Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective To investigate the anti-estrogenic activity of bisphenol A and its substitutes, and to analyze the relevant mechanisms. Methods Bisphenol A and its three most widely used substitutes (bisphenol S, bisphenol F and bisphenol AF) were selected as the docking ligand molecules, and estradiol was used as the control ligand molecule. The ligand molecules docking was simulated with estrogen receptor (ER) α and ERβ using AutoDock software. Results Bisphenol A forms a hydrogen bond with ERα at the His474 residue and with ERβ via three hydrogen bonds at Leu260, His428, and Asn431 residues. Similar to bisphenol A, bisphenol S, bisphenol F, bisphenol AF and estradiol primarily interact with ERα and ERβ through hydrophobic interactions and hydrogen bonds, but with varying optimal binding sites and affinities. The binding forces of the optimal binding sites for bisphenol A, bisphenol F, bisphenol AF, bisphenol S and estradiol with ERα were -4.15, -4.19, -2.73, -4.62 and -5.37 kcal/mol, respectively, and with ERβ were -3.76, -3.91, -2.86, -3.93, and -4.98 kcal/mol, respectively. The affinity ranking for two ERs with these five molecules from high to low was estradiol > bisphenol S> bisphenol F> bisphenol A > bisphenol AF. Conclusion The affinity between bisphenol compounds with ERα and ERβ is mainly based on the hydrophobic interaction with non-polar residues of the receptor and hydrogen bonding with key residues. Bisphenol S, bisphenol F and bisphenol AF showed similar or even stronger endocrine disrupting effects than bisphenol A.

Objective To investigate the immunotoxicity effect of triphenyl phosphate (TPHP) on thymus tissue of mice, and analyze the related mechanism. Methods Specific pathogen free BALB/c mice were randomly divided into control group, low-, medium- and high-dose groups, with 12 mice per group (equal gender distribution). Mice in these four groups were orally administered doses of 0, 1, 10, and 150 mg/kg body weight of TPHP daily for 60 days. After the exposure, the complete blood count of mice was detected, thymus tissue was collected, coefficient of thymus organs was calculated, and the histopathology changes of thymus were observed. Real-time quantitative polymerase chain reaction was used to assess the expression of genes related to inflammation, oxidative stress, cellular autophagy, and apoptosis in thymic tissues. Results During the exposure period, male mice in the high-dose group had poor fur condition, whisker loss, and increased irritability, while these phenomena were not observed in female mice. At the end of the exposure period, there were no significant changes in mice body weight or thymus organ coefficients among the groups. However, male mice in the high-dose group showed cellular apoptotic changes in the thymic tissue. The amount of white blood cell, lymphocyte, neutrophil granulocyte, red blood cell distribution width, platelet and the plateletcrit of male mice was lower in the high-dose group than that in the control group (all P<0.05). The relative mRNA expression of interleukin (Il)-1β, Il-6, catalase (Cat), P62, as well as the ratio of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax)/Bcl-2 in thymic tissue of male mice were higher in the low-dose group than that in the control group (all P<0.05). The relative mRNA expression of nuclear factor erythroid-2 related factor 2 (Nrf2), superoxide dismutase 1 (Sod1), glutathione peroxidase 1 (Gpx1), P62, as well as the ratio of Bax/Bcl-2 in the thymic tissue of male mice were higher in the medium-dose group than that in the control group (all P<0.05). The relative mRNA expression of Nrf2, Cat, Sod1, Gpx1, P62, cysteinyl aspartate specific proteinase-3, as well as the ratio of Bax/Bcl-2 in the thymic tissue of male mice were higher in the high-dose group than that in the control group (all P<0.05). The relative mRNA expression of Il-1β and the ratio of Bax/Bcl-2 in thymic tissue of female mice were higher in the low- and medium-dose group (all P<0.05), while the relative mRNA expression of interferon-γ, Nrf2, Cat, P62, microtubule-associated protein light chain 3, as well as the ratio of Bax/Bcl-2 in thymic tissue of female mice were higher in the high-dose group than that in the control group (all P<0.05). Conclusion Although TPHP exposure had not significantly affected the body weight, thymus organ coefficient and histopathology of mice, it induced changes in oxidative stress-related indicators in thymic tissue, promoted cellular autophagy, apoptosis, and inflammation in the thymic tissue, with observed gender difference.

Objective:To study the correlation between spontaneous cerebrospinal fluid rhinorrhea and increased intracranial pressure.Methods:Clinical data of patients with spontaneous cerebrospinal fluid rhinorrhea treated in the Department of Otorhinolaryngology of the Provincial Hospital of Shandong First Medical University from January 2019 to December 2023 and their epidemiology, clinical symptoms and signs, preoperative cerebrospinal fluid pressure, imaging data, leakage site, repair method and the presence or absebce of increased intracranial pressure were analysed. SPSS 23.0 software was used for statistical analysis.Results:Of the 57 patients with cerebrospinal fluid nasolacrimal leakage, 84.2%(48/57) were females and 15.8%(9/57) were males; 80.7%(46/57) were between 40 and 60 years old; and overweight and obese patients accounted for 75.4%(43/57). Of 57 patients, 35 patients received cranial MRI+magnetic resonance venography, and among them, 12(34.3%) patients were clinically with headache symptoms; the incidences of empty pterygoid and venous sinus stenosis were 40.0%(14/35) and 51.4%(18/35), respectively; and 33 patients underwent preoperative lumbar puncture examination, of whom 25(75.8%) patients had the increased cerebrospinal fluid pressure and 1 patient had idiopathic intracranial hypertension. All 57 patients underwent dural repair of the skull base, the postoperative follow-up period ranged from 3 to 60 months, and the success rate of surgery was 94.7%. The success rate was 100% in female patients and 33.3%(3/9) in male patients, including one with surgical failure receiving reoperation and two with postoperative recurrence in other areas of the skull base, with significant difference in the success rate of surgery between males and females (χ 2=16.890, P<0.001). Conclusions:Most patients with spontaneous cerebrospinal fluid rhinorrhea have the increased cerebrospinal fluid pressures, but very few fulfil the diagnosis of idiopathic intracranial hypertension. The success rate of surgical repair alone is high, but some recurrences still exist, especially in male patients.

Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Objective:To investigate the predictive value of the neutrophil/lymphocyte ratio (NLR) and triglyceride-glucose (TyG) index for no early neurological improvement (ENI) of non-diabetic patients with acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Non-diabetic patients with AIS received intravenous thrombolysis in the First Affiliated Hospital of Bengbu Medical University from January 2023 to December 2023 were retrospectively included. Their demographic and baseline clinical data were collected. ENI was defined by a ≥8-point improvement in the National Institutes of Health Stroke Scale (NIHSS) or an NIHSS score of 0 or 1 at 24 hours after intravenous thrombolysis. Multivariate logistic regression analysis was used to determine the independent influencing factors of ENI in patients with AIS after intravenous thrombolysis. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of NLR and TyG index for no ENI. Results:A total of 122 non-diabetic patients with AIS were enrolled, including 90 males (73.8%), aged 64.43±9.59 years, and 37 (30.3%) patients achieved ENI. Multivariate logistic regression analysis showed that the baseline NIHSS score (odds ratio [ OR] 1.110, 95% confidence interval [ CI] 1.007-1.224; P=0.036), NLR ( OR 1.199, 95% CI 1.001-1.437; P=0.001) and higher TyG index ( OR 2.069, 95% CI 1.009-4.244; P=0.047) were the independent predictors of no ENI. ROC curve analysis showed that the area under the curve of NLR predicting no ENI was 0.682 (95% CI 0.581-0.783; P=0.001). The optimal cutoff value was 3.44, and the specificity and sensitivity were 75.7% and 57.6%, respectively. The area under the curve of TyG index for predicting no ENI was 0.648 (95% CI 0.539-0.757; P=0.009). The optimal cutoff value was 8.785, and the specificity and sensitivity were 62.2% and 74.1%, respectively. Conclusion:NLR and TyG index have certain predictive value for no ENI in non-diabetic patients with AIS after intravenous thrombolysis.

Aim To dynamically characterize neuronal damage in the cortex and hippocampus of mice follow-ing acute cerebral ischemia/reperfusion(I/R).Meth-ods Male C57BL/6J mice weighing 25-28 g under-went middle cerebral artery occlusion using the fila-ment method,followed by 1 hour of reperfusion to es-tablish the acute cerebral I/R injury mouse model.The experiment comprised a sham surgery group,I/R-6 h group,I/R-24 h group,and I/R-72 h group.Longa neurological function score was used to assess the neu-rological function.Triphenyltetrazolium chloride(TTC)staining was conducted to detect cerebral in-farct volume.Hematoxylin and eosin(HE)staining was utilized to observe brain tissue pathological dam-age.Nissl staining was performed to evaluate neuronal damage.Immunofluorescence histochemistry staining was employed to assess the activation of astrocytes and microglia,as well as neuronal loss.Transmission elec-tron microscopy was used to examine mitochondrial damage in hippocampal neurons.Western blot analysis was conducted to detect the expression levels of mito-chondrial fission-fusion-related proteins p-Drp1/Drp1,Mff,Fis1,and OPA1.Results With prolonged cere-bral I/R time,neurological functional impairment,cerebral infarct volume,neuronal damage in the cortex and hippocampus,glial cell activation,neuronal loss,and mitochondrial damage gradually worsened in mice.The expression of mitochondrial fission-related proteins increased gradually,while the expression of mitochon-drial fusion-related proteins decreased gradually.Con-clusions Neuronal pathological damage,such as glial cell activation,neuronal loss,and mitochondrial dam-age,is gradually aggravated with prolonged cerebral I/R time,which may be associated with mitochondrial dynamics imbalance.

Objective To conduct a scoping review of research on the application of mobile health(mHealth)in the management of home enteral tube feeding,so as to provide references for future research and clinical practice.Methods A literature search was performed in the PubMed,Cochrane Library,Embase,Web of Science,CINAHL,CNKI,Wanfang,and CMB databases to identify relevant studies.The search period spanned from the establishment of databases until February 18,2024.According to the scoping review framework,2 researchers independently screened the studies,extracted the data of the included studies,and collaborated on the final analysis.Results A total of 24 studies were included.9 studies were conducted with interventions based on nursing models such as discharge planning model,"Hospital to Home"nutrition management model,guided care nursing model.The management forms included application,network communication software,and website.The content elements included education,assessment,consultation,referral,self-management,electronic health archive,appointment service,peer support.The outcome indicators included patients'physical and mental health,self-management ability,caregiver competence,family burden and user assessment.Conclusion The mHealth has played a positive role in the management of home enteral tube feeding.In the future,it is recommended to establish a multidisciplinary team to conduct high-quality research and continuously improve the form and content of mHealth management.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Humans ; Child ; COVID-19/complications* ; Brain Diseases ; Myositis/complications* ; Kidney ; Liver Failure, Acute/complications* ; Acute Kidney Injury/complications*