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Huan Ma,1 Lei Wang,1 Daozheng Huang,2 Guoqing Liu,3 Minzhou Zhang1 1Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, 2Department of Critical Care Medicine, Guangdong General Hospital, 3Medical Imaging Central, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: Cardiovascular disease is the leading cause of death worldwide, with coronary heart disease as the major contributor to this related mortality. There is a growing trend in the application of Chinese medicine in clinical practice for the treatment of coronary heart disease. However, there is a lack of knowledge surrounding the pharmacological, toxicological, and biological profiles of Chinese medicine. In this case report, we describe the therapeutic effects of Tongguan capsule in a 40-year-old woman diagnosed with stable angina pectoris. To the best of the authors’ knowledge, this is the first case documented of the therapeutic effect of Tongguan capsule in the treatment of coronary heart disease.Keywords: Chinese medicine, Tongguan capsule, cardiovascular disease, stable angina pectoris

The kidney has a local intrarenal dopaminergic system, and in the kidney, dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption, antagonizes the renin-angiotensin system, and inhibits oxidative stress. The current study examined the effects of alterations in the intrarenal dopaminergic system on kidney structure and function in models of type 1 diabetes. We studied catechol-O-methyl-transferase (COMT)(-/-) mice, which have increased renal dopamine production due to decreased dopamine metabolism, and renal transplantation was used to determine whether the effects seen with COMT deficiency were kidney-specific. To determine the effects of selective inhibition of intrarenal dopamine production, we used mice with proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC(-/-)). Compared with wild-type diabetic mice, COMT(-/-) mice had decreased hyperfiltration, decreased macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased glomerulopathy, and inhibition of expression of markers of inflammation, oxidative stress, and fibrosis. These differences were also seen in diabetic mice with a transplanted kidney from COMT(-/-) mice. In contrast, diabetic ptAADC(-/-) mice had increased nephropathy. Our study demonstrates an important role of the intrarenal dopaminergic system to modulate the development and progression of diabetic kidney injury and indicate that the decreased renal dopamine production may have important consequences in the underlying pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Abstract: Multiple sclerosis (MS) is a common disabling autoimmune disease in young adults which does not have an effective treatment. The prevalence of immune-mediated diseases is higher in developed countries with hygienic environments, suggesting that helminthic infection may protect from autoimmune diseases. Previously, we reported that soluble egg antigens (SEA) from Schistosoma japonicum suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS, through up-regulating T helper-2 (Th2) immune responses in both the peripheral and central target organs. Neurotrophins (NTs) are not exclusive to the nervous system. While immune cells, especially Th2 cells, can produce and secrete a variety of NTs resulting in neuroprotective immunity. NTs can also modulate immune responses by augmenting Th2 responses and downregulating Th1 responses. Interestingly, nerve growth factor (NGF) has been found in liver granulomas of Schistosoma mansoni-infected mice. Moreover, in the central nervous system of chronic schistosomiasis, NGF is increased. A hypothesis is hereby proposed – SEA derived from S. japonicum bears neuroprotective properties beyond its immunomodulatory effects. SEA can induce the expression of NTs, which in turn augment Th2 immune responses induced by SEA; whereby a positive regulatory circuit between Th2 responses and NTs comes into being. [Copyright &y& Elsevier]

LeuRS and PPO are important targets in the development of green pesticides; novel diphenyl-(thio)ether-containing benzoxaborole derivatives were designed and synthesized as novel dual-target enzyme inhibitors; their antifungal activities against six kinds of common plant pathogens in vitro and their herbicidal activities against purslane and barnyard grass were studied. Most of the target compounds showed excellent antifungal activity against six kinds of plant pathogenic fungi in vitro, and this is highlighted by compounds 6c and 6h , both displayed 100.0% inhibition effects against three kinds of the tested plant pathogenic fungi under the concentrations of 50.0 μg/mL, and the EC 50 value of compound 6r against Rhizoctonia solani was 0.763 μg/mL, significantly lower than that of boscalid (1.20 μg/mL). In addition, compound 6c was also used in negative control experiments, and the results revealed that compound 6c had no significant effect on the growth of noninfected plants. Meanwhile, most of the compounds also demonstrated promising herbicidal activity, as compounds 6b , 6h , 6m , and 7e showed effective control on purslane and barnyard grass. Beyond that, compound 6s demonstrated certain safety against rape. Enzymatic inhibition experiments further confirmed that compound 7e exhibited remarkable inhibitory activity against NtPPO. Moreover, the molecular docking results between 6c and 7g and tLeuRS and Nt PPO further revealed the mechanisms of action for their biological activities. In summary, compounds 6b , 6c , 6h , 7e , and 7g showed excellent antifungal and herbicidal activities and can be further studied as new antifungal and herbicidal agents in the next step.

