Objective To investigate the distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Lüliang City, Shanxi Province, so as to provide insights into assessment of the visceral leishmaniasis transmission risk and formulation of visceral leishmaniasis control measures. Methods A total of 12 natural villages were sampled from Shilou County, Lishi District, Lanxian County, Linxian County and Wenshui County in Lüliang City, Shanxi Province from June to September, 2023, and sandflies were captured using light traps from 7 breeding habitats, including farmers’ houses, sheep pens, cattle pens, chicken coops, pig pens, mule and horse pens, and loess-cave dwellings. Following morphological identification of the sandfly species, the distribution of sandflies and the seasonal fluctuations of the sandfly density were analyzed. In addition, the Leishmania was detected in sandflies using a real-time fluorescence quantitative PCR assay. Results A total of 2 831 sandflies were captured with 156 light traps in Lüliang City from June to September, 2023, including 2 638 female sandflies (93.18%) and 193 male sandflies (6.82%), and the average density was 16.91 sandflies/(light-night). The seasonal fluctuations of the sandfly density all appeared a unimodal distribution in all survey sites, and the sandfly density peaked in July and then declined rapidly. Among all types of breeding habitats, the greatest sandfly density was found in sheep pens [39.04 sandflies/(light-night)]. In addition, 4.08% (2/49) of the sandfly samples were tested positive for Leishmania nucleic acid as revealed by the real-time fluorescence quantitative PCR assay. Conclusions Sandflies were widely distributed in Lüliang City, Shanxi Province in 2023, and the peak of the sandfly density was observed in July, which had a visceral leishmaniasis transmission risk. Intensified surveillance of visceral leishmaniasis and sandfly vectors is required and targeted vector control is recommended.

Objective:A comparison was made between the predictive efficacy of the Padua Score and the simplified Assessment Scheme Recommended by Chinese experts (hereinafter referred to as the Simplified Method) for the risk assessment of venous thromboembolism (VTE) in medical inpatients, aiming to provide a reference for the clinical selection of appropriate risk assessment tools.Methods:A retrospective cohort study was conducted, selecting 42 257 internal medicine inpatients discharged from Peking University Shenzhen Hospital between May 1, 2021, and April 30, 2022, using a convenience sampling method. Data collected included general information upon admission, VTE-related information, occurrences of VTE during hospitalization, and results from the two assessment tools. The predictive efficacy of the tools was evaluated by plotting ROC curves and calculating AUC, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy.Results:Among 42 257 patients, there were 21 065 male and 21 192 female participants, aged (55.04 ± 15.17) years old. The incidence rate of VTE among medical inpatients was 2.24% (948/42 257). The AUC for Padua Score and the Simplified Method in medical patients were 0.735 (95% CI 0.717-0.753) and 0.582 (95% CI 0.561-0.602), respectively. Sensitivities were 49.4% and 18.2%, specificities were 89.6% and 98.1%, positive predictive values were 9.9% and 17.7%, negative predictive values were 98.7% and 98.1%, and predictive accuracy were 88.7% and 96.3%, respectively. The departments with the highest incidence rates of VTE during hospitalization were rehabilitation medicine, emergency, neurology, geriatrics, and respiratory medicine. Within these departments, the AUC values for the Padua Score and the Simplified Method were as follows: 0.864 and 0.612, 0.782 and 0.653, 0.792 and 0.664, 0.850 and 0.551, 0.867 and 0.664, respectively. Conclusions:The Padua Score demonstrated better predictive efficacy compared to the Simplified Method. However, the Simplified Method had more accessible assessment criteria and could serve as an initial VTE risk screening tool in emergency situations or when complete data are not available.

