Prehabilitation programs - a systematic review of the economic evidence.

Introduction: Prehabilitation, which involves improving a patient's physical and psychological condition before surgery, has shown potential benefits but has yet to be extensively studied from an economic perspective. To address this gap, a systematic review was conducted to summarize existing economic evaluations of prehabilitation interventions. Methods: The PRISMA Protocols 2015 checklist was followed. Over 16,000 manuscripts were reviewed, and 99 reports on preoperative interventions and screening tests were identified, of which 12 studies were included in this analysis. The costs are expressed in Pounds (GBP, £) and adjusted for inflation to December 2022. Results: The studies were conducted in Western countries, focusing on specific surgical subspecialties. While the interventions and study designs varied, most studies demonstrated cost savings in the intervention group compared to the control group. Additionally, all cost-effectiveness analysis studies favored the intervention group. However, the review also identified several limitations. Many studies had a moderate or high risk of bias, and critical information such as time horizons and discount rates were often missing. Important components like heterogeneity, distributional effects, and uncertainty were frequently lacking as well. The misclassification of economic evaluation types highlighted a lack of knowledge among physicians in prehabilitation research. Conclusion: This review reveals a lack of robust evidence regarding the economics of prehabilitation programs for surgical patients. This suggests a need for further research with rigorous methods and accurate definitions.

Programming lipopeptide nanotherapeutics for tandem treatment of postsurgical infection and melanoma recurrence.

Tumor recurrence and chronic bacterial infection constitute two major criteria in postsurgical intervention for malignant melanoma. One plausible strategy is the equipment of consolidation therapy after surgery, which relies on adjuvants to eliminate the residual tumor cells and inhibit bacterial growth. Until now, a number of proof-of-concept hybrid nanoadjuvants have been proposed to combat tumor recurrence and postsurgical bacterial infection, which may suffer from the potential bio-unsafety or involve complex design and synthesis. The batch-to-batch inconsistencies in drug composition further delay the clinical trials. To circumvent these issues, herein we develop a programmable strategy to generate lipopeptide nanotherapeutics with identical constitution for tandem intervention of postsurgical bacterial infection and cancer recurrence of melanoma. Increasing the number of hydrophobic linoleic acid within lipopeptides has been found to be a simple and practical strategy to improve the therapeutic outcomes for both tumor cells and bacteria. Self-assembled lipopeptide nanotherapeutics with two linoleic acid molecules possesses excellent antitumor activity and antimicrobial function toward both susceptible strains and drug-resistant bacteria. Arising from the incorporation of unsaturated linoleic acid, the unavoidable hemolysis of cationic peptide drugs was effectively alleviated. In vivo therapeutic abilities of postsurgical infection and tumor recurrence were investigated in BALB/c nude mice bearing a B16-F10 tumor model, with an incomplete surgical resection and in situ infection by methicillin-resistant Staphylococcus aureus (MRSA). Self-assembled lipopeptide nanotherapeutics could effectively inhibit cancer cell growth and bacterial infection, as well as promote wound healing. The easily scalable large-scale production, broad-spectrum antitumor and antibacterial bioactivities as well as fixed component endows lipopeptide nanotherapeutics as promising adjuvants for clinically postsurgical therapy of melanoma.

Mechanism of m6A methyltransferase 3 in the pathogenesis of diabetic cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the role and mechanism of N6-methyladenosine(m6A)methyltransferase 3(METTL3)in the pathogenesis of diabetic cataract.METHODS: We cultured SRA01/04 cells in low and high sugar media for 24h and measured changes in epithelial-mesenchymal transition(EMT)indicators(E-Cadherin, N-Cadherin, ZO-1 and α-SMA)using RT-qPCR and Western blot assays. Cell migration was also assessed using transwell and scratch assays. To investigate the expression level and localization of METTL3 in human lens anterior capsules tissues. Additionally, we used m6A dot blot assay to detect the m6A methylation level of cells cultured in low and high glucose media for 24h, and employed RT-qPCR and Western blot experiments to detect RNA and protein expression of METTL3 in cells. We then treated the cells with METTL3 inhibitor and measured changes in EMT markers by RT-qPCR and Western blot; m6A methylation level was detected by m6A dot blot test; cell migration was detected by Transwell. Finally, the expression of transforming growth factor-β(TGFβ1)in cultured cells was assessed by immunofluorescence staining and the expression levels of TGFβ1 and SNAIL in cells were determined using RT-qPCR and Western blot.RESULTS: Under high glucose conditions, the expression of EMT markers, METTL3, and m6A methylation levels were significantly increased in cells(P<0.05). Furthermore, the migratory ability of cells was higher in high-sugar medium than in low-sugar medium. In human lens anterior capsules, METTL3 expression was higher in patients with diabetic cataract compared to those with age-related cataract. Importantly, treatment with the METTL3 inhibitor STM2457 inhibited EMT in cells, the expression of TGFβ1 and SNAIL, as well as m6A methylation levels in cells(all P<0.05)compared to high-sugar + dimethyl sulfoxide(DMSO)group. Moreover, the migratory capacity of cells was reduced after the addition of STM2457 compared to the high-sugar + DMSO group.CONCLUSION:METTL3 promotes the EMT in human lens epithelial cells under high glucose conditions by activating the TGFβ1/SNAIL pathway, thus contributing to the development of diabetic cataracts.

