OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. METHODS: A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56). RESULTS: The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c.289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. CONCLUSION The homozygous c.289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.
Humans ; Male ; Spastic Paraplegia, Hereditary/genetics* ; Child, Preschool ; Female ; Exome Sequencing ; Child ; Infant ; Adaptor Protein Complex 4/genetics* ; Phenotype ; Mutation

Objective:To investigate the feasibility and clinical efficacy of percutaneous vertebroplasty (PVP) with measured saturated bone cement injection in the treatment of elderly patients with stage Ⅱ Kümmell's disease.Methods:A retrospective analysis was conducted to analyze the clinical data of the 41 elderly patients with stage Ⅱ Kümmell's disease who had been treated at Department of Spinal Orthopedics, Zhengzhou Orthopedic Hospital from June 2017 to June 2023 by PVP with bone cement injection into the intravertebral vacuum cleft. According to the amount of bone cement injected, the patients were divided into a saturated volume group (bone cement injection metered ≥ 150% of the cleft volume preoperatively measured) in which there were 21 cases, 4 males and 17 females, aged (78.4±5.2) years and a conventional volume group (bone cement injection metered was 100% to 120% of the cleft volume preoperatively measured) in which there were 20 cases, 6 males and 14 females, aged (79.5±7.4) years. The operative time, vacuum cleft volume measured, actual volume of bone cement injected, and percentage of bone cement injected were compared between the 2 groups. Visual analogue scale (VAS) for pain and Oswestry disability index (ODI) were compared between preoperation, postoperative 3 days, and the final follow-up in the 2 groups, as well as between the 2 groups. Cement leakage and other complications were documented.Results:The differences in the preoperative general data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). All the 41 elderly patients successfully completed their surgery. Follow-up time was (18.1±3.3) months. The operative time [(39.7±7.5) min], actual volume of bone cement injected [(5.6±0.9) mL], and percentage of bone cement injected (1.8%±0.3%) in the saturated volume group were all significantly greater than those in the conventional volume group [(35.5±4.9) min, (4.4±1.0) mL, and 1.2%±0.1%] ( P<0.05). Postoperatively, the incisions healed completely in all patients, with no such complications as cement-related adverse reactions. Cement leakage occurred in 2 patients in the conventional volume group, leading to lumbar pain or discomfort after activity, which was relieved by cement reinforcement and nail-rod internal fixation. VAS pain scores and ODIs at 3 d postoperatively and at the final follow-up were significantly improved in all patients compared with preoperation ( P<0.05). At the final follow-up, both VAS pain score and ODI in the saturated volume group improved significantly greater than those in the conventional volume group ( P<0.05). None of the patients had complications like cement displacement at the final follow-up. Conclusion:PVP with measured saturated bone cement injection into the intravertebral vacuum clefts is a safe and effective treatment for stage Ⅱ Kümmell's disease in elderly patients, offering a new minimally invasive option.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

Objective:To investigate the feasibility and clinical efficacy of percutaneous vertebroplasty (PVP) with measured saturated bone cement injection in the treatment of elderly patients with stage Ⅱ Kümmell's disease.Methods:A retrospective analysis was conducted to analyze the clinical data of the 41 elderly patients with stage Ⅱ Kümmell's disease who had been treated at Department of Spinal Orthopedics, Zhengzhou Orthopedic Hospital from June 2017 to June 2023 by PVP with bone cement injection into the intravertebral vacuum cleft. According to the amount of bone cement injected, the patients were divided into a saturated volume group (bone cement injection metered ≥ 150% of the cleft volume preoperatively measured) in which there were 21 cases, 4 males and 17 females, aged (78.4±5.2) years and a conventional volume group (bone cement injection metered was 100% to 120% of the cleft volume preoperatively measured) in which there were 20 cases, 6 males and 14 females, aged (79.5±7.4) years. The operative time, vacuum cleft volume measured, actual volume of bone cement injected, and percentage of bone cement injected were compared between the 2 groups. Visual analogue scale (VAS) for pain and Oswestry disability index (ODI) were compared between preoperation, postoperative 3 days, and the final follow-up in the 2 groups, as well as between the 2 groups. Cement leakage and other complications were documented.Results:The differences in the preoperative general data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). All the 41 elderly patients successfully completed their surgery. Follow-up time was (18.1±3.3) months. The operative time [(39.7±7.5) min], actual volume of bone cement injected [(5.6±0.9) mL], and percentage of bone cement injected (1.8%±0.3%) in the saturated volume group were all significantly greater than those in the conventional volume group [(35.5±4.9) min, (4.4±1.0) mL, and 1.2%±0.1%] ( P<0.05). Postoperatively, the incisions healed completely in all patients, with no such complications as cement-related adverse reactions. Cement leakage occurred in 2 patients in the conventional volume group, leading to lumbar pain or discomfort after activity, which was relieved by cement reinforcement and nail-rod internal fixation. VAS pain scores and ODIs at 3 d postoperatively and at the final follow-up were significantly improved in all patients compared with preoperation ( P<0.05). At the final follow-up, both VAS pain score and ODI in the saturated volume group improved significantly greater than those in the conventional volume group ( P<0.05). None of the patients had complications like cement displacement at the final follow-up. Conclusion:PVP with measured saturated bone cement injection into the intravertebral vacuum clefts is a safe and effective treatment for stage Ⅱ Kümmell's disease in elderly patients, offering a new minimally invasive option.