Objectives: To summarize and discuss 3-day MRI changes after uterine artery embolization (UAE) and their predictive value for efficacy., Methods: From August 2016 to April 2023, 52 patients underwent enhanced MRI within 3 days post-embolization. We retrospectively analysed clinical and imaging data, focusing on MR characteristics at the 3-day mark, comparing pre- and post-embolization images. Patients were categorized based on 3-day MR findings into complete and incomplete necrosis groups, with clinical efficacy compared over 6 months., Results: Our study included 30 cases of multiple leiomyomas and 22 of single leiomyomas. Postoperative MRI revealed complete necrosis in 31 tumours and incomplete necrosis in 21 tumours. At 3 days, MR ADC imaging showed increased signals in necrotic areas, mildly increased signals on T2-weighted images, and minimal changes on T1-weighted images. Six-month follow-up showed no significant difference in symptom improvement between groups (P = .524, P = .587, P = .615). However, a significant difference was found in leiomyoma volume reduction, with 70.63 ± 15.53% in the complete necrosis group and 51.36 ± 25.20% in the incomplete necrosis group (P < .001), highlighting the impact of necrosis extent on volumetric reduction., Conclusion: Short-term MRI changes after UAE can reflect changes in blood supply to fibroids and normal uterine tissue, and have good predictive value for medium-term embolization efficacy., Advances in Knowledge: This study describes short-term MR manifestations of complete and incomplete embolism, aiding in predicting long-term outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Uric acid (UA) serves as an important biochemical marker of various diseases, making the development of a novel method for its rapid and straightforward visual detection highly valuable. In this study, a uricase-based cellulose membrane biosensor (UCMB) was constructed by immobilizing uricase via a Schiff base reaction and nitroblue tetrazolium chloride (NBT) through adsorption. The UCMB detects UA through a mechanism in which uricase catalyzes the oxidation of UA, generation O 2 -· radicals that subsequently oxidize NBT to formazan, producing a distinctive color change from yellow to purple. The UCMB demonstrated successful visual detection of UA within 15 min, allowing for rapid naked-eye analysis. Additionally, the biosensor quantitatively detected UA over a broad linear range from 0 to 1000 μM, with a low detection limit of 3.88 μM. Most notably, the UCMB has accurately measured UA in human serum samples, comparable to the results from a commercial UA meter. These findings suggest that the UCMB can serve as a simple and reliable tool for early diagnosis of UA-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plants encounter various abiotic stresses throughout growth and development, with aluminum stress emerging as a major global agricultural challenge that hinders plant growth and limits crop yields in acidic soils. In this study, nanomaterials with dual functions, controlled release and adsorption, were constructed to alleviate aluminum toxicity. Specifically, two metal-organic frameworks, UiO-66 and ZIF-8, were used to load naphthylacetic acid and tryptophan, respectively. These two controlled-release systems were then combined with a chitosan-based matrix (NT@CS@UZ) to enable the regulated release of both compounds at distinct rates. Concurrently, the porous structure of these materials facilitates the adsorption of soluble aluminum in the plant rhizosphere. Results show that the acidic environment accelerates ZIF-8 degradation, triggering an early release of tryptophan under aluminum stress conditions. This early release promotes plant growth and alleviates stress damage. Naphthylacetic acid is subsequently released at a slower, sustained rate to stimulate root growth and further mitigate aluminum toxicity in roots. Additionally, NT@CS@UZ effectively adsorbs aluminum ions, limiting Al 3+ uptake by plants and creating a low-aluminum barrier to protect roots. These dual function nanomaterials significantly boost crop yield and enhance stress resilience, presenting new avenues for food security and sustainable agricultural practices., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The efficacy and safety of different Chinese patent medicines in the treatment of stable chronic obstructive pulmonary disease(COPD) were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for stable COPD were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to February 2024. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool. RevMan 5.4 and Stata 16.0 were used to establish the risk of bias diagram and perform the network Meta-analysis. A total of 113 RCTs were included, involving 8 265 patients and 14 Chinese patent medicines. The network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of improving the forced expiratory volume in 1 second to forced vital capacity(FEV1/FVC) ratio, the top three treatments were Jingshuibao Capsules + conventional western medicine, Yupingfeng San + conventional western medicine, and Sanzi Zhike Capsules + conventional western medicine.(2) In terms of improving the clinical efficacy, the top three treatments were Yifei Capsules + conventional western medicine, Yupingfeng Granules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3) In terms of improving the percentage of predicted FEV1(FEV1%pred), the top three treatments were Jingshuibao Capsules + conventional western medicine, Bufei Granules + conventional western medicine, and Bailing Capsules + conventional western medicine.(4) In terms of improving the distance in 6 min walking test(6MWT), the top three treatments were Jingshuibao Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Jianpi Yifei Oral Liquid + conventional western medicine.(5) In terms of reducing the COPD assessment test(CAT), the top three treatments were Bufei Granules + conventional western medicine, Yifei Capsules + conventional western medicine, and Yifei Huoxue Granules + conventional western medicine.(6) In terms of reducing the frequency of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) within 1 year, the top three treatments were Yupingfeng Capsules + conventional western medicine, Yupingfeng San + conventional western medicine, and Jianpi Yifei Oral Liquid + conventional western medicine.(7) In terms of safety, 28 RCTs have reported adverse reactions, mainly involving the digestive system, circulatory system, and nervous system. The results showed that Chinese patent medicines combined with conventional western medicine improved FEV1/FVC, FEV1%pred, clinical efficacy, and 6MWT, while reducing CAT and the frequency of AECOPD within 1 year. However, due to the limitations of the included studies and the lack of direct comparisons between different interventions, these results need further validation.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future., (© 2024 Wiley Periodicals LLC.)

