Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×10⁹/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO₂ >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0–10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

The role of corticosteroids in the treatment of Coronavirus disease 2019 (COVID-19) is controversial. In the present study, we evaluated the effects of adjuvant corticosteroids treatment on the outcome of patients with COVID-19 (n=966), using Propensity Score Matching to adjust for potential differences between the corticosteroids group (n=289) and the non-corticosteroids group (n=677). Analysis of data without adjusting differences in baseline characteristics indicated that the proportion of mechanical ventilation and the mortality was higher in the corticosteroids treatment group in total or severe/critical patients. The duration of viral shedding was longer in the non-corticosteroids treatment group in total or general/mild patients. After adjusting the difference between the corticosteroids and non-corticosteroids treatment group, the analysis revealed that the use of corticosteroids had no effect on the duration of viral shedding, in-hospital mortality or 28-day mortality.

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented threat to health care providers (HCPs) in Wuhan, China, especially for nurses who were frequently exposed to infected or suspected patients. Limited information was available about the working experience of nurses in fighting against the pandemic. To learn the physical and psychological responses of nurses during the pandemic and explore the potential determinants, we conducted a large-scale survey in Wuhan. This multicenter cross-sectional study enrolled 5521 nurses who worked in designated hospitals, mobile cabins, or shelters during the pandemic. A structured online questionnaire was distributed to assess the physical discomforts, emotional distress and cognitive reactions of nurses at work, and the log-binomial regression analysis was performed to explore potential determinants. A considerable proportion of nurses had symptoms of physical discomforts [3677 (66.6%)] and emotional distress [4721 (85.5%)]. Nurses who were directly involved in the care of patients (i.e., care for severe patients: RR, 2.35; 95% CI, 1.95–2.84), with irregular work schedules (RR, 2.36; 95% CI, 1.95–2.87), and working overtime (RR, 1.34; 95% CI, 1.08–1.65) were at a higher risk for physical discomforts. Nurses who were directly involved in the care of patients (i.e., care for severe patients: RR, 1.78; 95% CI, 1.40–2.29), with irregular work schedules (RR, 3.39; 95% CI, 2.43–4.73), and working overtime (RR, 1.51; 95% CI, 1.12–2.04) were at a higher risk for emotional distress. Therefore, formulating reasonable work schedules and improving workforce systems are necessary to alleviate the physical and emotional distress of nurses during the pandemic.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Positive nucleic acid (NA) results have been found in recovered and discharged COVID-19 patients, but the proportion is unclear. This study was designed to analyze the recurrent positive rate of NA results after consecutively negative results, and the relationship between the specific antibody production and positive NA rate. According to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, data of inpatients in Sino-French New City Branch of Tongji Hospital between Jan. 28 and Mar. 6, 2020 were collected. A total of 564 COVID-19 patients over 14 years old who received the examinations of NA and antibodies against SARS-CoV-2 were included. Days of viral shedding and specific antibodies were recorded and assessed. Among NA tests in respiratory samples (throat swabs, nasopharyngeal swabs, sputum and flushing fluid in alveoli), the patients with all-negative NA results accounted for 17.20%, those with single-positive results for 46.63%, and those with multiple-positive results for 36.17% respectively. Besides, the recurrent positive NA results after consecutively negative results appeared in 66 patients (11.70%). For multiple-positive patients, median viral shedding duration was 20 days (range: 1 to 57 days). Of the 205 patients who received 2 or more antibody tests, 141 (68.78%) had decreased IgG and IgM concentrations. IgM decreased to normal range in 24 patients, with a median of 44 days from symptom onset. Viral shedding duration was not significantly correlated with gender, age, disease severity, changes in pulmonary imaging, and antibody concentration. It is concluded that antibody level and antibody change had no significant correlation with the positive rate of NA tests and the conversion rate after continuous negative NA tests. In order to reduce the recurrent positive proportion after discharge, 3 or more consecutive negative NA test results with test interval more than 24 h every time are suggested for the discharge or release from quarantine.