Objective:To analyze the microdeletion and microduplication characteristics of pathogenic copy number variations (pCNVs) and clinical phenotypes in children with neurodevelopmental disorders, and to clarify the genetic pathogenic cause of children with neurodevelopmental disorders.Methods:Children who were identified as neurodevelopment disorders such as global developmental delay and mental disorder, by next generation sequencing-based whole genomic copy number variation testing from January 2017 to November 2019 at the First Affiliated Hospital of Anhui Medical University were enrolled, and the clinical phenotypes and pCNVs were reviewed analyzed.Results:There were 36 pCNVs in total 31 children, consisting of 24 microdeletion segments (66.67%)and 12 microduplication segments (33.33%), with sizes ranging from 320.00 kb to 93.26 Mb (mean 11.33 Mb). pCNVs frequently occurred in chromosome 15 , chromosome 8 and chromosome X, there were 9 children with 9 pCNVs in chromosome 15(25.00%), 3 children with 5 pCNVs in chromosome 8(13.89%)and 3 children with 4 pCNVs in chromosome X(11.11%) .The mainly clinical manifestations were motor disorder (30 children, 96.77%), mental disorder (22 children, 70.97%), speech development delay(22 children, 70.97% )accompanied by the malformation(11 children, 35.48%), abnormal face(11 children, 35.48%) and epilepsy(8 children, 25.81%), multisystem abnormalities generally exist in one individual.Conclusion:This study demonstrates the clinical utility of whole genome CNVs testing in the genetic diagnosis of children with neurodevelopment disorders.Genetic pathogenesis of children with neurodevelopmental disorders can be revealed by the analysis of pCNVs.

Objective: To investigate an occupational hazardous gas poisoning incident caused by gas leakage in the process of hazardous waste treatment. Methods: An investigation was conducted on a case of occupational acute hazardous gas poisoning caused by waste treatment gas leakage in Shandong province in December 2017. Meanwhile, the clinical data of 5 cases of poisoning patients were analyzed, and the accident related poison test report and other relevant data were analyzed. Results: The incident was caused by the toxic waste did not do labeling work, the workers' protection measures were not in place, the illegal operation and the blind rescue, resulting in a total of 5 people died on the spot, 12 people were hospitalized with poisoning. Among them, 5 patients admitted to our hospital showed varying degrees of damage to the nervous system and respiratory system. After active treatment, they all got better and were discharged. Conclusion The poisoning is mainly caused by hydrogen sulfide dichloromethane hydrogen cyanide gas leakage serious production liability accident, clinical main performance for the nervous system circulatory system respiratory system and other system damage.

Objective: To report a case of rat poison with multiple hemorrhage after trauma. Methods: The clinical data of a case of rodenticide poisoning with hemorrhage as the first symptom admitted to a third-class a hospital in July 2018 were analyzed and summarized. Results: This patient is a rodent drug poisoning patient with hemorrhage as the first symptom.The disease was diagnosed as bromohamelin and bromadiolone poisoning through the analysis of poison detection because the rodent drug was taken in the market and the history of taking poison was concealed. The patient was given active comprehensive treatment of vitamin K1 and other drugs for clinical cure. Conclusion For patients with clinically unexplained hemorrhage, the possibility of rodenticide poisoning should be considered and the toxicant detection should be improved actively.

