Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Objective:To prepare a fluorescent probe Cetuximab-IRDye800CW targeting epidermal growth factor receptor (EGFR) and investigate its application value in surgical navigation of glioblastoma (GBM).Methods:The fluorescence properties of Cetuximab-IRDye800CW were determined by fluorescence spectrophotometer. The specificity of Cetuximab-IRDye800CW bound to GBM cells was verified by Western blot. The competitive binding method of enzyme-linked immunosorbent assay (ELISA) was used to prove whether the probe could achieve tumor targeting by binding to EGFR. Subcutaneous models of 6 nude mice of GBM were divided into experimental group ( n=3; injected with Cetuximab-IRDye800CW) and control group ( n=3; injected with IRDye800CW), and images were obtained at 5 min, 24 h, 48 h and 72 h after injection. Differences of mean fluorescence intensity (MFI) and tumor to background ratio (TBR) between experimental group and control group were compared. In situ models of GBM nude mice were established ( n=6), and MRI and intraoperative navigation were conducted, which were compared with pathological distribution. Independent-sample t test was used to analyze the data. Results:The maximum emission wavelength of Cetuximab-IRDye800CW was 820 nm, which could be received by near infrared fluorescence imaging equipment. Western blot showed that Cetuximab-IRDye800CW was only bound to GBM cells. The competitive binding of ELISA showed that Cetuximab-IRdye800CW could achieve tumor targeting by binding with EGFR. At 5 min, 24 h, 48 h and 72 h after injection of fluorescent materials, the MFI values of experimental group were 109.00±3.81, 73.36±9.93, 55.24±8.82, 37.71±6.11, which were higher than those of control group (91.32±4.17, 42.91±5.39, 25.08±6.05, 8.33±1.00; t values: 4.36-9.40, P values: 0.011-0.049). The TBR of experimental group was higher than that of control group at 24 h and 48 h after injection (24 h: 2.40±0.28 vs 1.57±0.07, t=4.94, P=0.039; 48 h: 2.07±0.12 vs 1.22±0.08, t=9.85, P=0.010). GBM in situ model was successfully constructed and verified by MRI, and the tumor was visualized under the fluorescence device navigation. Pathological distribution of the tumor with HE staining was consistent with fluorescence imaging. Conclusion:Cetuximab-IRDye800CW has fluorescence imaging capability and can identify tumor boundaries in intraoperative navigation of GBM, which has potential clinical application value.

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism* ; N-Acetylneuraminic Acid ; Immunoglobulins/metabolism* ; Receptors, Immunologic ; Ligands

Objective:To explore the effect of moderate intensity physical exercise on depression, anxiety and cognitive function of schizophrenic patients and its possible biochemical mechanism.Methods:Totally 148 patients with schizophrenia who were hospitalized in hospital from March 2019 to March 2021 were randomly divided into control group ( n=75) and exercise group ( n=73). The patients of the two groups were given drug treatment and routine exercise according to clinical practice, and the patients in exercise group were given additional medium-intensity physical exercise.Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the poor mental state of the subjects.The verbal fluency task(VFT), digital span test(DST), trail making test-A(TMT-A) and the positive and negative symptom scale (PANSS) were used to evaluate cognitive function.The levels of endocannabinoids (eCBs) receptors were detected by high performance liquid chromatography, and the levels of monoamine neurotransmitters and eCBs in the patients' serum were determined by enzyme-linked immunosorbent assay (ELISA). SPSS 19.0 software was used for statistical analysis.The measurement data between the two groups were compared by t-test and the counting data between the two groups were compared by χ2 test. Results:(1) After effective intervention, the scores of SAS, SDS, TMT-A and PANSS of the two groups were significantly lower than those before intervention, and the difference before and after intervention between the two groups was statistically significant( t=6.00, 6.52, 25.79, 17.03, all P<0.01). The scores of SAS, SDS, TMT-A and PANSS after intervention in the exercise group were significantly lower than those in the control group( t=4.66, 20.88, 6.61, 8.95; all P<0.01). The number of VFT and DST in the two groups after intervention were significantly higher than those before intervention, and the differences before and after intervention between the two groups were statistically significant( t=13.78, 22.76, both P<0.01). After effective intervention, the number of VFT and DST in exercise group were significantly higher than those in the control group( t=5.02, 5.15, both P<0.01). (2) After effective intervention, the contents of monoamine neurotransmitters and eCBs in serum of the two groups were significantly higher than those before intervention, and HVA level ((63.68±6.99) pg/mL), MHPG level ((175.90±16.22) pg/mL), 5-HIAA level ((29.94±4.19) pg/mL) and CBR1 level ((6.70±1.40)μg/L), 2-AG level ((61.90±5.73)pmol/g) and AEA level ((76.48±6.59) pmol/g) in exercise group were significantly higher than those in the control group ((52.97±5.37)pg/mL, (138.50±11.52)pg/mL, (23.87±3.15)pg/mL, (5.71±1.29)μg/L, (52.13±5.14)pmol/g, (67.66±5.88)pmol/g)( t=10.43, 16.21, 10.91, 8.65, all P<0.01). Conclusion:Moderate intensity physical exercise can significantly improve their depression, anxiety and cognitive function, which may be related to regulating the levels of ECBS and their receptors in patients with chronic schizophrenia to increase monoamine neurotransmitters.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

