Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study.

BACKGROUND: Since the end of 2022, Azvudine was widely used to treat hospitalized coronavirus disease 2019 (COVID-19) patients in China. However, data on the real-world effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. METHODS: From 1 November 2022 to 1 July 2023, an SARS-CoV-2 Omicron BA.5 dominant period, we conducted a single-center retrospective cohort study based on hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from a tertiary hospital in Shihezi, China. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients received usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use at admission, and baseline complete blood cell count. The primary outcomes were all-cause death and short-term (60 days) PCC post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) of Azvudine treatment for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on a part of the matched covariates. RESULTS: A total of 2,639 hospitalized patients with SARS-CoV-2 infection were initially identified, and 2,069 ineligible subjects were excluded from analyses. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was relatively lower in the Azvudine group than in control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significantly lower risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses suggested protection of Azvudine against the risks of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical differences were not observed between the Azvudine group and the control group for the risks of invasive mechanical ventilation or short and long-term PCC. CONCLUSIONS: Our findings indicated that Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection in a real-world setting. Further investigation is needed to explore the effectiveness of Azvudine against the PCC after discharge.

This study aims to evaluate the real-world effectiveness of Azvudine among hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominant epidemic phase. Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for all-cause death. We found that the use of Azvudine was associated with a significantly reduced risk of all-cause death among hospitalized patients with SARS-CoV-2 infection.

Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is caused by perinatal hypoxia and subsequent reductions in cerebral blood flow and is one of the leading causes of severe disability or death in newborns. Despite its prevalence, we currently lack an effective drug therapy to combat HIE. Celastrol (Cel) is a pentacyclic triterpene extracted from Tripterygium Wilfordi that can protect against oxidative stress, inflammation, and cancer. However, whether Cel can alleviate neonatal hypoxic-ischemic (HI) brain damage remains unclear. METHODS: Here, we established both in vitro and in vivo models of HI brain damage using CoCl2-treated PC12 cells and neonatal rats, respectively, and explored the neuroprotective effects of Cel in these models. RESULTS: Analyses revealed that Cel administration reduced brain infarction size, microglia activation, levels of inflammation factors, and levels of oxidative stress markers by upregulating levels of p-AMPKα, Nrf2, HO-1, and by downregulating levels of TXNIP and NLRP3. Conversely, these beneficial effects of Cel on HI brain damage were largely inhibited by AMPKα inhibitor Compound C and its siRNA. CONCLUSIONS: We present compelling evidence that Cel decreases inflammation and oxidative stress through the AMPKα/Nrf2/TXNIP signaling pathway, thereby alleviating neonatal HI brain injury. Cel therefore represents a promising therapeutic agent for treating HIE. IMPACT: We firstly report that celastrol can ameliorate neonatal hypoxic-ischemic brain injury both in in vivo and in vitro, which represents a promising therapeutic agent for treating related brain injuries. Celastrol activates the AMPKα/Nrf2/TXNIP signaling pathway to relieve oxidative stress and inflammation and thereby alleviates neonatal hypoxic-ischemic brain injury.

Degradation of petroleum hydrocarbon contaminants by Rhodococcus erythropolis KB1 synergistic with alfalfa (Medicago sativa L.).

