This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

In this study, sonography video urodynamic studies (SVUDS), which combined synchronically urodynamic studies with trans-perineal and trans-abdominal sonography, were used to detect female bladder outlet obstruction (FBOO). The dynamic changes of urethra and surrounding pelvic floor structure during storage and voiding phase were observed by SVUDS and the causes of FBOO were analyzed. And the findings were as follows: 13 patients showed organ prolapse, there was an urethral angulation deformity during urination; 5 cases had abnormal urination as the urethral opening was not good in the middle of urination period; 4 cases had urethral stricture, as the proximal end of the obstruction dilated during urination, and the obstruction site showed no relaxation; 1 case had primary bladder neck obstruction with an incomplete opening of the bladder neck during urination; 3 cases had idiopathic bladder outlet obstruction and the sphincter of bladder neck and urethra opened well during urination.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

Objective To study binocular rivalry (BR)objectively and the correlation between fusiform face area (FFA)and visual cortex.Methods Six subjects participated in this study,with one eye presented a normal face expres-sion picture flickered at 8.57 Hz,while the other presented a fearful face flickered at 12 Hz or 15 Hz,respectively.Electro-encephalogram(EEG)was recorded during this process.Steady state visual evoked potential(SSVEP)evoked by two flick-ering rates was analyzed by time-frequency analysis of short time fourier transformation(STFT).The time index of BR was estimated and the correlation coefficient between FFA and visual cortex compared.Results The total average time was (411.6 ±73.8)ms for the left eye and (547.6 ±126.7)ms for the right eye.The switch rate of the two groups was not different,but the left FFA was more sensitive than the right FFA in process of the fearful face.Neither side of FFA had any frequency preference to the flickered fearful face.Conclusion SSVEP can be used as a frequency tag of BR or as a tool to evaluate visual sensation under BR objectively.SSVEP combined with BR can be used in research of neural mechanisms of visual awareness.

1cm, there was a significant statistical difference in median survival of 61 and 12 months, respectively (? 2 =16.60, P =0.0001). The median survival for patients with and without peritoneal chemotherapy were 27 and 12 months, respectively (? 2 =3.45, P =0.0633). Residual disease, FIGO stage, recurrent ascites, uterus muscle involvement were independent prognostic determinants of survival identified by Cox's stepwise regression analysis. Conclusions Aggressive surgical cytoreduction should be performed in elderly AEOC patients as well as in younger patients, but multi-course platinum-based chemotherapy should be used in accordance with the performance status of elder women.

Objective To investigate the timing and role of systemic retroperitoneal lymphadenectomy in patients with ovarian cancer. Methods From Jan. 1987 to Feb. 1994, 50 patients with ovarian cancer, who underwent retroperitoneal lymphadenectomy on second-look laparotomy (SLL), were retrospectively studied. Results The median age was 49 years. Overall survival at 3 and 5 years were 72% and 62%, respectively. Twenty of 50 (40%) women were found SLL(+),and the rates of positive SLL were related to International Federation of Gynecology Obstetrics (FIGO) stage, with 16% in stage ⅠandⅡ, 64% in stage Ⅲ and Ⅳ (P

6 months was 42.3 months, longer than 17.5 months for patients with PFI ≤ 6 months, no statistical significance was found ( P =0.1418). Multivariate analysis strongly suggested that PFI and the courses of second line chemotherapy were independent prognostic factors of survival after secondary treatment for epithelial ovarian cancer. For those patients with PFI ≤ 6 months, the smaller the size of residual lesion ( P =0.0003) and the more the cycle of effective second line chemotherapy ( P =0.0004), the longer the survival after the secondary cytoreduction. Conclusions:The results suggested that successful secondary cytoreductive surgery combined with multicycles second line chemotherapy may be an effective way to lengthen the survival on retreatment for patients with platinum resistant and recurrent epithelial ovarian cancer.

Objective To investigate individualized and multi-phase management of recurrent epithelial ovarian carcinoma in order to improve survival of the patients. Methods From 1998 to 2002, 70 patients with recurrent epithelial ovarian carcinoma were enrolled in the present study. The treatments were divided into: (1) Induction of tumor remission:platinum sensitive patients were treated with paclitaxol + cisplatin (TP) or carboplatin + cyclophosphamide(CP)regimen; platinum resistant patients used Taxol + mitomycin(TM)or etoposide+ mitomycin(VM)regimen. Resection of tumors was done in an attempt to reduce the residual tumor with a diameter less than 1cm. Local radiotherapy was performed for those with residual tumor and who achieved clinical response after chemotherapy or surgery. (2) Consolidation therapy: chemotherapy with lower doses was administrated after disease remission. Interferon was used as immunotherapy during chemotherapy and radiotherapy. Survial analysis was done. Results (1) The 1, 2, 3, 4, 5-year survival rates were 67%, 51%, 45%, 38%, 32% . Median survival was 38.57 months. (3)The 1,2,3-year progression-free survival rates of the research arm were 41%, 37%, 24%. Median progression-free survival was 12.00 months. (4) Multivariate analysis revealed that platinum-free interval (P