OBJECTIVE: To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation. METHODS: A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241). RESULTS: MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c.1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c.2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+PM2_Supporting+PM3+PP1) and likely pathogenic (PM2_Supporting+PM3+PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
Humans ; Male ; Pedigree ; Cholestasis, Intrahepatic/diagnostic imaging* ; Adenosine Triphosphatases/genetics* ; Female ; Adult ; Exome Sequencing ; Mutation ; East Asian People

Objective:To investigate possible neuromodulatory mechanisms involved in the involvement of parvalbu-min(PV)expression in the basal ganglia output nuclei,entopeduncular nucleus(EPN)and substantia nigra pars etic-ulata(SNr),in exercise-induced chronic fatigue impairs working memory capacity.Methods:Male SD rats were divid-ed into control group and Fatigue group by random number method,and a three-stage incremental load treadmill training program was selected to establish a chronic exhaustion exercise-induced fatigue rat model.The working memory ability of rats was assessed by the Y-maze autonomous alternation experiment.Immunohistochemical staining was used to ob-serve the expression of parvalbumin(PV)positive neurons and cysteine aspartate-specific protease-3(caspase-3)in EPN and SNr of rats.Results:The accuracy of voluntary alternation in the fatigue group was obviously lower than that in control group(P＜0.05).The results of immunohistochemical staining showed that the density of PV positive neu-rons and the degree of positive fiber staining in EPN and SNr in the fatigue group were obviously lower than those in the control group(P＜0.05,P＜0.01).The number of caspase-3 positive cells per unit area of EPN and SNr in the fa-tigue group was obviously higher than that in the control group(P＜0.05,P＜0.01).Conclusion:The mechanism of impairing working memory in rats caused by exercise-induced chronic fatigue may be related to the apoptosis of PV posi-tive neurons in EPN and SNr.

Objective To retrospectively investigate and analyze the specially permitted aeromedical evaluation results of overage military flying personnel,in order to provide references for health management and related evaluation methods improvement.Methods The clinical data and evaluation results of overage flying personnel were collected from 2012 to 2023.Disease spectrum was analyzed,and qualified rates among different airplane types and aviation duties were compared.Results 79.57%of the 509 flying personnel were detected with diseases,and the top ten were hyperlipidemia,fatty liver,thyroid nodule,renal cyst,hepatic cyst,gallbladder polyps,hyperuricemia,carotid artery arteriosclerosis,hypertension and hepatic hemangioma.96.08%of the personnel were qualified to continue flying,1.96%were disqualified and 1.96%were temporarily disqualified.The qualified rates among different airplane types and aviation duties were not significantly different(P?>?0.05).Conclusion Overage military flying personnel could apply for specially permitted aeromedical evaluation to extend their flying lifespan.Attention should be paid to metabolic and cardiovascular diseases in aeromedical support and evaluation for these experienced flying personnel.

Objective : To investigate the effect of paederosidic acid methyl ester (PAME) on postoperative learning and memory impairment in mice and its mechanism. Methods : C57BL/6J male mice were randomly divided into Sham group , operation group , operation + PAME group ( PAME group) , operation + NADPH oxidase 4(Nox4) adeno⁃associated virus overexpression group (Nox4 overexpression group) , operation + Nox4 adeno⁃associated virus no⁃laden group ( AAV no⁃load group) , and operation + PAME + Nox4 overexpression group ( PN group) . Exploratory laparotomy was performed. PAME(20 mg/kg) was administered by continuous gavage for 7 days after operation , and adeno⁃associated virus was injected into the hippocampus 28 days before operation. Morris water maze test and conditioned fear test were used to detect the learning and memory ability of mice. The expression of Nox4 protein was observed by immunofluorescence. The protein expressions of Nox4 , long chain acyl CoA synthetase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) were detected by Western blot. Reactive oxygen species (ROS) and iron content were determined by spectrophotometry. Results : Compared with the Sham group , the learning and memory ability of the operation group , the Nox4 overexpression group and the AAV no⁃load group decreased , the protein expression of Nox4 and ACSL4 increased , the protein expression of GPX4 decreased , and the ROS and iron content increased. After PAME treatment , the postoperative learning and memory ability of mice was improved , and Nox4 and ferroptosis in hippocampal neurons were alleviated. Conclusion Conclusion PAME treatment can improve the learning and memory ability of postoperative mice , which may be related to the inhibition of hippocampal Nox4⁃mediated ferroptosis.

Objective To explore the effectiveness of virtual autopsy-based postmortem computed tomography(PMCT)liver three dimensional slicer(3D slicer)artificial intelligence(AI)volume reconstruction to assist forensic practice.Methods Twenty cases of the deceased who underwent both virtual autopsy and traditional autopsy in our center were selected and subjected to liver volume segmentation by 3D slicer method,Tada's formula method and literature method,and the data obtained from the traditional autopsy were compared and analyzed to obtain the accuracy rate.Results The 3D slicer method yielded higher consistency(95%confidence interval),lower volumetric variability(standard deviation),and a smaller region(variance)of uncertainty than the Tada formula method and the methods mentioned in the literature.Conclusion 3D slicer AI reconstruction based on virtual autopsy can visualize virtual anatomy,help increase the diagnostic accuracy of traditional autopsy,assist in pathological diagnosis,and provide new directions and tools for the development of imaging histology of virtual autopsy.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To summarize the nursing care of 3 cases of spinal muscular atrophy (SMA) with intrathecal injection of Nusinersen sodium injections.Methods:From March 2020 to March 2021, 3 children patients with SMA received Nusinersen sodium injections. Multidisciplinary care was applied, the key points of nursing care include: multidisciplinary individualized assessments, multidisciplinary care based on case management model, preoperative and intraoperative care cooperation, and postoperative observations and management of complications.Results:All the three children successfully completed intrathecal injection and were discharged on the second day after surgery. No serious complications occurred.Conclusions:Collaborative multidisciplinary care shows positive significance for children with intrathecal Nusinersen sodium injections.

