Introduction: Current education on diabetes self-management is time-consuming as it is conducted face-to-face. This study aimed to evaluate the effectiveness of diabetes education via mobile application on hemoglobin A1c (HbA1c). Methodology: This was a double-blinded randomized controlled study conducted in the Department of Endocrinology, Hospital Pulau Pinang and Hospital Raja Permaisuri Bainun. Participants were stratified randomized according to HbA1c to intervention group (using T-Manis) and control group. The primary objective was to assess the difference in HbA1c between the groups. Secondary objectives were to assess the difference in body weight, hospitalization related to diabetes, diabetes knowledge between groups and usability and satisfaction of T-Manis. Laboratory investigations and questionnaires were conducted at baseline, 4 months and 8 months. Results: A total of 112 participants were randomized into two groups each with 56 participants. Mean age was 51 years with similar diabetes duration of 16 years in both groups. Participants comprised of 61.6% females with ethnic distribution of 49.1% Malay, 30.4% Chinese, 19.6% Indian and 0.9% Siamese. Baseline HbA1c levels were comparable between intervention and control groups (10.04% versus 9.91%; mean difference 0.13%; 95% CI −0.56 to 0.81; p = 0.718). At 4 months, HbA1c of the intervention group demonstrated a significant reduction compared to the control group (8.93% versus 9.80%; mean difference −0.86; 95% CI −1.59 to −0.14; p = 0.02). Sustained reduction of HbA1c in the intervention group was observed at 8 months (mean difference −1.01; 95% CI −1.85 to −0.16; p = 0.02). Baseline body weight was 77 kg, with no betweengroup differences in body weight, hospitalization related to diabetes and diabetes knowledge scores, although diabetes knowledge scores improved at 4 months in the intervention group. 89.3% of participants reported satisfaction with T-Manis Conclusion The T-Manis mobile application aided in significantly improving glycemic control with high user satisfaction, supporting its feasibility as an adjunct to standard diabetes care.
Diabetes Mellitus, Type 2 ; Glycemic Control ; Mobile Applications ; Pangolins

Risk prediction models for postoperative pulmonary complications (PPCs) can assist healthcare professionals in assessing the likelihood of PPCs occurring after surgery, thereby supporting rapid decision-making. This study evaluated the merits, limitations, and challenges of these models, focusing on model types, construction methods, performance, and clinical applications. The findings indicate that current risk prediction models for PPCs following lung cancer surgery demonstrate a certain level of predictive effectiveness. However, there are notable deficiencies in study design, clinical implementation, and reporting transparency. Future research should prioritize large-scale, prospective, multi-center studies that utilize multiomics approaches to ensure robust data for accurate predictions, ultimately facilitating clinical translation, adoption, and promotion.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To investigate the impacts of the radiosensitivity of cell lines on a microdosimetric kinetic model (MKM) used in carbon-ion radiotherapy.Methods:The saturation-corrected specific energy ( ) of monoenergetic carbon ions was calculated using the Kiefer-Chatterjee (K-C) track structure model. Correction curve f(LET) was derived from experimental data on relative biological effectiveness (RBE) (RBE DSB-LET) defined based on the double-strand DNA break of the Chinese hamster ovary (CHO) and Fibroblast cell lines irradiated using carbon ions with varying linear energy transfer (LET) values. Then, based on the MKM, the D10-LET curves, as well as α and β databases, of the CHO and Fibroblast cell lines with varying radiosensitivity were determined. Results:Compared to the clinically applied MKM, the predicted D10 after correction while accounting for cell line radiosensitivity agreed better with experimental D10 values of the CHO and Fibroblast cell lines. Specifically, compared to experimental values in the literature, the D10 values calculated in the study and determined using the MKM showed mean squared errors (MSEs) of 0.04 and 0.71, for the CHO cell line and 0.35 and 0.55, respectively, for the Fibroblast cell line. For monoenergetic carbon ions with varying LET values, the calculated α and β values generally increased with cellular radiosensitivity. Conclusions:Incorporating cellular radiosensitivity into the MKM framework serves as a more specific method for RBE assessment while also providing a reference for advancing MKM applications and achieving the fine-scale calculations of RBE in carbon-ion radiotherapy.

Objective:To explore the clinical efficacy of periosteal induction technique combined with transfer of sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect.Methods:Clinical data, from January 2017 to December 2022, of 17 patients in the Army Institute for Traumatic Orthopaedics, the 920th Hospital of Joint Service Force of the Chinese People’s Liberation Amy with post-traumatic calcaneal osteomyelitis combined with soft tissue defect were retrospectively studied. The patients were 11 males and 6 females, with 46.5 (17-68) years in average. All patients received surgical treatment with periosteal induction technique in 2 phased surgies. Thorough debridement, antibiotics blended bone cement filling and wound coverage with sural neurovascular flap were carried out in phase-I surgery; The phase-II surgery were performed at 6-8 weeks after infection control to remove bone cement and then to transfer bone grafts for periosteal induction. After surgery, flap healing and infection control were observed. The infection control, pain improvement, recovery of ankle function and improvement of quality of life were evaluated by comparison of following parameters before and after surgery per phase: infection indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], Visual Analogue Scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and MOS 36-item Short form Health Survey (SF-36, Boston Institute of Health, USA).Results:All 17 patients completed the two-phased surgical treatment, with an average interval of 9.4 (8-16) weeks between phase-I and phase-II surgery. All patients were included in the postoperative follow-up of 25.8 (13-40) months. After debridement in phase-I surgery, the sizes of soft tissue defect were found at 3.0 cm×2.0 cm-6.0 cm×8.0 cm. All flaps survived from the reconstructive surgery of sural neurovascular flap. Postoperative distal flap necroses occurred to 4 patients but all healed after further debridement. Recurrence of postoperative infection occurred to 2 patients and the infection control was achieved after the phase-I rescue surgery. Good outcomes without recurrence of infection were achieved after phase-II surgery. The postoperative follow-up at 1 year after phase-II surgery showed a statistically significant improvement of infection in blood indicators and reductions in VAS score, AOFAS ankle-hindfoot score and SF-36 score in comparison with those before surgery ( P<0.05). In addition to WBC, there were also significant differences in pairwise comparisons between each group at different time points ( P<0.05). Conclusion:In the treatment of post-traumatic calcaneal osteomyelitis with soft tissue defect, a combination of periosteal induction technique and sural neurovascular flap is beneficial to infection control, bone defect reconstruction, recovery of ankle function and improvement of quality of life.

