ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

Objective:To identify early potential risk factors for sepsis-associated liver injury and to provide a reference for early clinical identification and intervention.Methods:The clinical data of septic patients admitted to the intensive care unit (ICU) in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from March 2020 to April 2023 were retrospectively analyzed. Patients with sepsis were categorized into the liver injury group and the non-liver injury group according to whether liver injury occurred or not, univariate and multivariate logistic regression analyses were used to explore the risk factors for SALI, receiver operating characteristic (ROC) curve analysis was used to assess its predictive effect for SALI, and performed subgroup analyses basing on the cut-off point.Results:Among 530 eligible patients, 403 patients were included. The incidence of liver injury was 39.45% in 159 cases with liver injury and 244 cases without liver injury. Multivariate logistic regression analysis showed that serum prealbumin, lactate and lactate dehydrogenase were independent risk factors for SALI. ROC curve analysis showed that all single indicators had some predictive value for SALI, the area under the curve was prealbumin (AUC: 0.752, 95% CI: 0.703-0.801), lactate (AUC: 0.679, 95% CI: 0.627-0.732), lactate dehydrogenase (AUC: 0.664, 95% CI: 0.611-0.718), respectively, The AUC for predicting SALI by lactate/prealbumin ratio (L/P) and lactate dehydrogenase/prealbumin ratio were 0.808 (95% CI: 0.766-0.850) and 0.795 (95% CI: 0.750-0.840), respectively, with the best efficacy of L/P in predicting SALI. Subgroup analyses showed that the incidence of liver injury was significantly higher in septic patients with L/P ≥0.23 than that in septic patients with L/P <0.23, at the same time, the acute physiology and chronic health evaluation II score, shock probability, and hospital mortality rate also increased accordingly, the differences were all statistically significant (all P < 0.001). Conclusions:L/P is early independent risk factor of SALI, for sepsis patients with L/P≥0.23 should be alerted to the development of liver injuryis.

Objective:To analyze the characteristics of inhibitory control and cognitive flexibility in hearing-impaired children.Methods:From March to April 2023, a convenience sampling method was used to select 33 hearing-impaired children from a special education school in Meizhou City, Guangdong Province, and 35 normal-hearing children from two ordinary schools as participants. Inhibitory control and cognitive flexibility of the participants were assessed by the Flanker task and the dimensional change card sorting (DCCS) task. Statistical analysis was conducted using SPSS 26.0 software, and independent sample t-test was used to compare the differences in reaction time and accuracy rate between two groups of participants. Results:There were no significant differences in the Flanker task reaction time ((558.39±123.65) ms vs (566.11±118.20) ms) and accuracy rate((0.93±0.10) vs (0.96±0.04))between hearing-impaired children and normal-hearing children ( t=-0.295, -1.645, both P>0.05). The hearing-impaired children had significantly longer reaction time ((1 019.60±131.08) ms)than the normal-hearing children ((857.85±129.19) ms) ( t=4.046, P=0.001) in the DCCS task, while there was no statistically significant difference in the accuracy rate between hearing-impaired children (0.62±0.16) and normal-hearing children (0.57±0.15) ( t=-1.602, P>0.05). Conclusion:There is no difference in inhibitory control ability between hearing-impaired children and normal-hearing children, but the hearing-impaired children have a lag in cognitive flexibility.

Objective To compare image quality of 5.0T and 3.0T non-contrast MRI for displaying insulinoma.Methods Twelve patients with insulinoma were prospectively enrolled,and non-contrast abdominal T1WI,T2WI as well as diffusion-weighted imaging(DWI)were acquired using 5.0T and 3.0T MR scanners,respectively.The subjective scores of image quality of each sequence of 5.0T and 3.0T MRI,also of tumor-pancreas parenchyma contrast scores were compared.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of insulinomas were observed,and the displayed rate of insulinoma by each sequence and overall MRI were compared.Results The subjective scores of 5.0T T1WI and DWI were higher than those of 3.0T T1WI and DWI(both P＜0.05),but not significantly different between 5.0T and 3.0T T2WI(P=0.166).Furthermore,the tumor-pancreas parenchyma contrast score of 5.0T T1WI was higher than that of 3.0T T1WI(P=0.023),but not significantly different between 5.0T and 3.0T T2WI,nor between 5.0T and 3.0T DWI(both P＞0.05).SNR of insulinomas on 5.0T T2WI were higher than on 3.0T T2WI(P=0.015),however,no significant difference of SNR was found between 5.0T and 3.0T T1WI,nor between 5.0T and 3.0T DWI(both P＞0.05).CNR of insulinomas on all 5.0T MRI were not significantly different with those on 3.0T MRI(all P＞0.05).The displayed rate of insulinoma on 5.0T T1WI,T2WI and DWI was 100％(12/12),66.67％(8/12)and 83.33％(10/12),respectively,on 3.0TT1WI,T2WI and DWI was 75.00％(9/12),58.33％(7/12),66.67％(8/12),respectively.The overall displayed rate of insulinoma on 5.0T and 3.0T MRI was 100％(12/12)and 83.33％(10/12),respectively.Conclusion Compared with 3.0T MRI,5.0T MRI was superior for displaying insulinoma,hence being helpful for diagnosis.

