Enterotoxigenic Escherichia coli(ETEC)is the main cause of diarrhea in piglets,which seriously threatens the development of animal husbandry.In order to effectively prevent and con-trol piglet diarrhea,the neutralizing epitopes of the screened K88(FTDYEGASVELRKPDGGT-NK),K99(NVGNGSGGANIN),987P(LAAPAENNTSQAN),F41(VMAADWTEGQPGDII)and F18(PPNAQTYPLSSGDLK)ETEC adhesins were assembled to construct the multi-epitope fusion antigen(MEFA),whose immunogenicity was verified by in silico simulations and in vitro.The computer simulation results showed that MEFA has excellent physicochemical properties and reasonable prediction results of secondary and tertiary structures and exhibits strong interaction force when docking with toll-like receptor 3,and the kinetic simulation shows that it can be stably presented.In vitro validation results showed that anti-K88,K99,987P,F18 and F41 IgY could spe-cifically recognize MEFA proteins.After immunization of laying hens with MEFA,the titers of IgY antibodies against the five ETEC were higher than those of non-specific IgY.In addition,specific anti-MEFA IgY significantly inhibited the adhesion of K88,K99,987P,F41 and F18 ETEC strains to piglet intestinal IPEC-J2 cell lines.These results indicate that MEFA has strong immunogenicity and can be used as an ideal vaccine candidate for the prevention of K88,K99,987P,F41 and F18 ETEC infection,and provide reference and technical support for the development of multivalent broad-spectrum ETEC vaccine candidates.

Enterotoxigenic Escherichia coli(ETEC)is the main cause of diarrhea in piglets,which seriously threatens the development of animal husbandry.In order to effectively prevent and con-trol piglet diarrhea,the neutralizing epitopes of the screened K88(FTDYEGASVELRKPDGGT-NK),K99(NVGNGSGGANIN),987P(LAAPAENNTSQAN),F41(VMAADWTEGQPGDII)and F18(PPNAQTYPLSSGDLK)ETEC adhesins were assembled to construct the multi-epitope fusion antigen(MEFA),whose immunogenicity was verified by in silico simulations and in vitro.The computer simulation results showed that MEFA has excellent physicochemical properties and reasonable prediction results of secondary and tertiary structures and exhibits strong interaction force when docking with toll-like receptor 3,and the kinetic simulation shows that it can be stably presented.In vitro validation results showed that anti-K88,K99,987P,F18 and F41 IgY could spe-cifically recognize MEFA proteins.After immunization of laying hens with MEFA,the titers of IgY antibodies against the five ETEC were higher than those of non-specific IgY.In addition,specific anti-MEFA IgY significantly inhibited the adhesion of K88,K99,987P,F41 and F18 ETEC strains to piglet intestinal IPEC-J2 cell lines.These results indicate that MEFA has strong immunogenicity and can be used as an ideal vaccine candidate for the prevention of K88,K99,987P,F41 and F18 ETEC infection,and provide reference and technical support for the development of multivalent broad-spectrum ETEC vaccine candidates.

Late-onset cobalamin C (cblC) deficiency is an inherited organic acid metabolic disorder characterized by clinical heterogeneity, which often presents challenges in accurate diagnosis. This article presents a case study of a young female patient who initially experienced epileptic-like seizures. Over a span of 9 years, she subsequently developed psychotic symptoms. Her condition has been steadily deteriorating over a period of 16 years, leading to mutism, loss of ambulation, dysphagia, and urinary and fecal incontinence. Although electroencephalography and cranial computed tomography did not show significant findings during the course of the illness, cranial magnetic resonance imaging showed evidence of cerebral atrophy. Biochemical analysis revealed elevated levels of blood homocysteine and urinary methylmalonic acid-2. Genetic testing identified two pathogenic mutations in the MMACHC gene, confirming the diagnosis of late-onset cobalamin C (cblC) deficiency. Despite receiving interventions such as antiepileptic and antipsychotic medications during the diagnostic and therapeutic phases, the patient′s clinical progress remained limited.Following the definitive diagnosis, targeted metabolic therapy was initiated, leading to significant clinical improvement. This article provides a comprehensive review of the patient′s clinical data, along with a synthesis of relevant literature, in order to enhance the awareness of psychiatric practitioners regarding this rare disorder. The primary objective is to promote early identification, prompt diagnosis, and timely intervention.