Methyltransferase-like 3-mediated N6-methyladenosine methylation modification regulates the biological activity of vascular endothelial cells via the Notch pathway / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the role and mechanism of methyltransferase-like 3(METTL3)-mediated N6-methyladenosine(m6A)methylation modification in regulating biological activity of vascular endothelial cells in the pathogenesis of choroidal neovascularization.METHODS: Human umbilical vein endothelial cells(HUVEC)cultured in vitro were divided into the following groups: control group(normal culture), low density lipoprotein(LDL)group, fluorescence-labelled LDL(Dil-LDL)group, 12.5μg/mL and 25μg/mL oxidized LDL(ox-LDL)groups, 12.5μg/mL and 25μg/mL fluorescence-labelled ox-LDL(Dil-ox-LDL)groups, DMSO group, STM2457(METTL3 inhibitor)group, DAPT group; and monkey retina-choroidal endothelial cells(RF/6A)cultured in vitro were divided into control group, DMSO group, 12.5 μg/mL ox-LDL group, and DAPT group. Endocytosed lipoprotein level was examined through fluorescence microscopy. RNA m6A methylation level was detected through a dot blot assay. Protein and RNA levels of METTL3 or angiogenesis-related markers were measured through Western blot assays and real-time quantitative polymerase chain reaction(RT-qPCR), respectively. METTL3 expression and localization were investigated through immunofluorescence. Cell migratory and tube formation capacities were assessed through transwell migration and tube formation assays, respectively.RESULTS: Endocytosed lipoprotein levels in HUVECs exposed to Dil-LDL, 12.5μg/mL and 25μg/mL Dil-ox-LDL groups were significantly higher than those in the control group. 12.5μg/mL and 25μg/mL ox-LDL groups significantly increased m6A methylation(all P<0.05), METTL3 protein expression(all P<0.01), and cell migration and angiogenesis capacities(all P<0.01). METTL3 mRNA level was significantly unregulated in the 12.5μg/mL ox-LDL group(P<0.05). In comparison to the DMSO group, the addition of STM2457 caused significant decrease in m6A methylation level(P<0.05), expression of VEGF and other angiogenesis-related markers(all P<0.05), cell migration and angiogenesis capacities(all P<0.01)and the expression of NICD(P<0.05). However, there were no significant differences in METTL3 protein and mRNA levels(all P>0.05). The expression of VEGF and NICD(all P<0.05), as well as the ability of cell migration and angiogenesis of RF/6A, was all significantly decreased in the DAPT group compared to the DMSO group(all P<0.01).CONCLUSION: METTL3-mediated m6A methylation modification promotes angiogenesis in vascular endothelial cells via the Notch signaling pathway in the pathogenesis of choroidal neovascularization.

S373P Mutation of Spike Protein in SARS-CoV-2 Stabilizes Omicron

Recently, a cluster of several newly occurring mutations on Omicron, which is currently the dominant SARS-CoV-2 variant, are found at the (mechanically) stable {beta}-core region of spike proteins receptor-binding domain (RBD), where mutation rarely happened before. Notably, the binding of SARS-CoV-2 to human receptor ACE2 via RBD happens in a dynamic airway environment, where mechanical force caused by coughing or sneezing occurs and applies to the proteins. Thus, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to measure the stability of RBDs and found that the unfolding force of Omicron RBD increased by 20% compared with the wild-type. Molecular dynamics simulations revealed that Omicron RBD showed more hydrogen bonds in the {beta}-core region due to the closing of the -helical motif caused primarily by the S373P mutation, which was further confirmed by the experiment. This work reveals the stabilizing effect of the S373P mutation and suggests mechanical stability becomes another important factor in SARS-CoV-2 mutation selection.

