OBJECTIVE To investigate the clinical efficacy and safety of dupilumab in patients with severe asthma-chronic obstructive pulmonary disease （COPD） overlap （ACO）. METHODS A retrospective analysis was conducted on 150 patients with severe ACO treated at Nantong Third People’s Hospital during Jan. 2022-Dec. 2023. Patients were divided into the control group [conventional therapy with inhaled corticosteroids （ICS）+long-acting beta-2 agonists （LABA）+long-acting muscarinic anticholinergic （LAMA）， n＝90] and the observation group （conventional therapy plus dupilumab， n＝60） based on different treatment regimens. Propensity score matching （PSM） was performed at a ratio of 1.5∶1. Symptom control scores [Asthma Control Test （ACT） score， COPD Assessment Test （CAT） score] and pulmonary function parameters [forced vital capacity （FVC）， forced expiratory volume in 1 second （FEV1）， the FEV1 in percentage of predicted value （FEV1%pred）， the ratio of FEV1 and FVC （FEV1/FVC）， peak expiratory flow （PEF） and maximal mid-expiratory flow （MMEF）] before treatment and at 1， 3， and 12 months after treatment， as well as the levels of biomarkers [peripheral blood eosinophil （EOS） count， immunoglobulin E （IgE）， C-reactive protein （CRP）， fractional exhaled nitric oxide （FeNO）]， annual acute exacerbation frequency， quality-of-life scores [Asthma Quality of Life Questionnaire （AQLQ） score， St George’s Respiratory Questionnaire （SGRQ） score， and Medical Outcomes Study 36-item Short Form Health Survey （SF-36） score] before treatment and 12 months after treatment， and the occurrence of adverse reactions were compared. RESULTS After PSM， 120 patients were included， involving 72 cases in the control group and 48 cases in the observation group. Compared with before treatment， both groups showed significant improvements in ACT scores at 1， 3， and 12 months after treatment， FVC， FEV1， FEV1%pred （except at 3 months after treatment in the control group）， （except at 3 months after treatment in the control group）， PEF （except at 3 and 12 months after treatment in the control group） and MMEF （including at 1 month after treatment in the observation group） at 3 and 12 months after treatment， as well as AQLQ and SF-36 scores at 12 months after treatment （P＜0.05）. CAT scores at 1， 3 and 12 months after treatment， annual acute exacerbation frequency and SGRQ score at 12 months after treatment， FeNO levels at 12 months after treatment in the control group， as well as EOS count， IgE， CRP and FeNO levels at 12 months after treatment in the observation group were significantly reduced （P＜0.05）. The improvements of above indicators in the observation group were mostly greater than in the control group （P＜0.05）. The incidence of adverse reactions did not differ significantly between the two groups （P＞0.05）. CONCLUSIONS Dupilumab provides superior efficacy over conventional therapy in improving clinical symptoms， pulmonary function， and quality of life， while reducing biomarker levels in patients with severe ACO， with a comparable safety profile to standard therapy.

Objective To explore the the correlation between cystatin C(Cys C),beta-2 microglobulin(β2-MG)and ischemic cerebral small vessel disease(CSVD)and its subgroups.Methods Totally 234 patients with CSVD were assigned to the study group,and 92 elderly people with no abnormal findings in head MRI were selected as controls.The CSVD patients were further divided into the subgroups of lacunar infarction(LI),white matter lesion(WML)and LI+WML.Each group was compared risk factors include the blood level of Cys C and β2-MG.Results There were statistically significant differences between CSVD group and control group in cystatin C(Cys C)and β2-MG(P<0.05).Cystatin C(Cys C)and β2-MG there were statistically significant differences between WML group and control group(P<0.05),and also between WML+LI group and control group(P<0.05).Logistic regression analysis and comparison across subgroups showed Cys C and β2-MG to be the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.Conclusion Cys C and β2-MG are the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.The risk factors vary across different CSVD subgroups.

AIM: To investigate the effect of 3-bro-mopyruvate cholesterol ester (3-BP-Cl) on the sensitivity of breast cancer to tamoxifen (TAM). METHODS: MTT assay and Calcein AM/PI staining were used to detect the effect of drugs on the viability of breast cancer cells. Kim's formula was used to detect synergistic anti-breast cancer effect of cholesterol 3-bromopyruvate and tamoxifen. The inhibitory effect of drugs on proliferation of breast cancer cells was detected by colony-forming assay. Flow cytometry was used to detect the apoptosis of breast cancer cells. Western blot assay was used to detect the expression of hexokinase 2, Bcl-2 and Bax proteins. RESULTS: MTT results showed that combination 3-BP-Cl and TAM could significantly inhibit the activity of MCF-7 cells (P<0.05). The results of King's formula showed that 3-BP-Cl and TAM had synergistic inhibitory effect on the proliferation of MCF-7 cells (q>1.15). Calcein AM / PI staining showed that the number of dead cells was the highest in the combination group. Colony-forming assay showed that the combination group had stronger inhibitory effect on the proliferation of MCF-7 cells than that of single drug groups. AnnexinV flow cytometry results showed that, the cell apoptosis in the combination group was significantly increased (P<0.01). Western blot results showed that 3-BP-Cl inhibited the expressions of hexoktokinase 2 and Bcl-2, and enhanced the expression of Bax in MCF-7 cells. CONCLUSION: 3-BP-Cl could increase the sensitivity of breast cancer cells to tamoxifen, and synergically inhibit the proliferation of breast cancer cells. The mechanism is possibly related to its effects of inhibiting the expression of HK2/Bcl-2, and enhancing the expression of Bax.