Objective:To investigate the necessity of internal fixation of the fibular fracture in the treatment of degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification in children.Methods:A retrospective study was conducted to analyze the data of 69 children with ankle fracture (degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification) who had been treated at Department of Orthopedic Trauma, The People's Hospital of Weifang and Department of Pediatric Orthopedics, Tianjin Hospital from January 2015 to October 2021. There were 41 males and 28 females with an age of (10.1±1.4) years, and 37 left and 32 right sides affected. The patients were divided into 2 groups according to whether internal fixation of the fibular fracture was performed. Group A consisted of 21 cases with fibular internal fixation and group B of 48 cases without fibular internal fixation. The preoperative data, operation time and operation expenses were recorded and compared between the 2 groups. At the last follow-up, the anteroposterior and lateral radiographs of bilateral full length lower limbs and ankle joints were taken; the lateral distal tibial angle (LDTA) and the anterior distal tibial angle (ADTA) on the affected side, and the disparity between bilateral ankle tibiotalar angles were measured; ankle function was assessed according to the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS); the occurrence of premature physeal closure (PPC) was recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.5±4.1) months. At the last follow-up, the LDTA on the affected side was 89.6° (87.9°, 90.5°) in group A and 88.6°±1.9° in group B; the ADTA on the affected side was 80.9° (79.0°, 81.4°) in group A and 80.0° (78.6°, 81.2°) in group B; the disparity between bilateral ankle tibiotalar angles was 1.1°±0.5° in group A and 1.2°±0.5° in group B; the AOFAS ankle-hindfoot score was (89.5±5.2) points in group A and 89.0 (87.0, 92.0) points in group B. There was no statistically significant difference between the 2 groups in the above items ( P>0.05). The incidence of PPC was, respectively, 14.3% (3/21) and 14.6% (7/48) in groups A and B, showing no statistically significant difference ( P>0.05). Conclusions:In the treatment of degree Ⅱ ankle supination-external rotation injury in children, internal fixation of the fibular fracture has no significant effect on the imaging angles or the function of the ankle joint. After anatomic reduction of the distal tibia, the fibular fracture can be treated without internal fixation to reduce operational trauma, shorten operation time and reduce operation expenses.

Objective:To develop a wearable gait analysis system based on "Lab-in-Shoe" intelligent footwear for quantitative assessment of gait dysfunction in patients with ankle injuries.Methods:In this study, integration of inertial sensors and insole-type plantar pressure distribution sensors into footwear formed the hardware core of the "Lab-in-Shoe" intelligent footwear system. In terms of algorithms, acceleration data from the inertial sensors were integrated to obtain spatial parameters of gait. The insole-type plantar pressure sensors were employed to acquire the data concerning foot pressure distribution, as well as temporal parameters and mechanical parameters of gait, including support phase, swing phase, and zero velocity moments. To validate the accuracy of this system, 8 young and healthy participants [age: (25.6±1.3) years; height: (175.4±2.2) cm] were recruited for gait data collection in an optical motion capture laboratory. By comparing the gait data between the "Lab-in-Shoe" intelligent footwear system and the gold standard Vicon optical motion capture system, the effectiveness and reliability of the intelligent footwear system were respectively tested. Additionally, a calibration experiment was conducted for the sensing units of the plantar pressure sensors to examinate the accuracy of the pressure data.Results:The tested system accurately captured the following gait parameters of the participants: step length, step width, step frequency, walking speed, gait phase division, foot pressure distribution, and center of pressure curve, among other core spatiotemporal gait parameters. Moreover, the system demonstrated its ability to replicate the dual-foot posture during gait. Compared with the gold standard Vicon optical motion capture system through Bland-Altman, the Lab-in-Shoe smart shoe system showed stride length mean error within 3.12% (range: 2.76% to 4.24%) across 3 different walking speeds [slow speed (0.68±0.05) m/s, preferred speed (1.10±0.07) m/s, and fast speed (1.40±0.13) m/s]. 90% of the results fell within the 95% limits of agreement, indicating good consistency. The intraclass correlation coefficients (ICC) for stride parameters within the slow, preferred, and fast walking speed groups were 0.93, 0.917, and 0.893, respectively, indicating good reliability. The calibration data of multiple sensor units from the plantar pressure sensors all fell within the 95% linear regression range, with a correlation coefficient of r=0.949 ( P<0.05). The plantar pressure data collected by the intelligent footwear system presented a distinct bimodal characteristic. Conclusions:The "Lab-in-Shoe" smart shoe system developed by our institute is capable of collecting and calculating gait parameters conveniently and quickly, and demondtrates good reliability and validity across different walking speeds. Therefore, it is valueable for large-scale gait data collection in a clinical setting.

