Sepsis is a systemic inflammatory response syndrome in which the host response to infection is dysregulated, leading to circulatory dysfunction and multi-organ damage. It has a high mortality rate and its incidence is increasing year by year, posing a serious threat to human life and health. Mesenchymal stem cells (MSC) have the following properties: hematopoietic support, provision of nutrients, activation of endogenous stem/progenitor cells, repair of tissue damage, elimination of inflammation, immunomodulation, promotion of neovascularization, chemotaxis and migration, anti-apoptosis, anti-oxidation, anti-fibrosis, homing, and many other effects. A large number of studies have confirmed that MSC from different sources have their own characteristics. This article reviews the pathogenesis of sepsis, the biological properties of MSC, and the advantages and disadvantages of different sources of MSC for the treatment of sepsis and their characteristics. dysregulated multiorgan multi organ damage health (MSC support nutrients stemprogenitor progenitor inflammation immunomodulation neovascularization migration antiapoptosis, antiapoptosis anti apoptosis, apoptosis anti-apoptosis antioxidation, antioxidation oxidation, oxidation anti-oxidation antifibrosis, antifibrosis fibrosis, fibrosis anti-fibrosis homing effects characteristics

Abstract Objective: This trial aimed to identify the Minimum Effective Concentration (MEC90, defined as the concentration which can provide successful block in 90% of patients) of 30 mL ropivacaine for single-shot ultrasound-guided transmuscular Quadratus Lumborum Block (QLB) in patients undergoing Total Hip Arthroplasty (THA). Methods: A double-blind, randomized dose-finding study using the biased coin design up-and-down sequential method, where the concentration of local anesthetic administered to each patient depended on the response from the previous one. Block success was defined as a Numeric Rating Scale (NRS) score during motion ≤ 3 at 6 hours after arrival in the ward. If the block was successful, the next subject received either a 0.025% smaller dose (probability of 0.11) or the same dose (probability of 0.89); otherwise, the next subject received a 0.025% higher ropivacaine concentration. MEC90, MEC95 and MEC99 were estimated by isotonic regression, and the corresponding 95% Confidence Intervals (95% CIs) were calculated by the bootstrapping method. Results: Based on the analysis of 52 patients, MEC90, MEC95, and MEC99 of ropivacaine for QLB were estimated to be 0.352% (95% CI 0.334–0.372%), 0.363% (95% CI 0.351–0.383%), and 0.373% (95% CI 0.363–0.386%). The concentration of ropivacaine at 0.352% in a volume of 30 ml can provide a successful block in 90% of patients. Conclusions: For ultrasound-guided transmuscular QLB in patients undergoing THA, 0.352% ropivacaine in a volume of 30 ml can provide a successful block in 90% of patients. Further dose-finding studies and large sample size are required to verify the concentration. Objective MEC90 MEC (MEC90 90 singleshot single shot ultrasoundguided ultrasound guided (QLB THA. THA . (THA) Methods doubleblind, doubleblind double blind, blind double-blind dosefinding finding upanddown up down method one NRS (NRS ward 0025 0 025 0.025 probability 0.11 011 11 0.89 089 89 0.89) otherwise MEC9 regression 95 (95 CIs Results 5 0352 352 0.352 0.334–0.372%, 03340372 0.334–0.372% , 334 372 0.334–0.372%) 0363 363 0.363 0.351–0.383%, 03510383 0.351–0.383% 351 383 0.351–0.383%) 0373 373 0.373 0.363–0.386%. 03630386 0.363–0.386% 386 0.363–0.386%) Conclusions (MEC9 9 (THA 002 02 0.02 0.1 01 1 0.8 08 8 (9 035 35 0.35 0334037 0.334–0.372 33 37 036 36 0.36 0351038 0.351–0.383 38 037 0.37 0363038 0.363–0.386 (MEC 00 0.0 0. ( 03 0.3 033403 0.334–0.37 035103 0.351–0.38 036303 0.363–0.38 03340 0.334–0.3 03510 0.351–0.3 03630 0.363–0.3 0334 0.334–0. 0351 0.351–0. 0.363–0. 033 0.334–0 0.351–0 0.363–0 0.334– 0.351– 0.363– 0.334 0.351 0.33

Abstract Introduction Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. Method This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. Results Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. Discussion The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections. yeast systems 4 continents indepth depth WholeGenome Whole fluconazoleresistant resistant C CA (CA01 patients patient s Beijing CA0 I (I BJCA BJCA00 BJCA002 Notably AT A T ERG ERG1 gene binds affinity Additionally RBF1 RBF I. . China level infections (CA0 BJCA0 (CA