Petroleum hydrocarbons are a stubborn pollutant that is difficult to degrade globally, and plant-microbial degradation is the main way to solve this type of pollutant. In this study, the physiological and ecological responses of alfalfa to petroleum hydrocarbons in different concentrations of petroleum hydrocarbon-contaminated soil with KB1 (Rhodococcus erythropolis) were analyzed and determined by laboratory potting techniques. The growth of alfalfa (CK) and alfalfa with KB1 (JZ) in different concentrations of petroleum hydrocarbons contaminated soil was compared and analyzed. The results of the CK group showed that petroleum hydrocarbons could significantly affect the activity of alfalfa antioxidant enzyme system, inhibit the development of alfalfa roots and the normal growth of plants, especially in the high-concentration group. KB1 strain had the ability to produce IAA, form biofilm, fix nitrogen, produce betaine and ACC deaminase, and the addition of KB1 could improve the growth traits of alfalfa in the soil contaminated with different concentrations of petroleum hydrocarbons, the content of soluble sugars in roots, and the stress resistance and antioxidant enzyme activities of alfalfa. In addition, the degradation kinetics of the strain showed that the degradation rate of petroleum could reach 75.2% after soaking with KB1. Furthermore, KB1 can efficiently degrade petroleum hydrocarbons in advance and significantly alleviate the damage of high concentration of petroleum hydrocarbons to plant roots. The results showed that KB1 strains and alfalfa plants could effectively enhance the degradation of petroleum hydrocarbons, which provided new ideas for improving bioremediation strategies.

Diagnostic value of circulating miRNA in the benign and malignant lung nodules: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from malignant lung nodules is of paramount importance. This meta-analysis aimed to evaluate the clinical utility of circulating microRNAs (miRNAs) for the differential diagnosis of benign and malignant lung nodules. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted across 4 electronic databases, without any temporal restrictions. The inclusion and exclusion criteria were strictly applied to assess the clinical applications of circulating miRNAs. A robust and transparent quality assessment was performed using the quality assessment of diagnostic accuracy studies-2 tool, and rigorous statistical analyses were conducted to synthesize the various diagnostic measures. RESULTS: In the meta-analysis of 11 studies, quality assessment of diagnostic accuracy studies-2 assessment revealed < 5% high-risk methodologies, ensuring robustness. Sensitivity and Specificity were consolidated at 0.83 (95% confidence interval [CI]: 0.72-0.90) and 0.81 (95% CI: 0.73-0.88), respectively. The positive likelihood ratio and negative likelihood ratio were 4.45 (95% CI: 3.03-6.54) and 0.21 (95% CI: 0.12-0.35), respectively. The diagnostic odds ratio was 21.31 (95% CI: 10.25-44.30) and area under the receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.91). Subgroup analysis highlighted significant variations in diagnostic accuracy by ethnicity and miRNA source, with non-Asian populations and serum-based tests showing higher diagnostic accuracy. CONCLUSION: This meta-analysis demonstrated that circulating miRNAs hold substantial diagnostic value in distinguishing between benign and malignant lung nodules.

Construction of 3D-Bioprinted cartilage-mimicking substitute based on photo-crosslinkable Wharton's jelly bioinks for full-thickness articular cartilage defect repair.

Three-dimensional (3D) bioprinted cartilage-mimicking substitutes for full-thickness articular cartilage defect repair have emerged as alternatives to in situ defect repair models. However, there has been very limited breakthrough in cartilage regeneration based on 3D bioprinting owing to the lack of ideal bioinks with printability, biocompatibility, bioactivity, and suitable physicochemical properties. In contrast to animal-derived natural polymers or acellular matrices, human-derived Wharton's jelly is biocompatible and hypoimmunogenic with an abundant source. Although acellular Wharton's jelly can mimic the chondrogenic microenvironment, it remains challenging to prepare both printable and biologically active bioinks from this material. Here, we firstly prepared methacryloyl-modified acellular Wharton's jelly (AWJMA) using a previously established photo-crosslinking strategy. Subsequently, we combined methacryloyl-modified gelatin with AWJMA to obtain a hybrid hydrogel that exhibited both physicochemical properties and biological activities that were suitable for 3D bioprinting. Moreover, bone marrow mesenchymal stem cell-loaded 3D-bioprinted cartilage-mimicking substitutes had superior advantages for the survival, proliferation, spreading, and chondrogenic differentiation of bone marrow mesenchymal stem cells, which enabled satisfactory repair of a model of full-thickness articular cartilage defect in the rabbit knee joint. The current study provides a novel strategy based on 3D bioprinting of cartilage-mimicking substitutes for full-thickness articular cartilage defect repair.

