AIM:To investigate the protective ef-fect of osthole(Ost)on APAP-induced liver injury in mice and its molecular mechanism.METHODS:We established the APAP-induced liver injury model in mice,and Ost was used to intervene.The expres-sion of AST,ALT,SOD,ROS,MDA,LDH,GSH-PX in mice plasma were detected by biochemical meth-od.HE staining was used to observe the changes of liver tissue structure.Immunofluorescence assay was used to detect the expression of Tif1γ and Smad4 in liver tissue.The mRNA expression of IL-1β,IL-6,TNF-α,Smad4,and Tif1γ were detected by qRT-PCR.Western blot was applied to assess the protein expression of Smad2/3 and pSmad2/3 in liver tissue.RESULTS:Compared with the control group,the liver structure destruction and hepato-cyte death was increased,ALT,AST,ROS,MDA and LDH were increased,while SOD and GSH-PX were decreased,and the mRNA expressions of IL-1β,IL-6 and TNF-α were increased in the model group.Compared with the model group,the Ost interven-tion group had improved liver structure and de-creased liver cell death;decreased ALT,AST,ROS,MDA and LDH,increased SOD and GSH-PX,and de-creased expression of IL-1β,IL-6 and TNF-α mRNA.Compared with the control group,liver tissues of model mice showed increased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and de-creased Tif1γ protein and mRNA.Compared with the model group,the liver tissues of the Ost inter-vention group showed decreased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and in-creased expression of Tif1γ protein and mRNA.CONCLUSION:Ost can improve liver function,re-duce oxidative stress and inflammatory reaction,and protect hepatocyte damage induced by APAP in mice,which may be related to the up-regulation of Tif1γ and inhibition of TGF-β1/Smad signaling pathway.

AIM:To investigate the protective ef-fect of osthole(Ost)on APAP-induced liver injury in mice and its molecular mechanism.METHODS:We established the APAP-induced liver injury model in mice,and Ost was used to intervene.The expres-sion of AST,ALT,SOD,ROS,MDA,LDH,GSH-PX in mice plasma were detected by biochemical meth-od.HE staining was used to observe the changes of liver tissue structure.Immunofluorescence assay was used to detect the expression of Tif1γ and Smad4 in liver tissue.The mRNA expression of IL-1β,IL-6,TNF-α,Smad4,and Tif1γ were detected by qRT-PCR.Western blot was applied to assess the protein expression of Smad2/3 and pSmad2/3 in liver tissue.RESULTS:Compared with the control group,the liver structure destruction and hepato-cyte death was increased,ALT,AST,ROS,MDA and LDH were increased,while SOD and GSH-PX were decreased,and the mRNA expressions of IL-1β,IL-6 and TNF-α were increased in the model group.Compared with the model group,the Ost interven-tion group had improved liver structure and de-creased liver cell death;decreased ALT,AST,ROS,MDA and LDH,increased SOD and GSH-PX,and de-creased expression of IL-1β,IL-6 and TNF-α mRNA.Compared with the control group,liver tissues of model mice showed increased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and de-creased Tif1γ protein and mRNA.Compared with the model group,the liver tissues of the Ost inter-vention group showed decreased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and in-creased expression of Tif1γ protein and mRNA.CONCLUSION:Ost can improve liver function,re-duce oxidative stress and inflammatory reaction,and protect hepatocyte damage induced by APAP in mice,which may be related to the up-regulation of Tif1γ and inhibition of TGF-β1/Smad signaling pathway.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