The rapid discovery of highly active butyrylcholinesterase (BChE) inhibitors is key to the treatment of the late stages of Alzheimer's disease. Herein, a colorimetric cellulose membrane (CM)-based biosensor was developed. The CM was employed as a carrier, which can be immobilized with the BChE and 5,5'-dithio-(2-nitrobenzoic acid) (DTNB) to prepare the biosensor for the solid-phase enzyme-catalyzed reaction. Specifically, the CM was oxidized to the oxidized cellulose membrane (OCM), which can further covalently bind the BChE to prepare the BChE-immobilized cellulose membrane (BCM). Then, the DTNB was adsorbed to the BCM to prepare the BDCM biosensor. The BDCM biosensor can visually detect S-butyrylthiocholine iodide at the yellow light signal with several characters, including sensitivity (LOD 1.56 μM), affinity (K m  = 140.48 ± 5.42 μM), stability (over 1 month), via the BChE-catalyzed solid-phase reaction. Furthermore, the BDCM biosensor was applied to screen and determine the specific commercial BChE inhibitors tacrine and rivastigmine, with the IC 50 values of 30.99 ± 12.20 nM and 2.02 ± 0.13 μM, respectively, from 13 different commercial inhibitors. This work provided a new method of visual BChE inhibitor screening and a useful strategy for the design of enzyme-based immobilization technology cellulose membrane biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To examine the association of household fuel use with prehypertension regression among middle-aged and older people based on the China Health and Retirement Longitudinal Study (CHARLS), we included a total of 3501 participants with prehypertension at baseline, and they were followed up from 2011-2012 to 2015-2016 with information on blood pressure and household solid fuel use (heating and cooking fuels). Cox proportional hazards regression models were used to explore the hazard ratio (HR) and 95% confidence interval (CI) between fuel use and prehypertension regression. Additionally, we investigated the impact of switching fuels (2011-2013) on the regression to normotension during the 4-year follow-up. Linear regression was used to examine the effect of household fuel use on changes in blood pressure. Compared to solid fuel users, those who used clean fuel for heating at baseline had a positive effect on the regression of prehypertension (HR: 1.28, 95% CI: 1.08-1.53). Participants who used clean fuels for both heating and cooking had increased odds for the regression of prehypertension (HR: 1.32, 95% CI: 1.09-1.60). Compared to consistent solid fuel users, those who consistently used clean fuel for heating had a higher likelihood of transitioning from prehypertension to normotension (HR: 1.36, 95% CI: 1.06-1.73) and exhibited 2.45 mmHg lower systolic blood pressure. In conclusion, household clean fuel use for heating was positively associated with the regression of prehypertension to normotension. Furthermore, switching from solid fuel to clean fuel for heating could reduce the risk of prehypertension in Chinese middle-aged and older adults., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The continual emergence of tick-borne rickettsioses has garnered widespread global attention. Candidatus Rickettsia barbariae ( Candidatus R. barbariae), which emerged in Italy in 2008, has been detected in humans from northwestern China. However, the lack of Candidatus R. barbariae genome and isolated strains limits the understanding of its biological characteristics and genomic features. Here, we isolated the Rickettsia for the first time from eggs of Rhipicephalus turanicus in northwestern China, and assembled its whole genome after next-generation sequencing, so we modified the proposed name to Rickettsia barbariae ( R. barbariae ) to conform to the International Code of Nomenclature of Prokaryotes. Phylogenetic analysis based on the whole genome revealed that it was most closely related to the pathogenic Rickettsia parkeri and Rickettsia africae . All virulence factors, present in the pathogenic spotted fever group rickettsiae, were identified in the R. barbariae isolate. These findings highlight the pathogenic potential of R. barbariae and the necessity for enhanced surveillance of the emerging Rickettsia in the human population.

Objective: To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK)., Methods: We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022., Results: Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein-Barr virus (EBV) expression. The 5-years overall survival rate was 83%., Conclusion: Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.

It remains unclear whether elevated ventricular wall pressure and left ventricular enlargement in patients with left ventricular systolic dysfunction (LVSD) can lead to left bundle branch block (LBBB). In this study, 801 consecutive hospitalized patients with a left ventricular ejection fraction of < 50% were enrolled. The primary outcome was the occurrence of new-onset LBBB or heart failure-related hospitalization, all-cause mortality, ventricular tachycardia, or implantation of an implantable cardioverter-defibrillator (ICD) /cardiac resynchronization therapy (CRT). During a median follow-up of 56 months, 70 cases of new-onset LBBB were observed, with a cumulative incidence rate of 10.1%. Multivariate Cox regression analysis demonstrated that paroxysmal atrial fibrillation (PAF) (hazard ratio [HR] 2.907, 95% confidence interval [CI] 1.552-5.444, P = 0.001), coronary artery disease (CAD) (HR 6.680, 95% CI 3.451-12.930, P < 0.001), dilated cardiomyopathy (DCM) (HR 6.394, 95% CI 3.501-11.675, P < 0.001), QRS duration (HR 1.018, 95% CI 1.010-1.027, P < 0.001), left ventricular end-diastolic dimension (LVEDD) (HR 1.032, 95% CI 1.006-1.059, P = 0.016), and β-blockers (HR 0.327, 95% CI 0.199-0.536, P < 0.001) were independent predictors of new-onset LBBB. A Kaplan-Meier survival curve analysis demonstrated that patients with new-onset LBBB had a higher incidence of composite endpoint events (P < 0.001), heart failure-related hospitalization (P < 0.001), and ventricular tachycardia or implantation of an ICD or CRT (P < 0.001) than patients without new-onset LBBB. Moreover, new-onset LBBB (HR 1.603, 95% CI 1.207-2.129, P = 0.001) was an independent predictor of composite endpoint events.DCM, LVEDD, CAD, PAF, and QRS duration were independent predictive factors for the subsequent development of LBBB in patients with LVSD. New-onset LBBB was independently associated with a poor prognosis.