Expert consensus on the management of adverse events of CDK4/6 inhibitors in breast cancer / 中华肿瘤杂志

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

Promoting effect of the Maillard reaction products produced during the stir-frying process of Hordei Fructus Germinatus on the intestinal absorption of active ingredients in Hordei Fructus Germinatus.

This study was designed to evaluate the absorption promoting capacity of Maillard Reaction Products (MRPs) produced during the stir-frying process of Hordei Fructus Germinatus on catechin, ferulic acid, quercetin and kaempferol by the ex vivo rat everted gut sac model, in situ single-pass intestinal perfusion model and the whole animal model. Moreover, verapamil, EDTA and mannitol were used for determining the transport mechanism of catechin, ferulic acid, quercetin and kaempferol. The tight junction (TJ) proteins including zonula occudens-1(ZO-1) and claudin-1 were chosen to investigate the promoting mechanism of MRPs by quantitative real-time PCR (qRT-PCR) and western blot analyses. The results showed that the MRPs produced during the stir-frying process of Hordei Fructus Germinatus could improve the intestinal absorption of catechin, ferulic acid, quercetin and kaempferol. And the absorption-promoting effect of MRPs was related to chelating effect and the reduced expression of claudin-1 and ZO-1. Our results suggested that MRPs could be promising oral absorption promoters, which might be another processing mechanism of Hordei Fructus Germinatus.

Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β1 of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca2+/NFAT Signaling Pathway / 中国实验方剂学杂志

Objective:This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁），and to explore the mechanism of regulating Wnt5a/Ca²⁺/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells. Method:TGF-<italic>β</italic>₁（10 μg·L^-1）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca²⁺/NFAT signaling pathway， and intracellular Ca²⁺ concentration. Result:Compared with the blank group， TGF-<italic>β</italic>₁ could significantly enhance the invasion and migration ability of MGC-803 cells（<italic>P</italic><0.01）， down-regulate the level of E-cadherin（<italic>P</italic><0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（<italic>P</italic><0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca²⁺（<italic>P</italic><0.01）. Compared with the TGF-<italic>β</italic>₁ group， modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） could significantly inhibit this phenomenon，and 40 mg·L^-1 had the best effect（<italic>P</italic><0.05，<italic>P</italic><0.01）.The specific inhibitors of Wnt5a/Ca²⁺/NFAT signaling pathway （<italic>R</italic>）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L^-1） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-<italic>β</italic>₁， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca²⁺（<italic>P</italic><0.05，<italic>P</italic><0.01）.Moreover， （<italic>R</italic>）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L^-1） had stronger inhibitory effect（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-<italic>β</italic>₁ via Wnt5a/Ca²⁺/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.

Molecular transmission characteristics of human immunodeficiency virus type 1 in northern Zhejiang Province / 中华传染病杂志

Objective:To construct the molecular transmission network of human immunodeficiency virus type 1 (HIV-1) epidemic strains in northern Zhejiang Province (Jiaxing City and Huzhou City) and to explore the HIV-1 transmission characteristics in this region.Methods:A total of 371 newly diagnosed human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Jiaxing City and Huzhou City in 2017 were included as study subjects, and the blood samples were collected and the basic demographic and epidemiological information were obtained. RNA in plasma was extracted, and the pol region gene sequence was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (PCR) to construct phylogenetic tree for identifying subtypes. The pairwise genetic distances were calculated, and the optimal threshold of genetic distance was selected, and finally the molecular transmission network was constructed. Chi-square test was used for statistical analysis. Results:The pol region gene sequences of 336 samples were successfully obtained, and 11 subtypes were detected, mainly including circulating recombinant form (CRF)07_BC (40.8%, 137/336) and CRF01_AE (31.2%, 105/336). Based on the 1.0% genetic distance threshold, the molecular transmission network of HIV-1 was plotted. A total of 38 transmission clusters (cluster sizes ranging from two to 28) including 119 patients were found, with males predominantly (82.4%, 98/119) and most of the patients aged over 40 (include 40) years old (52.9%, 63/119), mainly infected with CRF07_BC subtype (57.1%, 68/119) and CRF01_AE (24.4%, 29/119). The clustering rate of CRF07_BC (49.6%, 68/137) was significantly higher than that of CRF01_AE (27.6%, 29/105), the difference was statistically significant ( χ2=5.27, P=0.022). Two large clusters C1 (28 cases) and C2 (11 cases) were identified, the majority of which were men who have sex with men (17 cases and seven cases, respectively). High-risk cases generally sought sexual partners in local or nearby cities through mobile phone dating software, of which the infected sequences mostly had high homology with other economic developed regions (Guangdong Province, Beijing City and Hangzhou City, etc.). Conclusions:The HIV-1 subtypes are diverse in Jiaxing City and Huzhou City, mainly CRF07_BC and CRF01_AE. The HIV-1 transmission networks are complex, among which high-risk cases may be the key factor leading to the HIV-1 epidemic in the region. Therefore, it is urgent to deepen the transmission network monitoring and formulate timely precise intervention and prevention strategies.