Coronavirus disease 2019 (COVID-19) occurs in the influenza season and has become a global pandemic. The present study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with influenza A virus (IAV) in an attempt to provide clues for the antiviral interventions of co-infected patients. We described two patients who were co-infected with SARS-CoV-2 and IAV treated at Wuhan Union Hospital, China. In addition, we performed a review in PubMed, Web of Science and CNKI (from January 1 up to November 1, 2020) with combinations of the following key words: “COVID-19, SARS-COV-2, influenza A and co-infection”. A total of 28 co-infected patients were enrolled in the analysis. Of the 28 patients, the median age was 54.5 years (IQR, 34.25–67.5) and 14 cases (50.0%) were classified as severe types. The most common symptoms were fever (85.71%), cough (82.14%) and dyspnea (60.71%). Sixteen patients had lymphocytopenia on admission and 23 patients exhibited abnormal radiological changes. The median time from symptom onset to hospital admission was 4 days (IQR, 3–6), and the median time of hospital stay was 14 days (IQR, 8.5–16.75). In conclusion, patients with SARS-COV-2 and IAV co-infection were similar to those infected with SARS-COV-2 alone in symptoms and radiological images. SARS-COV-2 co-infection with IAV could lead to more severe clinical condition but did not experience longer hospital stay compared with patients infected with SARS-COV-2 alone.

Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.

In recent years, the impact of new major infectious diseases on people’s normal life is becoming more and more frequent, which has brought great impact on people’s life safety and social economy, especially the corona virus disease 2019, which has been sweeping the globe. Public health and disease prevention and control systems in different countries have different performances in response to the pandemic, but they all have exposed many shortcomings. Countries around the world urgently need to improve the monitoring, early warning and emergency response systems for new major infectious diseases. As the outpost and main part of medical rescue, the hospital urgently needs to establish a set of scientifically advanced emergency response mechanism that is suitable for the business process of the medical system and unified standards in order to improve the response efficiency and quality of emergency treatment.

The infectious coronavirus disease 2019 (COVID-19) has spread all over the world and been persistently evolving so far. The number of deaths in the whole world has been rising rapidly. However, the early warning factors for mortality have not been well ascertained. In this retrospective, single-centre cohort study, we included some adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Renmin Hospital of Wuhan University who had been discharged or had died by Apr. 8, 2020. Demographic, clinical and laboratory data at admission were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable analysis, Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve to explore the early warning factors associated with in-hospital death. A total of 159 patients were included in this study, of whom 86 were discharged and 73 died in hospital. Hypertension (52.1% vs. 29.1%, P=0.003) and coronary heart disease (28.8% vs. 12.8%, P=0.012) were more frequent among non-survived patients than among survived patients. The proportions of patients with dyspnoea (67.1% vs. 25.6%, P<0.001), chest distress (58.9% vs. 26.7%, P<0.001) and fatigue (64.4% vs. 25.6%, P<0.001) were significantly higher in the non-survived group than in the survived group. Regression analysis with the Cox proportional hazards mode revealed that increasing odds of in-hospital death were associated with higher IL-6 (odds ratio 10.87, 95% CI 1.41-83.59; P=0.022), lactate (3.59, 1.71–7.54; P=0.001), older age (1.86, 1.03–3.38; P=0.041) and lower lymphopenia (5.44, 2.71–10.93; P<0.001) at admission. The areas under the ROC curve (AUCs) of IL-6, lymphocyte, age and lactate were 0.933, 0.928, 0.786 and 0.753 respectively. The AUC of IL-6 was significantly higher than that of age (z=3.332, P=0.0009) and lactate (z=4.441, P<0.0001) for outcome prediction. There was no significant difference between the AUCs of IL-6 and lymphocyte for outcome prediction (z=0.372, P=0.7101). It was concluded that the potential risk factors of higher IL-6, lactate, older age and lower lymphopenia at admission could help clinicians to identify patients with poor prognosis at an early stage.

The Coronavirus disease 2019 (COVID-19) outbreak has been brought under control through a nationwide effort, and now it has become a global pandemic and the situation seems grim. We summarized the measures taken in Wuhan and analyzed the effects to comprehensively describe the factors involved in controlling the COVID-19 in China. In China, several measures such as the lockdown of Wuhan, restriction of traffic and communities, increasing hospital beds, nationwide support from medical staff, epidemic prevention equipment and supplies, and establishment of makeshift shelter hospitals have been taken. The lockdown of Wuhan reduced the propagation of cases to other cities in Hubei province and throughout China, traffic and community restrictions reduced the flow of population and the spread of disease, increasing wards and beds and medical personnel reduced the incidence of severe cases and mortality, the establishment of the Fangcang shelter hospitals provided a good isolation and monitoring environment, and further reduced the spread and fatality of the disease. The fact that China was able to control the spread of COVID-19 within three months without a specific drug or vaccine suggests that these measures are more adequate and effective.