Late-onset cobalamin C (cblC) deficiency is an inherited organic acid metabolic disorder characterized by clinical heterogeneity, which often presents challenges in accurate diagnosis. This article presents a case study of a young female patient who initially experienced epileptic-like seizures. Over a span of 9 years, she subsequently developed psychotic symptoms. Her condition has been steadily deteriorating over a period of 16 years, leading to mutism, loss of ambulation, dysphagia, and urinary and fecal incontinence. Although electroencephalography and cranial computed tomography did not show significant findings during the course of the illness, cranial magnetic resonance imaging showed evidence of cerebral atrophy. Biochemical analysis revealed elevated levels of blood homocysteine and urinary methylmalonic acid-2. Genetic testing identified two pathogenic mutations in the MMACHC gene, confirming the diagnosis of late-onset cobalamin C (cblC) deficiency. Despite receiving interventions such as antiepileptic and antipsychotic medications during the diagnostic and therapeutic phases, the patient′s clinical progress remained limited.Following the definitive diagnosis, targeted metabolic therapy was initiated, leading to significant clinical improvement. This article provides a comprehensive review of the patient′s clinical data, along with a synthesis of relevant literature, in order to enhance the awareness of psychiatric practitioners regarding this rare disorder. The primary objective is to promote early identification, prompt diagnosis, and timely intervention.

Antipsychotic medications are commonly used to treat schizophrenia,but they can have negative effects on lipid metabolism,leading to an increased risk of cardiovascular diseases,reduced life expectancy,and difficulties with treatment adherence.The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood.Sterol regulatory element-binding proteins(SREBPs)are important transcriptional factors that regulate lipid metabolism.Proprotein convertase subtilisin/kexin type 9(PCSK9),a gene regulated by SREBPs,plays a critical role in controlling levels of low-density lipoprotein cholesterol(LDL-C)and has become a focus of research on lipid-lowering drugs.Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway.A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.

Objective:To investigate the prognosis and risk factors for children diagnosed with all types of subaortic stenosis(SAS) who developed recurrent left ventricular outflow tract obstruction after surgical treatment.Methods:The study retrospectively included patients aged 0-18 years old who underwent open heart SAS surgery at Fuwai Hospital from 2016-2019. Children with hypertrophic obstructive cardiomyopathy were excluded. Detailed operative notes, medical records and ultrasound information, and follow-ups were extracted. Recurrent SAS was defined as left ventricular outflow tract gradient 30 mmHg(1 mmHg=0.133 kPa) 1 month after SAS surgical treatment.Results:A total of 137 children were included in this study. The medium age of children at the time of SAS surgery was 4.6 years old(3 months-17.8 years old). After a median follow-up of 4.36 years(3.2-5.7 years), a total of 30 patients developed recurrent LVOTO, with a recurrence rate of 21.9%, and 7(5.1%) underwent a second surgery. Compared to the non-recurrent group, children in the recurrent group were younger at the time of surgery( P=0.0443), had a smaller body surface area( P=0.0485), and a longer length of stay( P=0.0380). In Cox analysis, when only considering preoperative variables, the independent risk factor for LVOTO recurrence were a peak left ventricular outflow tract gradient higher than 50 mmHg( HR=5.25, P=0.001), a BSA less than 0.9( HR=2.5, P=0.023), and a length of SAS 5 mm( HR=2.29, P=0.050). When both preoperative and intraoperative variables were considered, preoperative peak left ventricular outflow tract gradient 50 mmHg( HR=4.91, P=0.002) and peeling from the aortic valve( HR=3.23, P=0.010) were independent risk factors for postoperative recurrence. Conclusion:Recurrent LVOTO after SAS surgical repair is common, and regular postoperative follow-up is crucial to evaluate whether a secondary intervention is required. Regular postoperative follow-up is needed for children at high risk.

OBJECTIVE: To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD). METHODS: Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, =46) versus absence (HAM-D3 score=0, =31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters. RESULTS: There was less stage N3 [(55±41)min, =-4.731, <0.05] and the reduced percentage of N3 [(15±11)%, =-4.194, <0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both <0.05). CONCLUSIONS Suicidal ideation is associated with less N3 sleep in LLD patients.