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5’end or 3’end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5’ end or 3’ end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications. Introduction aging (TL trait disease (TERC operation elderly Methods leukocytes (BIS analyses 5end 5 3end 3 detected 10 surgery Results r 078 0 78 0.78 0.001, 0001 0.001 , 001 0.001) 084 84 0.84 0.004, 0004 0.004 004 0.004) 083 83 0.83 085 85 0.85 0.029. 0029 0.029 . 029 0.029) 0.58, 058 58 (0.58 021 21 0.21 019 19 0.19 0.12 012 12 variables However Conclusions complications 1 07 7 0.7 000 0.00 00 08 8 0.8 002 0.02 02 0.58 05 (0.5 2 0.2 01 0.1 0. 0.0 0.5 (0. (0 (

Abstract To investigate the safety and efficacy of intraoperative intraperitoneal chemotherapy in treating advanced gastric cancer. A randomized controlled trial (RCT) of gastric cancer surgery combined with intraoperative intraperitoneal chemotherapy for the efficacy and safety were screened by computer search PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang and China National Knowledge Infrastructure (CNKI) with the last report up to October 2019. The control group underwent radical gastrectomy, and the experimental group underwent intraoperative intraperitoneal chemotherapy and radical gastrectomy. A total of 997 (Experimental group 453; Control group 544) participants were considered in this meta-analysis. Compared with the control group, the experimental group has higher 1-year survival rate [OR=2.40, 95%CI (1.34, 4.33), P=0.003], 2-year survival rate [OR=3.45, 95%CI (2.08, 5.75), P<0.00001], 3-year survival rate [OR=2.70, 95%CI (2.05, 3.54), P<0.00001] and 5-year survival rate [OR=2.90, 95%CI (1.93, 4.37), P<0.00001]. There is no significant difference in postoperative bleeding (P=0.95), postoperative infection (P=0.26), postoperative anastomotic leakage (P=0.41), and postoperative intestinal obstruction (P=0.11). Intraoperative intraperitoneal chemotherapy with advanced gastric cancer in the Chinese population can improve patients’ survival rate after surgery and does not increase the incidence of postoperative complications, so it is clinically significant and safe.

Abstract The present study aimed to investigate the anti-inflammatory effects of Baicalein on human osteoarthritic chondrocytes and its molecular mechanisms, and to explore the related molecular events that may occur. The extracted human osteoarthritic chondrocytes were stimulated with interleukins. After administered with different concentrations of Baicalein, the survival rate of chondrocytes was observed. Apoptosis was detected by apoptosis assay kit. The effect on NO production was detected using the Griess reagent kit. The expressions of IL-6 and PGE2 were detected by ELISA. The apoptotic proteins and PI3/Akt, NF-kB and MAPK cascade proteins were detected by WB assay. Baicalein significantly increased the survival rate of chondrocytes and decreased the expressions of NO, IL-6 and PGE2. The expressions of COX-2 and induced iNOS were significantly reduced in a dose-dependent manner under the administration of Baicalein. In addition, Baicalein significantly reduced the NF-κB signaling pathway, inhibited the activation of the induced PI3/Akt, JNK, ERK and p38 MAPK cascades. Inflammatory mediators play a key role in the pathogenesis of osteoarthritis. Baicalin significantly inhibits the expression of inflammatory mediators in chondrocytes of human osteoarthritis and regulates the JNK/ERK/p38 MAPK and PBK/Akt signaling cascades. The experiment evaluated the anti-inflammatory and anti-osteomyelitis effects of Baicalein in order to discover new treatment strategies.

Abstract Paeonia ostii is the representative of oil-utilized peony, its roots (PR) and leaves (PL) are discarded as by-products, resulting in a waste of resources. The exploration of extraction process of active ingredients from PR/PL is beneficial to the comprehensive utilization. In this work, the optimum process of Ultrasound-Assisted Extraction (UAEo) of total flavonoids content (TFC) from PR and PL was determined by single factor and response surface methodology. The results showed that UAEo was 80 min, 1:5 g/mL, 250 W, 33.83 mg Rutin/g dw for PR and 60 min, 1:10 g/mL, 250 W, 25.85 mg Rutin/g dw for PL. Then, Homogenization-Assisted Extraction (HAE), Homogenization-Ultrasound-Assisted Extraction (HUAEo) and Ultrasound-Homogenization-Assisted Extraction (UHAEo) were further analyzed. The highest PR(PL)-TFC by HUAEo at homogenization 5 min was 49.58 ± 0.25 mg/g with an increase of 46.6% (33.02 ± 0.04 mg/g with an increase of 27.7%). The highest PR/PL-total phenolic content by the HUAEo reached 77.84 ± 0.52 mg/g dw and 146.62 ± 2.77 mg/g dw for homogenization 3 min. However, there was no significant difference between HUAEo and UHAEo. In conclusion, the TFC increased with the extension of HAE time, and the combined extraction was higher yield than the single extraction.