Internet use and depression among Chinese older adults: The mediating effect of interpersonal relationship.

The number of elderly Internet users has increased significantly in the past few years, and the Internet has greatly changed the way that older adults access information and communicate. Generally, those who regularly use the Internet may expand their range of interpersonal interactions, which has positive effects on their health. Depression is the leading cause of ill health, and is closely related to people's mental health. We sought to investigate whether internet use help reduce depression level among older adults. Using data from the 2020 China Family Panel Studies (CFPS), a total of 4,714 respondents were included to explore the effects of Internet use on the elderly's depression levels in China, along with the mediating role of interpersonal relationship in the above relationship. Regression results indicated that Internet use significantly reduced depression levels among the elderly. Further analysis showed that different Internet usage had different effects on depression among the elderly. Wechat chatting, video browsing, and online shopping were positively correlated with lower levels of depression. However, playing online games and online learning did not predict reduced levels of depression. Moreover, interpersonal relationship mediated the relationship between Internet use and depression levels. Internet use was associated with a higher level of interpersonal relationship, which in turn reduced depression levels in older adults. Regarding gender and regional differences, the coefficient of Internet use for urban older adults was significantly negative at 0.001 level, while it was not significant for rural older adults. A mediating effect of interpersonal relationship between Internet use and depression levels was only found for male elderly. To reduce the level of depression and promote mental health in the course of aging, Internet use and the improvement of interpersonal relationships merit special attention.

Influence of selection of domain shape on parameters of microdosimetric kinetic model / 中华放射医学与防护杂志

Objective:To calculate the single-event dose-averaged specific energy of particles delivered in spherical domains based on the track structure model and using triple integration, and to investigate the influence of the domain shape on the key model parameters of microdosimetric kinetic model (MKM) and its corresponding physical significance.Methods:The domains are assumed to be cylinders and spheres, respectively. With α 0, domain radius, rd, and nucleus radius, Rn, as undetermined coefficients, the nuclear charge numbers, kinetic energies and their corresponding LETs of three kinds of charged particles ( 3He, 12C, 20Ne) as independent variables, D10 as dependent variable, the mean value of squared residuals, J2, between the D10 calculated values and D10 experimental values as the optimization objective, the final fitting values of the above undetermined coefficients of human salivary gland (HSG) cells and Chinese hamster lung (V79) cells obtained after iteration by the robust least square method are the optimal model parameter values of MKM. Results:For HSG cells, cylindrical domain: α 0=0.073/Gy, rd=0.29 μm, Rn=4.1 μm, J2=0.039 7 Gy 2; spherical domain: α 0=0.023/Gy, rd=0.29 μm, Rn=4.4 μm, J2=0.039 3 Gy 2; For V79 cells, cylindrical domain: α 0=0.114/Gy, rd=0.25 μm, Rn=3.8 μm, J2=0.097 4 Gy 2; spherical domain: α 0=0.095/Gy, rd=0.26 μm, Rn=4.1 μm, J2=0.096 9 Gy 2. Conclusions:For the same type of cells, cylindrical and spherical domains were selected respectively, and there are significant differences in MKM parameters obtained by fitting. The fitting values of the domain radius, rd of the two shapes of domains show no significant difference, while the fitting values of α0 of spherical domains are smaller than those of cylindrical domains, the fitting values of nucleus radius, Rn, of spherical domain are larger than those of cylindrical domains, closer to the nucleus radius observed by fluorescence microscopy. In the low LET (<20 keV/μm) region, D10 calculated according to the parameters of the two different shapes of domains are different, so the selection of the domain shape will cause differences in the relative biological effectiveness(RBE) calculation of proton in the region near Bragg peak.

Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/β-catenin signaling pathway / 中国中药杂志

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Analysis of spontaneous nystagmus and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis / 中华内科杂志

Objective: To investigate the spontaneous nystagmus (SN) and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis (VN). Methods: This is a cross-sectional study. A total of 61 patients with VN admitted to the Department of Neurology of Shanxi Bethune Hospital from June 2020 to October 2021, 39 were male and 22 were female, with a mean age of (46±13) years old and male to female ratio of 1.77∶1. According to SN characteristics, 61 patients were divided into non-nystagmus group(nSN), horizontal nystagmus group(hSN) and horizontal-torsional nystagmus group (htSN). Clinical data were collected, and SN, unilateral weakness (UW), directional preponderance (DP), and video head impulse test (vHIT) gain were used as observation indicators. Statistical analysis by SPSS23.0 software. Normal distributed quantitative data (age, semicircular canal gain, SN intensity) were expressed by x¯±s, non-normal distributed quantitative data (disease course, UW, DP) were expressed by M(Q1,Q3), qualitative data were expressed by rate and composition ratio, difference analysis by one-way ANOVA, rank sum test, Chi-square test or Fisher's exact probability method, considered by P value<0.05. Results: (1)The disease course of nSN, hSN and htSN was 7.0 (4.0, 12.5), 6.0 (3.5, 11.5), and 3.0 (2.0, 6.5) days respectively, and there were statistical differences (χ2=7.31,P=0.026).(2)The horizontal nystagmus intensity of htSN was (16.8±8.6)°/s, which was significantly higher than that of (9.8±4.7)°/s in hSN (t=3.71, P<0.001). There was no significant difference in the positive rate of UW between the three groups (P=0.690), and there was a significant difference in the positive rate of DP in the three groups (χ2=12.23, P=0.002). The horizontal nystagmor intensity in the htSN was positively correlated with the vertical nystagmus intensity (r=0.59, P=0.001).(3)The gain of the affected horizontal canal of the three groups was statistically different (F=8.28, P=0.001), and the gain of the horizontal canal of hSN and htSN was significantly lower than that of nSN (t=2.74, P=0.008; t=4.05, P<0.001); The gain of the affected anterior canal in the three groups was statistically different (F=5.32, P=0.008). The gain of the anterior canal in both nSN and hSN was significantly higher than that in htSN (t=3.09, P=0.003; t=2.15, P=0.036). The horizontal canal gain of htSN is positively correlated with the anterior canal gain (r=0.74, P<0.001).(4)The affected semicircular canals in the two groups with no-vertical-component nystagmus (nSN and hSN) and the htSN were counted. The composition ratio of the affected semicircular canals in the two groups was different (χ2=8.34, P=0.015). Conclusion: The occurrence of SN in patients with VN is related to many factors, such as the disease course, low and high frequencies, and the severity of the condition in the affected semicircular canal.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

The impact of symptom distress on health-related quality of life in liver cancer patients receiving arterial chemoembolization: the mediating role of hope.

BACKGROUND: Trans-hepatic arterial chemoembolization (TACE) is a treatment option for liver cancer patients. It can prolong patients' survival but can also cause symptom distress. Symptom distress (SDs) can directly impact quality of life (QOL) and may indirectly influence QOL by lessening hope. In this study, we wanted to explore the mediating effect of hope on the relationship between SDs and QOL among patients with liver cancer receiving TACE. METHODS: A cross-sectional study was conducted from December 20, 2017, to August 6, 2018, at a gastroenterology ward of a medical center. The participants were 92 liver cancer patients (69.6% male, mean age 67.8) who were admitted for TACE treatment. Information on SDs, hope, and QOL was collected by questionnaire on discharge day. Hayes' PROCESS model was used to test the mediating effect of hope on the relationship between SDs and QOL. RESULTS: The mean score and standard deviation (SD) of SDs, hope, and QOL were 32.08 (SD = 6.22), 27.09 (SD = 3.51), and 55.16 (SD = 17.33), respectively. SDs negatively impacts quality of life. The total effect of SDs on QOL was - 1.41 (95% confidence interval [CI]: - 1.96, - 0.86). The indirect effect via the mediation of hope was - 0.95 (95% CI: - 1.7, - 0.45). Hope partially mediated the effect of SDs on QOL. CONCLUSION: SDs after TACE is vital; it directly reduces a patient's overall QOL and can indirectly hinder it by reducing the patient's hope. In addition to symptom management, interventions that help patients maintain their hope are key to improving QOL among patients receiving TACE.

