Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Purpose To analyze the relationship between different molecular types and imaging manifestations of simultaneous bilateral breast cancer.Materials and Methods Eighty-one patients with simultaneous bilateral breast cancer confirmed by surgery and pathology in the Affiliated Hospital of Qingdao University from January 2016 to May 2022 were retrospectively analyzed,80 patients received mammography and 38 patients received MRI.Imaging features referred to the 5th edition of the breast imaging reporting and data system standards.Molecular typing was evaluated and classified according to the 2013 revised St.Gallen international expert consensus recommended the determination.The clinicopathological and imaging features of the index and contralateral breast cancer were compared,and the imaging features of different molecular types of the index and contralateral breast cancer were also compared.Results There were statistically significant differences in histological types and molecular typing between the index and contralateral cancers(x2=39.72,12.23,P＜0.05).Mammograph showed that the index cancer was mostly a mass(51.9％,40/77),while the contralateral cancer was mostly calcification(38.4％,28/73);the index cancer was mostly polymorphic calcification(68.8％,22/32),while the contralateral cancer was mostly amorphous calcification(45.2％,19/42)(x2=33.15,10.47,P＜0.05).There was a statistically significant difference in the MRI enhancement between the index cancer and the contralateral cancer(x2=6.79,P＜0.05).For contralateral cancer,mammograms showed statistically significant differences in the four molecular subtypes on tumor density,as well as MRI enhancement patterns,early enhancement degree,and time-signal intensity curve(x2=26.72,7.49,8.95,13.44,12.85,P＜0.05).There was a significant difference in the distribution of calcification among the four molecular subtypes on the X-ray of the first cancer(x2=20.15,P＜0.05).Conclusion The molecular typing and some imaging characteristics of simultaneous bilateral breast cancer are different,and some imaging characteristics can provide reference for predicting the molecular typing of simultaneous bilateral breast cancer.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Objective:To investigate the effects of transepithelial photorefractive keratectomy (TransPRK) and femtosecond small incision lenticule extraction (SMILE) on corneal biomechanics measured by the Ocular Response Analyzer in the early postoperative period.Methods:A cohort study was conducted.The right eyes of 56 patients who underwent TransPRK and 52 patients who underwent SMILE in Dalian Medical University Affiliated Dalian Third People's Hospital from November 2020 to June 2021 were continuously included.The postoperative follow-up was 3 months.The central corneal thickness (CCT) and keratometry (Km) were measured 1 month and 3 months after surgery.The corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF), corneal hysteresis (CH), and 19 repeatable mechanical infrared signal waveform parameters measured by the Ocular Response Analyzer were recorded before the surgery, 1 month and 3 months after the surgery, respectively.The measurement indexs at different time points between two groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Dalian Medical University Affiliated Dalian Third People's Hospital (No.2019-KT-010). Written informed consent was obtained from each patient before surgery.Results:There was no significant difference in CCT, Km, and IOPcc between the two groups at 1 month and 3 months after the surgery (all at P>0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1, dive2 and mslew1 were decreased, while path1, path2, path11, and aplhf were increased at 1 month after the surgery compared with before surgery, showing statistically significant differences (all at P<0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1 decreased, while path1, path2, path11, and aplhf were increased at 3 months after the surgery in comparison with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, the dive2 were decreased at 3 months after the surgery compared with before surgery, and the difference was statistically significant ( P<0.01). At 1 month after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, dive1 and dive2 were higher, while CH, path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). At 3 months after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h2, h21, dive1 and dive2 were higher, while path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). Conclusions:Corneal biomechanics are weakened after both TransPRK and SMILE.In the early postoperative period, the mechanical infrared waveform parameters measured by the Ocular Response Analyzer are better after TransPRK than after SMILE.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Human Gasdermin B (GSDMB) gene, as a member of the Gasdermin (GSDM) gene family, may be associated with the development of asthma, tumor and immune system diseases. Recent studies have found that cell pyroptosis can be mediated by GSDMB protein. The N-terminus of GSDMB cleaved by Granzyme A (GZMA), which is secreted by cytotoxic lymphocytes, can directly promote cell pyroptosis. Moreover, GSDMB protein promotes the cleavage of Gasdermin D (GSDMD) by binding to cysteinyl aspartate specific proteinase-4 (caspase-4), thus indirectly promoting cell pyroptosis. This article summarized the progress in the mechanism of GSDMB gene-mediated cell pyroptosis and the related diseases.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

Objective:To comparative analyze mammographic and clinicopathological findings of ductal carcinoma in situ (DCIS) and DCIS with microinvasion (DCISM), and to investigate the predictive factors for DCISM.Methods:A total of 626 patients with DCISM and DCIS confirmed by surgery and pathology in the Affiliated Hospital of Qingdao University from January 2016 to July 2020 were collected and underwent preoperative mammography. The X-ray findings of DCISM and DCIS patients were classified and diagnosed according to the Breast Imaging Reporting and Data System (BI-RADS) criteria. The differences in clinicopathological and radiographic findings between DCISM and DCIS patients were analyzed using χ 2 test or Fisher exact test. The risk factors of DCISM were evaluated by using univariate and multivariate binary logistic regression analysis. Results:Among the 626 cases, 171 were diagnosed as DCISM, 455 were diagnosed as DCIS. Large diameter (≥2.7 cm), high nuclear grade, comedo type, axillary lymph node metastasis, high Ki67 proliferation index, negativity of estrogen receptor and progesterone receptor were found to be predictors of DCISM in the univariate analysis (all P<0.05). And large diameter (≥2.7 cm)(OR 2.229,95% CI 1.505-3.301, P<0.001), high nuclear grade(OR 1.711,95%CI 1.018-2.875, P=0.043) and axillary lymph node metastasis(OR 4.140,95% CI 1.342-12.773, P=0.013) were found to be independent predictors of DCISM in the multivariate analysis (all P<0.05). Mammographically, the lesion types, the presence and distribution of calcification were statistically significant between DCIS and DCISM patients (χ 2=17.42, 9.65, 9.10, P<0.05). Up to 17.6% (80/455) of DCIS were occult leisions, and DCISM showed more lesions with calcification in mass, asymmetry, and architectural distortion (49.1%, 84/171). Grouped calcifications were usually associated with DCIS (41.5%, 120/289), while regional calcification were commonly found in DCISM (35.9%, 47/131). Conclusions:Lesions with calcification and regional calcification were more likely associated with DCISM on mammography. Large diameter (≥2.7 cm), high nuclear grade and axillary lymph node metastasis were found to be independent predictors of DCISM.