Tumor surface antigen human epidermal growth factor receptor 2 (Her2) is a type I receptor tyrosine kinase, which belongs to human epidermal growth factor receptor family. Her2-overexpression is associated with tumorigenesis and metastasis. Due to significant clinical effects, Her2-targeted cancer therapy especially therapeutic antibody has become the hot spot in the field of cancer treatment. Anti-Her2 antibody drugs include monoclonal antibodies, antibody-drug conjugates, bispecific antibodies and emerging "two in one" antibody. Based on structure and function of Her2, this review focuses on recent advances in active mechanisms and clinical researches of these antibodies.

Objective To report the clinical and neuroimaging features in three cases of neurosyphilis with mesiotemporal lobe lesions; and to discuss possible pathogenesis and differential diagnosis.Methods The clinical manifestations,laboratory examinations,neuroimaging features,differential diagnosis and curative effect of 3 cases of neurosyphilis with mesiotemporal lobe lesions were analyzed retrospectively.The possible pathogenesis was discussed.Results All of 3 cases had positive and high titer index of syphilis in both serum and cerebrospinal fluid.The onset symptom was abnormal cognitive functions with acute aggravation or rapid progression.Cerebrospinal fluid analysis implied lymphocyte predominant inflammatory reaction with increased protein.Electroencephalography showed localized slow waves as to the lesions.On brain magnetic resonance imaging,unilateral or asymmetrical bilateral mesiotemporal lobe was affected with long T2 signal.Herpes simplex virus encephalitis and paraneoplastic limbic encephalitis should beconsidered in differential diagnosis.The symptoms and laboratory indexes improved significantly after anti-syphilis treatment.Conclusions Neurosyphilis should be evaluatedin a patient with onset of abnormal cognitive functions and having mesiotemporal lobe lesions on magnetic resonance imaging.Promptly diagnosis and early treatment could achieve good prognosis.

Strains from the cellulose-containing environment were collected. Primary screening(by filter-paper Hutchison solid culture medium and sodium carboxymethylcellulose solid culture medium) and reelection(by filter-paper inorganic salt culture medium and sodium carboxymethylcellulosc Congo red coltnre medium) indicated that five strains obtained were best suited for high performance cellulose degradation. Determination of sodium carboxymethylcellulose activity(CMCA) and filter paper activity(FPA) was accomplished for each of the five. The strongest of the five in CMCA and FPA was applied to the production of cellulose bioethanol by separate hydrolysis and fermentation(SHF) and simultaneous saccharification and fermentation(SSF) respectively.

Objective To report a case presented with atypical clinical and radiological appearance in the early stage and finally pathologically confirmed as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids ( CLIPPERS) , aiming to improve the understanding of the disorder. Methods The clinical, imaging, laboratory and pathological features as well as treatment and prognosis of a pathologically confirmed CLIPPERS patient with repeated relapsing-remitting course and stepwise progression in nine years were retrospectively analyzed. Results There were five relapsing-remitting processes in total clinical course of nine years. The clinical and radiological appearance was atypical in the early stage. At the first attack, the patient presented with fever, headache, altered consciousness and epileptic seizure. In the following courses, the patient presented with ataxia, blurred vision and limb weakness. Brain MRI (2006-2009) showed multiple abnormal signals including supratentorial white matter, pons and cerebellum with patchy gadolinium enhancement. Treatment with steroids resulted in a favorable clinical and radiological improvement. The symptoms of this attack included limb weakness, blurred vision, dysdipsia and dysarthria. Physical examination showed cognitive dysfunction, multiple cranial nerves injuries and bilateral pyramidal signs. Brain MRI showed multiple abnormal signals involved pons and cerebellum predominantly as well as supratentorial white matter with punctate gadolinium enhancement peppering the pons and cerebellum. A characteristic predominantly T lymphocytic perivascular infiltration was seen on brain biopsy. Both the imaging and histological findings were consistent with the CLIPPERS features. High-dose steroids treatment was given and obvious clinical and radiological improvements were observed. After discharge, steroids were reduced slowly combined with the use of immunosuppressant to avoid relapse of the disorder. Conclusions There is heterogeneity in clinical manifestations of CLIPPERS with repeated relapsing-remitting course and imaging presentations are sometimes atypical in the early stage, which leads to the misdiagonsis and missed diagnosis. Distinctive pathology is the “gold standard” for definite diagnosis. The nosological position of CLIPPERS is still unclear. Repeated relapse-remitting leads to secondary cerebral atrophy and degeneration, with the risk of progressing to primary central nervous system lymphoma. Early and vigorous steroids treatment with continuing maintenance immunotherapy results in the decreased relapse and best long-term prognosis. The neurologist should strengthen the understanding of CLIPPERS for early correct diagnosis and treatment aiming to reduce the functional disability.

