In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

Objective: To systematically evaluate the association between maternal adverse childhood experiences (ACEs) and offspring social behavior, so as to provide a theoretical basis for further research on intergenerational social behavioral development. Methods: Relevant research literature about maternal ACEs and the development of children s maladaptive social behaviors were collected, from China National Knowledge Infrastructure (CNKI), VIP, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library, Embase and SpringLink databases, covering the period from the inception of each database to May 2025. The Chinese database matched and searched through three groups of keywords: "Pregnant women" "Mothers" and "Women"; "Bad childhood experience" "Bad early experience" and "Bad adolescent experience"; "Children" "Teenagers" "Children s behavior" "Children s development" "Teenagers behavior" "Internalized behavior" and "Externalized behavior". The English database was searched by three groups of keywords: "Female" "Pregnant women" "Mothers"; "Adverse childhood experiences" "Adverse early childhood experiences" "Adverse experiences of adolescent"; "Child behavior" "Child development" "Adolescent behavior" "Internalized behaviors" "Externalized behaviors". The selected literature was evaluated for quality and data extraction, with OR and 95% CI as effect indicators. Stata 16.0 software was used for heterogeneity testing, subgroup analysis, and publication bias analysis. Results: A total of 14 studies involving 64 302 mother-child pairs were included. The Meta analysis results showed a significant correlation between maternal ACEs and both offspring maladaptive internalized behaviors ( OR=1.75, 95%CI=1.42-2.15, P <0.01) and externalized behaviors ( OR=1.82, 95%CI=1.51-2.20, P <0.01). The results of subgroup analyses showed that in different regions[internalized behaviors:domestic, foreign OR (95% CI )=2.03(1.49-2.76), 1.55(1.19-2.03); externalized behaviors: domestic, foreign OR (95% CI )=2.41(1.52-3.82), 1.65(1.36-2.01)], study type[internalized behaviors: cohort study, cross sectional study OR (95% CI )=1.64(1.34-2.00), 1.85(1.30-2.65); externalized behaviors: cohort study, cross sectional study OR (95% CI )=1.76(1.46-2.12), 2.12(1.40-3.20)], sample size [internalized behaviors: ≥4 000, <4 000 pairs OR (95% CI )=1.69(1.13-2.55), 1.77( 1.41 -2.24); externalized behaviors: ≥3 000, <3 000 pairs OR (95% CI )=1.72(1.37-2.17), 2.13(1.44-3.15)], there were significant and positive association between mothers ACEs and children s internalizing and externalizing behaviors (all P <0.05). Conclusion A substantial positive association exists between maternal ACEs and the development of offspring maladaptive internalized and externalized behaviors, but the result needs to be continued to be validated by more research.

Visual electrophysiology measurements have become a routine method of functional examination in ophthalmology. Small animal visual electrophysiology is an important tool for exploring the functionality of the visual system in small animals, finding widespread applications in neuroscience and drug research and development. This guide aims to offer a standardized operational guide for the operation of visual electrophysiological norms in small animals to ensure the accuracy and repeatability of the test. The study emphasizes different types of visual electrophysiological tests, such as electroretinogram(ERG)and visual evoked potential(VEP), evoked in small animals, and their application in different disease models. Detailed descriptions are provided regarding the selection and preparation of experimental animals, including the requirements of animal species, anesthesia methods and test environment. In terms of operational procedures, this guide highlights the correct electrode placement, the selection of stimulus parameters, and the key steps for signal acquisition and processing. According to different animal models, the corresponding operation suggestions were provided, and the troubleshooting methods of common problems were introduced. Beyond fundamental operations, this guide also focuses on the interpretation and reporting of test results. It explains various types of electrophysiological waveforms. In summary, this operational specification for small animal visual electrophysiology provides a comprehensive and detailed framework for researchers to ensure the standardization and reliability of tests. By following these guidelines, researchers can effectively utilize small animal visual electrophysiology techniques to gain insight into the function and abnormalities of the visual system.

