Association between mechanical power during one-lung ventilation and pulmonary complications after thoracoscopic lung resection surgery: a prospective observational study.

BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.

Ginkgo biloba L. exocarp petroleum ether extract inhibits methicillin-resistant Staphylococcus aureus by modulating ion transport, virulence, and biofilm formation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.

Responses of soil nematode abundance and food web to cover crops in a kiwifruit orchard.

Soil biodiversity plays an important role in both agricultural productivity and ecosystem functions. Cover crop species influence the primary productivity of the ecosystem and basal resources. However, it remains poorly understood how different cover crop treatments influence the community of soil nematodes in an orchard ecosystem. In this study, field experiments were conducted to investigate the effects of cover crop treatments with different species numbers, i.e., no cover crop (CK), two cover crop species (C2), four cover crop species (C4), and eight cover crop species (C8), on weed biomass, together with composition, abundance, and metabolic footprint of soil nematode community in a kiwifruit orchard. As compared to the CK group, the groups of cover crop treatments had lower weed biomass, which decreased with the increase of the cover crop diversity. Moreover, for the abundance of total nematodes, fungivores exhibited higher levels in C4 and C8 treatments than that in CK, bacterivores had a higher abundance in C4 treatment, and plant parasites had a higher abundance in C2 and C8 treatments. Cover crop treatments also changed the structure of nematode community and enhanced the nematode interactions and complexity of nematode community network. In addition, C4 increased the Wasilewska index but decreased the plant-parasite index. The metabolic footprints of fungivores were higher in cover crop treatments compared with CK, and C4 and C8 also increased the functional metabolic footprint of nematode. Soil nematode faunal analysis based on nematode metabolic footprints showed that C8 improved the soil nutrient status and food wed stability. Mantel test and redundancy analysis showed that soil microbial biomass nitrogen and carbon, organic carbon, nitrate nitrogen, moisture content, pH, and cover crop biomass were the main factors that affect soil nematode community. In conclusion, cover crop treatments with four or eight plant species displayed a positive role in weed control, improvement of soil health, and promotion of energy flow in the soil food web through the increase in the metabolic footprints of nematodes in kiwifruit orchard.

[Determination of four aflatoxins in feeds by high throughput automated immunoaffinity magnetic beads purification-ultra performance liquid chromatography].