[Investigating effect of Faeces Bombycis on intestinal microflora in rats with syndrome of damp retention in middle-jiao by high-throughput sequencing].

The aim of this paper was to investigate the effect of Faeces Bombycis(FB) on the intestinal microflora in rats with syndrome of damp retention in middle-jiao, and to explore its mechanism in regulating intestinal microflora from the perspective of microorganisms contained in FB. The contents of antidiuretic hormone(ADH) and C-reactive protein(CRP) in serum and aquaporin 3(AQP3) in jejunum were determined by enzyme-linked immunosorbent assay(ELISA). Illumina Miseq platform was used for high-throughput sequencing of the rat feces and FB. The ELISA results showed that as compared with the normal control group, the contents of ADH and CRP in the model group were significantly increased(P<0.05), and the content of AQP3 was significantly decreased(P<0.05). After drug administration, the ADH, CRP and AQP3 contents were recovered. Sequencing of rat feces showed that the ACE, Chao1 and Shannon indexes of the intestinal microflora were the lowest in the model group. As compared with the normal control group, the levels from phylum to genus were all significantly changed in model group, and Proteobacteria, Acinetobacter, Anaerobacter, Pseudomonas, and Parabacteroides levels were significantly increased(P<0.05), while Marvinbryantia level was significantly decreased(P<0.05). As compared with the model group, Proteobacteria was significantly decreased in the FB low and high dose groups(P<0.05), and Acinetobacter, Anaerobacter, Pseudomonas, Parabacteroides levels were significantly decreased in the low, medium and high dose groups(P<0.05), while Lachnoanaerobaculum, Intestinimonas and Marvinbryantia were increased significantly in the high dose group(P<0.05). Sequencing analysis of FB showed that the relative abundance of Leclercia, Pantoea, Brachybacterium, Shimwellia, Hartmannibacter, Klebsiella, Serratia, Aurantimonas, Paenibacillus and Bacillus was high in the FB, but they were basically not present or little in the rat feces. In conclusion, FB may play a role in the treatment of "syndrome of damp retention in middle-jiao" by balancing the intestinal microflora, and this effect may be related to the metabolites of microorganisms in the FB.

Revealing the binding and drug resistance mechanism of amprenavir, indinavir, ritonavir, and nelfinavir complexed with HIV-1 protease due to double mutations G48T/L89M by molecular dynamics simulations and free energy analyses.

Infection by human immunodeficiency virus type 1 (HIV-1) not only destroys the immune system bringing about acquired immune deficiency syndrome (AIDS), but also induces serious neurological diseases including behavioral abnormalities, motor dysfunction, toxoplasmosis, and HIV-1 associated dementia. The emergence of HIV-1 multidrug-resistant mutants has become a major problem in the therapy of patients with HIV-1 infection. Focusing on the wild type (WT) and G48T/L89M mutated forms of HIV-1 protease (HIV-1 PR) in complex with amprenavir (APV), indinavir (IDV), ritonavir (RTV), and nelfinavir (NFV), we have investigated the conformational dynamics and the resistance mechanism due to the G48T/L89M mutations by conducting a series of molecular dynamics (MD) simulations and free energy (MM-PBSA and solvated interaction energy (SIE)) analyses. The simulation results indicate that alterations in the side-chains of G48T/L89M mutated residues cause the inner active site to increase in volume and induce more curling of the flap tips, which provide the main contributions to weaker binding of inhibitors to the HIV-1 PR. The results of energy analysis reveal that the decrease in van der Waals interactions of inhibitors with the mutated PR relative to the wild-type (WT) PR mostly drives the drug resistance of mutations toward these four inhibitors. The energy decomposition analysis further indicates that the drug resistance of mutations can be mainly attributed to the change in van der Waals and electrostatic energy of some key residues (around Ala28/Ala28' and Ile50/Ile50'). Our work can give significant guidance to design a new generation of anti-AIDS inhibitors targeting PR in the therapy of patients with HIV-1 infection.