Objective: To explore the risk of endometrial polyp (EP) based on lipid metabolism and vaginal micro- ecology combined with uterine volume line drawing model. Methods: 143 EP patients treated by hysteroscopic sur- gery were selected as the experimental group , and 113 healthy women were selected as the control group at the same time. The data were randomly divided into training set and validation set according to the ratio of 7 : 3. The clinical data of the two groups were collected and recorded , and t/χ2 test , LASSO regression and multifactorial lo- gistic regression analysis were used to screen the independent risk factors , construct the prediction model , and draw the column line graph. The performance of the model was evaluated by applying subject operating characteristic (ROC) curves , calibration curves , Hosmer-Lemeshow test and clinical decision-making (DCA) curves. Results: Multifactorial logistic regression analysis showed that total cholesterol ( TC) , low-density lipoprotein cholesterol (LDL-C) , vaginal microecological balance , and uterine volume were independent risk factors for the development of EP. ROC curve analysis showed that the AUC values of the training and validation sets of the column line graph model were 0. 935 and 0. 887 , respectively , and its sensitivity and specificity were 90. 21% , 83. 46% and 86. 29% , 80. 66% respectively , The Hosmer-Lemeshow test showed that the model fits well ( training set : χ2 = 2. 261 , P = 0. 840 ; validation set : χ2 = 4. 837 , P = 0. 441) and the calibration curves of the training and validation sets were close to the ideal curves , which indicated that the model had good prediction accuracy; the analysis of DCA curves of the training and validation sets both showed that the column-line graph model had a good clinical benefit rate in predicting EP. Conclusion TC , LDL-C , vaginal microecological balance and uterine volume are independent risk factors for EP , and the column-line diagram model constructed by the model has high clinical ben- efit , calibration and accuracy in predicting the risk of EP.

Objective The quantitative analysis model of mifepristone binary mixed crystal system was established by infrared spectroscopy to improve the quality control level of Mifepristone raw material.Methods Two mifepristone polymorphs samples were prepared and characterized,and the quantitative analysis model of infrared spectral data was constructed by classical linear regression method and chemometrics method respectively.On this basis,the influence of different factors on the model quality was investigated comprehensively.Results Infrared spectroscopy combined with classical linear regression method and stoichiometric method can build a quantitative analysis model for binary mifepristone polymorphs system,and the model has good linear regression coefficient(R2)and root mean square error of cross validation(RMSECV)values.Conclusions The two polymorphs of mifepristone have independent infrared spectral characteristic peaks that can be used for quantitative study,so the classical linear regression method has more significant methodical advantages for this system.The chemometrics method is more suitable for the quantitative study of complex mixed polymorphs system.

In recent years,the demand for single enantiomer drugs has gradually increased,and the separation technology of chiral drugs has also been developed rapidly.In this article,we summarized the application and progress of cocrystal technology in chiral drug resolution,focusing on the existence forms of cocrystal former formations(single compound molecules,ions,and claths),the common preparation methods of cocrystal resolution,the physical and chemical factors affecting the resolution efficiency(co-formed chirality,solvent system,temperature)and the computer-aided prediction method of chiral cocrystal in the process of chiral drug resolution,to provide a reference for related research on chiral resolution using cocrystal technology.

Objective:To investigate the clinical effect of probiotic-assisted minocycline in the treatment of elderly patients with chronic periodontitis(CP).Methods:95 elderly patients with CP in our hospital from January 2021 to March 2023 were selected and divided into observation group(49 cases)and control group(46 cases)by random number table method.Both groups received oral health education,the control group received standard periodontal treatment,the observation group was given probiotic lozenges,and both groups were treated for 4 weeks.The therapeutic effect and occurrence of adverse reactions in the 2 groups were analyzed,and the periodontal index[loss of attachment(AL),probing depth(PD),bleeding index(BI)],oral flora(concentrations of Lac-tobacillus salivary and porphyromonas gingivalis)and oral health status[oral health assessment tool(OH AT)score]before and after treatment were compared.Results:No cases were excluded in 2 groups.After treatment,the total effective rate of observation group was 95.92％higher than that of control group 80.43％(P＜0.05).After treatment,the values of AL,PD and BI in the 2 groups were lower than before treatment(P＜0.05),and the values of AL,PD and BI in the observation group were lower than those in the control group(P＜0.05).After treatment,the concentration of porphyromonas gingivalis in saliva in 2 groups was lower than that be-fore treatment,and the concentration of lactobacillus in saliva was higher than that before treatment(P＜0.05).The concentration of porphyromonas gingivalis in saliva in observation group was lower than that in control group,and the concentration of lactobacillus in saliva was higher than that in control group(P＜0.05).After treatment,the OH AT score of the 2 groups was lower than that before treatment(P＜0.05),and the OHAT score of the observation group was lower than that of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Probiotics assisted mino-cycline in the treatment of elderly patients with CP can reduce periodontal index,regulate oral flora and improve oral health without increasing adverse reactions.

