Ankle inversion proprioception measured during stair descent can identify chronic ankle instability.

BACKGROUND: Individuals with chronic ankle instability (CAI) may experience recurrent ankle sprains and symptoms during daily activities such as stair descent, where the associated proprioceptive deficit is largely unevaluated. OBJECTIVES: To evaluate the reliability and validity of an ankle inversion discrimination apparatus for stair descent, and examine whether proprioceptive scores from this apparatus are associated with patient-reported symptoms. DESIGN: Cross-sectional study. METHOD: Sixty-six participants volunteered in this study. The ankle inversion discrimination apparatus was purpose-built to assess ankle proprioception across four positions of ankle inversion (10°, 12°, 14°, and 16°) during stair descent. The Area Under the Receiver Operating Curve (AUC) was employed as the ankle proprioceptive discrimination score. RESULTS: Test-retest reliability ICC (3,1) for the whole group was 0.825, with 0.747 for the non-CAI group (95%CI = 0.331-0.920) and 0.701 for CAI (95%CI = 0.242-0.904). The CAI group performed at a significantly lower level than non-CAI on the ankle inversion discrimination apparatus for stair descent assessment (0.769 ± 0.034 vs. 0.830 ± 0.035, F = 33.786, p < 0.001). CAIT scores were strongly and significantly correlated with scores from this apparatus (Spearman's rho = 0.730, p < 0.001). CONCLUSIONS: The ankle inversion discrimination apparatus for stair descent is reliable and valid for assessing task-specific ankle proprioceptive impairments in CAI. The strong and significant relationship found between ankle proprioception during stair descent and the severity of CAI suggests that rehabilitation programs focusing on deficits in ankle inversion proprioception during stair descent may improve self-reported instability in CAI.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

A Unique Surgical Case of Mixed Metaplastic Breast Carcinoma With Heterologous Mesenchymal Differentiation and Conventional Adenocarcinomatous Elements.

Metaplastic breast carcinoma (MBC) is very rare among all invasive breast carcinomas, accounting for less than 1.0% of them. MBCs are classified into five subtypes, including mixed MBC - where the mix might be multiple metaplastic elements or a mixture of epithelial and mesenchymal elements. Overall survival for mixed MBC tends to correlate with a significantly worse outcome. Therefore, an early accurate diagnosis and surgical treatment for mixed MBCs must allow for an improved quality of life and better prognosis. However, there have not been many recently published papers describing the detailed cytological features of mixed MBCs on fine-needle aspiration (FNA) specimens. A 60-year-old female presented with a history of a hard breast mass on the left lateral side, showing an ill-defined and marginally enhanced tumor nodule on magnetic resonance imaging. The cytologic specimens of FNA contained a large number of three-dimensional, cohesive and sheet-like clusters, or non-cohesive single cells, of highly atypical spindled sarcomatoid to oval epithelioid cells having hyperchromatic pleomorphic nuclei and mitotic figures, in a necrotic and hemorrhagic background. A small amount of osteoid matrix-like substance was rarely seen, associated with a very small number of osteoclast-like giant cells. We first interpreted it as an invasive breast carcinoma of high grade. A mastectomy was performed, and a gross examination of the neoplasm revealed a hemorrhagic solid tumor lesion with a gray-whitish cut surface, measuring approximately 35 × 24 × 21 mm in diameter. On a microscopic examination, the tumor was predominantly composed of the proliferation of highly atypical oval to spindled cells predominantly in a sarcomatous growth fashion with focal production of chondroid and osteoid matrix, peripherally coexisted with a smaller volume of conventional invasive breast carcinoma. Immunohistochemistry showed that the sarcomatous tumor cells were specifically positive for vimentin, α-smooth muscle actin, or epithelial membrane antigen. Therefore, we finally made a diagnosis of invasive mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements. To the best of our knowledge, this would most recently be the first case report of mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements, with a focus on its FNA cytomorphologic findings. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of MBC, based on multiple and adequate samplings.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

The Effectiveness of Low-dose Esmketamine Versus Remifentanil Adjunct to Propofol for Sedation in Patients Undergoing Radiofrequency Thermocoagulation for Trigeminal Neuralgia.