Indole-3-propionic Acid Attenuates HI-Related Blood-Brain Barrier Injury in Neonatal Rats by Modulating the PXR Signaling Pathway.

The blood-brain barrier (BBB) is an important physiological barrier of the human body contributing to maintaining brain homeostasis and normal function. Hypoxic-ischemic (HI)-related brain injury is one of the main causes of neonatal acute morbidity and chronic disability. The previous research of our group confirmed that there was serious BBB destruction during HI brain injury. However, at present, the protection strategy of BBB is very limited, and further research on the protection mechanism is warranted. Indole-3-propionic acid (IPA) is a bacterial metabolism with anti-inflammatory and antioxidant properties, having neuroprotective effects and protective effects on the mucosal barrier. However, the role of IPA in BBB is not clear. In this research, we demonstrated the protective effect of IPA on BBB disruption from HI brain injury and hypothesized that it involves the amelioration of inflammation, oxidative stress, and MMP activation, thereby inhibiting apoptosis of rat brain microvascular endothelial cells (rBMECs). We demonstrated that expression levels of several inflammatory markers, including iNOS, TNF-α, IL-6, and IL-1ß, were significantly increased from HI damage or OGD injury. However, IPA treatment inhibited the increase significantly. Moreover, we demonstrated that IPA reduced intracellular ROS levels and MMP activation in rBMECs from OGD injury. Further research on the underlying detailed molecular mechanisms suggested that IPA attenuates inflammation by inhibiting NF-κB signaling. Finally, we investigated the mechanism of the relationship between PXR activation and NF-κB inhibition. The results suggested overexpression of PXR in rBMECs could significantly counteract the decrease of junction proteins and downregulate the increased p-IκB-α and p-NF-κB from OGD injury. However, the protective effects of IPA were reversed by antagonists of the PXR. Taken together, IPA might mitigate HI-induced damage of the BBB and the protective effect may be exerted through modulating the PXR signaling pathway.

Identification of early invisible acute ischemic stroke in non-contrast computed tomography using two-stage deep-learning model.

Rationale: Although non-contrast computed tomography (NCCT) is the recommended examination for the suspected acute ischemic stroke (AIS), it cannot detect significant changes in the early infarction. We aimed to develop a deep-learning model to identify early invisible AIS in NCCT and evaluate its diagnostic performance and capacity for assisting radiologists in decision making. Methods: In this multi-center, multi-manufacturer retrospective study, 1136 patients with suspected AIS but invisible lesions in NCCT were collected from two geographically distant institutions between May 2012 to May 2021. The AIS lesions were confirmed based on the follow-up diffusion-weighted imaging and clinical diagnosis. The deep-learning model was comprised of two deep convolutional neural networks to locate and classify. The performance of the model and radiologists was evaluated by the area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and accuracy values with 95% confidence intervals. Delong's test was used to compare the AUC values, and a chi-squared test was used to evaluate the rate differences. Results: 986 patients (728 AIS, median age, 55 years, interquartile range [IQR]: 47-65 years; 664 males) were assigned to the training and internal validation cohorts. 150 patients (74 AIS, median age, 63 years, IQR: 53-75 years; 100 males) were included as an external validation cohort. The AUCs of the model were 83.61% (sensitivity, 68.99%; specificity, 98.22%; and accuracy, 89.87%) and 76.32% (sensitivity, 62.99%; specificity, 89.65%; and accuracy, 88.61%) for the internal and external validation cohorts based on the slices. The AUC of the model was much higher than that of two experienced radiologists (65.52% and 59.48% in the internal validation cohort; 64.01% and 64.39% in external validation cohort; all P < 0.001). The accuracy of two radiologists increased from 62.00% and 58.67% to 92.00% and 84.67% when assisted by the model for patients in the external validation cohort. Conclusions: This deep-learning model represents a breakthrough in solving the challenge that early invisible AIS lesions cannot be detected by NCCT. The model we developed in this study can screen early AIS and save more time. The radiologists assisted with the model can provide more effective guidance in making patients' treatment plan in clinic.