Objective: The aim of this study was to investigate the associations between residential greenness, air pollution (PM 2.5 , PM 10 , and NO 2 ), and the risk of visual impairment in Chinese middle-aged and elderly adults., Methods: The data were used from the China Health and Retirement Longitudinal Study (CHARLS), focusing on adults aged 45 years and older. Exposure to residential greenness was assessed using the Normalized Difference Vegetation Index (NDVI), while air pollution exposure (PM 2.5 , PM 10 , and NO 2 ) was estimated from the ChinaHighAirPollutants dataset. Visual impairment was self-reported and categorized as distance visual impairment (DVI) and near visual impairment (NVI). Cox proportional hazards models were applied to investigate the associations between residential greenness, air pollution, and visual impairment. Furthermore, we investigated the potential modification and mediation relationship between residential greenness, air pollution and visual impairment., Results: A total of 9,591 participants were included in this study. During a 7-year period, 2,650 cases of DVI and 3,130 cases of NVI were identified. In the single exposure model, a higher level of residential greenness was associated with a significantly reduced risk of both DVI and NVI. Specifically, for every 0.1 unit increase in NDVI, the hazard ratio (HR) was 0.68 (95%CI: 0.65,0.71) for DVI, and 0.67 (95%CI: 0.64,0.69) for NVI. Conversely, exposure to air pollution was positively associated with increased risks for both DVI and NVI. For each 10 µg/m 3 increase in PM 2.5 , the HR was 1.60 (95%CI: 1.56,1.65) for DVI and 1.64 (95%CI: 1.60,1.69) for NVI. Similarly, PM 10 and NO 2 exposure showed elevated risks with HR of 1.28 (95%CI: 1.27,1.30) and 1.73 (95%CI: 1.62,1.85) for DVI, and 1.30 (95%CI: 1.28,1.32) and 1.82 (95%CI: 1.72,1.94) for NVI, respectively. The multiple exposure model also showed significant association between residential greenness, air pollution and visual impairment risk. Additionally, the adverse effects of PM 2.5 , PM 10 , and NO 2 were attenuated in areas with the highest levels of residential greenness. Mediation analysis revealed that air pollution mediated a significant portion of the association between residential greenness and visual impairment., Conclusion: This study suggests that increased residential greenness may reduce the risk of visual impairment, partially by mitigating air pollution exposure. These findings highlight the environmental benefits to improve air quality and enhance green spaces, thereby promoting visual health in aging populations., Competing Interests: Declarations. Ethics approval and consent to participate: The data used in this study were approved by the Biomedical Ethics Review Committee of Peking University (Approval Number: IRB00001052-11015). Written informed consent was obtained from all participants. All methods in this study on humans described in the manuscript were performed in accordance with national law and the Helsinki Declaration of 1975. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The pivotal role of endothelial nitric oxide synthase (eNOS) in diabetic nephropathy (DN) has been demonstrated using global eNOS knockout (eNOSGKO) mice. However, the precise role of endothelially expressed eNOS and how its deficiency advances DN are still unclear. Here, we targeted endothelial eNOS expression (E-eNOSKO) after the onset of diabetes using the floxed eNOS and endSCL-CreER T alleles. Diabetes was induced by low-dose streptozotocin injections. To evaluate the role of nuclear factor of activated T cells-2 (NFAT2) in podocyte injury in this condition, podocyte-specific NFAT2KO mice were also generated on eNOSGKO mice. The mechanisms of podocyte injury were investigated using cultured podocytes. Compared with diabetic wild-type mice, diabetic E-eNOSKO mice showed more advanced DN accompanied by NFAT2 expression in podocytes. NO donor suppressed NFAT2 expression and activation in high-glucose cultured podocytes as well as in diabetic E-eNOSKO mice. Furthermore, podocyte-specific deletion of NFAT2 attenuated DN in diabetic eNOSGKO mice accompanied by decreased heparanase (HPSE) expression in podocytes. Consistent with this finding, HPSE was upregulated by NFAT2 transfection and suppressed by NFAT2 siRNA or NO donor treatment in cultured podocytes. HPSE transfection reduced podocyte attachment to extracellular matrix concurrent with syndecan-4 (SDC4) shedding, and this effect was attenuated by co-transfection of SDC4. Finally, HPSE inhibitor treatment attenuated podocyte injury in diabetic E-eNOSKO mice with increased SDC4 expression in podocytes. Collectively, our data suggest that endothelial eNOS deficiency causes podocyte HPSE expression in diabetic mice through NFAT2, and HPSE promotes podocyte detachment in part through SDC4 shedding, advancing DN., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Conflicts of Interest: Zhong X, None; Li T, None; Du YL, None; Zhang MZ, None.