Aflatoxin (AFT) is an extremely toxic and highly toxic carcinogenic substance. This is particularly problematic due to the risk of aflatoxin contamination in raw feed materials and products during production, transportation, and storage. In this study, immunoaffinity magnetic beads (IMBs) were prepared for the purification of four aflatoxins (aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2)). The aflatoxin contents were then determined rapidly and accurately using ultra performance liquid chromatography (UPLC). More specifically, the coupling ratio of magnetic beads (MBs) to the aflatoxin monoclonal antibody was initially optimized, wherein an MB volume of 1 mL and an antibody content of 2.0 mg was found to meet the purification requirements of this method. The magnetic properties of the MBs and the IMBs were then investigated using a vibrating sample magnetometer (VSM) at room temperature. As a result, the maximum saturation super magnetizations of the MBs and the IMBs were determined to be 28.61 and 23.22 emu/g, respectively, indicating that the saturation magnetization intensity of the IMBs was reduced by coupling with a non-magnetic antibody. However, the saturation magnetization intensity remained sufficiently high to permit magnetic separation from the solution. In addition, the appearance of the IMBs was examined using a biomicroscope, and it was clear that the magnetic cores were wrapped in agarose gel. Furthermore, the reaction time between the IMBs and the aflatoxins was investigated, and the optimal reaction time for meeting the purification requirements was determined to be 2 min. The stability of the IMBs was then evaluated under refrigerated storage conditions at 4 ℃. It was found that the prepared IMBs maintained a high aflatoxin enrichment capacity for at least eight months. Through the examination of three different extraction solutions, a mixture of acetonitrile and water (70∶30, v/v) was found to be optimal for the extraction of aflatoxins from the feed samples. Moreover, five sample dilutions and purification effects were also examined, and phosphate-buffered saline (containing 0.5% Tween-20) was selected as the preferred sample dilutant. With the optimized conditions, the effectiveness of using IMB for the purification of different feed samples was investigated. The resulting UPLC chromatogram showed no spurious peaks close to the target peaks, demonstrating a good purification performance. Following matrix spiking (5, 20, and 40 µg/kg, calculated based on AFB1) of the four feed samples (i. e., soybean meal, distillers dried grains with solubles, pig feed, and chicken feed), the spiked recoveries of the four aflatoxins ranged from 91.1% to 119.4% with a relative standard deviation (RSD) of <6.9%. In addition, the inter-day precision was 4.5% to 7.5%, and the method exhibited a good reproducibility. Subsequently, the developed method was used to detect AFB1 using reference materials. The test value was 18.6 µg/kg with an accuracy of 110.3%, thereby constituting satisfactory results. Upon testing 21 randomly purchased feed samples using this method, four of these samples contained AFB1, and the test results obtained using the developed method and stable isotope dilution LC-MS/MS were comparable. It was therefore apparent that the IMB purification method combined with UPLC analysis exhibited a good accuracy for aflatoxin determination. Thus, an automatic purification system was established to facilitate the operation and use of IMBs. This system was able to purify 24 samples simultaneously in 30 min. An IMB purification kit for was also designed and produced for aflatoxin detection in feed samples. The kit contained the sample dilutant, IMBs, the washing solution, and the eluent. After extraction of the feed sample, the extraction solution was added to the sample wells provided in the kit, and the purification system automatically completed the steps of aflatoxin enrichment, impurity washing, and elution of the target toxin. It should be noted that the purification process does not require the operator to manually add the solution, thereby simplifying operation. Overall, the purification method established in this study achieved the high-throughput and automatic purification of the four aflatoxins in feed samples.

Covalent immobilization of tyrosinase on magnetic multi-walled carbon nanotubes for inhibitor screening.

The inhibition of tyrosinase is considered to be a common therapeutic strategy for some hyperpigmentation disorders. Screening of tyrosinase inhibitors is of great significance to the treatment of pigmentation diseases. In this study, tyrosinase was covalently immobilized on magnetic multi-walled carbon nanotubes for the first time, and the immobilized tyrosinase was applied for ligand fishing of tyrosinase inhibitors from complex medicinal plants. The immobilized tyrosinase was characterized by transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, and thermo-gravimetric analyzer, which indicated that tyrosinase was immobilized onto magnetic multi-walled carbon nanotubes. The immobilized tyrosinase showed better thermal stability and reusability than the free one. The ligand was fished out from Radix Paeoniae Alba and identified as 1,2,3,4,6-pentagalloylglucose by ultra-performance liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. 1,2,3,4,6-pentagalloylglucose was found to be a tyrosinase inhibitor with similar half maximal inhibitory concentration values of 57.13 ± 0.91 µM compared to kojic acid (41.96 ± 0.78 µM). This work not only established a new method for screening tyrosinase inhibitors but also holds considerable potential for exploring the new medicinal value of medicinal plants.

Combined impacts of environmental and socioeconomic covariates on HFMD risk in China: A spatiotemporal heterogeneous perspective.

