Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

OBJECTIVE To conduct rapid health technology assessment （HTA） of ulinastatin （UTI）， and to evaluate the efficacy， safety and cost-effectiveness of UTI in the treatment of acute pancreatitis （AP）. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang database， CBM and official websites of HTA institutions， the systematic review （SR）/meta-analysis， economic evaluation and HTA reports of UTI in the treatment of AP were collected from the inception to Apr. 2024. Two researchers independently conducted screening， quality evaluation and data extraction according to the admission and exclusion criteria， and descriptive analysis was adopted to analyze and summarize the data. RESULTS A total of 19 studies were included， involving 15 SR/meta-analysis and 4 economic studies， and no HTA report was retrieved. In the treatment of AP， UTI showed clear advantages over conventional treatment alone in terms of improving the overall effective rate， shortening the recovery time of amylase， reducing the time required to relieve abdominal pain and distension， lowering the mortality rate， and decreasing the average hospital stay. Compared to other positive drugs （carbendate mesylate， octreotide， somatostatin， etc.）， its efficacy is similar， with a favorable safety profile. As far as the current research was concerned， UTI had obvious economic advantages over other positive drugs. CONCLUSIONS UTI is safe and effective in the treatment of AP， and has economic advantages.

Objective:To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration.Methods:A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson′s correlation to assess the relationship between MAA and degree of hearing loss.Results:MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss ( r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration ( F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions:The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.

Objective:To study the effects and the related molecular mechanisms of miR-148a-3p on the proliferation,invasion and migration of salivary adenoid cystic carcinoma SACC-LM cells.Methods:miR-148a-3p mimics and inhibitors,siRNA targeting EG-FR and their corresponding controls were transfected into SACC-LM cells.Bioinformatics was used to predict the potential target genes of miR-148a-3p.EGFR and miR-148a-3p mRNA expression levels were examined by qRT-PCR and the protein levels of EG-FR were detected by Western blotting.CCK-8,scratch,and Transwell assays were used to study the proliferation,migration,and invasion of SACC-LM cells,respectively.The direct targeting relationship between miR-148a-3p and EGFR was examined by using the double luciferase reporter gene assay.Statistical analysis of the data was performed by SPSS 22.0 software.Results:Overexpres-sion or inhibition of miR-148a-3p significantly inhibited or promoted the proliferation,invasion and metastasis of SACC-LM cells re-spectively(P＜0.05).Bioinformatics and double luciferase assay showed that miR-148a-3p directly targeted and regulated the expres-sion of EGFR(P＜0.001).Downregulation of EGFR inhibited the proliferation,migration and invasion of SACC-LM cells(P＜0.05)and partially reversed the promoting effect of miR-148a-3p inhibition(P＜0.05).Conclusion:The downregulation of miR-148a-3p leads to the abnormally high expression of its target gene EGFR,and promotes the proliferation,invasion,and migration of salivary adenoid cystic carcinoma cells.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Periodontitis is closely related to systemic health,especially adverse pregnancy.Periodontal pathogens are actively in-volved in the formation and development of intrauterine infections.Studies have shown that infection by periodontal pathogens is an im-portant risk factor for adverse pregnancy.Periodontal pathogens reach the uterus via the hematogenous or retrograde route,and the bacte-ria,their virulence factors,and the immunoinflammatory mediators produced by the pathogens promote each other and together mediate the development of intrauterine infections and ultimately lead to adverse pregnancies.This article reviews the role of periodontitis and perio-dontal pathogens in adverse pregnancies and their mechanisms of infection to provide new possibilities for improving the birth rate.