RESUMO A Ciência Forense Digital surgiu da necessidade de tratar problemas forenses na era digital. Seu mais recente desafio está relacionado ao surgimento das mídias sociais, intensificado pelos avanços da Inteligência Artificial. A produção massiva de dados nas mídias sociais tornou a análise forense mais complexa, especialmente pelo aperfeiçoamento de modelos computacionais capazes de gerar conteúdo artificial com alto realismo. Assim, tem-se a necessidade da aplicação de técnicas de Inteligência Artificial para tratar esse imenso volume de informação. Neste artigo, apresentamos desafios e oportunidades associados à aplicação dessas técnicas, além de fornecer exemplos de seu uso em situações reais. Discutimos os problemas que surgem em contextos sensíveis e como a comunidade científica tem abordado esses tópicos. Por fim, delineamos futuros caminhos de pesquisa a serem explorados.

ABSTRACT Digital Forensics emerged from the need to perform forensic tasks in the digital age. Its most recent challenges are related to the popularization of social media and were intensified by the advance of Artificial Intelligence. The generation of massive social media data made forensic analyses more complex, mainly due to improvements in computational models able to artificially create highly realistic content. Because of this, Artificial Intelligence techniques have been studied and used to process the massive volume of information. This paper discusses the challenges and opportunities associated with such methods and provides real case examples, as well as the problems that arise when using these approaches in sensitive contexts and how the scientific community has approached these topics. Finally, it draws future research paths to be explored.

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

ABSTRACT Purpose To investigate the effect of ischemic postconditioning (IPostC) on skeletal muscle and its optimal protocol. Methods This article is about an animal study of rat model of crush syndrome. Sixty rats were randomized into nine different IPostC intervention groups and a control group. The anesthetized rats were subjected to unilateral hindlimb 3-kg compression with a compression device for 6 h, followed by nine different IPostC intervention protocols. Results Serum levels of creatine kinase (CK) at 3 h post-crush became 2.3-3.9 times among all 10 groups after crush. At 72 h post-crush, serum CK level was reduced to 0.28-0.53 time in all intervention groups. The creatinine (CREA) level in the control group was elevated to 3.11 times at 3 h post-crush and reduced to1.77 time at 72 h post-crush. The potassium (K+) level in the control group was elevated to 1.65 and 1.41 time at 3 and 72 h post-crush, respectively. Conclusions Our IPostC intervention protocols can effectively protect rats from crush-induced elevation of serum CK, CREA, and K+ levels. The timing of IPostC intervention should be as early as possible, to ensure the protective effect.

Abstract Dried unripe raspberries (Rubus chingii), a kind of Chinese herbal medicine, have been used for many years in China. They were prepared as unpurified raspberry extract (URE) by ethanol extraction, and purified raspberry extract (PRE) by macroporous resin. Synergistic effects between the URE (or the PRE) and ampicillin, erythromycin, tetracycline or streptomycin against Escherichia coli, Staphylococcus aureus and Salmonella enterica were carried out using checkerboard microdilution and time-kill curves, respectively. The results showed that all pairwise combinations revealed synergistic effects, with 0.10 ≤ fractional inhibitory concentration index ≤ 0.50 and more than 2 × log10 reduction in colony-forming units/mL. In particular, the erythromycin concentration in the combinations was reduced to 1/50-1/100 of its dose alone while retaining its effectiveness against S. aureus and E. coli. The synergistic effects of raspberry extracts and four antibiotics against three bacteria were related to the abundance of polyphenols in the extracts, especially ellagic acid. The extracts may be a dietary supplement and/or natural antimicrobials.