New treatment for amblyopia based on rules of synaptic plasticity: a randomized clinical trial.

Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex. We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input. Experiments on normal adults showed that repetitive brief exposure of grating stimuli, with the onset of each stimulus delayed by 8.3 ms in one eye, results in a shift in perceptual eye dominance. Clinical studies (Clinical trial registration number: ChiCTR2100049130), using popular 3D movies with similar asynchrony between the two eyes (amblyopic eye stimulated first) to treat anisometropic amblyopia, established that just 10.5 h of conditioning over <3 weeks produced improvement that met criteria for successful treatment. The benefits of asynchronous conditioning accumulate over 20-30 45 min sessions, and are maintained for at least 2 years. Finally, we demonstrate that asynchronous binocular treatment alone is more effective than patching only. This novel treatment is popular with children and is some 50 times more efficient than patching alone.

Verification of the range calculation accuracy of a commercial proton treatment planning system / 中华放射肿瘤学杂志

Objective:In Shanghai Advanced Proton Therapy Facility (SAPT) of Ruijin Hospital Proton Therapy Center, the calculation accuracy of the commercial proton treatment planning system RayStation (V10), especially the accuracy of the proton range calculation, was measured and verified, aiming to provide reference for the clinical application of the treatment planning system.Methods:A head phantom was used to verify the calculation accuracy of RayStation. The phantom CT was imported into treatment planning system (TPS). The phantom was followed closely by a water tank with a one-liter cubic target. A single field verification plan with the prescribed dose of 200 cGy (relative biological effectiveness) was designed and implemented. Then, the measured distribution results were compared with the calculation results.Results:When the verification plan of the phantom was designed with the default settings of RayStation, the measured longitudinal dose distribution was approximately 4 mm deeper than that of TPS, indicating that RayStation overestimated the water equivalent thickness (WET) of the tissue substitute materials in the phantom. To study the range error, the actual beam was used to measure the WET of the soft tissue substitute material. The default setting of RayStation was fine-tuned according to the measured results. It was found that the error between the measured SOBP and TPS calculations was reduced to only 2 mm.Conclusions:Using the default setting of RayStation to calculate the stopping power of the phantom may cause a large range error. A method that combines tissue segmentation with the measured WET of the tissue substitute material is proposed to improve the range calculation accuracy of the TPS. The results show that the proposed method can improve the dose and range accuracy of the commercial TPS including RayStation for tissue substitute materials.

Intraocular Amphiregulin antibody and axial elongation in nonhuman primates.

Purpose: To examine the effect of intraocularly applied amphiregulin antibody on physiological axial elongation in young nonhuman primates. Methods: The experimental study included six male 12-months-old macaque nonhuman primates (body weight:2.46 ± 0.25kg;range:2.20-2.90kg). In the experimental group (n=3 animals), three intravitreal injections of amphiregulin antibody (100µg/50µl) were applied to the left eyes at intervals of 4-6 weeks, and injections of phosphate buffered solution (50µl) were applied to the right eyes. Three other animals were assigned to a blank control group. Results: During the study period of 23.6 weeks, axial length in the experimental group did not change in the left eyes (18.91 ± 0.37mm to 18.94 ± 0.67mm;P=0.90), while it linearly increased in the right eyes (18.87 ± 0.38mm to 19.24 ± 0.53mm;P=0.056) and in the control group (left eyes:19.15 ± 0.22mm to 19.48 ± 0.22mm;P=0.009; right eyes:19.17 ± 0.15 mm to 19.46 ± 0.23 mm;P=0.024). The interocular difference in axial elongation increased in the experimental group from -0.11 ± 0.12mm at 4 weeks after baseline to -0.34 ± 0.15mm at the study end, while in the control group, the interocular side difference did not change significantly (from 0.01 ± 0.10 mm to 0.03 ± 0.08 mm;P=0.38). The difference in the interocular difference in axial elongation between the two groups was significant at 8 weeks (P=0.01), 15 weeks (P=0.007), and at study end (P=0.02). The interocular difference in axial length correlated with the interocular difference in vitreous cavity length (standardized regression coefficient beta:0.85;P<0.001). The interocular axial length difference was inversely associated with the interocular refractive error difference (beta:-0.49;P<0.001). Conclusions: Intraocularly applied amphiregulin antibody (100µg) reduced the physiological ocular axial elongation in juvenile nonhuman primates.