OBJECTIVE To systematically evaluate the hemostatic effect and safety of snake venom hemocoagulase drugs in abdominal surgery， so as to provide evidence-based evidence for clinic. METHODS Retrieved from Embase， Cochrane Library， PubMed， China Biomedical Literature Database， CNKI and Wanfang database， randomized controlled trials （RCTs） about 3 kinds of snake venom hemocoagulase drugs （Hemocoagulase injection， Hemocoagulase Bothrops atrox for injection， Haemocoagulase Agkistrodon for injection） in abdominal surgery were collected from the establishment of the database to Aug. 2023. Screening， quality evaluation， and data extraction were conducted on literature according to the inclusion and exclusion criteria， and Cochrane 5.1 was used for literature quality evaluation. The risk bias diagram and network diagram were drawn by Stata 15.1 software， and the Bayesian network meta-analysis was carried out by using R 3.6.2 software and Markov chain-Monte Carlo method. RESULTS A total of 11 studies were included， involving 1 401 patients， 852 in the study group， and 549 in the control group. In terms of hemostatic effect， Hemocoagulase injection was significantly superior to Haemocoagulase Agkistrodon for injection [MD＝－2.45， 95%CI （－4.39，－0.24）， P＜0.05]， and the probability of reducing intraoperative bleeding was ranked as follows： Hemocoagulase injection＞hemocoagulase B. atrox for injection＞Haemocoagulase Agkistrodon for injection； in terms of safety， there was no statistically significant difference between the three snake venom hemocoagulase drugs and placebo （P＞0.05）. CONCLUSIONS The hemostatic effect of Hemocoagulase injection in abdominal surgery is significantly better than that of Haemocoagulase Agkistrodon for injection； all three snake venom hemocoagulase drugs have good safety.

Hospice care requires all-round care provided by medical staff for end-stage patients. Due to the particularity of its objects, nursing staff need to have a broader vision and practice ability, so as to play a professional role in the care of end-stage patients and their families. By combing the core elements of nursing staff’s hospice care practice ability, this paper analyzed the influencing factors of nursing staff’s hospice care practice ability, systematically summed up the intervention measures to improve nursing staff’s hospice care practice ability, and put forward the cultivation prospect and development expectation of nursing staff’s hospice care practice ability in China, so as to lay the foundation for the management and training of hospice care nursing staff.

OBJECTIVE According to the rapid Health Technology Assessment （HTA） for postmenopausal osteoporosis （PMOP），To evaluate the efficacy ，safety and economy of calcitonin in the treatment of PMOP ，and provide evidence -based medical evidence for clinical drug decision . METHODS Retrieved from the Cochrane Library ，PubMed，Embase，CNKI，Wanfang database，CBM and HTA official website ，systematic review/meta -analysis，pharmacoeconomics research and HTA reports about calcitonin in the treatment of PMOP were retrieved from the inception to Sept . 30th，2022. Two researchers independently carried out screening ，data extraction and quality evaluation ，and analyzed the data results descriptively . RESULTS A total of 18 studies were included ，including 12 SR/meta-analysis and 6 economic studies ，and no HTA report was retrieved . In terms of effectiveness ， the results of the included studies were basically consistent ：calcitonin had a certain advantage in reducing the incidence of vertebral fracture compared with calcium and lasoxifene alone ，but did not show clinical advantage compared with other positive drugs . In terms of reducing the incidence of non -vertebral fractures ， calcitonin had some advantages ，compared with calcium al one and raloxifene ，but did not show clinical advantage compared with other positive drugs . In terms of improving bone mineral density（BMD），only 2 studies showed that calcitonin had a certain advantage over calcium but no advantage was observed compared with other positive drugs . In terms of improving non - vertebral BMD ，only 1 study showed that calcitonin combined with calcium had certain advantages compared with calcium alone in improving femoral BMD ，but there was no advantage compared with other positive drugs . In terms of lowering bone pain scores ， both included studies demonstrated short -term benefit of nasal calcitonin in reducing acute pain was found in patients with vertebral fractures，but not in patients with chronic pain . In terms of safety ，the three included studies showed that calcitonin caused mild adverse reactions compared with other positive drugs ，but there was a risk of malignant tumors after long -term use . In terms of economy，only 1 study showed the use of nasal calcitonin in the treatment of PMOP had more economic advantages than no treatment or etidronate . CONCLUSIONS Calcitonin has a certain effect on reducing acute pain in patients with PMOP vertebral fracture，and its safety needs further investigation . No obvious economic advantage has been found .