Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Most patients with initial diagnosed lung cancer are at advanced ages.125I seeds implantation for treating lung cancer has advantages of high intratumoral dose and low radiation damage to surrounding tissue,especially suitable for elderly patients not able to tolerate surgery nor external radiotherapy.The efficacy and prospects of 125I seeds implantation for treating middle-late stage lung cancer in elderly patients were reviewed in this article.

Objective:To explore the potential categories and associated factors of mild cognitive impairment (MCI) in community-dwelling older adults.Methods:A total of 393 community-dwelling older adults with MCI in Huzhou City were selected through multistage random sampling from January to July 2022.The survey was conducted by the general information questionnaire, Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI) and 15-item geriatric depression scale(GDS-15). Latent profile analysis (LAP) was applied to explore latent categories based on the characteristics of cognitive impairment, and Logistic regression analysis was performed to examine the factors associated with these MCI categories. The statistical software was SPSS 26.0.Results:The community-dwelling older adults with MCI was categorized into four subgroups: generalized mildly impaired subgroup, mixed impaired with visuospatial executive dysfunction subgroup, narrative memory dysfunction impaired subgroup, and high-risk severely impaired subgroup, with corresponding MoCA scores of (23.10±0.96), (21.87±0.92), (20.43±0.93), (19.00±0.00), PSQI scores of (6.00 (4.00)), (7.00 (6.00)), (7.00 (6.00)), (10.00 (3.00)), and GDS-15 scores of (4.00 (4.00)), (4.00(5.00)), (6.00(5.00)), (8.00 (3.00)), respectively. Logistic regression analysis revealed that compared to generalized mildly impaired subgroup, gender, age, exercise habits, sleep quality, depressive symptoms, chronic disease count, and medication count significantly affected other three subgroups, with female, older age, and never/irregular exercise as common risk factors. Poor sleep quality and depressive symptoms could positively predict mixed impaired with visuospatial executive dysfunction subgroup and narrative memory dysfunction impaired subgroup( B=0.82, OR=2.27, 95% CI=1.26-4.08; B=1.12, OR=3.06, 95% CI=1.36-6.91).Additionally, poor sleep quality, depressive symptoms, chronic disease and medication count could significantly predict high-risk severely impaired subgroup ( B=4.13, OR=62.32, 95% CI= 1.71->999.99; B=3.31, OR=27.49, 95% CI=1.37-549.99; B=1.20, OR=3.32, 95% CI= 1.06-10.41 and B=0.80, OR=2.22, 95% CI=1.04-4.71). Conclusion:Four latent MCI categories are identified among community-dwelling older adults, and each category was characterized by unique cognitive impairment features and factors. Healthcare professionals are advised to customize assessments and management strategies according to these specific characteristics to effectively slow cognitive decline.

Objective:To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome (XFS).Methods:A total of 20 patients were enrolled in the Department of Ophthalmology, People's Hospital of Hotan District from June 2020 to January 2021, including 10 patients with age-related cataract and 10 XFS patients combined with cataract, which were classified as cataract group and XFS group, respectively.A total of 50 to 100 μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group, and the differentially expressed proteins (DEPs) in XFS group were screened according to P<0.05 and fold change >1.5.Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-21).Written informed consent was obtained from each subject. Results:In comparison with the cataract group, 25 DEPs were identified in the XFS group, primarily involved in cell adhesion, receptor, hydrolase, and molecular transport.Specifically, there were 14 down-regulated proteins including complement factor H-related protein 1 (CFHR1), endoplasmic reticulum chaperone BiP (HSPA5), biglycan (BGN), FRAS1-related extracellular matrix protein 2 (FREM2), hemoglobin subunit delta (HBD), hemoglobin subunit gamma-1 (HBG1), lysosomal thioesterase PPT2 (PPT2) etc., and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2 (LTBP2), very low-density lipoprotein receptor (VLDLR), laminin subunit alpha-2 (LAMA2), coagulation factor Ⅸ (F9).Among them, FREM2 was the most significantly differentially expressed protein in XFS group with consistent expression levels across individual samples.GO analysis revealed that these DEPs mainly localized to the extracellular matrix of collagen, bound globin-hemoglobin complex, plasma lipoprotein particles and lysosomes.Molecular functions and biological processes showed that HBD and HBG1 were involved in cellular detoxification, PPT2 in hydrolase activity, and BGN and LTBP2 in glycosaminoglycan binding.KEGG signaling pathway analysis indicated that CFHR1 and F9 were associated with complement and coagulation cascade pathways, and FREM2 and LAMA2 were linked to the extracellular matrix interaction pathway.Conclusions:Disease progression of XFS may be associated with changes in extracellular matrix proteins, disruption of the blood-aqueous humor barrier, and potential inflammatory responses.The significant down-regulation of FREM2 protein may be a potential biomarker for XFS.

