Objective:To study the correlations of neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)with arte-riovenous fistula(AVF)stenosis in hemodialysis(HD)patients.Methods:Data were collected from 625 patients who underwent arterio-venous fistula hemodialysis at the Department of Nephrology,Affiliated Hospital of North Sichuan Medical College between January 2021 and June 2022.Of these,395 eligible patients with complete information were selected as subjects of study.The 245 patients with AVF stenosis were designated as group 1 and the 150 patients with-out AVF stenosis were designated as group 2.The routine biochemi-cal parameters and complete blood count were recorded for all pa-tients.Results:①Compared with patients in group 2,those in group 1 showed significantly higher NLR(5.07(4.00,6.66)vs.3.46(2.63,4.15),P<0.001),PLR(169.52(127.56,227.11)vs.125.66(89.31,165.31),P<0.001),and C-reactive protein(Hs-CRP)(1.90(0.80,2.99)vs.0.82(0.42,1.27),P<0.001).②Multivariate logistic regression analysis,which was corrected for age,sex,body mass index,AVF anastomosis,puncture method,and diabetes,showed that NLR(OR=2.195,95%CI=1.674～2.878,P<0.001),PLR(OR=1.008,95%CI=1.002～1.012,P=0.007),and Hs-CRP(OR=2.170,95%CI=1.607～2.751,P<0.001)were independent risk factors for AVF ste-nosis in HD patients.③Receiver operating characteristic curve analysis showed that the area under the NLR curve(0.799,95%CI=0.756～0.838,P<0.001),PLR(0.694,95%CI=0.646～0.740,P<0.001),and Hs-CRP(0.717,95%CI=0.670～0.761,P<0.001)could be used to predict AVF stenosis.Their optimal critical values for prediction were 4.08,122.49,and 1.62,respectively.Their combina-tion showed improved prediction effect(AUC 0.870,95%CI=0.833～0.901,P<0.001),high sensitivity(79.18%),and high specificity(81.33%).Conclusion:NLR,PLR,and Hs-CRP were independent risk factors and predictors of AVF stenosis,and their combination has higher predictive value.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

BACKGROUND:Previously,a SENP1 gene-silenced human alveolar epithelial cell line was successfully constructed in vitro,and the role of SENP1 in hyperoxic lung injury was investigated at the cellular level.OBJECTIVE:To construct a mouse model of alveolar type II epithelial cell-specific knockout of SENP1 gene based on the Cre-loxP recombinase system.METHODS:SENP1flox/-mice were self-crossed to obtain SENP1flox/flox and SENP1flox/-mice;Sftpc-Cre+/+mice were crossed with wild-type mice to obtain more Sftpc-Cre+/-mice.Sftpc-Cre+/+or offspring Sftpc-Cre+/-mice were crossed with SENP1flox/-or offspring SENP1flox/flox mice to obtain SENP1flox/-Sftpc-Cre+/-double heterozygous mice.SENP1flox/-Sftpc-Cre+/-mice were then crossed with SENP1flox/flox mice to obtain SENP1flox/floxSftpc-Cre+/-mice.The genomic DNA was extracted by tail clipping and amplified by PCR.The amplified product was subjected to agarose gel electrophoresis to determine the mouse genotypes.Lung tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were subjected to immunofluorescence double-labelling and western blot assay to verify the knockdown effect of SENP1 gene.Heart,liver,lung and kidney tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were stained with hematoxylin-eosin to observe the histomorphology of each organ in the two groups of mice.RESULTS AND CONCLUSION:SENP1flox/floxSftpc-Cre+/-mice were correctly screened by agarose gel electrophoresis.Immunofluorescence double-labeling experiments showed that the mean fluorescence intensity of SENP1 was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with that of SENP1flox/flox mice(P<0.01)and no significant co-localization of SENP1 and Sftpc was observed(P<0.01).Western blot results showed that SENP1 protein expression was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with SENP1flox/flox mice(P<0.001).Hematoxylin-eosin staining showed no significant alterations in the histomorphology of heart,liver,lung and kidney tissues in SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice.This study successfully constructed alveolar type II epithelial cell-specific knockout SENP1 gene mice using the Cre-loxP recombinase system,which provides a good tool for the subsequent study of the role of SENP1 gene in lung diseases such as bronchopulmonary dysplasia and idiopathic pulmonary fibrosis,in which alveolar type II epithelial cells are the main damage cells.

An 82-year-old female patient with atrial fibrillation and heart failure was treated with dabigatran etexilate 110 mg twice daily for 6 years. Two months ago, the patient′s lower limb edema was aggravated and urine output was reduced. Considering the worsening of the patient′s heart failure, torasemide tablets and spironolactone tablets were given, but her symptoms were not improved. Two days ago, the patient had scattered petechiae on the whole skin, tarry stools, and reduced urine (200 ml daily). Laboratory tests showed hemoglobin (Hb) 63 g/l, prothrombin time (PT) 39.5 s, activated partial thromboplastin time (APTT) 117.2 s, thrombin time (TT) >300 s, and international normalized ratio (INR) 3.64; the fibrinogen (Fib) could not be measured. Coagulation dysfunction and gastrointestinal bleeding caused by dabigatran etexilate were considered. Dabigatran etexilate was discontinued, and intravenous infusion of idarucizumab injection (2.5 g) was given twice. Then gastrointestinal bleeding in the patient disappeared and laboratory tests showed PT 12.7 s, APTT 42.4 s, TT 18.8 s, INR 1.18, and Fib 2.67 g/L. After 8 days, the patient′s cardiac function was improved, the skin ecchymosis subsided, and laboratory tests showed Hb 84 g/L, PT 14 s, APTT 37.8 s, TT 41.2 s, INR 1.3, Fib 2.26 g/L, and negative fecal occult blood test.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

Objective To compare the differences in clinical prognosis and safety between thoracic endovascular aortic repair(TEVAR)combined with bare metal stent(BMS)implantation therapy and TEVAR alone in patients with type B aortic dissection(TBAD)after 6 months.Methods The clinical and imaging data of patients diagnosed with TBAD and treated with TEVAR or TEVAR combined with BMS implantation in Nanyang Central Hospital from March 2023 to March 2024 were retrospectively collected.The patients were divided into TEVAR group and TEVAR+BMS group according to different treatment methods.The aortic remodeling indicators and postoperative complications at discharge and 6 months after surgery were compared between the two groups.Results A total of 37 patients were included,including 20 patients in the TEVAR group and 17 patients in the TEVAR+BMS group.There were no statistically significant differences in baseline data between the two groups(all P＞0.05);at discharge and 6 months after surgery,the true lumen diameters and true lumen ratios of the abdominal aorta(proximal level of the celiac trunk and proximal level of the left renal artery)in the TEVAR+BMS group were better than those in the TEVAR group(all P＜0.05);the degree of thrombosis of the false lumen at 6 months after surgery was better in the TEVAR+BMS group than in the TEVAR group(P＜0.05);there was no statistically significant difference in postoperative complications between the two groups(P＞0.05).Conclusions TEVAR combined with BMS implantation therapy can significantly improve the aortic remodeling effect of patients with TBAD,without increasing the risk of postoperative complications and death caused by aortic-related factors.Bare stent implantation as an auxiliary treatment method for endovascular repair is a safe and effective optimized treatment plan.