Research Progress on Antitumor Active Components and Mechanism of Xiao Xianxiongtang / 中国实验方剂学杂志

Tumor is one of the diseases that seriously endanger human health， and how to treat tumor effectively is still one of the important problems in the field of medicine. At present， most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept， traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages， such as multiple channels， multiple levels， multiple links， multiple targets and less toxicity， and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors， and relevant pharmacological studies have also confirmed the effectiveness of this formula， but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now， with alkaloids， ketones， sterols and phenols in Xiao Xianxiongtang as the starting point， this study mainly focuses on inhibition of tumor cell proliferation， invasion and migration， induction of tumor cell apoptosis and autophagy， inhibition of tumor cell cycle， enhancement of tumor cell sensitivity， inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition， function and mechanism of drugs. In this paper， effective components， main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed， in order to provide a new idea for subsequent antitumor research and development of this prescription.

Investigating effect of Faeces Bombycis on intestinal microflora in rats with syndrome of damp retention in middle-jiao by high-throughput sequencing / 中国中药杂志

The aim of this paper was to investigate the effect of Faeces Bombycis(FB) on the intestinal microflora in rats with syndrome of damp retention in middle-jiao, and to explore its mechanism in regulating intestinal microflora from the perspective of microorganisms contained in FB. The contents of antidiuretic hormone(ADH) and C-reactive protein(CRP) in serum and aquaporin 3(AQP3) in jejunum were determined by enzyme-linked immunosorbent assay(ELISA). Illumina Miseq platform was used for high-throughput sequencing of the rat feces and FB. The ELISA results showed that as compared with the normal control group, the contents of ADH and CRP in the model group were significantly increased(P<0.05), and the content of AQP3 was significantly decreased(P<0.05). After drug administration, the ADH, CRP and AQP3 contents were recovered. Sequencing of rat feces showed that the ACE, Chao1 and Shannon indexes of the intestinal microflora were the lowest in the model group. As compared with the normal control group, the levels from phylum to genus were all significantly changed in model group, and Proteobacteria, Acinetobacter, Anaerobacter, Pseudomonas, and Parabacteroides levels were significantly increased(P<0.05), while Marvinbryantia level was significantly decreased(P<0.05). As compared with the model group, Proteobacteria was significantly decreased in the FB low and high dose groups(P<0.05), and Acinetobacter, Anaerobacter, Pseudomonas, Parabacteroides levels were significantly decreased in the low, medium and high dose groups(P<0.05), while Lachnoanaerobaculum, Intestinimonas and Marvinbryantia were increased significantly in the high dose group(P<0.05). Sequencing analysis of FB showed that the relative abundance of Leclercia, Pantoea, Brachybacterium, Shimwellia, Hartmannibacter, Klebsiella, Serratia, Aurantimonas, Paenibacillus and Bacillus was high in the FB, but they were basically not present or little in the rat feces. In conclusion, FB may play a role in the treatment of "syndrome of damp retention in middle-jiao" by balancing the intestinal microflora, and this effect may be related to the metabolites of microorganisms in the FB.

Association of genetic polymorphisms with acute kidney injury after cardiac surgery in a Southeast Asian population.