Study on effect of restoring mitochondrial dynamics on NK2 activation of NK cells / 中国药理学通报

Aim To explore the internal mechanism of NK2 activation of NK cells from the perspective of "mitochondrial dysfunction-abnormal cell activation".Methods NK-92MI cells were divided into blank group, TSLP group, 1, 5, and 10 μmol·L-1 Mdivi-1 dose groups.The levels of IL-4, IL-5, and IFN-γ in the supernatant of each group were determined by ELISA; The expression of p-Drp1 and MnSOD protein in each group was determined by Western blotting; the ROS level of each group was detected by DHE staining and flow cytometry; mitochondrial morphology was observed by confocal laser in each group of cells.Results ELISA showed that compared with control group, the levels of IL-4 and IL-5 in cell supernatant of TSLP group significantly increased, and the level of IFN-γ was down-regulated(P<0.05); Compared with TSLP group, the levels of IL-4 and IL-5 in cell supernatant of 5 and 10 μmol·L-1 Mdivi-1 group decreased, and the IFN-γ concentration of the 10 μmol·L-1 Mdivi-1 group rose(P<0.05).DHE staining and flow cytometry showed that ROS level of cells in TSLP group was significantly higher than control group.Compared with TSLP group, ROS level of the 5 and 10 μmol·L-1 Mdivi-1 groups decreased(P<0.05).The laser confocal results showed that after TSLP stimulation, a large number of spherical mitochondria were formed in cells.This phenomenon was improved to a certain extent after the intervention of 5, 10 μmol·L-1 Mdivi-1.Western blot analysis showed that the p-Drp1 level of NK-92MI cells in TSLP group was significantly up-regulated, and the expression of MnSOD decreased, while the intervention of Mdivi-1 effectively reversed the changes in the expression of the above-mentioned molecules.Conclusions Mitochondrial dynamic imbalance may be one of the internal mechanisms of abnormal activation of NK cells, and it may be an important target for regulating NK2 activation of NK cells and improving the allergic inflammatory response mediated by it.

Comparative study on optic disc features of premature infants and full-term newborns.

BACKGROUND: To study optic disc features of premature infants and compare to that of term infants to explore the pattern and features of newborn optic disc development and provide the basis for the diagnosis of newborn optic disc disease. METHODS: This was a prospective clinical research. Newborns underwent newborn fundus disease screening from January 1st, 2016 to October 31st, 2016 in the neonatal ward of Ruian City Maternal and Child Health Hospital were selected. RetCam 3 Version6.1.25.0 Wide-Field Digital Pediatric Retinal Imaging System developed by Clarity Medical Systems, Inc was adopted to conduct fundus examination on both eyes, 130 degree wide-angle lens was used to film the images centering optic disc. RESULTS: For both premature infants and full-term newborns, vertical diameter of the optic disc to lateral diameter of the optic disc ratio was > 1, and the shape of the optic disc was a vertical oval. The difference of each optic disc parameter between premature infants and full-term newborns was not statistically significant (P > 0.05). There's a difference of constitution of sclerotic ring type on optic disc between premature infants and full-term newborns. Among which, the proportion of single ring type and double ring type in premature infants was higher than that in full-term newborns (P < 0.05). The proportion of no ring type in full-term newborns was higher than that in premature infants (P < 0.05). The proportion of mixed type had no significant difference (P > 0.05) between premature infants and full-term newborns. CONCLUSIONS: We found that The proportion of mature types (single ring type and double ring type) in full-term newborns was higher than that in premature infants. While there's no statistical difference of the proportion of mixed types between premature infants and full-term newborns. Double ring type was a normal stage of the development of optic disc.