Background: Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy in cervids. The disease is caused by a pathogenic prion, namely PrP Sc . Currently, diagnosis of CWD relies on IHC detection of PrP Sc in the obex or retropharyngeal lymph nodes (RPLN) or ELISA screening of obex and RPLN followed by IHC confirmation of positive results. In this study, we assessed the performance characteristics of two immunoassays: CWD Ag-ELISA and TeSeE ELISA, RT-QuIC, and MEMS biosensor via testing 30 CWD + and 30 CWD- white-tailed deer RPLN samples., Results: Both CWD Ag-ELISA and TeSeE ELISA correctly identified all CWD + and CWD- samples. A greater intra-assay coefficient of variation (CV) in S/P ratios was observed for the TeSeE ELISA (16.52%), compared to CWD Ag-ELISA (9.49%). However, the high CV did not affect the qualitative results of triplicate assays when the corresponding manufacturer's cutoff was used. The MEMS biosensor not only correctly identified all CWD + and CWD- RPLN samples, but also demonstrated a 100% detection rate for all CWD + samples at dilutions from 10 - 0 to 10 - 3 . Evaluation of RT-QuIC indicated that the rate of false negative reactions decreased from 21.98% at 10 - 2 dilution to 0% at 10 - 4 and 10 - 5 dilutions; and the rate of false positive reactions reduced from 56.42% at 10 - 2 dilution to 8.89% and 2.22% at 10 - 4 and 10 - 5 dilutions, respectively. Based on a stringent threshold of 2 x the first 10 fluorescent readings of each well and a final cutoff of 2/3 positive reactions for each sample, RT-QuIC correctly identified all positive and negative samples at 10 - 4 and 10 - 5 dilutions. Both MEMS biosensor and RT-QuIC achieved 100% sensitivity and 100% specificity under the experimental conditions described in this study., Conclusions: The two immunoassays (CWD Ag-ELISA and TeSeE ELISA) performed comparably on white-tailed deer RPLN samples. MEMS biosensor is a reliable portable tool for CWD diagnosis and RT-QuIC can be used for routine testing of CWD if appropriate testing parameters and interpretive criteria are applied., Competing Interests: Declarations Ethics approval and consent to participate This research did not involve live animals. Retropharyngeal lymph nodes were collected from hunter-harvested dead deer by MDC as part of Misosuri CWD surveillance program. Sample collection and submission protocols were reviewed and approved by MDC Science Committee. Comparative study protocol was approved by the University of Missouri Institutional Biosafety Committee (protocol number: 11721 2.2). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Abstract: According to the diagnostic criteria for human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network in 2017, there is a group of HHV-8-negative patients with multicentric Castleman disease (MCD) who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000 to 2021. With a median follow-up time of 46.5 months (range, 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between a diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range, 3-60). During follow-up, 7 patients died; 3 of them died from progression of MCD. Despite that, 37.7% of patients received systemic treatment targeting MCD; this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all patients with aMCD was 94.1% (95% confidence interval, 88.8-99.6). Transformation to iMCD was an important predictor of death (log-rank P = .01; 5-year estimated survival, 83.3%). This study suggests that patients with aMCD may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV., Methods: In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses., Findings: A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations., Interpretation: Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms., Funding: National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Distal gastrectomy remains the predominant therapeutic approach for gastric cancer, with digestive tract reconstruction as an integral procedure. The implementation of Braun anastomosis following Billroth II anastomosis is common in distal gastrectomy. This retrospective cohort study evaluated the clinical utility of Braun anastomosis by comparing the outcomes and quality of life between Billroth II (B-II) and Billroth II with Braun (B-IIB) anastomosis in the treatment of gastric cancer., Methods: A retrospective cohort study examined clinical and pathological data from 377 patients who underwent distal gastrectomy for gastric cancer treatment at The Affiliated Lihuili Hospital, Ningbo University, from October 2016 to October 2021.185 patients received B-II anastomosis, while the other 192 received B-IIB anastomosis, forming the B-II and B-IIB groups, respectively. Baseline characteristics, perioperative variables, short-term and long-term complications, and nutritional indicators at 1 mo and 1 y postsurgery were compared across both groups. Additionally, gastric endoscopy results at 6 mo and 1 y postsurgery were evaluated. Quality of life at 1 y postsurgery was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30., Results: Baseline characteristics between the two groups revealed no statistically significant differences (all P > 0.05), confirming their equivalence. All 377 patients successfully underwent curative distal gastrectomy for gastric cancer without intraoperative procedural modifications. No intraoperative complications or perioperative mortality occurred. Notable differences included extended operative time (222.1 ± 41.0 vs. 199.4 ± 24.9 min, P < 0.001), reduced postoperative nasogastric tube removal time (1.8 ± 0.9 vs. 2.2 ± 1.1 d, P < 0.001), decreased average gastric drainage volume (100.7 ± 35.2 vs. 112.2 ± 32.0 mL, P = 0.001), and increased incidence of internal hernia and ileus (4.7% vs. 1.1% and 8.3% vs. 3.2%, P = 0.038 and P = 0.035) in the B-IIB group compared to the B-II group. No significant differences were observed in estimated blood loss, lymph node dissection, postoperative flatus time, transition to a semiliquid diet, length of hospital stay, or short-term and long-term complications (all P > 0.05). Nutritional assessments conducted 1 mo and 1 y postsurgery indicated no statistically significant differences in body mass index, total protein, and serum albumin levels between the two groups (all P > 0.05). Gastric endoscopy evaluations at 6 mo and 1 y postsurgery, including food residue grade, gastritis severity, extent of gastritis, and bile reflux, demonstrated no significant discrepancies between the groups (all P > 0.05). At the 1-y follow-up, neither group exhibited tumor recurrences, deaths from tumor-related diseases, postoperative complications, or other diseases. Additionally, quality of life assessments using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core revealed no significant differences across various domains or items between the groups (all P > 0.05)., Conclusions: A comparative analysis between B-II and B-IIB anastomosis demonstrated no notable variations in intraoperative parameters, postoperative nutritional outcomes, gastric endoscopic results, or postoperative quality of life. Nevertheless, incorporating Braun anastomosis can extend the duration of surgery and may elevate the likelihood of postoperative internal hernia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Remimazolam and propofol can be used interchangeably for general anesthesia. However, no dosing recommendations exist for the intravenous bolus administration of remimazolam during general anesthesia induction in pediatric patients. Determining the appropriate dose for anesthesia induction in pediatric patients is crucial for safe and effective surgical procedures., Objectives: The study aimed to determine the median effective dose (ED50) for loss of consciousness (LOC) with remimazolam and propofol in pediatric patients and establish the dose equivalence between these anesthetics., Study Design: A prospective, randomized, single-center trial., Setting: A tertiary pediatric hospital in China from January 2023 to July 2023., Methods: Pediatric patients aged 3 to 15 years, undergoing elective surgery under general anesthesia, were included. Patients were randomized to receive either remimazolam (in doses of 0.1, 0.15, 0.2, 0.25, and 0.3 mg/kg-1) or propofol (in doses of 0.75, 1.0, 1.25, and 1.5 mg/kg-1) via intravenous bolus. The primary measure consisted of determining the ED50 for LOC with remimazolam, and the secondary measure consisted of establishing the dose equivalence between remimazolam and propofol., Results: The calculated ED50 for remimazolam was 0.19 mg/kg-1 (95% CI: 0.10-0.35), and that for propofol was 1.11 mg/kg-1 (95% CI: 0.53-2.15). This finding indicates that remimazolam is approximately 5.8 times more potent than propofol., Limitations: In this study, the anesthesiologist could not be blinded to the different appearances of remimazolam and propofol, and the LOC assessment method may have introduced bias. Furthermore, the recommended dose for remimazolam induction was not tested directly within this trial, suggesting a need for further research., Conclusions: Remimazolam demonstrates significantly higher sedative efficacy for pediatric patients than does propofol. An induction dose of 0.34 mg/kg-1 remimazolam could be recommended for general anesthesia induction, considering the safety and effectiveness of a 2 mg/kg-1 dose of propofol.

