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.

Abstract To promote the high quality development of school meal services, and to shape civilized and healthy eating habits for children and adolescents, the study analyzes Finnish school meal services. Finnish school meal services are not only free of charge, nutritionally balanced, safe and hygienic, but also carry the educational function of edutainment in meals. In order to ensure the high quality and efficient operation of the school meal service system, Finland has built a horizontal collaborative governance model, that is, the departments of education, finance, health and quality inspection have a clear division of labor and respective responsibilities. China can learn from the experience of Finnish schools in meal services, strengthen financial and legal guarantees, develop the educational functions of school meal services, and make full use of information technology such as the Internet, the Internet of things, and big data to promote the high quality development of school meal services.

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

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 traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

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: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 To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.

Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.