Objective:To study the trend of menarche age in Han and Mongolian women born from 1951 to 2005 in Mongolian region.Methods:A cross-sectional cluster sampling survey method was adopted, From 2003 to 2019, a retrospective survey was carried out in three banners/counties in Tongliao region on the female population of Han and Mongols nationalities aged 16 to 46 and conducted under standardized survey procedures and quality control standards. The basic data of menarche age of women born between 1951 and 2005 were obtained. The changes and rules were analyzed by taking 1 year, 5 years and 10 years as nodes.Results:Totally 46 and conducted under standardized survey procedures and quality control standards 928 pepole (24 450 Han and 22 478 Mongolian) were recruited, the survey response rate was 96.09% (46 928/48 836). In one-year-period analysis, the menarche age gradually decreased from 1951 to 2005. The mean menarche age of Han and Mongolian women changed from (16.22±0.52) years and (15.86±1.24) years in 1951 to (12.37±1.15) years and (12.33±0.98) years in 2005, respectively. The mean menarche age of Han and Mongolian women decreased 3.85 years and 3.54 years. The trend of the mean menarche age's change showed a significant negative correlation with the years (all P<0.000 1). In five-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.54±1.45) years and (15.53±1.48) years from 1951 to 1955 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.13 years (3.41 months ahead of schedule every 5 years on average) and 3.06 years (3.34 months ahead of schedule every 5 years on average) in Han and Mongolian women respectively. In ten-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.79±0.95) years and (15.53±1.33) years from 1951 to 1960 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.38 years (6.76 months ahead of schedule every 10 years on average) and 3.06 years (6.12 months ahead of schedule every 10 years on average) in Han and Mongolian women respectively. During the 15 years from 1951 to 1965, 1966 to 1970, 1971 to 1990, and 1991 to 2000, they were concentrated at the ages of 15-16, 14-15, 13-14, and 12-13, respectively. The proportion of women at 11 years, 12 years and 13 years menarche age were 26.79% (457/1 706), 73.27% (1 250/1 706), and 92.85% (1 584/1 706) during 2001—2005 in Han women, while the proportion were 23.25% (653/2 809), 62.01% (1 742/2 809), and 90.14% (2 532/2 809) in Mongolian women. Conclusion:The menarche age decreased in Han and Mongolian women from 1951 to 2005, and the ethnic groups tended to be the same. It is recommended to start adolescent education at the age of 8-9 years and pay attention to the changing pattern of early onset of menarche.

Objective:To study the trend of menarche age in Han and Mongolian women born from 1951 to 2005 in Mongolian region.Methods:A cross-sectional cluster sampling survey method was adopted, From 2003 to 2019, a retrospective survey was carried out in three banners/counties in Tongliao region on the female population of Han and Mongols nationalities aged 16 to 46 and conducted under standardized survey procedures and quality control standards. The basic data of menarche age of women born between 1951 and 2005 were obtained. The changes and rules were analyzed by taking 1 year, 5 years and 10 years as nodes.Results:Totally 46 and conducted under standardized survey procedures and quality control standards 928 pepole (24 450 Han and 22 478 Mongolian) were recruited, the survey response rate was 96.09% (46 928/48 836). In one-year-period analysis, the menarche age gradually decreased from 1951 to 2005. The mean menarche age of Han and Mongolian women changed from (16.22±0.52) years and (15.86±1.24) years in 1951 to (12.37±1.15) years and (12.33±0.98) years in 2005, respectively. The mean menarche age of Han and Mongolian women decreased 3.85 years and 3.54 years. The trend of the mean menarche age's change showed a significant negative correlation with the years (all P<0.000 1). In five-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.54±1.45) years and (15.53±1.48) years from 1951 to 1955 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.13 years (3.41 months ahead of schedule every 5 years on average) and 3.06 years (3.34 months ahead of schedule every 5 years on average) in Han and Mongolian women respectively. In ten-year-period analysis, the mean menarche age of Han and Mongolian women changed from (15.79±0.95) years and (15.53±1.33) years from 1951 to 1960 to (12.41±0.97) years and (12.47±0.96) years from 2001 to 2005, the mean menarche age decreased 3.38 years (6.76 months ahead of schedule every 10 years on average) and 3.06 years (6.12 months ahead of schedule every 10 years on average) in Han and Mongolian women respectively. During the 15 years from 1951 to 1965, 1966 to 1970, 1971 to 1990, and 1991 to 2000, they were concentrated at the ages of 15-16, 14-15, 13-14, and 12-13, respectively. The proportion of women at 11 years, 12 years and 13 years menarche age were 26.79% (457/1 706), 73.27% (1 250/1 706), and 92.85% (1 584/1 706) during 2001—2005 in Han women, while the proportion were 23.25% (653/2 809), 62.01% (1 742/2 809), and 90.14% (2 532/2 809) in Mongolian women. Conclusion:The menarche age decreased in Han and Mongolian women from 1951 to 2005, and the ethnic groups tended to be the same. It is recommended to start adolescent education at the age of 8-9 years and pay attention to the changing pattern of early onset of menarche.

