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Xiao Chen,* Yuanhe Fan,* Hongliang Tu,* Jie Chen Department of Orthopedics, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Chen, Department of Orthopedics, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China, Email 342918992@qq.comObjective: Postoperative delirium (POD) commonly occurs in elderly individuals following hip fracture surgery, with unclear pathophysiological mechanism. Inflammation is a known factor affecting the onset of delirium. The current work aimed to examine the associations of preoperative immune inflammation-related indicators with POD occurrence in elderly cases following hip fracture surgery.Methods: The current retrospective cohort study included 437 elderly cases administered hip fracture surgery from January 2018 to December 2023. The clinicodemographic data and laboratory findings of all cases were retrospectively analyzed. Immune inflammation-related indicators were assessed, eg, MLR, NLR and PLR, as well as SII and SIRI. The bootstrap method was employed to assign cases at 7:3 to the training (48 and 258 cases in the POD and no-POD groups, respectively) and internal validation (13 and 118 cases in the POD and no-POD groups, respectively) cohorts. Next, LASSO, univariable and multivariable logistic regression analyses were applied to determine risk factors in the training cohort, based on which a nomogram model was built. The obtained nomogram was examined for accuracy by calibration plot analysis. Finally, the nomogram’s clinical value was assessed by decision curve analysis (DCA), followed by internal validation based on the training cohort.Results: Of all 437 cases, 61 developed POD, indicating a POD incidence of 13.96%. LASSO regression and multivariable analyses revealed preoperative SIRI independently predicted POD in the training cohort. The developed nomogram had an area under the curve (AUC) of 0.991 (95% CI 0.983~0.998) in the training cohort versus 0.986 (95% CI 0.966~1.000) in the validation cohort. Calibration curve analysis revealed nomogram-predicted and actual probabilities were in line. DCA demonstrated the novel nomogram could confer net benefits for POD prediction in elderly cases administered hip fracture surgery.Conclusion: The immune inflammation-related indicators SIRI could predict POD in elderly cases following hip fracture surgery.Keywords: postoperative delirium, hip fracture, elderly, immune inflammation related indicators, nomogram

Yanping Guo,1 Zhangbin Yu,2 Huiying Tu,2 Biying Zheng,1 Jiamin Li,1 Ying Liu1 1Department of Pediatrics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Neonatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yanping Guo; Ying Liu, Tel +86-15919990131 ; +86-13902992158, Email guoyanping1223@163.com; 13902992158@139.comBackground and Objectives: To examine the correlation between the concentration of vitamin D (VD) in venous blood at approximately 4 weeks of age (± 4 weeks of age) and neonatal outcomes in preterm infants (birth weight < 1500 g or gestational age < 32 weeks) in two neonatal intensive care units (NICUs) located in Shenzhen, China.Methods and Study Design: Preterm infants were split into two groups based on their VD concentration at ± 4 weeks of age: VD insufficiency (VDI) group (≤ 20 ng/mL) and VD sufficient (VDS) group (> 20 ng/mL). Binary logistic regression analysis was used to examine relationships between outcomes and VDI.Results: Of 230 infants in total, 119 (51.7%) were assigned to the VDI group and 111 to the VDS group (48.3%). No correlation was found between serum VD at ± 4 weeks of age and gestational age (p> 0.05). The starting point of the two groups for oral VD intake did not differ significantly (p> 0.05). At ± 4 weeks of age, oral VD dose (P< 0.05) was greater in the VDS group. Gestational diabetes mellitus was associated with VDI (OR=1.94, 95% CI 1.01– 3.75, p=0.047) after controlling for this risk. Following correction for gestational age and oral VD dosage at ± 4 weeks old, VDI was also linked to a significant risk of retinopathy of prematurity (OR=2.00, 95% CI 1.08– 3.68, p< 0.027).Conclusion: Preterm newborns (gestational age < 32 weeks or birth age < 1500 g) in NICUs in Shenzhen, China continue to have significantly high VDI. Higher VDI is associated with gestational diabetes mellitus and retinopathy of prematurity.Keywords: very preterm birth, very low birth weight infant, vitamin D, 4 weeks of age, outcome