Objective:To summarize the clinical characteristics and efficacy of hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy.Methods:Eleven patients with hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy admitted to Neurosurgical Center, 988 th Hospital of PLA Joint Logistic Support Force from June 2011 to September 2019 were chosen in our study; primary diseases included meningioma in 7 patients, contusion and laceration of frontal lobe in 2, hypertensive cerebral hemorrhage in 1, and obsessive-compulsive disorder in 1 patient. Epilepsy was the first symptom after craniotomy. Clinical characteristics and efficacy of these patients were analyzed retrospectively; seizure control efficacy was evaluated by Engel grading. Results:First seizure occurred 4 h-7 d after craniotomy in these 11 patients, including 2 with focal sensory retention seizure, 3 with focal bilateral tonic-clonic seizure, and 6 with general tonic-clonic seizure. Follow-up cranial CT revealed hematoma in surgical region, adjacent cortex or subcortex in 9 patients (hematoma volume: 15-50 mL); emergency craniotomy (hematoma clearance) and decompressive craniectomy was performed in 5 patients; only emergency craniotomy (hematoma clearance) was performed in 3 patients; conservative treatment was performed in 1 patient. A small amount of diffuse bleeding with severe cerebral edema in the surgical region appeared in 2 patients, and the transient limb paralysis gradually recovered after 2 months of conservative treatment. Follow-up was performed for (4.5±1.7) years ([2.3-7.0] years). During the last follow-up, 4 patients were normal, 5 patients had mild to moderate hemiplegia, 1 had mild decreased vision in the right eye, and 1 had long-term coma. Epileptic control efficacy analysis indicated that 8 had Engel grading I and 3 grading II.Conclusion:Complete removal of hematoma and inactivated brain tissues can effectively control seizures and rebleeding in patients with hemorrhage resulted from cortical venous infarction.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People's Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.
Male ; Child ; Humans ; Autism Spectrum Disorder/genetics* ; Heart Defects, Congenital/genetics* ; Computational Biology ; Genomics ; Mutation ; RNA, Messenger/genetics* ; Histone-Lysine N-Methyltransferase/genetics*

Objective:To learn about the prevalence of iodized salt in coastal counties (cities and districts, hereinafter referred to as counties) of Shandong Province, evaluate the iodine nutritional status of children and pregnant women, so as to provide data support for timely targeted prevention and control measures and scientific adjustment of intervention strategies.Methods:In 2021, in 37 coastal counties of Shandong Province, one township was selected from each of the five directions of the east, west, south, north, and middle of each county, one primary school was selected from each township, 40 non-boarding students aged 6 - 12 years old were selected from each primary school. In addition, 20 pregnant women were selected from each township. Children's and pregnant women's household salt samples and urine samples were collected to detect salt iodine and urinary iodine contents. The children from 19 counties selected from the 37 coastal counties of Shandong Province were examined by B-mode ultrasound, and the goiter rate of children was calculated.Results:Totally 7 736 household edible salt samples from the children were tested, and the coverage rate of iodized salt, iodized salt qualified rate and qualified iodized salt consumption rate was 74.3% (5 746/7 736), 74.3% (4 267/5 746) and 55.2% (4 267/7 736), respectively. A total of 7 740 urine samples were collected from the children, the median urinary iodine was 174.0 μg/L. A total of 4 344 children were selected for thyroid examination, and the goiter rate was 3.0% (131/4 344). Totally 4 513 household edible salt samples from the pregnant women were tested, and the coverage rate of iodized salt, iodized salt qualified rate and qualified iodized salt consumption rate was 83.7% (3 779/4 513), 77.6% (2 933/3 779) and 65.0% (2 933/4 513), respectively. A total of 7 740 urine samples were collected from the pregnant women, the median urinary iodine was 133.5 μg/L.Conclusions:Children in 37 coastal counties of Shandong Province are generally at the appropriate level of iodine, but pregnant women still have the risk of iodine deficiency. Comprehensive prevention and control measures for iodine deficiency disorders need to be continuously implemented to consolidate and deepen the achievements of iodine deficiency prevention and control.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.