWE) is used to quantitatively analyze the hardness of the tissue by Young's modulus.The hardness of the tissue is visualized in the form of color coding to distinguish the benign and malignant tissue detected.SWE has higher sensitivity,accuracy and specificity compared with traditional color doppler,which is more objective than elastography,safer,cheaper and simpler than MRI.SWE has a good application prospect in the diagnosis,clinical staging and curative effect monitoring of cervical cancer.

Objective To investigate the effect of different uterine positions upon the dose distribution and target area conformability of organ at risk ( OAR) and explore the population suitable for 2-dimensional brachytherapy by comparing the dosimetry between CT-guided 3-and 2-dimensional brachytherapy for cervical cancer. Methods Thirty patients with cervical cancer received 72 cycles of 3-dimensional brachytherapy and then 2-dimensional brachytherapy was designed. The deviation angle of the uterus from the longitudinal asix on the coronal and sagittal CT images was measured. The obtained data were divided into the A to D and the group Ⅰ to Ⅳ according to the deviation angle ( T) of uterus position from the longitudinal axis on the sagittal CT images and the volume of HRCTV ( VHRCTV) to identify the optimal uterine position and range of VHRCTV for 2-dimensional brachytherapy. Statistical analysis was performed by paired t-test. Results The deviation angle of uterine position was not significantly correlated with the target CI index or D90 of HRCTV in both brachytherapy plans ( P value between 0. 077-0. 633 ) , whereas it was positively correlated with the D2 cm3 of bladder ( P value between 0. 001-0. 030) and negatively associated with the D2 cm3 of rectum in both 2-and 3-dimensional brachytherapy (P value between 0. 011-0. 016).In group B (|T|≤10°) and group Ⅲ(VHRCTVvalue between 86-96 cm3),the OAR parameters and CI index did not significantly differ between two brachytherapy plans ( P value between 0. 040-0. 463 ) , whereas varying degree of statistical differences was observed among other groups (P value between 0. 000-0. 940). Conclusions Although uterine position exerts no effect upon the conformal index of target area, it can affect the dose distribution of OAR. No statistical significance is noted in the dosimetry between 3-and 2-dimensional brachytherapy plans when the uterine position is almost flat (|T|≤10° ) and the radiotherapy target area is appropriate ( VHRCTVvalue between 86-96 cm3 ) . In this situation, 2-dimensional brachytherapy is the optimal option.