BACKGROUND: Understanding geospatial impacts of multi-sourced influencing factors on the epidemic of hand-foot-and-mouth disease (HFMD) is of great significance for formulating disease control policies tailored to regional-specific needs, yet the knowledge is very limited. We aim to identify and further quantify the spatiotemporal heterogeneous effects of environmental and socioeconomic factors on HFMD dynamics. METHODS: We collected monthly province-level HFMD incidence and related environmental and socioeconomic data in China during 2009-2018. Hierarchical Bayesian models were constructed to investigate the spatiotemporal relationships between regional HFMD and various covariates: linear and nonlinear effects for environmental covariates, and linear effects for socioeconomic covariates. RESULTS: The spatiotemporal distribution of HFMD cases was highly heterogeneous, indicated by the Lorenz curves and the corresponding Gini indices. The peak time (R2 = 0.65, P = 0.009), annual amplitude (R2 = 0.94, P<0.001), and semi-annual periodicity contribution (R2 = 0.88, P<0.001) displayed marked latitudinal gradients in Central China region. The most likely cluster areas for HFMD were located in south China (Guangdong, Guangxi, Hunan, Hainan) from April 2013 to October 2017. The Bayesian models achieved the best predictive performance (R2 = 0.87, P<0.001). We found significant nonlinear associations between monthly average temperature, relative humidity, normalized difference vegetation index and HFMD transmission. Besides, population density (RR = 1.261; 95%CI, 1.169-1.353), birth rate (RR = 1.058; 95%CI, 1.025-1.090), real GDP per capita (RR = 1.163; 95%CI, 1.033-1.310) and school vacation (RR = 0.507; 95%CI, 0.459-0.559) were identified to have positive or negative effects on HFMD respectively. Our model could successfully predict months with HFMD outbreaks versus non-outbreaks in provinces of China from Jan 2009 to Dec 2018. CONCLUSIONS: Our study highlights the importance of refined spatial and temporal data, as well as environmental and socioeconomic information, on HFMD transmission dynamics. The spatiotemporal analysis framework may provide insights into adjusting regional interventions to local conditions and temporal variations in broader natural and social sciences.

Postoperative pulmonary complications after sugammadex reversal of neuromuscular blockade: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Sugammadex has been reported to lower the incidence of postoperative residual neuromuscular blockade. Despite the advantages, until recently the effects of sugammadex on postoperative pulmonary complications (PPCs) were controversial. We conducted a systematic review and meta-analysis to determine whether reversal with sugammadex was associated with a lower risk of PPCs compared with neostigmine. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to May 2022. Randomized controlled trials (RCTs) and observational studies comparing PPCs in patients receiving sugammadex or neostigmine as reversal agent at the end of surgery were included. The primary outcomes focused on PPCs including desaturation, pneumonia, atelectasis, noninvasive ventilation (NIV) and reintubation. Trial sequential analysis was performed on the primary outcomes to confirm whether firm evidence was reached. RESULTS: Meta-analysis of included studies showed that the rate of desaturation (43.2% vs 45.0%, RR = 0.82; 95% CI 0.63 to 1.05; p = 0.11) were comparable between the two groups. When looking at other primary outcomes, significantly lower risk of pneumonia (1.37% vs 2.45%, RR = 0.65; 95% CI 0.49 to 0.85; p = 0.002), atelectasis (24.6% vs 30.4%, RR = 0.64; 95% CI 0.42 to 0.98; p = 0.04), NIV (1.37% vs 2.33%, RR = 0.65; 95% CI 0.43 to 0.98; p = 0.04) and reintubation (0.99% vs 1.65%, RR = 0.62; 95% CI 0.43 to 0.91; p = 0.01) in the sugammadex group were detected compared with the neostigmine group. CONCLUSIONS: We concluded that sugammadex is more effective at reducing the incidence of PPCs including pneumonia, atelectasis, NIV and reintubation compared with neostigmine. Further evidence, preferably from RCTs, is required to confirm these findings.

NKHs27, a sevenband grouper NK-Lysin peptide that possesses immunoregulatory and antimicrobial activity.