Tinnitus, acute or chronic, is one of the most common and refractory disorders. Acute tinnitus is a symptom that is a warning sign when compared with chronic tinnitus. Although hearing loss initiates acute tinnitus, the relationship between hearing loss and tinnitus is far from straightforward. Other factors beyond the auditory system may play important roles in the occurrence of acute tinnitus. To address this issue, we propose an integrated regulation theory of the possible physical causes of acute tinnitus, and summarize a classification system for acute tinnitus based on this regulation theory to help guide clinical treatment.

Insulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.

Fibulin-1 (FBLN-1), an elastin-associated extracellular matrix protein, has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease (CVD). We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity (baPWV) in patients with asymptomatic hyperuricemia (AHU). In total, 66 patients with AHU and 66 gender- and age-matched healthy individuals were enrolled. The plasma fibulin-1 levels were measured by immunochemistry. Patients with AHU presented significantly higher vascular age [median (interquartile range): 54 (22) vs. 48 (14) years, P=0.01] and baPWV [mean±SD: 1373±223 vs. 1291±177 cm/s, P=0.02] than the healthy subjects; however, no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects [median (interquartile range): 4018 (3838) vs. 3099 (3405) ng/mL, P=0.31]. A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU (r=0.29, P=0.02); and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age (r=0.22, P=0.08). However, these associations were rendered insignificant after adjustments for potential confounders. In healthy subjects, no correlation was observed between fibulin-1 levels and CVD risk. This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU, but the relationship is not robust.

Osteoarthritis (OA) is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity. As a bacterial synthesis of quinine, pyrroloquinoline quinone (PQQ) is a strong redox cofactor with a variety of biological benefits, including antioxidant, anti-inflammation-induced mitochondrial metabolism regulation. This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes. Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α 50 ng/mL, TNF-α 50 ng/mL + PQQ 10 µmol/L for 24 h. Then, morphological study, functional study and mechanism study were taken. The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ, evidenced by elevated number of mitochondria, well-kept mtDNA integrity, preserved ATP level, reestablished mitochondrial membrane potential, and prevented mitochondrial function. The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-α and the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α. PQQ might be a potential chemical for OA intervention.

Microtubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G₂/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

The incidence of colorectal cancer (CRC) is increasing in China, with high mortality. Here, we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China. The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively. KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction (q-PCR) in 410 CRC patients, with mutation frequencies of KRAS, NRAS and BRAF of 47.56%, 2.93% and 4.15%, respectively. The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed. The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes. The BRAF gene mutation was also associated with cancer thrombosis in blood vessels. Cox regression analysis showed that there was no statistically significant difference in the overall survival (OS) between patients with KRAS, NRAS mutants and wild-type CRC patients, while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients. It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.

The stemness of different side population (SP) cell subtypes in ovarian cancer cells was studied, and the heterogeneity of ovarian cancer stem cells was analyzed. The cisplatin-resistant human serous ovarian cancer cell line C13 was stained with the bisbenzimide Hoechst 33342. A flow cytometry-based fluorescence-activated sorting method was used to obtain lower-SP (LSP) cells, upper-SP (USP) cells, and non-SP cells (NSP) based on their sensitivity to the staining time and Hoechst dye concentration. The sphere-forming capability, expression levels of stem cell markers, resistance to high concentrations of cisplatin, and subcutaneous tumorigenicity in NOD/SCID mice of the different cell subtypes were evaluated. The C13 cells contained SP cells with stemness characteristics, and the LSP cell subtype expressed higher levels of stem cell markers, had higher in vitro sphere-forming capability, higher cisplatin resistance and higher in vivo subcutaneous tumorigenesis than USP cells (P<0.05). NSP cells had no stemness. In conclusion, different subtypes of ovarian cancer SP cells have different stemness levels, and ovarian cancer stem cells may be heterogeneous.