INTRODUCTION: Genetic polymorphisms are important in explaining the wide interpatient variability that exists in the development of acute kidney injury (AKI) post cardiac surgery. We hypothesised that polymorphisms in 4 candidate genes, namely angiotensin-converting enzyme (ACE), apolipoprotein-E (ApoE), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) are associated with AKI. METHODS: 870 patients who underwent cardiac surgery in Singapore were analysed. All patients who fulfilled stage 1 KDIGO criteria and above were considered to have AKI. This was investigated against various demographic, clinical and genetic factors. RESULTS: Increased age, history of hypertension, anaemia and renal impairment remained important preoperative risk factors for AKI. Intraoperatively, longer cardiopulmonary bypass (CPB) time and the use of intra-aortic balloon pump (IABP) were shown to be associated with AKI. Among the genetic factors, ACE-D allele was associated with an increased risk of AKI while IL6-572C allele was associated with a decreased risk of AKI. CONCLUSION: ACE-D allele was associated with the development of AKI similar to other studies. On the other hand, IL6-572C was shown to have a protective role against the development of AKI, contradictory to studies done in the Caucasian population. This contradictory effect of IL6-572C is a result of a complex interplay between the gene and population specific modulating factors. Our findings further underscored the necessity of taking into account population specific differences when developing prediction models for AKI.

Epidemiological characteristics of molecular transmission cluster among reported HIV/AIDS cases in Jiaxing city, Zhejiang province, 2017 / 中华流行病学杂志

Objective To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city,Zhejiang province,2017 in order to select those people under high-risk and providing basis for programs on prevention.Methods During 2017,newly diagnosed HIV/AIDS cases in this city were recruited.Plasma samples were collected from subjects,followed by RNA extraction,RT-PCR and nest-PCR for pol gene amplification,before being sequenced and aligned.Mega 6.0 software was used to construct phylogenetic tree,and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters.Cases within the large transmission clusters were investigated,using a field-epidemiology-questionnaire.Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used.Results In the large transmission cluster with subtype identified as CRF07_BC,in Jiaxing,2017,26 cases of the total 30 cases were investigated.A total of 80.8％ (21/26) could be identified as newly infected within the last two years and 30.8％(8/26) could be identified as newly infected within the last one year,including 22 cases infected locally.Among several infected cases who were at age 45 years or older,they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues.Conclusions This molecular cluster had been formed and scaled up quickly in recent two years,it has played an important role in promoting and scaling up the HIV transmission.Three cases identificed as high risk played an importantrde role in scaling up this cluster.

Epidemiological characteristics of molecular transmission cluster among reported HIV/AIDS cases in Jiaxing city, Zhejiang province, 2017 / 中华流行病学杂志

Objective To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city,Zhejiang province,2017 in order to select those people under high-risk and providing basis for programs on prevention.Methods During 2017,newly diagnosed HIV/AIDS cases in this city were recruited.Plasma samples were collected from subjects,followed by RNA extraction,RT-PCR and nest-PCR for pol gene amplification,before being sequenced and aligned.Mega 6.0 software was used to construct phylogenetic tree,and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters.Cases within the large transmission clusters were investigated,using a field-epidemiology-questionnaire.Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used.Results In the large transmission cluster with subtype identified as CRF07_BC,in Jiaxing,2017,26 cases of the total 30 cases were investigated.A total of 80.8％ (21/26) could be identified as newly infected within the last two years and 30.8％(8/26) could be identified as newly infected within the last one year,including 22 cases infected locally.Among several infected cases who were at age 45 years or older,they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues.Conclusions This molecular cluster had been formed and scaled up quickly in recent two years,it has played an important role in promoting and scaling up the HIV transmission.Three cases identificed as high risk played an importantrde role in scaling up this cluster.

Correlation Analysis Between HPLC Fingerprint and Anti-inflammatory Activity of Speranskiae Tuberculatae Herba / 中国实验方剂学杂志

Objective: The aim of this study was to investigate high performance liquid chromatography (HPLC) fingerprint,anti-inflammatory activity as well as the correlation between them in Speranskiae Tuberculatae Herba. Method: Fingerprint by HPLC was established on Speranskiae Tuberculatae Herba from different sources. The common peaks were evaluated on the basis of similarity evaluation together with hierarchical cluster analysis (HCA) and principal component analysis (PCA). Ear swelling induced by xylene in mice model was used to study the anti-inflammatory activity. Grey relational analysis (GRA) and partial least square regression analysis (PLSR) were used to study the relationship between the HPLC fingerprint and the anti-inflammatory activity. Result: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established and 24 common peaks were determined,with the similarity above 0.907 (except for S2 and S5). Four peaks were identified by comparing to reference substances. The result of HCA showed that Speranskiae Tuberculatae Herba from different sources were clustered into four categories,in consistent with the result of PCA. Combined with discriminant analysis of partial least squares discrimination analysis (PLS-DA),three signature compounds represented by 5,6,7 peaks were responsible for the differences between groups. Different sources of Speranskiae Tuberculatae Herba differed in anti-inflammatory activity. The sectrum-activity relationship showed that the peaks 1,4,5,6,and 10 were positively correlated with the anti-inflammatory activity. Conclusion: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established,and 5 components closely related to the anti-inflammatory activity were determined. The present study provide more comprehensive reference for quality control of the Speranskiae Tuberculatae Herba.