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.

Objective:To identify objective markers between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson′s disease (PD).Methods:Retrospective analysis was performed on 10 patients with MSA-P, 15 patients with PD, and 15 healthy control group during the period from August 2016 to February 2019 in Baoshan Branch of Shanghai First People′s Hospital.We combined the novel tract based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups with diffusion tensor imaging. By TBSS, we performed pairwise comparisons of mean diffusivity and fractional anisotropy (FA) maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses.Results:FA values in the left anterior thalamic radiation(ATR) (ROI values were 0.371(0.287-0.535), 0.472(0.390-0.594), 0.473(0.388-0.555); P values were 0.008, 0.008) and left superior longitudinal fasciculus (SLF)(ROI values were 0.397(0.291-0.469), 0.456(0.338-0.560), 0.473(0.427-0.530); P values were 0.013,<0.001) were significantly decreased in MSA-P compared with PD or controls, and significantly correlated with clinical data(( r =-0.807, P =0.005),( r =-0.455, P =0.022)). Conclusion:Our findings indicate the abnormalities of left ATR and left SLF as specific biomarkers for differential diagnosis.

The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected non-invasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls (including the samples used in the discovery phase) using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state (area under the curve = 0.999). In summary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.
Adult ; Aged ; Aged, 80 and over ; Biomarkers ; metabolism ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay ; Eye Proteins ; metabolism ; Female ; Humans ; Male ; Mass Spectrometry ; Middle Aged ; Persistent Vegetative State ; metabolism ; Proteome ; Proteomics ; ROC Curve ; Tears ; metabolism ; Young Adult

Prognostication of coma patients after brain injury is important, yet challenging. In this study, we evaluated the predictive value of amplitude-integrated electroencephalography (aEEG) for neurological outcomes in coma patients. From January 2013 to January 2016, 128 coma patients after acute brain injury were prospectively enrolled and monitored with aEEG. The 6-month neurological outcome was evaluated using the Cerebral Performance Category Scale. aEEG monitoring commenced at a median of 7.5 days after coma onset. Continuous normal voltage predicted a good 6-month neurological outcome with a sensitivity of 93.6% and specificity of 85.2%. In contrast, continuous extremely low voltage, burst-suppression, or a flat tracing was correlated with poor 6-month neurological outcome with a sensitivity of 76.5% and specificity of 100%. In conclusion, aEEG is a promising predictor of 6-month neurological outcome for coma patients after acute brain injury.
Brain ; physiopathology ; Brain Injuries ; complications ; diagnosis ; physiopathology ; Coma ; diagnosis ; etiology ; physiopathology ; Electroencephalography ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neurophysiological Monitoring ; methods ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; Severity of Illness Index

OBJECTIVE: To investigate the relationship between insulin-like growth factor-1 (IGF-1) in the serum and the vascular endothelial function in patients with hypercholesterolemia and the underlying mechanism. METHODS: We examined the flow-mediated arterial diastolic function (FMD), the levels of IGF-1, asymmetric dimethylarginine (ADMA), NO, and the activity of nitric oxide synthase (NOS) in the serum from 25 patients with hypercholesterolemia and from healthy controls. An endothelial cell injury model was established by incubation of the human umbical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL) for 24 hours. Cells were treated with IGF-1 30 min before ox-LDL treatment. The levels of ADMA, NOS, and NO in the cell supernatant, the activity of dimethylarginine dimethylamine hydrolase (DDAH) in the cell lysate were measured. Beta-galactosidase staining was used to assess the degree of endothelial cell senescence by calculating the senescence rate of cells. RESULTS: Compared with the control group, the FMD, the levels of IGF-1 and NO, and the activity of NOS in the serum from patients with hypercholesterolemia decreased significantly accompanied with a dramatic increase at ADMA level. Multiple linear regression analysis showed that the change in IGF-1 was positively correlated with FMD while the change in ADMA was negatively correlated with FMD. Compared with the control group, ox-LDL treatments significantly decreased the activities of DDAH and NOS, and the level of NO, accompanied with an increase in ADMA. Betagalactosidase staining showed that the senescence rate of cells increased in the ox-LDL group. The effect of ox-LDL on HUVECs was significantly attenuated at the presence of IGF-1. CONCLUSION The decrease in IGF-1 in the peripheral blood may contribute to vascular endothelial dysfunction in patients with hypercholesterolemia. IGF-1 can protect HUVECs against ox-LDL-induced senescence, which is likely involved in the regulation of DDAH/ADMA pathway.
Adult ; Arginine ; analogs & derivatives ; blood ; Case-Control Studies ; Cells, Cultured ; Endothelium, Vascular ; physiology ; Female ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Hypercholesterolemia ; blood ; physiopathology ; Insulin-Like Growth Factor I ; metabolism ; physiology ; Lipoproteins, LDL ; pharmacology ; Male ; Middle Aged ; Nitric Oxide ; blood ; Protective Agents ; metabolism ; Vasodilation ; physiology