Impact of Social Cognition on the Self-Rated Health of the Elderly and Its Mechanisms: Evidence From China's Comprehensive Social Survey.

Whether and how the differentiated social cognition of the elderly affects their self-rated health has not been deeply discussed. Based on social cognition theory and Chinese situation, this study constructs the social cognitive dimension of Chinese elderly including social attitude, class identity and perception of social relations. Using the data from Chinese General Social Survey in 2017, this study screens out 1,728 elderly people aged 60 and over, and discusses the impact mechanism of social cognition on self-rated health of Chinese elderly people aged 60 and over by the construction of structural equation model and mediation effect test method. The results show that social attitude, class identity and perceptions of social relationships have significantly positive effects on the self-rated health levels of elderly individuals. Among them, the path coefficient of social attitude to self-rated health was 0.049, the path coefficient of class identity to self-rated health was 0.171, and the path coefficient of social relationship perception to self-rated health was 0.248; both class identity and perception of social relationship have significant mediating effects on elderly self-rated health through social engagement. This study shows that social cognition rarely studied in existing literature has significant effects on the self-rated health of older adults, providing fruitful insights for enhancing the self-rated health level of elderly individuals.

Correlation of diopters and ocular biometric parameters in youth with myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the correlation of myopia severity(SE)with axial length(AL), intraocular pressure(IOP), central corneal thickness(CCT), anterior chamber depth(ACD), and mean keratometry(Km)in young myopia patients.<p>METHODS: In the retrospective study, we selected myopic patients who were diagnosed in Lanzhou Huaxia Eye Hospital from Mar. 2017 to Jul. 2019. They were divided into four myopia groups, A(mild), B(moderate), C(high), and D(hyper)based on the SE. We then measured and analyzed the correlation of the degree of myopia with AL, IOP, CCT, ACD, and Km. Differences between groups were analyzed by one-way analysis of variance. Relationships between the relevant factors were analyzed by Pearson correlation analysis.<p>RESULTS: The SE were(-2.38±0.49)D,(-4.60±0.82)D,(-7.40±1.08)D and(-11.58±1.23)D in the mild, moderate, high and hyper myopia groups respectively. The AL were(24.55±0.72)mm,(25.68±0.77)mm,(26.75±0.64)mm and(28.00±0.56)mm in the respective myopia groups. The IOP were(14.68±3.18)mmHg,(14.78±2.81)mmHg,(15.19±2.66)mmHg,(15.70±2.68)mmHg in the respective myopia groups. The ACD were(3.41±0.24)mm,(3.34±0.25)mm,(3.32±0.25)mm and(3.24±0.27)mm in the respective myopia groups. The Km were(42.96±1.22)D,(43.02±1.43)D,(43.29±1.47)D and(43.56±1.47)D in the respective myopia groups. There were no significant differences for CCT among the different groups. SE was significantly positive correlated to AL(<i>r</i>=0.851, <i>P</i><0.001), IOP(<i>r</i>=0.104, <i>P</i><0.001), CCT(<i>r</i>=0.066, <i>P</i><0.001)and Km(<i>r</i>=0.157, <i>P</i><0.001); SE was negative correlated to ACD(<i>r</i>=-0.129, <i>P</i><0.001).<p>CONCLUSION: In our study, there is a positive correlation between the progression of myopia and the increase in AL, IOP, CCT, and Km. There is a negative correlation between myopia and ACD.