Label-Free Alignment of Nonmagnetic Particles in a Small Uniform Magnetic Field.

Label-free manipulation of biological entities can minimize damage, increase viability and improve efficiency of subsequent analysis. Understanding the mechanism of interaction between magnetic and nonmagnetic particles in an inverse ferrofluid can provide a mechanism of label-free manipulation of such entities in a uniform magnetic field. The magnetic force, induced by relative magnetic susceptibility difference between nonmagnetic particles and surrounding magnetic particles as well as particle-particle interaction were studied. Label-free alignment of nonmagnetic particles can be achieved by higher magnetic field strength (Ba), smaller particle spacing (R), larger particle size (rp1), and higher relative magnetic permeability difference between particle and the surrounding fluid (Rµr). Rµr can be used to predict the direction of the magnetic force between both magnetic and nonmagnetic particles. A sandwich structure, containing alternate layers of magnetic and nonmagnetic particle chains, was studied. This work can be used for manipulation of nonmagnetic particles in lab-on-a-chip applications.

Inhibitory effect of compound W3D on LPS-induced release of inflammatory mediators of RAW264.7 cells through TLR4-MyD88-NF-κB signaling pathway / 中国药理学通报

Aim To investigate the effect of the novel benzoxazolone derivative 4-( 5′-dimethylamino )-naph-thalenesulfonyl-2 ( 3H )-benzoxazolone ( W3D ) on TLR4-MyD88-NF-κB signaling pathway in LPS-in-duced RAW264.7 cells. Methods The cell viability was detected by MTT assay, and the contents of TNF-α, IL-6, IL-1β and COX-2 in the cell supernatant were analyzed using ELISA methods. The protein ex-pression of IL-6, TLR4, MyD88, p-IRAK4 and NF-κB were investigated by western blot analysis, and the mRNA expressions of TLR4, MyD88 and IL-6 were an-alyzed by RT-PCR. Results W3D could obviously in-hibit the production of TNF-α, IL-6 and IL-1β in LPS- induced RAW264.7 cell supernatant, but it had no effect on the release of COX-2. Compared with the model group, the expressions of TLR4, MyD88 and IL-6 were decreased significantly in a dose dependent manner. Meanwhile, the expressions of p-IRAK4 and nucleus of NF-κB were decrease in W3D treated group compared with the model group. Conclusion The no-vel compound W3D could inhibit the release of the in-flammatory mediators through the regulation of TLR4-MyD88-NF-κB signaling pathway.

Analysis of transcriptional factors expression profile during dedifferentiation of liver cell cultured in vitro / 生物工程学报

Primary hepatocytes are widely used in drug metabolism and toxicity assessment. As the culture of primary hepatocytes in vitro is a process of dedifferentiation, hepatocytes lose normal metabolic detoxification function gradually. The mechanism of hepatocyte dedifferentiation has been not clear so far. TFs play an important role in the dedifferentiation and non-parenchymal cells can maintain the function of hepatocytes in vitro. However, the current methods cannot be used in effective identification and quantitative analysis of a large number of TFs. In this paper, the mo-culture system (only primary hepatocytes) and co-culture system (primary hepatocytes and non-parenchymal cells) were established. The cells were cultured for 24 h, 48 h, 72 h as monolayer. The changes of TFs during the culture were obtained by TOT (Transcription factor response elements on tip) transcription factor enrichment method and mass spectrometry. A total of 219 TFs were identified in three individual replicates. The result revealed that up-regulated TFs were enriched in cell proliferation, death and immune response pathways, and down-regulated TFs were involved in metabolism pathway. The establishment of such culture-TFs identification system is of great significance to reveal the mechanism of primary hepatocyte dedifferentiation and crosstalk between hepatocytes and non-parenchymal cells.