As an effective and broad-spectrum antimicrobial peptide, NK-Lysin is attracted more and more attention at present. However, the functions and action mechanism of NK-Lysin peptides are still not comprehensive enough at present. In this study, a sevenband grouper (Hyporthodus septemfasciatus) NK-Lysin peptide, NKHs27, was identified and synthesized, and its biological functions were studied. The results indicated that NKHs27 shares 44.44%∼88.89% overall sequence identities with other teleost NK-Lysin peptides. The following antibacterial activity assay exhibited that NKHs27 was active against both Gram-negative and Gram-positive bacteria, including Staphylococcus aureus, Listonella anguillarum, Vibrio parahaemolyticus and Vibrio vulnificus. Additionally, NKHs27 showed a synergistic effect when it was combined with rifampicin or erythromycin. In the process of interaction with the L. anguillarum cells, NKHs27 changed the cell membrane permeability and retained its morphological integrity, then penetrated into the cytoplasm to act on genomic DNA or total RNA. Then, in vitro studies showed that NKHs27 could enhance the respiratory burst ability of macrophages and upregulate immune-related genes expression in it. Moreover, NKHs27 incubation improved the proliferation of peripheral blood leukocytes significantly. Finally, in vivo studies showed that administration of NKHs27 prior to bacterial infection significantly reduced pathogen dissemination and replication in tissues. In summary, these results provide new insights into the function of NK-Lysin peptides in teleost and support that NKHs27, as a novel broad-spectrum antibacterial peptide, has potential applications in aquaculture against pathogenic infections.

Interactions between the gut micro-community and transcriptome of Culex pipiens pallens under low-temperature stress.

BACKGROUND: Culex pipiens pallens (Diptera: Culicidae) can survive at low temperature for long periods. Understanding the effects of low-temperature stress on the gut microflora and gene expression levels in Cx. pipiens pallens, as well as their correlation, will contribute to the study of the overwintering mechanism of Cx. pipiens pallens. METHODS: The gut bacteria were removed by antibiotic treatment, and the survival of Cx. pipiens pallens under low-temperature stress was observed and compared with the control group. Then, full-length 16S rRNA sequencing and the Illumina HiSeq X Ten sequencing platform were used to evaluate the gut microflora and gene expression levels in Cx. pipiens pallens under low-temperature stress. RESULTS: Under the low-temperature stress of 7 °C, the median survival time of Cx. pipiens pallens in the antibiotic treatment group was significantly shortened by approximately 70% compared to that in the control group. The species diversity index (Shannon, Simpson, Ace, Chao1) of Cx. pipiens pallens decreased under low-temperature stress (7 °C). Non-metric multidimensional scaling (NMDS) analysis divided all the gut samples into two groups: control group and treatment group. Pseudomonas was the dominant taxon identified in the control group, followed by Elizabethkingia and Dyadobacter; in the treatment group, Pseudomonas was the dominant taxon, followed by Aeromonas and Comamonas. Of the 2417 differentially expressed genes (DEGs), 1316 were upregulated, and 1101 were downregulated. Functional GO terms were enriched in 23 biological processes, 20 cellular components and 21 molecular functions. KEGG annotation results showed that most of these genes were related to energy metabolism-related pathways. The results of Pearson's correlation analysis showed a significant correlation between the gut microcommunity at the genus level and several DEGs. CONCLUSIONS: These results suggest that the mechanism of adaptation of Cx. pipiens pallens to low-temperature stress may be the result of interactions between the gut bacterial community and transcriptome.

The efficacy of intravenous iron for treatment of anemia before cardiac surgery: An updated systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Preoperative anemia is common in patients undergoing cardiac surgery with various etiologies, among which iron deficiency is the leading cause. However, the benefit of intravenous (IV) iron for the treatment of anemia before cardiac surgery is uncertain. This updated meta-analysis aimed to evaluate the efficacy of IV iron in adult cardiac surgery patients with preoperative anemia. METHODS: This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched Embase, PubMed and the Cochrane Central Register of Controlled Trials to identify eligible randomized controlled trials (RCTs) and observational studies. Quality was assessed using the Cochrane Collaboration risk of bias tool and Newcastle-Ottawa scale, and the strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Trial sequential analysis was performed on the primary outcome (transfusion rate) to confirm whether firm evidence was reached. RESULTS: Six RCTs (936 patients) and 5 observational studies (1350 patients) were included in this meta-analysis. The IV iron group and the control group were comparable in terms of transfusion rate [55.1% vs 60.9%, risk ratio (RR) = 0.91, 95% confidence interval (CI) 0.81-1.03, P = 0.13, low quality]. There were no significant differences in units transfused per patient, ICU stay and hospital length of stay between the two groups. And pooled data showed a benefit of IV iron compared to the control group on mortality (2.76% vs 3.75%, RR = 0.58, 95% CI 0.36-0.95, P = 0.03, moderate quality) and no mortality reduction existed when including only RCTs. CONCLUSIONS: This meta-analysis suggested that IV iron treatment for patients with anemia before cardiac surgery did not reduce the transfusion requirement (low quality), but it was associated with decreased mortality (moderate quality). More large-scale, high-quality randomized clinical trials are warranted to confirm or refute our findings. PROSPERO registry reference: CRD42022331875.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study.