Yuan Ze,1 Huiming Tu,2 Lin Zhang,3,4 Yu Bai,5 Yilin Ren,2 Xin Chen,1 Yuzheng Xue,2 Renjuan Sun,6 Yuling Yang,7 Jie Yang,2 Xuan Zhou,2 Li Liu8 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China; 4School of Population Medicine and Public Health, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Gastroenterology, Changhai Hospital of Shanghai, Shanghai, People’s Republic of China; 6Outpatient Nursing department, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 7Nursing department of Geriatrics Ward, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 8Data Center, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Huiming Tu, Department of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86-13861753621, Email tuhuiming1891@163.comObjective: To compare the screening efficacy of colonoscopy and pathologically confirmed single and combined Asia-Pacific colorectal screening (APCS), faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing protocols.Methods: From April 2021 to April 2022, 842 volunteers participated in primary colorectal cancer (CRC) screenings using APCS scoring, FIT and sDNA testing and 115 underwent a colonoscopy. One hundred high-risk participants were then identified from the results of both processes. The differences in the three CRC screening tests in combination with the colonoscopy pathology diagnostics were evaluated using Cochran’s Q test, the Dunn–Bonferroni test and area under the receiver operating characteristic curve (AUC) value analysis.Results: Both FIT and sDNA testing demonstrated a 100% performance in detecting CRC. For advanced adenoma, the sensitivity of the FIT + sDNA test scheme (double positive) was 29.2%, and the sensitivities of the combined FIT + sDNA test and APCS scoring + sDNA test schemes were 62.5% and 95.8%, respectively. The FIT + sDNA testing kappa value of advanced colorectal neoplasia was 0.344 (p = 0.011). The sensitivity for nonadvanced adenoma of the APCS score + sDNA test scheme was 91.1%. In terms of positive results, the sensitivity of the APCS score + FIT + sDNA detection protocol was significantly higher than that of the APCS score, FIT, sDNA detection, and FIT + sDNA detection methods (adjusted p < 0.001, respectively). For the FIT + sDNA test, the kappa value was 0.220 (p = 0.015) and the AUC was 0.634 (p = 0.037). The specificity of the FIT + sDNA test scheme was 69.0%.Conclusion: The FIT + sDNA test scheme demonstrated superior diagnostic efficacy, and the combined APCS score + FIT + sDNA test scheme demonstrated remarkable improvements in CRC screening efficiency and sensitivity for detecting positive lesions.Keywords: faecal immunochemical testing, stool DNA test, colonoscopy, primary screening, colorectal cancer

Asthma is a prevalent non-communicable disease that affects both children and adults. Many patients with severe, uncontrolled asthma could not achieve total control despite using anti-asthmatic drugs. There is increasing evidence that allergy to environmental allergens, including both indoor and outdoor allergens, is associated with asthma symptoms and severe asthma. Frequently reported sensitized allergens were dust mites, cockroaches, grass pollens, molds, pets, and rodents in allergic asthma patients, although the patterns of widespread allergens differed from each country. Allergen avoidance is the cornerstone of asthma management, especially in sensitized subjects. This review summarizes environmental allergen avoidance and clarifies their effects on asthma control. Despite contrasting results about the impact of allergen exposure reduction on asthma control, several studies supported the beneficial effects of reducing asthma-related symptoms or risk of exacerbations as a nondrug therapy. Identifying environmental allergens is helpful for asthma patients, and further studies on clinically effective avoidance methods are required.