Objectives: To access the effectiveness of propofol-esketamine versus propofol-remifentanyl in patients undergoing radiofrequency Thermocoagulation for Trigeminal Neuralgia of gasserian ganglion. Methods: In this clinical trial, 80 patients were candidates for RFT were randomly divided into two groups (n= 40). These patients aged from 21 to 81 years old. Before the start of the procedure, both groups received propofol TCI with a target level of 1.5 µgml-1. The intervention group (group E) received esketamine 0.15 mgkg-1, and the control group (group R) received remifentanyl 1.0 µgkg-1. The patients, the anesthetists and the surgeons were unaware of the medication regimen. Sedation level (based on a MOAA/S), blood pressure, oxygen saturation, the dosage of propofol, recovery time (based on Aldrete scores), postoperation pain (based on NRS), surgeons and patient satisfaction, and Pittsburgh Sleep Quality Index (PQSI) were recorded. Results: Data from 80 patients were analyzed. The sedative effects were equal in the two groups (P = .680) and the MOAA/s scores of both groups were basically maintained at or below 2 points, however, the dosage of propofol in group E was significantly less than that in group R [5.3mgkg-1h-1 (5.0 to 5.7) vs 5.8 mgkg-1h-1 ( 5.3 to 6.3), P = .000]. The group E had higher blood pressure levels during the procedure (PSBP = .002, PDBP = .023). Surgeons and patient satisfaction (Ps = .164, Pp = .580), recovery time (P = .228),The NRS values after 24hrs (P = .777)and PQSI showed no significant differences between the two groups (P = .133). Conclusions: Low-dose esketamine reduces the total amount of propofol necessary for sedation and incidence of respiratory depression during RFT of gasserian ganglion in American Society of Anesthesiologists I to III patients without affecting recovery time, satisfaction of surgeons and patients, cardiovascular adverse events, when compared with remifentanil.

Improvement of idiopathic pulmonary fibrosis through a combination of Astragalus radix and Angelica sinensis radix via mammalian target of rapamycin signaling pathway-induced autophagy in rat.

Background: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF) in clinic. Astragalus radix (AR; Huangqi) and Angelica sinensis radix (AS; Danggui) have been frequently used in the treatment of IPF. This study aimed to reveal the pharmacological effects and the mechanisms of the action of an AR-AS combination in treating IPF. Methods: Sprague-Dawley rats were randomly divided into six groups (n=5): control, bleomycin (BLM) model, AR, AS, AR + AS, and prednisone (PDN) groups. A transforming growth factor-ß1 (TGF-ß1)-induced MRC-5 cell model were also used. Pulmonary fibrosis, inflammation, oxidative stress, and autophagy were evaluated by performing hematoxylin and eosin (H&E) staining, Masson staining, immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and hydroxyproline assay following the treatment of AR, AS, and the AR-AS herb pair. Results: Rats administered the AR-AS herb pair had lower α-smooth muscle actin (α-SMA), collagen I, fibronectin, and vimentin levels in lung tissues, and lower inflammatory cytokine levels in rat serum. In addition, the AR-AS herb pair induced mammalian target of rapamycin (mTOR)-mediated autophagy and reduced oxidative stress in BLM-induced rats. The effects of the AR and AS combination were confirmed in MRC-5 cells treated with TGF-ß1. Specifically, the combination of AR and AS attenuated MRC-5 cell fibrosis, inflammation, and oxidative stress while inducing autophagy. Conclusions: The combination of AR and AS protects against IPF by inducing autophagy via inhibiting the mTOR signaling pathway. The synergistic action of AR and AS is superior to that of either AR or AS alone.

An RRM domain protein SOE suppresses transgene silencing in rice.

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum.

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

Unraveling power-law scaling through exponential cell division dynamics.

A primary objective of biology is the development of universal laws that define how organic form develops and how it evolves as a function of size, both ontogenetically and across evolutionary time. Scaling theory has been essential in reaching this goal by giving a complete perspective point, particularly in illuminating the fundamental biological features produced within scaling exponents defining families of equations. Nonetheless, the theoretical basis of the allometric equation within scaling theory are inadequately explained, particularly when it comes to establishing links between micro-level processes at the cellular level and macro-level phenomena. We proposed an unlimited cell bipartition, resulting in an exponential growth in cell numbers during an individual's lifespan, to bridge this conceptual gap between cellular processes and allometric scaling. The power-law scaling between body mass and organ weight was produced by the synchronous exponential increments and the allometric exponent is rate of logarithmic cell proliferation rate. Substituting organ weight for erythrocyte weight aided in the development of a power-law scaling relationship between body mass and metabolic rate. Furthermore, it is critical to understand how cell size affects the exponent in power-law scaling. We find that a bigger exponent will result from an increase in the average weight of organ cells or a decrease in the average weight of all cells. Furthermore, cell proliferation dynamics showed a complex exponential scaling between body mass and longevity, defying the previously reported power-law scaling. We discovered a quadratic link between longevity and logarithmic body mass. Notably, all of the parameters included in these relationships are explained by indices linked to cell division and embryonic development. This research adds to our understanding of the complex interaction between cellular processes and overarching scaling phenomena in biology.