Objective: To investigate the clinical value of multimodal navigation-based virtual reality (MNVR) in the needle biopsy of intracranial eloquent lesions. Methods: From January 2016 to January 2017, 20 patients with intracranial deep-seated lesions involving eloquent brain areas underwent MNVR-aided needle biopsy at Department of Neurosurgery, People′s Liberation Army General Hospital. Preoperatively, MNVR was used to propose and revise the biopsy planning. Intraoperatively, navigation helped trajectory avoid the eloquent structures. Intraoperative MRI (iMRI) was performed to prove the biopsy accuracy and detect the intraoperative complications. Perioperative neurological status, iMRI findings, intraoprative complications, surgical outcome and pathological diagnosis were recorded. Wilcoxon rank-sum test was conducted to compare the preoperative and postoperative neurological scores. Results: MNVR helped revised 45%(9/20) initial biopsy trajectories, which would probably injury the nearby eloquent structures. Navigation helped biopsy trajectories spare the eloquent structures during the operation. No statistical difference was found between postoperative and preoperative neurological status, despite all the lesions were adjacent to eloquent areas. Additionally, 20 patients totally received 21 iMRI scanning. iMRI helped revise incorrect biopsy site in one case and detected intraoperative hemorrhage in another case, both of cases were treated immediately and effectively. No MNVR related adverse events and complications occurred. Conclusions MNVR-aided needle biopsy of intracranial eloquent lesions is a safe, novel and efficient biopsy modality. This technique is helpful to reduce the incidence of surgery related neurological deficits.

Objective To discover the vital role of Rab27B in tumor cells and its potential molecular mechanism by means of quantitative proteomics analysis of Rab27B knockdown in MHCC97H.Methods The expression of Rab27B in MHCC97H cells was knocked down by the combination of Tet-on advanced inducible expression system and RNA interference technology.Then, proteins extracted from the cells were identified by LC-MS/MS system after FASP digestion and iTRAQ 4-plex labeling. Finally, the properties of differentially expressed proteins, including the subcellular localizations, biological processes and molecular functions, were analyzed by the bioinformatics method.Results There were 448 differentially expressed proteins (|Ratio|>1.21, P<0.05) identified in MHCC97H cells after Rab27B knock-down.The expression levels of 229 or 219 proteins were positively or negatively correlated with Rab27B, respectively. These differentially expressed proteins were mainly involved in vesicle transport, macromolecule localization, cellular response to stimulus.Furthermore, there were 26 differentially expressed proteins participating in 8 tumor-related signal pathways, eleven of which were in the focal adhesion signal pathway.Conclusion The analysis of quantitative proteomics in Rab27B-knockdown MHCC97H cell line by iTRAQ suggests that Rab27B not only has an impact on the exosomal secretion of tumor cells, but also regulates master proteins in signal pathways involved in cell proliferation and migration.

OBJECTIVETo evaluate and explore the optimal surgical strategy for the normalized treatment of pineal region tumors.

METHODSFrom September 2007 to February 2012, 43 patients were treated in Chinese People's Liberation Army General Hospital, including 30 male and 14 female patients, with pineal region tumors and non-communicating hydrocephalus were enrolled, who were 1-52 years old, mean age was (27 ± 4) years. The clinical records, treatment strategy, and prognosis were retrospectively analyzed. All the patients routinely underwent endoscopic third ventriculostomy (ETV) and tumor biopsy as the initial treatment. Twenty-seven cases (62.8%, pure endoscopic group) with histological diagnosis of germinoma (23 cases) or pineoblastoma (4 cases) were treated with chemotherapy with/without radiation therapy after ETV. The rest 16 cases (37.2%, craniotomy group) with histological diagnosis of non-germinoma and non-pineoblastoma (5 astrocytomas, 4 pineocytomas, 4 teratomas, 2 ependymomas, and 1 pineopappiloma) had craniotomy and tumor resection after ETV. All the cases had routine follow-up at 1, 3, and 6 months after the final surgery. The clinical, imaging, and tumor markers analysis were routinely examined at follow-up.

RESULTSIn the pure endoscopic group, 1 case had intra-ventricular hemorrhage after ETV, followed by external ventricular drainage and recovered after 1 week. Endoscopic procedure related short-term ( < 3 months) complication rate was 2.3% (1/43), while long-term morbidity was 0. All cases in the pure endoscopic group had chemotherapy with/without radiation therapy. Long-term follow-up results showed that all cases were cured or had progression free survival (PFS). In the craniotomy group, 2 cases (2/16) developed intra-cranial hemorrhage after surgery, and had to be operated again for hematoma evacuation. In the craniotomy group, the short-term ( < 3 months) morbidity rate was 6/16. At 3 months follow-up, 1 case still had homonymous hemianopia, which made the long-term morbidity rate was 1/16.

CONCLUSIONSFor pineal region tumors with non-communicating hydrocephalus, simultaneous ETV with tumor biopsy can be the most favorable initial diagnostic and therapeutic treatment. Second-stage treatment (chemotherapy, radiation therapy, or craniotomy with tumor resection) can be selected according to the histological diagnosis.

Adolescent ; Adult ; Brain Neoplasms ; surgery ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Hydrocephalus ; pathology ; Infant ; Male ; Middle Aged ; Pineal Gland ; Pinealoma ; surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Ventriculostomy ; Young Adult