Inadequate dietary potassium (K + ) consumption is a significant contributor to poor cardiovascular outcomes. A diet with reduced K + content has been shown to cause salt-sensitive increases in blood pressure. More recently, we have also shown that reductions in blood K + can cause direct kidney injury, independent of dietary sodium (Na + ) content. Here, we investigated the role of the kinase Ste20p-related proline-alanine-rich kinase (SPAK) in this kidney injury response. We observed that global SPAK deletion protected the kidney from the damaging effects of a diet high in Na + and low in K + . We hypothesized that kidney macrophages were contributing to the injury response and that macrophage-expressed SPAK is essential in this process. We observed SPAK protein expression in isolated macrophages in vitro. Culture in K + -deficient medium increased SPAK phosphorylation and caused SPAK to localize to cytosolic puncta, reminiscent of with-no-lysine kinase (WNK) bodies identified along the distal nephron epithelium. WNK1 also adopted a punctate staining pattern under low K + conditions, and SPAK phosphorylation was prevented by treatment with the WNK inhibitor WNK463. Macrophage-specific SPAK deletion in vivo protected against the low K + -mediated renal inflammatory and fibrotic responses. Our results highlight an important role for macrophages and macrophage-expressed SPAK in the propagation of kidney damage that occurs in response to reduced dietary K + consumption. NEW & NOTEWORTHY Global Ste20p-related proline alanine-rich kinase (SPAK) deletion protects against harmful kidney effects of dietary K + deficiency. Exposure to low K + conditions increases SPAK phosphorylation and induces SPAK to adopt a punctate staining pattern. Macrophage-specific deletion of SPAK confers protection to low K + -induced kidney injury in vivo. Macrophage-expressed SPAK plays a key role in the development of kidney injury in response to a low K + diet.

The triglyceride-glucose (TyG) index, a reliable surrogate biomarker of insulin resistance (IR), is highlighted recently as related to cardiac disorders. However, the associations of the TyG index and its combination with blood pressure (BP) on cardiovascular and all-cause mortality in hypertension remain unclear. In this study, we included 9,635 hypertension patients from the National Health and Nutrition Examination Survey 1999-2018. During a median follow-up of 8.00 years, a total number of 853 and 2,489 in cardiovascular and all-cause deaths occurred, respectively. After full adjustments, the individual TyG index was positively associated with cardiovascular and all-cause mortality with J-shaped dose-response relationships. The lowest risk thresholds of the TyG index for cardiovascular and all-cause mortality were 9.5551 and 9.3405, respectively. In joint analyses, the highest risks of cardiovascular and all-cause mortality were observed among those with elevated levels of both BP and IR [1.64 (1.18, 2.28), P = 0.0031; 1.39 (1.14, 1.70), P = 0.0011; respectively]. In sensitivity and subgroup analyses, the results were generally robust. Our data appeal a hypothesis that future treatments for hypertension may require a combination of BP controlled and IR improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Peng, Guo, Zhao, Chen, Mai, Tan, Chen, Zeng and Zhang.)

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway., (© 2024. The Author(s).)