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION: Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Research progress on the structure of crystal protein of Bacillus thuringiensis and its mechanism / 中国热带医学

@#Abstract: Mosquitoes are involved in the transmission of serious diseases such as malaria, dengue, chikungunya, yellow fever, Zika virus disease, and filariasis, and their prevention and control have always been a research hotspot. Currently, mosquito control methods mainly include physical control, chemical control and biological control. Physical control methods are environmentally friendly, but they are slow to take effect and have unsatisfactory control effects; although chemical control can quickly eliminate mosquitoes, it has been eliminated due to its high pollution, high residual, and easy drug resistance; biological control uses natural enemies or pathogens to kill mosquitoes and reduce their ability to transmit disease. Therefore, environmentally friendly biological control has become the main measure for controlling and preventing mosquitoes. In recent years, significant progress has been made in bacterial mosquito control agents, among which Bacillus thuringiensis has been the most extensively studied. Bacillus thuringiensis is a Gram-positive soil microorganism, which is the pathogenic bacterium of a variety of agricultural pests such as Lepidoptera, Coleoptera and Diptera. During the sporulation process, its strains produce a variety of insecticidal crystal proteins (ICPs) or δ-endotoxins with insecticidal activity against mosquito larvae. This review firstly introduces the crystal proteins of Bacillus thuringiensis, describes in detail the types and structures of crystal proteins in detail, and also reveals the mechanism of action of crystal proteins related to receptors.

Efficacy and safety of remimazolam for non-obese patients during anesthetic induction in cardiac surgery: study protocol for a multicenter randomized trial.

BACKGROUND: Valvular heart disease remains common in both developed and developing countries, and it requires timely surgical treatment when necessary. However, the stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is difficult to maintain due to their impaired cardiac function. Remimazolam, a novel and ultrashort-acting intravenous sedative-hypnotic, may be beneficial to stable hemodynamics, but the evidence is limited. Therefore, this study aims to evaluate the effect of remimazolam induction on hemodynamics compared with midazolam and etomidate in patients undergoing valve replacement surgery. METHODS: This is a prospective, multicenter randomized controlled trial (RCT). Three hundred and sixty-three non-obese adult patients aged 45 to 80 years old undergoing valve surgery with cardiopulmonary bypass will be randomly allocated to receive remimazolam tosilate, midazolam, or etomidate during anesthetic induction. The primary outcome is the incidence of hypotension within 20 min after the administration of investigated drugs. The hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or a 30% reduction in SBP from baseline or the application of vasoactive drugs. Secondary outcomes include incidence of successful sedation, time to successful sedation, incidence of delirium and postoperative low cardiac output syndrome within 7 days after surgery, hospital mortality, mechanical ventilation time, ICU length of stay, and hospital length of stay. DISCUSSION: To our knowledge, this is the first prospective RCT to investigate the efficacy and safety of remimazolam induction in adult cardiac surgery compared with midazolam and etomidate. This study will provide important information on the application of remimazolam in cardiac surgery in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry chictr.org.cn ChiCTR2100050122. Registered on August 16, 2021.