Objective:To explore the effects of canagliflozin on cardiac function and its regulation of ferroptosis in rats with heart failure with preserved ejection fraction (HFpEF).Methods:Thirty-two 7-week-old Dahl salt-sensitive rats were selected and randomly divided into four groups: the control group (fed with low-salt diet), the HFpEF group (fed with high-salt diet), the canagliflozin 20 group (fed with high-salt diet and 20 mg·kg -1·d -1 canagliflozin), and the canagliflozin 30 group (fed with high-salt diet and 30 mg·kg -1·day -1 canagliflozin). Body weight and blood pressure of the rats in each group were monitored. Metabolic cage tests were conducted at the10 th week of the experiment, and echocardiography was performed at the 12 th week, after which the rats were killed. Blood and left ventricular samples were collected. HE staining, Masson staining, Prussian blue iron staining, and reactive oxygen species staining were performed to observe the cardiomyocyte size and shape, degree of interstitial fibrosis, iron staining, reactive oxygen species production under optical microscope. The ultrastructure of cardiomyocytes was observed under electron microscope. Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression levels of proteins and mRNA related to ferroptosis in left ventricular myocardial tissue of rats in each group. Results:After 1 week of adaptive feeding, all rats survived. Metabolic cage results showed that compared with control group, rats in the HFpEF group, canagliflozin 20 group and canagliflozin 30 group had more food intake, water intake and urine output, and lower body weight (all P<0.05). These changes were more pronounced in canagliflozin 20 group and canagliflozin 30 group than in HFPEF group, and only the body weight at the 12 th week showed a statistically significant difference between canagliflozin 20 group and canagliflozin 30 group ( P<0.05). The blood pressure of 6 th week and 12 th week, heart weight and left ventricular corrected mass of 12 th week of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while the ratio of early mitral valve peak velocity to late mitral valve peak velocity of 12 th week was lower (all P<0.05). HE and Masson staining showed that compared to control group, the myocardial fibers in the left ventricular myocardial tissue of rats in HFpEF group were disordered, with larger cell diameter ((0.032±0.004) mm vs. (0.023±0.003) mm, P<0.05), irregular shape, obvious proliferation of interstitial collagen fibers, and higher collagen volume fraction (0.168±0.028 vs. 0.118±0.013, P<0.05). Compared with HFpEF group, rats in the canagliflozin 20 group and canagliflozin 30 had more orderly arranged myocardial fibers, more regular cardiomyocyte shape, smaller cell diameter, and lower collagen volume fraction ( P<0.05). It was observed under electron microscopy that, compared to control group, most of the striated muscles in myocardial tissue of HFpEF group were broken, and the Z line and M line could not be clearly distinguished, some changes such as mitochondrial swelling, membrane thickening, cristae reduction or even disappearance occurred. In the canagliflozin 20 group and canagliflozin 30 group, the arrangement of striated muscles in the myocardial tissue of rats tended to be more regular, and the morphological changes of mitochondria were milder. Prussian blue iron staining results showed that the iron content in myocardial tissue of rats in HFpEF group was higher than that in control group, canagliflozin 20 group and canagliflozin 30 group. Reactive oxygen species staining results showed that the reactive oxygen species content in the myocardial tissue of rats in HFpEF group was higher than that of control group, canagliflozin 20 group and canagliflozin 30 group. Biochemical analysis of myocardial tissue showed that Fe 2+ and malondialdehyde content in myocardial tissue of rats in HFpEF group were higher than those in control group, canagliflozin 20 group and canagliflozin 30 group, while glutathione content was lower (all P<0.05). Western blot and RT-qPCR detection results showed that compared to control group, rats in HFpEF group had higher expression levels of transferrin receptor 1 (protein relative expression level: 1.37±0.16 vs. 0.31±0.12), acyl-CoA synthetase long-chain family member 4 (protein relative expression level: 1.31±0.15 vs. 0.63±0.09) protein and mRNA, and lower expression levels of ferritin heavy chain 1 (protein relative expression level: 0.45±0.08 vs. 1.41±0.15) protein and mRNA (all P<0.05). There was no statistically significant difference in these indicators between canagliflozin 20 group and the canagliflozin 30 group (all P>0.05). There was no significant difference in levels of glutathione peroxidase 4 protein and mRNA expression in myocardial tissue of rats in four groups( P>0.05). Conclusion:Canagliflozin improves cardiac function in HFpEF rats by regulating the ferroptosis mechanism.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

To summarise Professor WANG Xixing's experience in treating brain tumour from emotions and minds. Professor WANG regarded abnormal emotions and minds as the key to the treatment of brain tumor. Emotions and minds internal damage lead to malfunction of the five zang organs， resulting in phlegm， stasis， dampness， toxicity and other pathogenic qi gathering in the brain and developing into brain tumour. The treatment advocated regulating qi of the five zang organs and dispelling phlegm， blood stasis， dampness and toxins at the same time. The brain tumour is classified into four syndromes： heart-spleen deficiency， liver depression and spleen deficiency， failure of the heart and kidney to interact， and liver-kidney yin deficiency， with Guipi Yangshen Decoction （归脾养神汤） to fortify the spleen and nourish the heart， Guishao Shunzhi Decoction （归芍顺志汤） to soothe the liver and fortify the spleen， Liangui Tongshen Decoction （连桂通神汤） to restore interaction between the heart and the kidney， and Zishui Qingmu Huashen Decoction （滋水清木化神汤） to nourish the kidney and clear liver. At the same time， it was emphasised that the patient's emotional changes should be paid attention to， and psychological guidance should be given at the right time， so as to overcome the disease with emotions and mind.