Background: Calcaneal osteomyelitis (CO) still poses great challenges to orthopedic surgeons due to the unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases., Materials and Methods: The authors searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients published between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis., Results: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcers (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately., Conclusions: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To investigate the relationships of the dynamic changes in triglyceride glucose index-body mass index (TyG‑BMI) and cumulative TyG-BMI with the risk of hypertension among middle-aged and elderly Chinese., Methods: Data were used from the China Health and Retirement Longitudinal Study (CHARLS). Participants who participated in the baseline study (2011-2012) and in subsequent surveys (2015-2018) were included in this study. The primary exposures were changes in TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in TyG-BMI were categorized using k-means clustering methods, while cumulative TyG-BMI was categorized into quartiles. Cox proportional hazards regression models were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with the incidence of hypertension. Linear regression analyzes were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with cumulative systolic blood pressure (SBP) and cumulative diastolic blood pressure (DBP)., Results: Of a total of 2,561 participants aged 56.93 ± 8.08 years old at baseline, 253 individuals (9.9%) developed hypertension during the 7-year follow-up period. The hazard ratios (HR) and 95% confidence interval (CI) for hypertension were 1.50 (1.10-2.03) for class 2 (persistently medium class) and 2.35 (1.61-3.42) for class 3 (persistently high class), compared to class 1 (persistently low class). Additionally, class 2 showed increases of 7.70 mmHg (95% CI: 5.18-10.21) in cumulative SBP and 6.53 mmHg (95% CI: 4.68-8.38) in cumulative DBP, while class 3 exhibited increases of 14.10 mmHg (95% CI: 10.56-17.64) in cumulative SBP and 12.64 mmHg (95% CI: 10.03-15.25) in cumulative DBP, compared with class 1. Regarding cumulative TyG-BMI, the HR for hypertension were 1.75 (95% CI: 1.18-2.59) for quartile 3 and 2.15 (95% CI: 1.43-3.23) for quartile 4, compared with quartile 1. In quartile 2, cumulative SBP increased by 3.99 mmHg (95% CI: 0.88-7.11) and cumulative DBP by 2.74 mmHg (95% CI: 0.45-5.02). Quartile 3 showed increases of 8.32 mmHg (95% CI: 5.09-11.54) in cumulative SBP and 7.13 mmHg (95% CI: 4.76-9.49) in cumulative DBP. Quartile 4 exhibited the highest increases, with cumulative SBP rising by 13.15 mmHg (95% CI: 9.70-16.60) and cumulative DBP by 12.20 mmHg (95% CI: 9.67-14.74). Furthermore, a linear relationship was observed between cumulative TyG-BMI and the risk of hypertension., Conclusions: Changes in TyG-BMI and cumulative TyG-BMI were associated with an increased risk of hypertension, as well as higher cumulative SBP and DBP in Chinese middle-aged and elderly population., (© 2024. The Author(s).)

The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca 2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-β-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Insulin resistance (IR) is a well-established major risk factor for type 2 diabetes mellitus, nonalcoholic fatty liver disease, and atherosclerotic cardiovascular disease. Previous studies have shown an association between increased serum albumin (ALB) levels and the risk of IR. However, there is a lack of studies simultaneously evaluating the association of total protein (TP), ALB, and globulin (GLB) with IR., Methods: A total of 14,828 individuals (average age 49 ± 18 years) with complete data from the National Health and Nutrition Examination Survey (NHANES) were enrolled and divided into two groups (non-IR group, n = 8,653 and IR group, n = 6,175). Spearman's correlation analysis, multivariable logistic regression models, restricted cubic spline curves, and subgroup analysis were performed to explore those associations., Results: After adjustment for potential confounders, multivariable logistic regression analysis revealed that scaled per 10g/L increment, the fully adjusted odds ratios (ORs) (95% confidence interval (CI)) for IR prevalence were 1.54 (95% CI 1.41-1.69, P < 0.0001), 1.09 (95% CI 0.95-1.25), P = 0.1995), and 1.62 (95% CI 1.47-1.79, P < 0.0001) for TP, ALB, and GLB respectively. Compared to those in the lowest quantiles, the prevalence of IR in subjects in the highest TP and GLB quantiles was 2.06 and 1.91 times, respectively. Furthermore, restrictive cubic curves confirmed that the relationship of TP, ALB, and GLB with IR prevalence was a linear relationship., Conclusions: The present cross-sectional study, for the first time, provided supportive evidence of positive associations of TP and GLB with IR, but not ALB, and demonstrated that TP and GLB might be useful markers for IR prevalence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zeng, Xu, Zhang, Tan, Kong, Zhang and Guo.)