To construct a eukaryotic expression plasmid containing the luciferase reporter gene (Fluc) to quickly detect apoptosis. Four amino acids, Asp-Glu-Val-Asp (DEVD), the recognize motif of Caspase-3, were introduced into the middle of the Fluc-C and N fragment. Meanwhile, four amino acids, Asp-Glu-Val-Gly (DEVG), were selected as a negative control. Subsequently, the recombinant gene was cloned into the N and C terminal end of the split intein, and named as pFluc-DEVD and pFluc-DEVG. Then the plasmids were transfected into cells and renilla luciferase was co-transfected in each sample as an internal control for transfection efficiency. Then the apoptosis level was detected by the double luciferase reporter gene and the Western blotting analysis. The results showed that when apoptosis occurred, the content of firefly luciferase expressed in the pFluc-DEVD plasmid transfected group was about 3 times higher than pFluc-DEVG plasmid transfected group. Furthermore, Western blotting detection indicated that the Fluc level was significantly increased in pFluc-DEVD transfected group when pre-treated by apoptosis stimulants. The activation degree of Caspase-3 was closely related to the expression of Fluc, and had a significant statistical difference. These results confirmed that firefly luciferase protein expressed by pFluc-DEVD plasmid can be cleaved by the intracellular Caspase-3 enzyme, and this plasmid can accurately reflect the cell apoptosis level, which provides a useful method for quantitative detection of apoptosis.
Apoptosis ; Genes, Reporter ; Luciferases, Firefly ; Transfection

Objectives To explore the differences in therapeutic efficacy between decitabine combined with low dose HAG(D+ HAG)and CAG in elderly patients with acute myeloid leukemia (AML).Methods Totally 32 elderly patients with AML in our department from July 2012 to July 2015 were retrospectively analyzed.15 patients were on a therapy of decitabine combined with low dose HAG,and 17 patients with CAG.Efficacy and side effects were compared between the two groups.Results In(D+HAG)versus CAG groups,the complete remission(CR)was 10 cases(66.7％)vs.6 cases (35.3 ％),partial remission(PR) was 2 cases (13.3％) vs.1 case(5.9 ％),non-remission(NR) was 3 cases(20％)vs.10 cases(58.8％),and the total efficacy rate(CR+PR)was 80％vs.41.2％ (P＜0.05).The side effects in two groups mainly included bone marrow depression,respiratory tract infection,gastrointestinal reaction,which were all alleviated after symptomatic treatments.The incidence rate of side effects had no statistical difference (P ＞ 0.05).Conclusions The treatment of decitabine combined with low dose of HAG is prior to CAG,and the side effects are all tolerated.So decitabine combined with low dose of HAG can be served as the first-line therapy for elderly AML patients.

This study was aimed to analyze the pathogen distribution,drug resistance and traditional Chinese medicine (TCM) syndrome of patients with primary nephrotic syndrome complicated with pulmonary infection for the guidance of clinical practice.The clinical data of 180 patients with primary nephrotic syndrome complicated with pulmonary infection were analyzed.The results showed that among 180 patients,117 were male,accounting for 65％;73.33％ of them were over 40 years old.Membranous nephropathy was the most common pathological type,accounting for 40％.Gram-negative bacteria were the main pathogen,accounting for 51.72％.The drug resistance rates of piperacillin/tazobactam,imipenem,amikacin,gentamicin were the lowest.The drug resistance rates of third generation of cephalosporins and quinolone antibiotics were in the middle.In TCM syndrome differentiation,central qi deficiency and phlegm syndrome occupied the highest proportion,accounting for 25.56％;and the phlegm heat in the lung syndrome,accounting for 17.78％;wind evil attacking the lung syndrome,accounting for 13.33％;qi deficiency and phlegm syndrome,accounting for 9.45％;qi deficiency,blood stasis and water stagnation syndrome,accounting for 8.89％;the mixture of deficiency and excess syndrome,accounting for 59.45％,with qi deficiency as the main part.It was concluded that middle-aged and older men,pathologic type of membranous nephropathy had the higher rate of suffering pulmonary infection.Gram-negative bacteria were the main pathogen.The choice of antibiotics should be based on piperacillin/tazobactam,and third generation of cephalosporins.Qi deficiency and phlegm syndrome was the most common TCM syndrome.

Objective Study configuration inversion of C-2-hydroxy in lycorine to provide a foundation for semi-synthesis of asiaticumine B .Methods Use instrumental analyses to explore the C-2-hydroxy configuration through oxidation and reduc-tion reactions .Results Accomplished configuration inversion of C-2-hydroxy in lycorine with 49% yield .Conclusion We identified a convenient and efficient method for the configuration inversion of C 2-hydroxy in lycorine .