Zhiquan Ding1 &ast;, Zhenzhong Zhong1 &ast;, Jun Wang1 &ast;, Run Zhang,2 Jinlian Shao,3 Yulong Li,1 Guiwei Wu,1 Huiru Tu,1 Wen Yuan,4 Haitao Sun,1,5 Qinghua Wang1,3 1Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Neurosurgery Center, Department of Neuro-oncological Surgery, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Emergency, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Laboratory Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghua Wang; Haitao Sun, Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email wqh1123@126.com; 2009sht@smu.edu.cnBackground: Neuroinflammation plays an important role following intracerebral hemorrhage (ICH). NLRP3 inflammasome-mediated pyroptosis contributes to the mechanism of neuroinflammation. It has been reported that dendritic cell-associated C-type lectin-1 (Dectin-1) activation triggers inflammation in neurological diseases. However, the role of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis after ICH remains unclear. Here, we aimed to explore the effect of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis and neuroinflammation after ICH.Methods: Adult male C57BL/6 mice were used to establish the ICH model. Laminarin, an inhibitor of Dectin-1, was administered for intervention. Expression of Dectin-1 was evaluated by Western blot and immunofluorescence. Brain water content and neurobehavioral function were tested to assess brain edema and neurological performance. Western blot was conducted to evaluate the level of GSDMD-N. ELISA kits were used to measure the levels of IL-1β and IL-18. qRT–PCR and Western blot were performed to evaluate the expressions of NLRP3 inflammasome, IL-1β, and IL-18.Results: The expression of Dectin-1 increased following ICH, and Dectin-1 was expressed on microglia. In addition, inhibition of Dectin-1 by laminarin decreased brain edema and neurological impairment after ICH. Moreover, inhibition of Dectin-1 decreased the expression of pyroptosis-related protein, GSDMD-N, and inflammatory cytokines (IL-1β and IL-18). Mechanistically, Dectin-1 blockade inhibits NLRP3 inflammasome activation, thereby alleviating neuroinflammatory injury by attenuating NLRP3 inflammasome-mediated pyroptosis both in vivo and in vitro.Conclusion: Our study indicates that the inhibition of Dectin-1 alleviates neuroinflammation by attenuating NLRP3 inflammasome-mediated pyroptosis after ICH.Keywords: intracerebral hemorrhage, Dectin-1, NLRP3 inflammasome, pyroptosis, microglia

Drug development for idiopathic pulmonary fibrosis (IPF) has been challenging due to poorly understood disease etiology, unpredictable disease progression, highly heterogeneous patient populations, and a lack of robust pharmacodynamic biomarkers. Moreover, because lung biopsy is invasive and dangerous, making the extent of fibrosis as a direct longitudinal measurement of IPF disease progression unfeasible, most clinical trials studying IPF can only assess progression of fibrosis indirectly through surrogate measures. This review discusses current state-of-art practices, identifies knowledge gaps, and brainstorms development opportunities for preclinical to clinical translation, clinical populations, pharmacodynamic endpoints, and dose optimization strategies. This article highlights clinical pharmacology perspectives in leveraging real-world data as well as modeling and simulation, special population considerations, and patient-centric approaches for designing future studies.

Wenjun Xu,1,2 Hui Tu,1 Xiaoyun Xiong,1 Ying Peng,1,2 Ting Cheng1,2 1Department of Nursing, the Second Affiliated Hospital of Nanchang University, NanChang, Jiangxi, 330000, People’s Republic of China; 2School of Nursing, Nanchang University, NanChang, Jiangxi, 330000, People’s Republic of ChinaCorrespondence: Hui Tu, Department of Nursing, the Second Affiliated Hospital of Nanchang University, 1 Minde Road, NanChang, Jiangxi, 330000, People’s Republic of China, Tel +86 135-76095925, Email 12674789@qq.comObjective: This study aimed to develop and validate a risk prediction model that can be used to identify percutaneous coronary intervention (PCI) patients at high risk for 30-day unplanned readmission.Patients and Methods: We developed a prediction model based on a training dataset of 1348 patients after PCI. The data were collected from January 2020 to December 2020. Clinical characteristics, laboratory data and risk factors were collected using the hospital database. The LASSO regression method was applied to filter variables and select predictors, and feature selection for a 30-day readmission risk model was optimized using least absolute shrinkage. Multivariate logistic regression was used to construct a nomogram. The performance and clinical utility of the nomogram were evaluated with a receiver operating characteristic (ROC) curve, a calibration curve, and decision curve analysis (DCA). Internal validation of the predictive accuracy was performed using bootstrapping validation.Results: The predictors included in the prediction nomogram were medical insurance, length of stay, left ventricular ejection fraction on admission, history of hypertension, the presence of chronic lung disease, the presence of anemia, and serum creatinine level on admission. The area under the receiver operating characteristic curve for the predictive model was 0.735 (95% CI: 0.711– 0.759). The P value of the Hosmer–Lemeshow goodness of fit test was 0.326, indicating good calibration, and the calibration curves showed good agreement between the classifications and actual observations. DCA also demonstrated that the nomogram was clinically useful. A high c-index value of 0.723 was obtained during the internal validation.Conclusion: We developed an easy-to-use nomogram model to predict the risk of readmission 30 days after discharge for PCI patients. This risk prediction model may serve as a guide for screening high-risk patients and allocating resources for PCI patients at the time of hospital discharge and may provide a reference for preventive care interventions.Keywords: percutaneous coronary intervention, 30-day readmission, nomogram, prediction model