Background: For patients with sepsis receiving non-invasive ventilation (NIV), early rehabilitation is crucial. The Sitting Baduanjin (SBE) is an efficient early rehabilitation exercise suitable for bed patients. There is no consensus about the effect of SBE on the early rehabilitation of septic patients with NIV. This study focused on how the SBE affected the early rehabilitation of sepsis patients with NIV., Methods: 96 sepsis patients with NIV were randomly assigned to either an Baduanjin group that received the SBE based on the routine rehabilitation exercise (n = 48) or a control group (n = 48) that received routine rehabilitation exercise. The primary outcome was the Medical Research Council(MRC)score, and the Barthel Index score, the duration of NIV, length of ICU stay, length of total stay, hospitalization expense as secondary outcomes., Results: A total of 245 sepsis patients were screened, with 96 randomly assigned. The study was completed by 90 patients out of the 96 participants.Results revealed that the MRC score increased in both groups, but the improvement of muscle strength in Baduanjin group was more obvious, with statistical significance (p < 0.001).There was statistically significantly difference between the two groups in Barthel Index at the day of transfer out of ICU(P = 0.028).The patients in the Baduanjin group had an average reduction of 24.09 h in the duration of NIV and 3.35 days in total length of hospital stay compared with the control group (p < 0.05).Of note, the Baduanjin group had significantly reduction the total hospitalization expense. No serious adverse events occurred during the intervention period., Conclusions: In patients with sepsis, the SBE appears to improve muscle strength and activities of daily living (ADL), and lowed the duration of NIV, the length of the total stay, and the hospitalization expense., Trial Registration: The study registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ), Clinical Trials identifier ChiCTR1800015011 (28/02/2018)., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people., Methods: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants., Results: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group., Conclusion: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC 50 = 0.170 μg/mL), outperforming carbendazim (EC 50 = 0.360 μg/mL) and boscalid (EC 50 = 1.36 μg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali , Botrytis cinerea , and Alternaria alternata with EC 50 values of 0.590, 0.870, and 1.71 μg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti- R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC 50 = 8.42 μM), surpassing that of the SDH fungicide boscalid (IC 50 = 15.6 μM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.

The colonization of alien plants in new habitats is typically facilitated by microorganisms present in the soil environment. However, the diversity and structure of the archaeal, bacterial, and fungal communities in the latitudinal spread of alien plants remain unclear. In this study, the rhizosphere and bulk soil of Chromolaena odorata were collected from five latitudes in Pu' er city, Yunnan Province, followed by amplicon sequencing of the soil archaeal, bacterial, and fungal communities. Alpha and beta diversity results revealed that the richness indices and the structures of the archaeal, bacterial, and fungal communities significantly differed along the latitudinal gradient. Additionally, significant differences were observed in the bacterial Shannon index, as well as in the structures of the bacterial and fungal communities between the rhizosphere and bulk soils. Due to the small spatial scale, trends of latitudinal variation in the archaeal, bacterial, and fungal communities were not pronounced. Total potassium, total phosphorus, available nitrogen, available potassium and total nitrogen were the important driving factors affecting the soil microbial community structure. Compared with those in bulk soil, co-occurrence networks in rhizosphere microbial networks presented lower complexity but greater modularity and positive connections. Among the main functional fungi, arbuscular mycorrhizae and soil saprotrophs were more abundant in the bulk soil. The significant differences in the soil microbes between rhizosphere and bulk soils further underscore the impact of C. odorata invasion on soil environments. The significant differences in the soil microbiota along latitudinal gradients, along with specific driving factors, demonstrate distinct nutrient preferences among archaea, bacteria, and fungi and indicate complex microbial responses to soil nutrient elements following the invasion of C. odorata., (© 2024. The Author(s).)

Objective: To investigate the effectiveness of child-centered playful companionship and sedative medication in alleviating preoperative anxiety in preschool children. Methods: A retrospective analysis was conducted on 3 825 preschool children (3-6 years) who underwent elective surgery at Shanghai Children's Medical Center from April 2021 to March 2022. The children were divided into three groups based on the preoperative anxiolytic intervention: child-centered playful companionship group ( n =2 198), pharmacological sedation group ( n =1 281), and no intervention group ( n =346). The pharmacological sedation group received intranasal dexmedetomidine at 2 μg/kg or oral midazolam syrup at 0.5 mg/kg. The child-centered playful companionship group received care from certified preoperative sedation nurses using a child-centered playful nursing model. The no intervention group did not receive any anti-anxiety measures due to various subjective and objective reasons. Preoperative separation anxiety scores (PSAS), sedation medication usage, and Ramsay sedation scores were recorded for all children. The primary outcome was the success rate of separation based on PSAS scores across different anxiolytic intervention groups, while the secondary outcome was the Ramsay sedation score. Results: The child-centered playful companionship group included 1 462 boys and 736 girls, with a median age [ M ( Q 1 , Q 3 )]of 59 (49, 69) months. The pharmacological sedation group included 824 boys and 457 girls, with a median age of 52 (42, 61) months; and the no intervention group included 212 boys and 134 girls, with a median age of 57 (48, 69) months. The success rate of separation in the child-centered playful companionship group was 95.6% (2 102/2 198), and in the pharmacological sedation group was 93.8% (1 202/1 281), both significantly higher than the 43.6% (151/346) of the no intervention group (all P <0.05). Among the 1 281 children in the pharmacological sedation group, 785 received oral midazolam and 496 received intranasal dexmedetomidine. Compared to the intranasal dexmedetomidine group, the oral midazolam group was younger, had a lower body weight and a higher proportion of American Society of Anesthesiologists (ASA) class Ⅲ (all P <0.05). The success rate of separation was 93.4% (733/785) in the oral midazolam group and 94.6% (469/496) in the intranasal dexmedetomidine group, with no statistically significant difference ( P =0.392). The Ramsay sedation score was 2 (2, 2) in the intranasal dexmedetomidine group, better than the 2 (2, 2) of the oral midazolam group ( P =0.024). Conclusion: Both child-centered playful companionship and pharmacological sedation effectively alleviate preoperative anxiety in preschool children.