Objective To investigate the effect of core decompression combined with bone-morphogenetic proteins(BMP)activity inducing rod implantation in the treatment of early-stage femoral head necrosis.Methods Retrospective analysis of 116 patients with early-stage femoral head necrosis from June 2018 to June 2022 were divided into core decompression combined with BMP activity inducing rod group(BMP group)and allograft bone group.Sixty cases in the BMP group were treated with core decompression combined with implantation of BMP-activated induced rods,and 56 cases in the allograft group were treated with core decompression combined with bone grafting of the allograft bone by punching and compression.The differences in hip Harris scores and visual analogue scores(VAS)of pain between the two groups at preoperative,6 months postoperative and 1 year postop-erative,and the patient treatment response and femoral head survival rate at 1 year postoperative were compared.Results All patients were followed-up,and the difference between the preoperative VAS score and Harris score of the two groups was not statistically significant(P＞0.05),and the VAS score and Harris score of the two groups were significantly improved at 6 months and 1 year after operation,and the BMP group was better than the allograft bone group,with significant difference(P＜0.05).At 1 year after surgery,the Harris hip score excellence rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05);the femoral head survival rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05).Conclusions Core decompression combined with BMP activity induced rod implantation was effective in the treatment of early femoral head necrosis,which accelerated the induction of new bone formation,improved the quality of new bone,provided biomechanical support for the femoral head,and effectively avoided femoral head collapse.Moreover,it has good biocompatibility and couldbe degraded and absorbed in the body,which is worthy of clinical promotion.

The vagus nerve plays an important role in maintaining physiological homeostasis,including reflex path-ways that regulate cardiac function.The anti-inflammatory potential of vagus nerve stimulation receives increasing atten-tion.This article reviews the application and possible mechanisms of vagus nerve stimulation in the treatment of cardiovas-cular disease,with the expectation that it will provide new therapeutic approaches for the treatment of cardiovascular dis-ease.

Objective:To explore the application effect of ultrasound evaluation of atelectasis in general anesthesia.Methods:Eighty patients who underwent general anesthesia surgery at the Second Affiliated Hospital of Wannan Medical College from January 2019 to December 2020 were selected as the study subjects. The gold standard was chest CT diagnosis of perioperative atelectasis, and they were divided into atelectasis group (39 cases) and control group (41 cases). Twelve regional images, including left upper anterior chest, left lower anterior chest, right upper anterior chest, right lower anterior chest, left upper chest, left lower chest, right upper chest, right upper chest, right lower chest, right upper chest, right lower chest, right upper chest, right lower chest, right lower chest, right lower chest, left upper chest, right lower chest, left upper chest, right lower chest, left upper posterior region, left lower chest, left lower posterior region, left lower posterior region, right upper posterior region, and right lower posterior region, were collected by pulmonary ultrasound (LUS) at time points T 1 after entering the room, 30 minutes after tracheal intubation (T 2), 30 minutes after extubation (T 3), 24 hours after surgery (T 4), and 48 hours after surgery (T 5), And an improved semi quantitative scoring method for evaluating lung ventilation was used to compare the LUS scores of the two groups at 5 time points. Results:There was no statistically significant difference in LUS scores between the two groups of patients in different lung zones at T 1 (all P>0.05); There are varying degrees of differences in LUS scores for the same lung partition at different times (all P<0.05). There was no statistically significant difference in LUS scores between T 2 and T 5 for left upper anterior chest, left lower anterior chest, right upper anterior chest, left upper chest, right upper chest, left upper posterior region, and right upper posterior region (all P>0.05); The LUS scores of the T 2-T 5 atelectasis group in the lower left chest, lower right chest, lower left posterior area, and lower right posterior area were higher than those of the control group (all P<0.05). Conclusions:LUS can be used to evaluate atelectasis during general anesthesia and has broad clinical application and promotion value.

Objective:To construct an analytic method aimed at the characteristics of the commonly method of supplementing and pouring of acupuncture based on the analysis and modeling of ultrasound images around acupoint region in the process of acupuncture.Methods:A total of 7 healthy subjects who underwent physical examination in Beijing Zhongguancun Hospital from June,2022 to June,2023 were selected,and their Kongzui acupoints were acupunctured by 10 acupuncturists with associate senior title as 4 kinds of acupuncture manipulations included reinforcing by twisting and rotating(RFTR),reducing by twisting and rotating(RDTR),reinforcing by lifting and thrusting(RFLT),and reducing by lifting and thrusting(RDLT).The B-ultrasound diagnostic device was used to collect the images of muscle and fascial tissue below the acupoint,so as to construct the model of images.The definition of virtual acupuncture point was adopted to study the regulation of perturbation of subcutaneous tissue that was caused after the skin was acupunctured by needle.The change regulation of the virtual acupuncture point of muscle bundle below skin at Zuikong acupoint of subjects was analyzed.Results:The difference value of average absolution value between peak and trough of the trajectory of virtual acupuncture point of twisting and rotating was 0.066±0.045,and the average value of amplitude of this method was less than that(0.428±0.276)of lifting and thrusting method,and the twisting and rotating method was uniform and symmetrical,and there was difference between two kinds of acupuncture methods.The characteristics of computer graphics was used to qualify the work effect of lifting and thrusting,and reinforcing and reducing,which showed the heavy insertion and light lifting of RFLT,and showed heavy lifting and light insertion of RDLT,thus distinguished the two methods[(RFLT)and(RDLT)].Conclusions:The ultrasound imaging and computer graphics can be used to analyze the regularity of the common"reinforcing and reducing"method of acupuncture and moxibustion.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Pancreatic Neoplasms ; Pancreas ; Needles