Objective:To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin.Methods:ApoE -/-mice fed on Western diet were randomly assigned into the model group ( n=10) and the canagliflozin group ( n=10). C57BL/6J mice fed on normal diet were chosen as the control group ( n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results:HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE -/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE -/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues ( P<0.05). Conclusion:Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.

AIM:To investigate the therapeutic efficacy of curcumin(Cur)-loaded engineered cell membrane mimetic nanoparticles(PD1-Cur@PLGA NPs)in treating breast cancer in mice,and to explore their tumor immunomodu-latory effects.METHODS:Engineered mouse breast cancer 4T1-PD1 cell line expressing programmed death 1(PD1)was established,and PD1 expression level was analyzed by flow cytometry.The 4T1-PD1 cell membranes were extracted and coated on the surface of Cur-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(Cur@PLGA NPs)using ice bath sonication to obtain PD1-Cur@PLGA NPs.The Cur loaded in various NPs was detected using UV-visible spectropho-tometry.Particle size and morphology were analyzed by using dynamic light scattering and transmission electron microsco-py.The 4T1 cells were divided into negative control(PLGA NPs and PD1-NVs),experimental(PD1-Cur@PLGA NPs),parallel control(Cur@PLGA NPs),and positive control(Cur)groups.In each group,cell viability was assessed by CCK-8 assay,and cell apoptosis was determined through flow cytometry.To perform treatment experiments in vivo,4T1 cell-bearing tumor mice were randomly divided into PBS,PD1-NVs,and PD1-Cur@PLGA NPs groups.At the end of treat-ments,tissues of major organs were stained to detect pathological changes,as well as indicators of tumor proliferation(Ki67),apoptosis(TUNEL),and infiltration and activity of T cells(CD4+and CD8+)in tumor tissues.RESULTS:The PD1 expression in 4T1-PD1 cell lines reached 78%.PD1-Cur@PLGA NPs exhibited a core-shell structure with particle sizes ranging from 100 to 200 nm.PD1-Cur@PLGA NPs enhanced the biocompatibility compared to free Cur and exhibited a strong apoptosis-inducing effect on 4T1 cells.Compared with control group,PD1-Cur@PLGA NPs significantly inhibited 4T1 breast tumor growth in vivo(P<0.01),without apparent toxic side effects.Treatment with PD1-Cur@PLGA NPs re-duced Ki67 expression,increased cell apoptosis,and enhanced infiltration and activity of CD4+and CD8+T cells in tumor tissues.CONCLUSION:PD1-Cur@PLGA NPs enhanced Cur biocompatibility and exhibited cytotoxicity against mouse breast cancer cells.This nanoformulation demonstrated promising therapeutic efficacy and safety in vivo,exerting poten-tial antitumor immune regulatory effects.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

Objective To analyze cognition,attitude,behavior status and influencing factor of neurological nurses for early rehabilitation of stroke.Methods A tatol of 182 neurological nurses from 8 tertiary hospitals in Urumqi were selected as the research subjects to investigate the cognition,attitude from December 2022 to June 2023,and behavior status of neurology nurses for early rehabilitation of stroke and analyze their influencing factors.Results The scores of 182 neurological nurses during early rehabilitation of stroke were(72.57士6.79),the scoring rate was 72.57％,which was in the middle level.The average score of attitude was(89.62±2.94),and the scoring rate was 89.62％,which was at a high level.The average score of behavior was(62.08±21.50),and the scoring rate was 62.08％,which was in the middle level.Multivariate regression analysis showed that age was the influence factor of nurses'early rehabilitation cognition dimension and attitude dimension(P＜0.05);The influence factors of nurses'early rehabilitation behavior were their professional title and whether stroke had occurred among relatives and friends(P＜0.05).Conclusion Neurological nurses have a positive attitude towards early rehabilitation of stroke,but they do not implement nursing measures enough.It is suggested that rehabilitation nursing training courses should be set up to encourage nurses to update their knowledge and strengthen their self-learning so as to improve nursing behavior and improve nursing quality.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.