Objective To summarize the short and mid-term outcome of adult patient suffered with aortic stenosis and small aortic root treated by aortic root enlargement with supraannular prostheses replacement or supraannular prostheses replace-ment.Methods From January 2005 to January 2017, 223 patients with aortic stenosis and small aortic root who underwent i-solated aortic valve replacement(AVR) were included in this retrospective study cohort.Patients with aortic insufficiency who underwent isolated AVR or those who underwent combined valve replacement were excluded from the study cohort .Aortic root enlargement with supraannular prostheses replacement was performed in 98 patients(ARE), and supraannular prostheses re-placement was performed in the remaining 125 patients as a control group(SP).The mean age and other baseline characteristics were compared between the two group, except that body surface area(BSA) in ARE were higher than that in SP[(1.62 ± 0.04)m2 vs(1.61 ±0.04)m2, P=0.015].Results Operative mortality occurred in 6 patients(2.7%), the cause of death including low cardiac output syndrome(LCOS, 3 patients), multiple organ failure(MOF, 2 patients) and stroke(1 patient). Reoperation for bleeding occurred in 5 patients and acute renal failure in 9 patients, pneumonia in 5 patients.The other nonfa-tal operative complications included wound complication(8 patients), temporary pacing therapy(24 patients), and new onset of acute mitral regurgitation(1 patient).The operative mortality and nonfatal complication were not statistically different be-tween the two groups.Patients in ARE received more bioprotheses and iEOA was higher than those in SP .Transvalvular pres-sure gradients and incidence of patient-prostheses mismatch were lower in ARE.At the 2 years of follow-up, transvalvular pres-sure gradients and left ventricular mass index were statistically lower in ARE compared with SP .The iEOA of ARE was higher than that in SP(1.22 ±0.13 vs 0.87 ±0.13, P<0.01).However, during the mid-term follow up(mean duration of follow-up was 6.31years), the overall survival rate was not statistically different between the two groups.Conclusion The strategy of aortic root enlargement with supraannular prostheses to treat adult patients with aortic stenosis and small aortic root can provide more optimal hemodynamic effect , effectively avoid PPM and was not associated with increased risk of mortality or adverse event when compared with strategy of supraannular prostheses replacement.However, the mid-term survival rate was not statistically different between the two strategies.

Objective: To explore the acute toxicity of Diquat in mice and to calculate the median lethal dose (LD₅₀) of Diquat to rats and observe the pathological changes of tissues and organs in rats with different concentrations of Diquat. Methods: Diquat solution of 50 mg/kg was prepared freshly with 1 000 mg of Diquat and dilute the solution with water to a total of 20 ml. A total of 99 healthy adult male Wistar rats were randomly divided into part one, part two and control groups. In the first part, 36 rats were randomly divided into 4 groups: 100 mg/kg group, 200 mg/kg group, 300 mg/kg group and 400 mg/kg group, which were treated with 100 mg/kg, 200 mg/kg, 300 mg/kg and 400 mg/kg of Diquat solution by gavage, respectively. The death and symptoms of poisoning after intragastric administration were recorded, and the maximum tolerated dose and absolute lethal dose were measured. In the second part, 54 rats were randomly divided into 6 groups: 200 mg/kg group, 220 mg/kg group, 240 mg/kg group, 260 mg/kg、280 mg/kg group and 300 mg/kg group, whichwere treated with 200 mg/kg, 220 mg/kg, 240 mg/kg, 260 mg/kg, 280 mg/kg and 300 mg/kg of Diquat solution by gavage, respectively. The survival of rats in different concentration of Diquat was observed and the LD₅₀ was calculated by Excel processing the formula of Koch's method. The control group were given equal volume water under the same experimental conditions. And moreover, the lungs, kidneys, hearts, livers, and brain tissues were collected and fixed by formaldehyde, embedded by paraffin, and sectioned for histopathological light microscopy. Results: The maximum tolerated dose was 240 mg/kg and the absolute lethal dose was 300 mg/kg. The LD₅₀ of Diquat for Rats was 280.58 mg/kg. The high-dose group had significantly more organ damage than the low-dose group after diquat poisoning. Conclusion The determination of the half-lethal dose of diquat, at the same time observed multiple organs damaged in rats after the diquat quickly poisoned. Kidneys, lungs and heart might be the main organ which was heavily damaged. With the extension of observation time, the organ damage of rats exposed to small doses gradually stabilized.