Hong Zhao,&ast; Huilan Tu,&ast; Xia Yu,&ast; Junwei Su, Xuan Zhang, Kaijin Xu, Yu Shi, Yunqing Qiu, Jifang Sheng State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jifang Sheng; Yunqing Qiu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel +86 571 8723 6491, Fax +86 571 8723 6491, Email jifang_sheng@zju.edu.cn; qiuyq@zju.edu.cnAim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19).Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient’s data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis.Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25– 14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03– 1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01– 1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45– 12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93– 0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21– 32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients.Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.Keywords: COVID-19, SARS-CoV-2, clearance, critical disease, viral load

In response to a call for help during a surge in coronavirus disease-19 (COVID-19) cases in Ho Chi Minh City in July 2021, the University of Medicine and Pharmacy at Ho Chi Minh City developed and implemented a community care model for the management of patients with COVID-19. This was based on three main principles: home care; providing monitoring and care at a distance; and providing timely emergency care if needed. One team supported patients at home with frequent contacts and remote monitoring, while a second team transferred and cared for patients requiring treatment at field emergency care facilities. COVID-19-related mortality rates at the two districts where this approach was implemented (0.43% and 0.57%) were substantially lower than the overall rate in Ho Chi Minh City over the same period (4.95%). Thus, utilization of a community care model can increase the number of patients with COVID-19 who can be effectively managed from home, and use of field emergency care facilities limited the number of patients that had to be referred for tertiary care. Importantly, the community care model also markedly reduced the mortality rate compared with traditional methods of COVID-19 patient management.

Hui Chi,1 Guanghua Chen,1 Yixin He,2 Guanghao Chen,1 Hualei Tu,3 Xiaoqi Liu,1 Jinglong Yan,1 Xiaoyan Wang1 1Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Burn, The Fifth Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Xiaoyan Wang; Jinglong YanDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, 246 XueFu Road, Harbin, Heilongjiang Province, People’s Republic of ChinaEmail wxyg7@hrbmu.edu.cn; yanjinglongg6@126.comBackground and Purpose: The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure.Methods: A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo.Results: The compressive modulus of the composite scaffolds reached 9.45± 0.32 MPa, which was similar to that of the 3D-HA scaffolds (p> 0.05). The pore size of the two scaffolds was 305± 47 um and 315± 34 um (p> 0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00± 6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85± 4.77% (p< 0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds.Conclusion: We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.Keywords: bone tissue engineering, extracellular matrix, stem cells, 3D printed scaffold, osteogenesis

In our inter-connected world, health-care professionals are the first line of defence to identify emerging diseases and public health events for rapid response. In Vietnam, event-based surveillance (EBS), critical for the early detection of emerging disease outbreaks and acute public health events, has been limited to media-based EBS until recently. In 2017–2018, the Ministry of Health of Vietnam, in collaboration with the World Health Organisation and the US Centres for Disease Control and Prevention, designed, implemented, and evaluated a hospital EBS demonstration pilot in six hospitals in two provinces in Vietnam. After the 9-month implementation period, we conducted a logbook review, eight interviews, and six focus group discussions with hospital and preventive medicine staff, and conducted thematic and descriptive analysis. During the implementation period, 11 signals were reported and confirmed as true events. Of the 11 signals, majority (N = 8, 72.7%) were detected in ICU, followed by the outpatient department (N = 2, 18.2%). The most common signal were clusters of food poisoning (N = 4, 36.4%). All (100%) signals were reported, risk-assessed, and responded to within 24 hours of signal detection. The hospital and preventive medicine staff reported that one of the main benefits of the pilot was their improved mutual relationship. This pilot formalised hospital event-based surveillance through a legal framework, standard operating procedures, a formal feedback mechanism to hospitals to facilitate a two-way conversation, and providing additional training and continued sensitisation. Most importantly, it fostered a trusting relationship between the curative medicine and public health sectors, marking an important step towards advancing the national event-based surveillance system in Vietnam.