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

Objective To evaluate the role of multi-disciplinary team (MDT) in improving the diagnosis and treatment of human herpes virus-6B (HHV-6B) encephalitis after liver transplantation. Methods MDT consultation was delivered for one rare case of HHV-6B encephalitis after liver transplantation to establish an effective individualized treatment regime. Results On the 16 d after liver transplantation, the patient developed headache, and suddenly presented with unresponsiveness, unconsciousness, coma complicated with involuntary limb twitching on the 18 d. Blood ammonia level was increased. Brain CT scan showed cerebral ischemic changes. Electroencephalography prompted the epileptic seizure. After MDT consultation, the possibility of nervous system infection after liver transplantation was considered, and medication therapy was given to control the epileptic seizure. Cerebrospinal fluid examination via lumbar puncture hinted increased intracranial pressure. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) of the cerebrospinal fluid demonstrated that the patient was tested positive for HHV-6B nucleic acid, which confirmed the diagnosis of HHV-6B encephalitis. The immunosuppressant regime was adjusted, intravenous ganciclovir was given for antiviral treatment, and active interventions were delivered to prevent and treat relevant complications. Epileptic seizure disappeared after 4 d, and neurological symptoms were significantly alleviated after 2 weeks. After 4-week antiviral treatment, the patient was tested negative for virology testing, and the neurological function was restored to normal. Conclusions HHV-6B encephalitis rarely occurs after adult liver transplantation, which is primarily associated with the virus reactivation after use of immunosuppressant. MDT pattern may be employed to deepen the understanding of the patient's condition, formulate more effective individualized treatment regime, and enhance the clinical efficacy and safety.

Objective:To analyze the characteristics of malaria epidemic situation before and after malaria elimination in Qiandongnan Prefecture, and to provide the basis for establishment of effective strategies and measures to consolidate the achievements of malaria prevention and control.Methods:The data of malaria cases in 16 counties (cities) of Qiandongnan Prefecture from 2005 to 2018 were collected, and descriptive epidemiological method was used to analyze the infection rate of Plasmodium among local residents and floating population before (2005-2011) and after (2012-2018) elimination of malaria, and the characteristics of population distribution, seasonal distribution, species of Plasmodium and types of malaria vectors were analyzed. Results:Before elimination of malaria, total of 1 412 cases of malaria were reported, among those cases, 1 361 cases were local cases, accounting for 96.39% of the total cases. After elimination of malaria, total of 17 cases were reported, all of them were imported cases. After comparison of malaria cases before and after the elimination, the proportion of people aged from 18 to 60 was 70.54% (996/1 412) before the elimination, all 17 imported cases were 18-60 years old after the elimination, and the proportion of children/students decreased from 24.65% (348/1 412) before the elimination to 0 after the elimination. The peak incidence of malaria cases before the elimination was from June to October, and cases occurred every month. After the elimination, the imported cases were sporadic. Plasmodium vivax was the main species of Plasmodium before the elimination (98.58%, 1 392/1 412), and Plasmodium falciparum was mainly imported after the elimination (70.59%, 12/17). Before and after the elimination, Anopheles sinensis, the malaria vector, was the dominant population, but no distribution of Anopheles minimus and Anopheles anthropophagus was found after 2015. Conclusions:After the elimination of malaria in Qiandongnan Prefecture, there is a risk of local malaria cases caused by imported cases. It is suggested that local authorities should focus on the treatment of suspected malaria cases and vector surveillance of overseas returnees in the future.

Objective To compare and study the value of multiple antigens dot immunogold filtration assay (DIGFA ) and ima-ging diagnosis for rapid diagnosis of two kinds of echinococcosises .Methods 167 cases of hydatid patients diagnosied by pathologi-cal examination were divided into the DIGFA group for diagnosis of DIGFA and the control group for imaging diagnosis .Results The diagnosis rate of cystic echinococcosis (CE) in the DIGFA group was 74 .60% and control group was 90 .48% (P<0 .01);the diagnosis of alveolar echinococcosis(AE) in the DIGFA group was 92 .68% and the control group was 73 .17% (P<0 .05);when the cystica<5 cm ,the diagnosis rate of AE and CE in the DIGFA group was 91 .67% and 61 .11% (P<0 .05) ,when the cystica 5- <10 cm ,the detection rate of AE and CE in the DIGFA group was 94 .12% and 71 .43% (P<0 .05) .When the cystica≥10 cm ,<5 cm or between 5 - < 10 cm ,the detection rate of CE in DIGFA group was 94 .12% ,61 .11% ,71 .43 ,respectively (P<0 .05);The totle detection rates of the AE and CE in DIGFA group were 92 .68% and 74 .60% (P<0 .05) .Conclusion Imaging di-agnosis for the CE was higher and the DIGFA diagnosis for the AE was higher and the DIGFA also had clinical significance espe-cially applicated to the early diagnosis of AE .With the help of the imaging diagnosis ,the DIGFA could diagnose two kinds of echi-nococcosises correctly and it provided the benefits of specificity and sensitivity and performed easily .