Angelicin: A leading culprit involved in fructus Psoraleae liver injury via inhibition of VKORC1.

ETHNOPHARMACOLOGICAL RELEVANCE: The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years. AIM OF THE STUDY: To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments. MATERIALS AND METHODS: Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components. RESULTS: Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role. CONCLUSION: The results indicate that six targets, especially VKORC1, are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1.

Factors influencing the implementation of early discharge hospital at home and admission avoidance hospital at home: a qualitative evidence synthesis.

BACKGROUND: Worldwide there is an increasing demand for Hospital at Home as an alternative to hospital admission. Although there is a growing evidence base on the effectiveness and cost-effectiveness of Hospital at Home, health service managers, health professionals and policy makers require evidence on how to implement and sustain these services on a wider scale. OBJECTIVES: (1) To identify, appraise and synthesise qualitative research evidence on the factors that influence the implementation of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home, from the perspective of multiple stakeholders, including policy makers, health service managers, health professionals, patients and patients' caregivers. (2) To explore how our synthesis findings relate to, and help to explain, the findings of the Cochrane intervention reviews of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home services. SEARCH METHODS: We searched MEDLINE, CINAHL, Global Index Medicus and Scopus until 17 November 2022. We also applied reference checking and citation searching to identify additional studies. We searched for studies in any language. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with qualitative data collection and analysis methods examining the implementation of new or existing Hospital at Home services from the perspective of different stakeholders. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, extracted study characteristics and intervention components, assessed the methodological limitations using the Critical Appraisal Skills Checklist (CASP) and assessed the confidence in the findings using GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research). We applied thematic synthesis to synthesise the data across studies and identify factors that may influence the implementation of Hospital at Home. MAIN RESULTS: From 7535 records identified from database searches and one identified from citation tracking, we included 52 qualitative studies exploring the implementation of Hospital at Home services (31 Early Discharge, 16 Admission Avoidance, 5 combined services), across 13 countries and from the perspectives of 662 service-level staff (clinicians, managers), eight systems-level staff (commissioners, insurers), 900 patients and 417 caregivers. Overall, we judged 40 studies as having minor methodological concerns and we judged 12 studies as having major concerns. Main concerns included data collection methods (e.g. not reporting a topic guide), data analysis methods (e.g. insufficient data to support findings) and not reporting ethical approval. Following synthesis, we identified 12 findings graded as high (n = 10) and moderate (n = 2) confidence and classified them into four themes: (1) development of stakeholder relationships and systems prior to implementation, (2) processes, resources and skills required for safe and effective implementation, (3) acceptability and caregiver impacts, and (4) sustainability of services. AUTHORS' CONCLUSIONS: Implementing Admission Avoidance and Early Discharge Hospital at Home services requires early development of policies, stakeholder engagement, efficient admission processes, effective communication and a skilled workforce to safely and effectively implement person-centred Hospital at Home, achieve acceptance by staff who refer patients to these services and ensure sustainability. Future research should focus on lower-income country and rural settings, and the perspectives of systems-level stakeholders, and explore the potential negative impact on caregivers, especially for Admission Avoidance Hospital at Home, as this service may become increasingly utilised to manage rising visits to emergency departments.

Density Functional Theory Calculations on Fluorescence-Enhanced Mechanisms of the Optical Sensor for Zinc Ions, ADPA.

N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) as a specific ion sensor for Zn2+ has been widely applied. Although the photo-induced electron transfer (PET) mechanism was proposed previously, its fluorescence-enhanced effect still remains somewhat ambiguous, according to unknown influences of non-radiative energy decay pathways, such as intersystem crossing and internal conversion. Herein, a thorough study using density functional theory has been performed for low-lying electronic states of the ADPA monomer and hydrated ADPA-Zn2+ complex. Based on interfragment charge transfer analyses, we quantitatively calculated the amount of transferred electrons in the monomer and complex, providing solid evidences for the PET mechanism and in line with the conclusion of frontier molecular orbital analyses. Moreover, the ISC process of S1→T2 was confirmed to play a considerable role in the excitation energy relaxation process of the ADPA monomer, but this influence was significantly suppressed in the hydrated ADPA-Zn2+ complex. These results provide additional clues for the design of new metal ion-specific fluorescence probes.