Objective To evaluate the effects of low-dose intrathecal morphine(ITM)combined with liposomal bupivacaine adductor canal block(LB-ACB)on postoperative analgesia and opioid-sparing efficacy in patients undergoing total knee arthroplasty(TKA).Methods In this randomized,double-blind,controlled trial,80 TKA patients were allocated to either an intervention group(ITM 0.1 mg+LB-ACB,n=40)or a control group(intrathecal saline+LB-ACB,n=40).Primary outcomes included resting/movement visual analog scale(VAS)scores at 6,12,24,48,and 72 hours postoperatively,48-hour morphine consumption,time to first rescue analgesia,and incidence of complications.Results(1)The intervention group showed significantly lower resting and movement VAS scores at 6,12,24,and 48 hours postoperatively compared with controls(all P<0.05),except at 72 hours(P>0.05).(2)The intervention group had a significant reduction in 48-hour morphine consumption(4.58±1.0 mg vs.9.34±4.8 mg,P=0.027),a significantly lower rescue analgesia rate(15.0%vs.47.5%,P=0.002),and a significantly prolonged time to first rescue analgesia(48.8±7.5 h vs.14.5±5.5 h,P<0.001).(3)The intervention group demonstrated a significant decrease in the incidence of nausea(from 15.0%to 35.0%,P=0.039)and vomiting(from 10.0%to 27.5%,P=0.045),but no significant differences were observed in the incidences of pruritus,urinary retention,or motor block(all P>0.05).Conclusion Low-dose ITM(0.1 mg)combined with LB-ACB significantly enhances early postoperative analgesia,reduces opioid consumption,and decreases nausea/vomiting risk,without increasing the risks of other complications.This regimen aligns with enhanced recovery after surgery(ERAS)principles.

Objective:To explore the latent class of childhood abuse and recent life stress in adolescent depression patients, and its effect on intermittent theta-burst stimulation (iTBS) treatment efficacy.Methods:From August 2023 to February 2024, a total of 60 adolescent patients with depression were enrolled. The Chinese version of the maltreatment and abuse chronology of exposure scale (MACE), adolescent self-rating life events check list (ASLEC), Montgomery-Asberg depression rating scale (MADRS)and suicidal ideation scale 5 (SSI-5)were used to assess all subjects. Using latent class analysis, subjects were divided into different subgroups according to 16 factors of MACE and ASLEC. Brain network analysis was conducted using the Dosenbach brain atlas with 160 regions of interest, which were divided into seven large-scale brain subnetworks: visual network (VN), somatosensory motor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), subcortical network (SCN), frontoparietal network (FPN), and default mode network (DMN). Brain network functional connectivity analysis was performed using the DPABI plugin on MATLAB R2022b platform to compare differences in functional connectivity at both edge and network levels between subjects. Data analysis was conducted using SPSS 27.0 software, employing Shapiro-Wilk test, chi-square test, independent samples t-test, and Mann-Whitney U test. Results:Based on latent class analysis, subjects were divided into high abuse-high stress group ( n=38) and low abuse-high stress group ( n=22). At baseline, the high abuse-high stress group showed significantly higher scores in SSI-5 (6.39±2.26 vs 3.45(0, 5.25)), Z=-3.628, P<0.001) and MADRS item 10 (3.00(2.00, 5.00) vs 2.00(0.75, 3.25), Z=-2.794, P=0.005) compared to the low abuse-high stress group, while there was no statistically significant difference in the total score of MADRS between the two groups (27.77±4.19, 26.59±4.74, t=1.972, P=0.053). There was no statistically significant difference in the D-value of MADRS score before and after treatment between the two groups (8.45±6.03, 7.27±5.99, t=0.729, P=0.469) and the D-value of MADRS item 10 score before and after treatment between the two groups (1.00 (0, 3.00), 1.00 (0, 1.00), Z=-1.189, P=0.234). The high abuse-high group showed significantly weakened functional connectivity at the edge level compared to low abuse-high stress group at baseline ( P<0.05, NBS corrected). In the high abuse-high stress group, the mean FC values in the differential brain regions at baseline showed significant negative correlation with baseline suicidal ideation scores ( r=-0.475, P=0.003). Conclusion:The different patterns of childhood abuse and recent life stress affect the baseline clinical presentation and brain network functional connectivity of adolescent depression patients. However, the high abuse-high stress group and low abuse-high stress group showed similar responses to iTBS treatment.

Objective This study aims to explore effective approaches for the transfer of medical scientific and techno-logical achievements to promote the development of research-oriented hospitals.Methods The technology transfer achievements of an affiliated hospital of a university in Guangdong Province over the past six years(2018-2023)were statistically analyzed.The challenges faced during the transfer process,the measures taken,and the current achievements were discussed.Results The number of patent authorizations and authorized departments in the hospital has increased year by year.The transfer rate has risen from 0％in 2019 to 6.69％in 2023.Currently,46 projects have been successfully transferred,with a total transfer amount exceeding 30 million yuan,indicating significant effectiveness in the transfer of medical scientific and technological achievements.Conclusion The hospital attaches great importance to and overall manages the transfer process,establishing a sound manage-ment structure,improving incentive and support systems,and regularly conducting special lectures,training,and guidance.These efforts guide researchers to start from clinical problems and ultimately serve clinical diagnosis and treatment,creating a fa-vorable environment for technology transfer,improving the transfer rate,and promoting the development of research-oriented hos-pitals.