Objective To investigate the changes of expression levels of interleukin?17(IL?17) and interleukin?21( IL?21) secreted by helper T cells 17 before and after treatment of three immune?related hematological diseases,and to explore the clinical significance??Methods Sixty patients with IRH admitted to the Department of Hematology,the First Affiliated Hospital of Hebei North University from May 2017 to October 2018 were selected as subjects??They were divided into aplastic anemia group (24 cases),immune thrombocytopenia group (20 cases) and autoimmune hemolytic anemia group (16 cases)??Another 60 healthy volunteers who had physical examination in our hospital at the same time were selected as the control group??In the 3 IRH groups,patients were treated with glucocorticoids or immunologic agents,and the control group was given vitamin C??At the time of initial diagnosis,2 weeks and 3 months after IRH treatment,all the patients in the 4 groups were examined for blood?related indicators,and the therapeutic effects of different stages and the plasma levels of IL?17 and IL?21 in the peripheral blood of the 4 groups before and after treatment were compared??Results At the initial diagnosis,the plasma IL?17 levels in the aplastic anemia group,immune thrombocytopenia group and autoimmune hemolytic anemia group were ((196??52± 17??46), (185??69± 18??19),(126??13 ± 11??22) ng／L),respectively,which were higher than those in control group ((72??36± 10??21) ng／L), the differences were statistically significant ( all P＜0??05)??The plasma IL?21 levels in the aplastic anemia group,immune thrombocytopenia group and autoimmune hemolytic anemia group were ((136??82±20??16),(145??92±22??18),(119??66±12??69)) ng／L,respectively,which were higher than those in control group (( 84??01 ± 9??87) ng／L), and the differences were statistically significant ( all P＜0??05)??After 2 weekly treatment,the levels of IL?17 and IL?21 in the 3 groups were significantly lower than those at the first visit (all P＜0??05)??After 3 months of treatment,the levels of IL?17 and IL?21 in the 3 groups were also significantly lower than those at the first diagnosis ( IL?17: aplastic anemia group ( 84??69 ±12??15) ng／L,immune thrombocytopenia group (90??56±11??64) ng／L,autoimmune hemolytic anemia group (62??83±5??68) ng／L;IL?21: aplastic anemia group ( 96??28± 8??84) ng／L,immunological thrombocytopenia group (103??21±10??62) ng／L,autoimmune hemolytic anemia group (78??64±9??68) g／L),and the difference were statistically significant ( all P＜0??05)??There was no significant change in the control group ( 83??84 ±9??95) ng／L(P＞0??05)??After 3 months of treatment,the total effective rates of treatment in the three groups (the aplastic anemia group 83??33%( 20／24), immunological thrombocytopenia group90??00%( 18／20), autoimmune hemolytic anemia group 75??00%( 12／16)) were higher than 2 weekly treatment ( aplastic anemia group 41??67%( 10／24 ), immunological thrombocytopenia group 40??00%( 8／20 ), autoimmune hemolytic anemia group25??00%(4／16)),and the differences were statistically significant( all P ＜0??05)??Conclusion The changes of plasma IL?17 and IL?21 levels are helpful to indicate the occurrence and progression of immune?related hematopathy,to find therapeutic targets and to improve prognosis,which has important clinical significance in the clinical diagnosis,prognosis and treatment of different types of IRH??

Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body′s own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.

OBJECTIVE: To analysis the characteristics of sudden sensorineural hearing loss (SSHL) patients with tinnitus, and explore the relationship of characteristics of tinnitus and audiology. METHOD: Patients diagnosed as SSHL with tinnitus were studied in the research. All patients' clinical features were analyzed, such as tinnitus frequency, pure tone audiometry, tinnitus, hearing loss degree, results of residual inhibition test. RESULT: Thirty cases were identified as mild degree hearing loss, 13 cases as moderate degree, 28 cases as severe degree and 34 cases as profound degree. And hearing impaired frequency of 13 cases was ascertained at low-frequency, 39 cases at middle-high-frequency, and 53 cases at full-range-frequency. The incidence of patients with low-frequency was about 41. 9% (44/105), and it was about 21. 9% (23/105) in those with middle-frequency. And it was 36. 2% (38/105) in cases of high-frequency tinnitus. The chi-square test show statistically significant differences between patients with the low-frequency, middle-frequency and high-frequency of the hearing loss (P<0. 05). In tinnitus residual inhibition test, positive rate of convergence type masking curve was about 72.0%, tinnitus separated type masking curve 20.0%, overlapping type was 57.9%, and the spacing type was 43.5%. There was a statistically significant difference among cases with different type masking curve (P<0. 05)with the spacing residual inhibition test positive rate. CONCLUSION There are individual differences of clinical characteristics among SSHL patients with tinnitus. Tinnitus frequency is consistent with the frequency of hearing loss. Patients had the more serious the degree of hearing loss, who had more serious tinnitus grading. Cases with the converged type curve will be fit for tinnitus masking. Therefore, combining the tinnitus detection with the audiological tests, we could obtain the clinical characteristics of SSHL patients with tinnitus.
Audiometry, Pure-Tone ; Deafness ; Hearing Loss ; Hearing Loss, Sensorineural ; complications ; pathology ; Humans ; Tinnitus ; complications ; pathology