RESUMO O nitrogênio (N) afeta fortemente o crescimento das plantas. No entanto, pouco se sabe sobre os efeitos da relação amônio/nitrato no pakchoi (Brassica rapa), especialmente no conteúdo de glucosinolatos (GSs) envolvidos na defesa das plantas e muitos deles benéficos à saúde humana. O objetivo deste estudo foi avaliar os efeitos de um suprimento constante de N (8 mM), mas com cinco proporções de amônio/nitrato (ou seja, 0/8 mM, 2/6 mM, 4/4 mM, 6/2 mM e 8/0 mM) sobre o crescimento de pakchoi em um sistema hidropônico em 2 anos. Nos dois anos, uma maior biomassa (peso seco) foi observada nos tratamentos 4/4 e 2/6 de amônio/nitrato (2,3 e 2,2 vezes em comparação com 8/0, respectivamente), sem diferença significativa na biomassa entre esses dois tratamentos. A biomassa então diminuiu com proporções crescentes de amônio no suprimento de N de mais de 10 g/vaso para menos de 5 g/vaso. Os teores de N e enxofre foram fortemente afetados nos tratamentos com nitrato ou amônio, assim como os teores de clorofila, luteína e β-caroteno. A maioria dos glucosinolatos individuais (GSs) detectados no pakchoi apresentou as maiores concentrações no tratamento com apenas amônio. A relação amônio/nitrato também afetou os tipos de GSs. A maior proporção de indolil GSs e a menor proporção de GSs aromático estavam no tratamento com apenas amônio. Concluímos que um alto nível de amônio diminui a biomassa, mas aumenta as concentrações de GSs no pakchoi. Estudos adicionais são necessários para explorar a diferença no metabolismo dos GSs entre plantas fornecidas com diferentes proporções de amônio/nitrato.

ABSTRACT Nitrogen (N) strongly affects plant growth. However, little is known about the effects of the ammonium/nitrate ratio on pakchoi (Brassica rapa), especially its glucosinolates (GSs) contents which are involved in plant defense and many of them benefit to human health. The aim of this study was to evaluate the effects of a constant N supply (8 mM) but with five ammonium/nitrate ratios (namely 0/8 mM, 2/6 mM, 4/4 mM, 6/2 mM and 8/0 mM) on the growth of pakchoi in a hydroponic system in 2 years. In both years, a higher biomass (dry weight) was in the 4/4 and 2/6 ammonium/nitrate treatments (2.3 and 2.2-fold compared to 8/0, respectively), with no significant difference in biomass between these two treatments. The biomass then decreased with increasing proportions of ammonium in the N supply from more than 10 g/pot to below 5 g/pot. The N and sulfur contents were strongly affected in the sole nitrate or ammonium treatments, as were the contents of chlorophyll, lutein, and β-carotene. Most of the individual glucosinolates (GSs) detected in pakchoi showed the highest concentrations in the sole ammonium treatment. The ammonium/nitrate ratio also affected the types of GSs. The highest proportion of indolyl GSs and the lowest proportion of aromatic GSs were in the sole ammonium treatment. We concluded that a high ammonium level decreases the biomass but increases the GSs concentrations in pakchoi. Further studies are required to explore the difference in GSs metabolism among plants supplied with different ammonium/nitrate ratios.

The novel coronavirus pneumonia (NCP) outbreak occurred in Wuhan, China at the end of 2019. Here, we report the clinical characteristics and therapeutic procedure for a case of severe NCP. The patient was started on glucocorticoids and non-invasive ventilator treatment. After treatment, the patient’s symptoms improved, and the status was confirmed as NCP negative. Our results may provide clues for the treatment of NCP.

Abstract Twelve typical polyphenols in raspberry leaf powder (RLP), raspberry leaf extract 1 (RLE) and raspberry leaf extract 2 (RLE-H) were analyzed by HPLC-MS. The sum of their contents in three samples were in the following order: RLP (8.6 mg g-1) < RLE (35.0 mg g-1) < RLE-H (44.1 mg g-1). Ellagic acid and quercetin-3-O-glucuronide were the principal compounds in the samples and accounted for more than 75% of the sum content. A gelled mixture of RLE, pectin, and sodium alginate administrated to mice via gavage resulted in reduced weight gain and adiposity percentage, increased teste percentage, prolonged exhaustion time, furthermore alleviated intestinal flatulence possibly induced by RLE or RLE-H alone. These results could help in making rational use of this high polyphenol extract from raspberry leaves.

Abstract The novel coronavirus pneumonia (NCP) outbreak occurred in Wuhan, China at the end of 2019. Here, we report the clinical characteristics and therapeutic procedure for a case of severe NCP. The patient was started on glucocorticoids and non-invasive ventilator treatment. After treatment, the patient’s symptoms improved, and the status was confirmed as NCP negative. Our results may provide clues for the treatment of NCP.