Triptolide, a component of the Chinese herb Tripterygium wilfordii Hook F, has been proved to be effective in the treatment of rheumatoid arthritis (RA). However, its underlying mechanisms on RA have not yet been well established. We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes (FLS) induced by the complex of interleukin-6 (IL-6) and the soluble form of the IL-6 receptor (sIL-6R). Furthermore, to clarify the underlying mechanisms, we treated FLS with the Janus-activated kinase 2 (JAK2) inhibitor/signal transducer and activator of transcription 3 (STAT3) activation blocker AZD1480. In this study, immunohistochemical staining was used to identify vimentin (+) and CD68 (−) in FLS. The FLS proliferation was measured by cell proliferation assay, and the cell cycles were analyzed by flow cytometry. Furthermore, ELISA was used to detect the expression of the inflammatory factors in culture solution. The expression levels of p-JAK2, JAK2, p-STAT3 and STAT3 were investigated through Western blotting analysis. The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines, including IL-6, interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF). Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3. The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway. It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.

The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P<0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.

Diabetic retinopathy (DR) is a common cause of blindness all over the world. Bone marrow mesenchymal stem cells (BMSCs) have been considered as a promising strategy for retinal regeneration in the treatment of DR. However, the poor viability and low levels of BMSCs engraftment limit the therapeutic potential of BMSCs. The present study aimed to examine the direct induction of BMSCs differentiation into the cell types related to retinal regeneration by using soluble cytokine ciliary neurotrophic factor (CNTF). We observed remarkably increased expression of cellular retinaldehyde-binding protein (CRALBP) and retinoid isomerohydrolase (RPE65) in BMSCs treated with CNTF in vitro, indicating the directional differentiation of BMSCs into the retinal pigment epithelium (RPE) cells, which are crucial for retinal healing. In vivo, the diabetic rat model was established by use of streptozotocin (STZ), and animals treated with BMSCs+CNTF exhibited better viability and higher delivery efficiency of the transplanted cells than those treated with BMSCs injection alone. Similar to the in-vitro result, treatment with BMSCs and CNTF combined led to the differentiation of BMSCs into beneficial cells (RPE cells), and accelerated retinal healing characterized by the activation of rod photoreceptor cells and phagocytosis function of RPE cells. In conclusion, CNTF contributes to the differentiation of BMSCs into RPE cells, which may help overcome the current stem cell therapy limitations in the field of retinal regeneration.

K⁺ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K⁺ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K⁺ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction. However, few studies have addressed the prognostic value of global circumferential strain (GCS) in dilated cardiomyopathy (DCM) patients with severely impaired systolic function. This study aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived GCS in DCM patients with severely reduced ejection. Consecutive DCM patients with severely reduced ejection fraction (EF <35%) who underwent CMR were included. GCS was calculated from CMR cine images. The clinical endpoint was a composite of all-cause mortality, heart transplantation, implantable cardioverter defibrillator (ICD) implantation and aborted sudden cardiac death (SCD). A total of 129 patients with a mean EF of 15.33% (11.36%–22.27%) were included. During a median follow-up of 518 days, endpoint events occurred in 50 patients. Patients with GCS ≥ the median (−5.17%) had significantly reduced event-free survival as compared with those with GCS < the median (P<0.01). GCS was independently associated with adverse events after adjusting for clinical and imaging risk factors including extent of late gadolinium enhancement (LGE) (P<0.05). Adding GCS into the model including the extent of LGE resulted in significant improvements in the C-statistic (from 0.706 to 0.742; P<0.05) with a continuous net reclassification improvement (NRI) of 29.71%. It was concluded that GCS derived from CMR could be useful for risk stratification in DCM patients with severely reduced EF, which may increase common imaging risk factors including LGE.

The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging (NODDI) in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion (MCAO) in rats at 3T MRI, and to validate NODDI metrics with histology. A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5, 2, 6, 12, 24 and 72 h. NODDI orientation dispersion index (ODI) and intracellular volume fraction (V_ic) metrics were compared between MCAO group and control group. The evolution of NODDI metrics was characterized and validated by histology. Infarction was consistent with significantly increased ODI and V_ic in comparison to control tissues at all time points (P<0.001). Lesion ODI increased gradually from 0.5 to 72 h, while its V_ic showed a more complicated and fluctuated evolution. ODI and V_ic were significantly different between hyperacute and acute stroke periods (P<0.001). The NODDI metrics were found to be consistent with the histological findings. In conclusion, NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology. This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.

The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1β and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

The article “CAR T Cell Therapy for Hematological Malignancies”, written by Xin YANG, Gao-xiang WANG, Jian-feng ZHOU, was originally published electronically on the publisher’s internet portal on December 2019 without open access.

The figure 6 in this article was previously published in a Letter to the Editor of the journal Surgical Innovation. The authors would like to apologize for the omission of a citation and add the reference 19 to this figure.