Objective To explore the walking ability and cognitive function changes in normal pressure hydrocephalus patients after cerebrospinal fluid ( CSF ) tap test for helping clinicians choose evaluation time and methods.Methods Twenty-seven patients with probable normal pressure hydrocephalus in Peking Union Medical College Hospital from 2013 to 2014 were included.All patients were evaluated using Minimum Mental State Examination, the Montreal Cognitive Assessment, Ability of Daily Life, and Idiopathic Normal Pressure Grade Scale, underwent 1.5 T head MRI scan and had ventriculo-peritoneal shunt after informerd consent.A lumbar tap with removal of 30 ml of CSF was performed in all patients.Evaluations included the 10 m walking time and steps, Trail Making Test A, number code and Stroop test.Those tests were performed 1 day before and 4, 8, 24, 72 hours after CSF tap test.The walking test and neuropsychological test results were compared between those before and after the CSF tap test.Correlation analysis was conducted between the normal pressure hydrocephalus featured MRI characters and CSF tap test responses including Evan′s index, callosum corpus angle, mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure associated with ventriculomegaly . Results Compared with 0 h walking time (23.56(14.00) s), the 10 m walking time on the 8 hours and 24 hours after CSF tap test, which were 19.41 ( 9.00 ) s and 19.67 ( 11.00 ) s respectively, were significantly improved ( Z values in Wilcoxon signed ranks test were -3.416 and -3.443 respectively,both P<0.01).There were no statistically significant differences on every evaluation time point.The neuropsychological tests changings were significant on 24 hours and 72 hours.Compared with 0 h neuropsychological test z scale (-10.28(21.60)), the z scale on the 24 hours and 72 hours after CSF tap test, which were -6.29 (26.72), -3.37(36.15)respectively, were significantly improved (Z values in Wilcoxon signed ranks test were -3.506,-2.701 respectively, both P<0.01).The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure were not statistically correlated with the response of CSF tap test.Conclusions Walking ability in normal pressure hydrocephalus patients was improved after the CSF tap test.The Evan′s index, callosum corpus and the feature of mismatch between narrowed high-convexity and medial subarachnoid spaces and enlarged Sylvian fissure might not be correlated with the response of CSF tap test.

The National Institute on Aging-Alzheimer's Association (NIA-AA) research framework of biological definition of Alzheimer's disease 2018 is introduced to Chinese counterparts to share a common "language" with dementia researchers.The abnormal definitions of Alzheimer's disease (AD),βamyloid deposition (Aβ) and tau,were proposed to be detected by biological methods,and a series of changes before dementia and dementia were proposed to be studied under a unified biological framework.The characteristic biomarkers were defined as AT(N):A is [β amyloid deposition,T is pathological tau protein,and (N) is neurodegeneration.The diversity of the pathological nature of dementia was emphasized,and AD combined with dementia was proposed not to be directly attributable to dementia due to AD.The definition of biomarkers requires more standardization and confirmation of autopsy pathology.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by localized neuronal loss,and the presence of eosinophilic intranuclear inclusions in neurons and glial cells.Biopsy samples of skin,rectal and sural nerve showed hyaline intranuclear inclusions.Reported NIID cases showed familial type according to family history,and three clinical subgroups (infantile,juvenile and adult form) according to onset and disease duration.NIID has been considered as a heterogeneous disease because of the highly variable clinical manifestations including cognitive dysfunction,parkinsonism,cerebellar ataxia,peripheral neuropathy and autonomic dysfunction.Additionally,some NIID cases presented episodes of conscious disturbance,cognitive decline,movement disorder or even fever.Head magnetic resonance imaging of some patients revealed symmetrical leukoencephalopathy in T2 image and fluid attenuated inversion recovery image and high intensity signal in corticomedullary junction in diffusion weighted image.But it is not the only abnormal finding of imaging,and other diseases may also present the similar changing.Other diseases including fragile X-associated tremor-ataxia syndrome,Huntington's disease and spinocerebellar ataxia should be considered in differential diagnosis.

Objective:To analyze the advantages of human epididymis protein 4 (HE4) compared with traditional tumor markers in the diagnosis and treatment of lung cancer.Methods:From February 2021 to June 2022, 230 lung cancer patients (138 males, 92 females; age (61.1±12.3) years), 96 benign lung disease patients (62 males, 34 females; age (60.2±14.8) years; including 43 cases of lung benign placeholder and 53 cases of pulmonary infection), and 60 healthy volunteers (40 males, 20 females; age (62.8±11.4) years) from the Second Affiliated Hospital of Soochow University were prospectively collected. Serum HE4, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen (CA)125 were detected by electrochemical analysis. The expression of HE4 in tumor tissues of 55 patients with lung cancer was detected by immunohistochemical method. χ2 test, Mann-Whitney U test, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. The diagnostic efficiencies of HE4 and other tumor markers were evaluated by ROC curve analysis and the difference of AUCs was analyzed by Delong test. Results:The positive expression rate of HE4 in adenocarcinoma tissue was significantly higher than that in non-adenocarcinoma tissue (93.1%(27/29) vs 23.1% (6/26); χ2=28.01, P<0.001). The level of serum HE4 in the lung cancer group (70.70(51.93, 109.05) pmol/L) was significantly higher than that in the pulmonary benign placeholder group (59.80(48.20, 73.50) pmol/L) and the healthy control group (55.25(44.60, 74.25) pmol/L), and that in the pulmonary infection group (97.90(76.62, 155.00) pmol/L) was higher than that in the lung cancer group ( H=46.19, all P<0.008 (Bonferroni correction method)). The levels of serum HE4 were significantly different in age, sex, smoking, disease stage and pathological types in early stage ( z values: from -5.07 to 9.83, all P<0.05). The ROC curve analysis indicated that the optimal cut-off value of serum HE4 for diagnosing lung cancer was 79.22 pmol/L, with the sensitivity and specificity of 41.30%(95/230) and 83.33%(50/60). Compared with other traditional tumor markers, serum HE4 and CA125 showed the higher diagnostic value (AUC CA125 (0.695)>AUC HE4(0.656)>AUC CEA(0.614)>AUC CYFRA21-1(0.599)>AUC ProGRP (0.501)>AUC NSE (0.470)). The combination of HE4 with other traditional tumor markers significantly improved the diagnostic efficacy (AUC=0.750; z=2.75, P=0.006). Conclusions:HE4 is highly expressed in lung adenocarcinoma by immunohistochemistry. Serum HE4 exhibits a great application value in the differential diagnosis between benign and malignant pulmonary nodules, and plays an important role in assessment of patients′ conditions.

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.