Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective To establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

OBJECTIVE To explore the ameliorative effect of ursolic acid on carbon tetrachloride-induced acute liver injury in mice,and the feasibility of multispectral optoacoustic tomography(MSOT)for characteristic structural and functional imaging of liver tissues.METHODS Kunming mice were randomly divided into the normal control group,model group,model+ursolic acid 30,60 mg·kg-1 groups and model+bifendate 5.625 mg·kg-1 group,with 14 mice in each.Each group was given the corresponding drug once daily for 7 days.An acute liver injury model was established in mice by intraperitoneal injection of 0.2％carbon tetrachloride in olive oil solution after the last administration.Blood was collected,liver tissues were taken 24 h after modeling,and the liver index was calculated,8 mice from each group and the levels of serum glutamic pyruciv transaminase(GPT)and glutamic oxaloacetic transaminase(GOT),as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in liver tissues were measured.The enzyme-linked immunosorbent assay(ELISA)method was used to detect the level ofα-glutathione S-transferase(α-GST)in serum.The histopathological changes of the liver were observed under a light microscope.The remaining 6 mice in each group underwent MSOT technique was used for characteristic structural and functional imaging of liver tissue.Levels of oxygenated hemoglobin(HbO2)and deoxygenated hemoglobin(Hb)were analyzed,oxygen saturation was calculated,and the extent of liver injury was assessed by examining the intrahepatic distribution of indocyanine green(ICG).RESULTS Compared with the normal group,the levels of GPT,GOT and α-GST in serum,content of MDA in liver tissues and the liver index in the model control group were significantly increased while the activity of SOD in liver tissues were significantly decreased.Compared with the model group,ursolic acid in each dose group significantly reduced the liver index of mice,lowered the serum levels of GPT and GOT as well as the level of α-GST,decreased the content of MDA in liver tissues,and elevated the activity of SOD in liver-injured mice.Hematoxylin-eosin staining showed that significant steatosis and hepatocyte necrosis and inflammatory cell infiltration in hepatocytes of mice in the model group.Ursolic acid significantly attenuated the degree of hepatocellular lesions and markedly reduced steatosis in mice.MSOT imaging showed that the HbO2 level and oxygen saturation were significantly lower while the Hb level was remarkably higher in the liver of mice in the model group.In each administration group,the level of HbO2 significantly increased,the level of Hb was significantly decreased,oxygen saturation was significantly increased in the liver of model mice and the accumulation of ICG dye probe was atten-uated in the body after hepatocyte injury.CONCLUSION Ursolic acid can elevate the hepatic oxygen saturation,improve the metabolism of ICG,reduce the degree of hepatic necrosis in mice,and help protect against carbon tetrachloride-induced hepatic injury in mice.The mechanism is probably related to the inhibition of oxidative stress.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

OBJECTIVE To explore the ameliorative effect of ursolic acid on carbon tetrachloride-induced acute liver injury in mice,and the feasibility of multispectral optoacoustic tomography(MSOT)for characteristic structural and functional imaging of liver tissues.METHODS Kunming mice were randomly divided into the normal control group,model group,model+ursolic acid 30,60 mg·kg-1 groups and model+bifendate 5.625 mg·kg-1 group,with 14 mice in each.Each group was given the corresponding drug once daily for 7 days.An acute liver injury model was established in mice by intraperitoneal injection of 0.2％carbon tetrachloride in olive oil solution after the last administration.Blood was collected,liver tissues were taken 24 h after modeling,and the liver index was calculated,8 mice from each group and the levels of serum glutamic pyruciv transaminase(GPT)and glutamic oxaloacetic transaminase(GOT),as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in liver tissues were measured.The enzyme-linked immunosorbent assay(ELISA)method was used to detect the level ofα-glutathione S-transferase(α-GST)in serum.The histopathological changes of the liver were observed under a light microscope.The remaining 6 mice in each group underwent MSOT technique was used for characteristic structural and functional imaging of liver tissue.Levels of oxygenated hemoglobin(HbO2)and deoxygenated hemoglobin(Hb)were analyzed,oxygen saturation was calculated,and the extent of liver injury was assessed by examining the intrahepatic distribution of indocyanine green(ICG).RESULTS Compared with the normal group,the levels of GPT,GOT and α-GST in serum,content of MDA in liver tissues and the liver index in the model control group were significantly increased while the activity of SOD in liver tissues were significantly decreased.Compared with the model group,ursolic acid in each dose group significantly reduced the liver index of mice,lowered the serum levels of GPT and GOT as well as the level of α-GST,decreased the content of MDA in liver tissues,and elevated the activity of SOD in liver-injured mice.Hematoxylin-eosin staining showed that significant steatosis and hepatocyte necrosis and inflammatory cell infiltration in hepatocytes of mice in the model group.Ursolic acid significantly attenuated the degree of hepatocellular lesions and markedly reduced steatosis in mice.MSOT imaging showed that the HbO2 level and oxygen saturation were significantly lower while the Hb level was remarkably higher in the liver of mice in the model group.In each administration group,the level of HbO2 significantly increased,the level of Hb was significantly decreased,oxygen saturation was significantly increased in the liver of model mice and the accumulation of ICG dye probe was atten-uated in the body after hepatocyte injury.CONCLUSION Ursolic acid can elevate the hepatic oxygen saturation,improve the metabolism of ICG,reduce the degree of hepatic necrosis in mice,and help protect against carbon tetrachloride-induced hepatic injury in mice.The mechanism is probably related to the inhibition of oxidative stress.

Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2～3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26％ and the specificity was 83.82％.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.

Objective:To systematically evaluate the efficacy and safety of obinutuzumab-based regimen versus rituximab-based regimen in treatment of B-cell non-Hodgkin lymphoma (B-NHL).Methods:The Cochrane clinical controlled trials database, PubMed, Embase, American Society of Hematology meeting proceedings, American Society of Clinical Oncology annual meeting proceedings and ClinicalTrails database were searched for studies on the use of regimens containing obinutuzumab or rituximab for the treatment of B-NHL. Patients were divided into obinutuzumab group and rituximab group according to their medication status. Review Manager 5.3 software was used to compare the efficacy and safety of the two groups.Results:A total of 7 randomized controlled trials were selected, including 4 235 patients (1 430 cases of follicular lymphoma, 2 102 cases of diffuse large B-cell lymphoma, and 703 cases of other B-NHL); 2 121 cases were in the obinutuzumab group and 2 114 cases were in the rituximab group. Among 4 162 patients who could be evaluated, the objective response rate (ORR) in the obinutuzumab group was higher than that in the rituximab group [75.1% (1 565/2 083) vs. 72.7% (1 512/2 079); OR = 1.19, 95% CI 1.01-1.41, P = 0.03]. Progression-free survival (PFS) in the obinutuzumab group was better than that in the rituximab group ( HR = 0.86, 95% CI 0.75-0.99, P = 0.03). Among 3 542 patients who could be evaluated for adverse reactions, the incidence of grade 3-4 adverse reactions in the otuzumab group was higher than that in the rituximab group [61.8% (1 098/ 1 776) vs. 54.2% (958/1 766); OR = 1.50, 95% CI 1.29-1.74, P < 0.001], the incidence of grade 3-4 infusive-related adverse reactions [7.5% (158/1 776) vs. 3.1% (65/1 766); OR = 2.56, 95% CI 1.91-3.45, P < 0.001] and neutropenia [34.1% (597/1 749) vs. 29.4% (511/1 738); OR = 1.27, 95% CI 1.09-1.47, P = 0.002] in the obinutuzumab group were higher than those in the rituximab group. Conclusions:The ORR and PFS of B-NHL patients treated with obinutuzumab-based regimen are better than those treated with rituximab-based regimen, but the influence of adverse reactions should be considered when selecting the regimen.

Objective To evaluate the role of high-mobility group box 1 protein ( HMGB1)∕Toll-like receptor 4 ( TLR4) signaling pathway in myocardial ischemia-reperfusion ( I∕R) injury in rats. Meth-ods Fifty-four clean-grade healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=18 each ) using a random number table method: sham operation group ( group Sham) , myocardial I∕R group ( group I∕R) and specific HMGB1 antibody group ( group H) . Myo-cardial I∕R was produced by 30-min occlusion of left anterior descending branch of coronary artery followed by 180-min reperfusion in anesthetized rats. Specific HMGB1 antibody 2 mg∕kg was injected through the femoral vein at 30 min of reperfusion in group H. Twelve rats in each group were randomly selected at 180 min of reperfusion, and blood samples were collected from the femoral vein for determination of plasma in-terleukin-6 ( IL-6) , IL-8, IL-12, tumor necrosis factor-alpha ( TNF-α) and cardiac troponin I ( cTnI ) concentrations. The rats were then sacrificed, hearts were removed and myocardial tissues were obtained forexamination of the pathological changes and for determination of the expression of intercellular adhesion mol-ecule 1 ( ICAM-1) and E-selectin ( by immunohistochemistry) , expression of TLR4 and NF-κB mRNA and protein (by quantitative real-time polymerase chain reaction or by Western blot), activities of glutathione peroxidase ( GSH-PX) , superoxide dismutase ( SOD) and myeloperoxidase ( MPO) and MDA content. Six rats were selected for measurement of the myocardial infarct volume, and the percentage of myocardial in-farct volume was calculated. Results Compared with group Sham, the serum concentrations of IL-6, IL-8, IL-12, TNF-α and cTnI, MPO activity and MDA content were significantly increased, the expression of ICAM-1, E-selectin, TLR4 and NF-κB protein and mRNA was up-regulated, activities of GSH-PX and SOD were decreased, and the percentage of myocardial infarct volume was increased in group I∕R ( P<0. 01) . Compared with group I∕R, the serum concentrations of IL-6, IL-8, IL-12, TNF-α and cTnI, MPO activity and MDA content were significantly decreased, the expression of ICAM-1, E-selectin, TLR4 and NF-κB protein and mRNA was down-regulated, activities of GSH-PX and SOD were increased, and the percentage of myocardial infarct volume was decreased in group H ( P<0. 01) . Conclusion HMGB1∕TLR4 signaling pathway is involved in myocardial I∕R injury in rats.