Role of potential bioactive metabolites from traditional Chinese medicine for type 2 diabetes mellitus: An overview.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR). The number of diabetic patients globally has been rising over the past decades. Although significant progress has been made in treating diabetes mellitus (DM), existing clinical drugs for diabetes can no longer fully meet patients when they face complex and huge clinical treatment needs. As a traditional and effective medical system, traditional Chinese medicine (TCM) has a unique understanding of diabetes treatment and has developed many classic and practical prescriptions targeting DM. With modern medicine and pharmacy advancements, researchers have discovered that various bioactive metabolites isolated from TCM show therapeutic on DM. Compared with existing clinical drugs, these bioactive metabolites demonstrate promising prospects for treating DM due to their excellent biocompatibility and fewer adverse reactions. Accordingly, these valuable metabolites have attracted the interest of researchers worldwide. Despite the abundance of research works and specialized-topic reviews published over the past years, there is a lack of updated and systematic reviews concerning this fast-growing field. Therefore, in this review, we summarized the bioactive metabolites derived from TCM with the potential treatment of T2DM by searching several authoritative databases such as PubMed, Web of Science, Wiley Online Library, and Springer Link. For the convenience of readers, the content is divided into four parts according to the structural characteristics of these valuable compounds (flavonoids, terpenoids, alkaloids, and others). Meanwhile, the detailed mechanism and future directions of these promising compounds curing DM are also summarized in the related sections. We hope this review inspires increasingly valuable and significant research focusing on potential bioactive metabolites from TCM to treat DM in the future.

A new biomarker to enhance the radiosensitivity of hepatocellular cancer: miRNAs.

Aims: This review summarizes findings regarding miRNAs that modulate radiation in hepatocellular carcinoma (HCC) and evaluates their potential clinical therapeutic uses. Materials & methods: We searched the relevant English-language medical databases for papers on miRNAs and radiation therapy for tumors to identify miRNAs that are linked with radiosensitivity and radioresistance, focusing on those associated with HCC radiation. Results: There were 88 papers assessed for miRNAs associated with tumor radiation, 56 of which dealt with radiosensitization, 21 with radioresistance and 11 with radiosensitization for HCC. Conclusion: Further work in this area would enable future evaluation of radiation responses and the potential use of miRNAs as therapeutic agents in HCC patients.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, with high mortality and poor clinical outcomes. Radiotherapy is necessary for around 70% of cancer patients. As the role of miRNAs in regulating tumor radiosensitivity is more investigated, their significance in the development of HCC and their potential to alter the function of radiation in HCC become increasingly apparent. This review addresses the function of miRNAs in controlling radiation in cancer cells, concentrating on miRNA expression during radiosensitization of HCC and therapeutic uses of these results.