Surveillance and outbreak reporting systems in Vietnam required improvements to function effectively as early warning and response systems. Accordingly, the Ministry of Health of Vietnam, in collaboration with the US Centers for Disease Control and Prevention, launched a pilot project in 2016 focusing on community and hospital event–based surveillance. The pilot was implemented in 4 of Vietnam’s 63 provinces. The pilot demonstrated that event-based surveillance resulted in early detection and reporting of outbreaks, improved collaboration between the healthcare facilities and preventive sectors of the ministry, and increased community participation in surveillance and reporting.

Zhiyou Cai,1 Chuanling Wang,1 Wenbo He,1 Hanjun Tu,2 Zhengang Tang,3 Ming Xiao,4 Liang-Jun Yan51Department of Neurology, Renmin Hospital, Hubei University of Medicine, 2Department of Basic Research Center, Hubei University of Medicine, 3Department of Neurosurgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 4Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USAAbstract: Cerebral small vessel disease (CSVD) is a group of pathological processes with multifarious etiology and pathogenesis that are involved into the small arteries, arterioles, venules, and capillaries of the brain. CSVD mainly contains lacunar infarct or lacunar stroke, leukoaraiosis, Binswanger’s disease, and cerebral microbleeds. CSVD is an important cerebral microvascular pathogenesis as it is the cause of 20% of strokes worldwide and the most common cause of cognitive impairment and dementia, including vascular dementia and Alzheimer’s disease (AD). It has been well identified that CSVD contributes to the occurrence of AD. It seems that the treatment and prevention for cerebrovascular diseases with statins have such a role in the same function for AD. So far, there is no strong evidence-based medicine to support the idea, although increasing basic studies supported the fact that the treatment and prevention for cerebrovascular diseases will benefit AD. Furthermore, there is still lack of evidence in clinical application involved in specific drugs to benefit both AD and CSVD.Keywords: dementia, cerebrovascular diseases, lacunar infarct, leukoaraiosis, cerebral microbleeds

Ying Li,1,* Jiani Yuan,1,* Qian Yang,1 Wei Cao,1 Xuanxuan Zhou,1 Yanhua Xie,1 Honghai Tu,2 Ya Zhang,1 Siwang Wang1 1Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Institute for Drug and Instrument Control, Xinjiang Military Area Command, Urumqi, Xinjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL) conjugated with anti-CD40 antibody (anti-CD40-BFL) showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm3 versus 270 mm3, respectively); the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic immunity while blocking systemic toxicity. Keywords: liposomes, bufalin, anti-CD40, chemoimmunotherapy

An all-fiber femtosecond Cherenkov radiation source is demonstrated for the first time, to the best of our knowledge. Using a stable monolithic femtosecond Ybdoped fiber laser as the pump source, and the combination of photonic crystal fibers as the wave-conversion medium, we have generated tunable Cherenkov radiation at visible wavelengths 580 – 630 nm, with pulse duration of sub-160 fs, and the 3 dB spectral bandwidth not exceeding 36 nm. Such femtosecond source can find applications in practical biophotonics such as bio-imaging and microscopy.

In our antioxidant screening of some Vietnamese plant extracts, the CHCl3-soluble fraction from Calotropis gigantea (L.) W.T.Aiton flowers showed moderate DPPH free radical scavenging activity with an IC50 value of 55.8 μg/mL. Thus, a further phytochemical study was carried out to obtain five alkaloids, including a new β-carboline-type alkaloid, caloside H (1). These known compounds were identified as 5-hydroxy-(2-methoxymethyl)pyridine (2), nicotinic acid (3), p-(acetylamino)phenol (4), and thymine (5). These structures were determined based on the NMR spectroscopic analysis. In antioxidant assay, caloside H at concentration of 100 μM showed DPPH radical scavenging capacity with a percentage of inhibition of 40.2%. In addition, a plausible biosynthetic pathway for the formation of caloside H was proposed based on the Schiff base formation and Mannich-like reaction. [ABSTRACT FROM AUTHOR]