The Progress and Prospects of Immune Cell Therapy for the Treatment of Cancer.

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body's natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.

Kinematic changes of the trunk and lower limbs during voluntary lateral sway postural control in adults with low back pain.

Introduction: Voluntary lateral weight shifting is essential for gait initiation. However, kinematic changes during voluntary lateral weight shifting remain unknown in people with low back pain (LBP). This study aims to explore the differences in kinematics and muscle activation when performing a voluntary lateral weight shifting task between patients with LBP and asymptomatic controls without pain. Methods: Twenty-eight participants volunteered in this study (14 in both the LBP group and the control group). The Sway Discrimination Apparatus (SwayDA) was used to generate a postural sway control task, mimicking lateral weight shifting movements when initiating gait. Kinematic parameters, including range of motion (ROM) and standard deviation of ROM (Std-ROM) of the lumbar spine, pelvis, and lower limb joints, were recorded using a motion capture system during lateral weight shifting. The electroactivity of the trunk and lower limb muscles was measured through surface electromyography using root mean square (RMS). The significant level was 0.05. An independent t-test was employed to compare kinematic parameters, and muscle activation between the LBP group and the control group. A paired-sample t-test, adjusted with Bonferroni correction (significant level of 0.025), was utilized to examine differences between the ipsilateral weight shifting towards side (dominant side) and the contralateral side. Results: The results of kinematic parameters showed significantly decreased ROM and std-ROM of the ipsilateral hip in the transverse plane (tROM = -2.059, p = 0.050; tstd-ROM = -2.670, p = 0.013), as well as decreased ROM of the ipsilateral knee in the coronal plane (t = -2.148, p = 0.042), in the LBP group compared to the control group. For the asymptomatic controls, significantly larger ROM and ROM-std were observed in the hip and knee joints on the ipsilateral side in contrast to the contralateral side (3.287 ≤ t ≤ 4.500, 0.001 ≤ p≤ 0.006), but no significant differences were found between the two sides in the LBP group. In addition, the LBP group showed significantly lower RMS of the biceps femoris than the control group (tRMS = -2.186, p = 0.044). Discussion: Patients with LBP showed a conservative postural control pattern, characterized by reduced ROM of ipsilateral joints and diminished activation of the biceps femoris. These findings suggested the importance of voluntary postural control assessment and intervention to maximize recovery.

Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study.

BACKGROUND: Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded. AIM: To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR. METHODS: Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC. RESULTS: HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn't show protective efficacy. CONCLUSION: DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Effects of environmental feedback on species with finite population.

In an unchanging environment, natural selection always selects species with high fitness. In this study, we build a co-evolutionary system to study the interaction between stochasticity in finite populations and environmental feedback. Positive feedback between species and environment is detrimental to the invasion success, whereas negative feedback is beneficial to invasion since feedback makes population size important enough to revise natural selection's preference. In competition scenario, positive and negative feedback will benefit the initially inferior species. When selection intensity is high, negative feedback may even cause natural selection to favor the initially inferior species. All of these effects are caused by feedback that allows the initially inferior species to have greater fitness than the initially dominant species. Our results emphasize that the effects of stochasticity in evolutionary path can be reinforced by feedback with environment and then reverse the preference of natural selection.

Relationship between trimethylamine N-oxide and the risk of hypertension in patients with cardiovascular disease: A meta-analysis and dose-response relationship analysis.

BACKGROUND: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized to be one of the risk factors for cardiovascular disease (CVD). However, there is a scarcity of data on the relationship between circulating TMAO levels and hypertension in patients with CVD. Meta analysis and a dose-response relationship were used in this study to assess the relationship between circulating trimethylamine N-oxide levels and the risk of hypertension in patients with CVD. METHODS: CNKI, Wanfang Database, Pubmed, Embase, Cochrane Library, and Web of Science were searched up to June 01, 2023. Meta-analysis and dose-response analysis of relative risk data from prospective cohort studies reporting on the relationship between circulating TMAO levels and hypertension risk in patients with CVD were conducted. RESULTS: Fifteen studies with a total of 15,498 patients were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher risk of hypertension in patients with CVD (RR = 1.14,95%CI (1.08, 1.20)). And the higher the TMAO level, the greater the risk of hypertension. The dose-response analysis revealed a linear dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD. The risk of hypertension increased by 1.014% when the circulating TMAO level increased by 1 µ mol/L. CONCLUSION: In patients with CVD, the level of circulating TMAO is significantly related to the risk of hypertension. The risk of hypertension increased by 1.014% for every 1 µ mol/L increase in circulating TMAO levels.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.