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Ginkgo biloba L. (Ginkgo nuts) has been used for a long time as a critical Chinese medicine material to treat cough and asthma, as well as a disinfectant. Similar records were written in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese) and Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese). Recent research has shown that Ginkgo biloba exocarp extract (GBEE) has the functions of unblocking blood vessels and improving brain function, as well as antitumour activity and antibacterial activity. GBEE was shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation as a traditional Chinese herb in our previous report in this journal. AIM OF THE STUD: yThe antibiotic resistance of clinical bacteria has recently become increasingly serious. Thus, this study aimed to investigate the Ginkgo biloba exocarp extract (GBEE) antibacterial lineage, as well as its effect and mechanism on S. haemolyticus biofilms. This study will provide a new perspective on clinical multidrug resistant (MDR) treatment with ethnopharmacology herbs. METHODS: The microbroth dilution assay was carried out to measure the antibacterial effect of GBEE on 13 types of clinical bacteria. Bacterial growth curves with or without GBEE treatment were drawn at different time points. The potential targets of GBEE against S. haemolyticus were screened by transcriptome sequencing. The effects of GBEE on bacterial biofilm formation and mature biofilm disruption were determined by crystal violet staining and scanning electron microscopy. The metabolic activity of bacteria inside the biofilm was assessed by colony-forming unit (CFU) counting and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2HY-tetrazolium bromide (MTT) assay. Quantitative polymerase chain reaction (qPCR) was used to measure the gene expression profile of GBEE on S. haemolyticus biofilm-related factors. RESULTS: The results showed that GBEE has bacteriostatic effects on 3 g-positive (G+) and 2 g-negative (G-) bacteria among 13 species of clinical bacteria. The antibacterial effect of GBEE supernatant liquid was stronger than the antibacterial effect of GBEE supernviaould-like liquid. GBEE supernatant liquid inhibited the growth of S. epidermidis, S. haemolyticus, and E. faecium at shallow concentrations with minimum inhibitory concentrations (MICs) of 2 µg/ml, 4 µg/ml and 8 µg/ml, respectively. Genes involved in quorum sensing, two-component systems, folate biosynthesis, and ATP-binding cassette (ABC) transporters were differentially expressed in GBEE-treated groups compared with controls. Crystal violet, scanning electron microscopy (SEM) and MTT assays showed that GBEE suppressed S. haemolyticus biofilm formation in a dose-dependent manner. Moreover, GBEE supernatant liquid downregulated cidA, cidB and atl, which are involved in cell lysis and extracellular DNA (eDNA) release, as well as downregulated the cbp, ebp and fbp participation in encoding cell-surface binding proteins. CONCLUSIONS: GBEE has an excellent antibacterial effect on gram-positive bacteria and also inhibits the growth of gram-negative bacteria, such as A. baumannii (carbapenem-resistant Acinetobacter baumannii) CRABA and S. maltophilia. GBEE inhibits the biofilm formation of S. haemolyticus by altering the regulation and biofilm material-related genes, including the release of eDNA and cell-surface binding proteins.

Two new Cd(II)/Zn(II) coordination polymers: luminescence properties and synergistic treatment activity with ultrasound therapy on uterine fibroids.

Through the self-assembly reaction of 5-substituted isophthalic acid and bis(imidazolyl) ligands with Cd(II) ion or Zn(II) ion, two new coordination polymers with the chemical formulae of [Cd(5-meo-ip)(bmip)]n (1) and [Zn(5-pro-ip)(bip)]n·2 n(H2O) (2) (5-meo-H2ip = 5-methoxyisophthalic acid, 5-pro-H2ip = 5-propoxyisophthalic acid, bmip = 1,3-bis(2-methylimidazolyl)propane bip = 1,3-bis(imidazolyl)propane) were successfully obtained and structurally characterized by a series of characterization techniques. Moreover, compounds 1-2 show intense blue luminescence at room temperature. Furthermore, the assessment of their treatment activity on the uterine fibroids combined with ultrasound therapy was evaluated and the specific mechanism was investigated at the same time. Firstly, the effect of compound treatment on uterine fibroids apoptosis was detected via flow cytometry. Next, the apoptotic signaling pathway activation was detected through the Caspase-3 and Caspase-8 Activity Assay Kit.

Role of Licochalcone A in Potential Pharmacological Therapy: A Review.

Licochalcone A (LA), a useful and valuable flavonoid, is isolated from Glycyrrhiza uralensis Fisch. ex DC. and widely used clinically in traditional Chinese medicine. We systematically updated the latest information on the pharmacology of LA over the past decade from several authoritative internet databases, including Web of Science, Elsevier, Europe PMC, Wiley Online Library, and PubMed. A combination of keywords containing "Licochalcone A," "Flavonoid," and "Pharmacological Therapy" was used to help ensure a comprehensive review. Collected information demonstrates a wide range of pharmacological properties for LA, including anticancer, anti-inflammatory, antioxidant, antibacterial, anti-parasitic, bone protection, blood glucose and lipid regulation, neuroprotection, and skin protection. LA activity is mediated through several signaling pathways, such as PI3K/Akt/mTOR, P53, NF-κB, and P38. Caspase-3 apoptosis, MAPK inflammatory, and Nrf2 oxidative stress signaling pathways are also involved with multiple therapeutic targets, such as TNF-α, VEGF, Fas, FasL, PI3K, AKT, and caspases. Recent studies mainly focus on the anticancer properties of LA, which suggests that the pharmacology of other aspects of LA will need additional study. At the end of this review, current challenges and future research directions on LA are discussed. This review is divided into three parts based on the pharmacological effects of LA for the convenience of readers. We anticipate that this review will inspire further research.

The Fusaric Acid Derivative qy17 Inhibits Staphylococcus haemolyticus by Disrupting Biofilm Formation and the Stress Response via Altered Gene Expression.

Staphylococcus haemolyticus (S. haemolyticus) is the second most commonly isolated coagulase-negative staphylococcus (CoNS) in patients with hospital-acquired infections. It can produce phenol-soluble modulin (PSM) toxins and form biofilms. Compared with the wealth of information on Staphylococcus aureus and Staphylococcus epidermidis, very little is known about S. haemolyticus. There is an urgent need to find an effective preparation to combat the harm caused by S. haemolyticus infection. Chinese herbs have been utilized to cure inflammation and infectious diseases and have a long history of anticancer function in China. Here, we modified fusaric acid characterized from the metabolites of Gibberella intermedia, an endophyte previously isolated from Polygonum capitatum. This study shows that fusaric acid analogs (qy17 and qy20) have strong antibacterial activity against S. haemolyticus. In addition, crystal violet analyses and scanning electron microscopy observations demonstrated that qy17 inhibited biofilm formation and disrupted mature biofilms of S. haemolyticus in a dose-dependent manner. Additionally, it reduced the number of live bacteria inside the biofilm. Furthermore, the antibiofilm function of qy17 was achieved by downregulating transcription factors (sigB), transpeptidase genes (srtA), and bacterial surface proteins (ebp, fbp) and upregulating biofilm-related genes and the density-sensing system (agrB). To further elucidate the bacteriostatic mechanism, transcriptomic analysis was carried out. The following antibacterial mechanisms were uncovered: (i) the inhibition of heat shock (clpB, groES, groL, grpE, dnaK, dnaJ)-, oxidative stress (aphC)- and biotin response (bioB)-related gene expression, which resulted in S. haemolyticus being unable to compensate for various stress conditions, thereby affecting bacterial growth; and (ii) a reduction in the expression of PSM-beta (PSMß1, PSMß2, PSMß3) toxin- and Clp protease (clpP, clpX)-related genes. These findings could have major implications for the treatment of diseases caused by S. haemolyticus infections. Our research reveals for the first time that fusaric acid derivatives inhibit the expression of biofilm formation-related effector and virulence genes of S. haemolyticus. These findings provide new potential drug candidates for hospital-acquired infections caused by S. haemolyticus.

Functional and expression characteristics identification of Phormicins, novel AMPs from Musca domestica with anti-MRSA biofilm activity, in response to different stimuli.

Antibiotic-resistant bacteria (including MRSA) in the clinic pose a growing threat to public health, and antimicrobial peptides (AMPs) have great potential as efficient treatment alternatives. Houseflies have evolved over long periods in complex, dirty environments, developing a special immune system to overcome challenges in harmful environments. AMPs are key innate immune molecules. Herein, two differentially expressed AMPs, Phormicins A and B, were identified by screening transcriptomic changes in response to microbial stimulation. Structural mimic assays indicated that these AMPs exhibited functional divergence due to their C-terminal features. Expression analysis showed that they had different expression patterns. Phormicin B had higher constitutive expression than Phormicin A. However, Phormicin B was sharply downregulated, whereas Phormicin A was highly upregulated, after microbial stimulation. The MIC, MBC and time-growth curves showed the antibacterial spectrum of these peptides. Crystal violet staining and SEM showed that Phormicin D inhibited MRSA biofilm formation. TEM suggested that Phormicin D disrupted the MRSA cell membrane. Furthermore, Phormicin D inhibited biofilm formation by downregulating the expression of biofilm-related genes, including altE and embp. Therefore, housefly Phormicins were functionally characterized as having differential expression patterns and antibacterial & antibiofilm activities. This study provides a new potential peptide for clinical MRSA therapy.