BACKGROUND:Pyroptosis,as a unique form of inflammatory cell death,plays an important role in the instability of atherosclerotic lesions.OBJECTIVE:To explore the action mechanism of recombinant B-cell lymphoma 2-related protein A1(BCL2A1)in atherosclerosis.METHODS:(1)Human umbilical vein endothelial cells were treated with 200 μg/mL oxidized low-density lipoprotein for 24 hours to induce endothelial injury.Subsequently,50 nmol/L BCL2A1 interfering plasmid(BCL2A1 short hairpin RNA,sh-BCL2A1)and 1.5 μg/mL histone deacetylase 1 gene(HDAC1)overexpression vector(pcDNA-HDAC1)was transfected into human umbilical vein endothelial cells,or both pcDNA-HDAC1 and BCL2A1 overexpression vector(pcDNA-BCL2A1)were transfected simultaneously.After 48 hours of cell culture,the expression levels of BCL2A1 and HDAC1,cell viability,cell pyroptosis level,and BCL2A1 acetylation level were detected.(2)The atherosclerosis mouse model was constructed by high-fat feeding APOE-/-mouse for in vivo verification.500 μL of BCL2A1 and HDAC1 lentiviral overexpression vectors were injected into mice via tail vein,respectively or simultaneously.The expression levels of BCL2A1 and HDAC1 and the damage of arterial tissue in mice were detected.RESULTS AND CONCLUSION:The expression of BCL2A1 was upregulated in human umbilical vein endothelial cells induced by oxidized low-density lipoprotein.Interference of BCL2A1 improved cell viability and inhibited pyroptosis and inflammatory response.In addition,HDAC1 was down-regulated in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells.Cell viability was elevated and pyroptosis and inflammatory response were inhibited by promoting BCL2A1 deacetylation.In vivo experiments showed that BCL2A1 was highly expressed in arterial tissues of mice fed with high-fat diet,while HDAC1 was lowly expressed.Additionally,HDAC1 alleviated high-fat diet-induced arterial tissue lesions in ApoE-/-mice by promoting the deacetylation of BCL2A1.It is concluded that HDAC1 may inhibit pyroptosis of human umbilical vein endothelial cells by deacetylating BCL2A1 to reduce atherosclerosis and inflammatory response.

Objective:To explore the characteristics of social skills and problem behaviors of children and adolescents with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), as well as the association with core symptoms.Methods:A total of 409 patients aged 5-18 years old with ASD or ADHD in the outpatient department of Nanjing Brain Hospital from 2023 to 2024, and 344 children and adolescents with typical development(TD) were recruited.All participants were matched in a ratio of 1∶1∶1 (ASD∶ADHD∶TD) according to gender and age, and 97 participants were included in each group for analysis.The Chinese version of the social skills improvement system rating scales(SSIS-RS-C) was used to evaluate social skills and problem behaviors, and autistic child behavior checklist(ABC), childhood autism rating scale(CARS), the Chinese version of the social communication questionnaire(SCQ) and the Chinese version of Swanson, Nolan, and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ) were used to evaluate the core symptoms of ASD and ADHD, respectively. SPSS 26.0 software was used to perform variance, Chi-square test, Spearman correlation analysis and multivariate Logistic regression analysis.Results:The social skills score of ASD group was lower than ADHD group ((61.53±24.26) vs (80.89±15.19), P<0.05), while the problem behavior score of ASD group was higher than ADHD group ((38.82±11.92) vs (34.00±12.45), P<0.05). In ASD group, the scores of ABC, CARS and SCQ were negatively correlated with the score of social skills ( r=-0.26--0.55, P<0.05). In ADHD group, the total score and each subscale of SNAP-Ⅳ were positively correlated with the score of problem behavior ( r=0.25-0.65, P<0.05). Multivariate Logistic regression analysis showed that empathy was a negative influencing factor of ASD ( B=-0.246, OR=0.782, P<0.05), and hyperactivity/inattention was a positive influencing factor of ASD ( B=0.589, OR=1.802, P<0.01), while only hyperactivity/inattention was a positive influencing factor of ADHD( B=0.779, OR=2.180, P<0.01). Conclusion:Children and adolescents with ASD and ADHD both have defects in social skills and problem behaviors, and these defects are associated with the core characteristics of their respective diseases.

OBJECTIVE To investigate the effect of dopamine receptor 3(D3R)on fear memory induced by intense electric shocks and the possible neurobiological mechanism.METHODS ① To prevent pain threshold differences from influencing the effect of intense electric shocks,wild-type(WT)and D3R knockout mice(D3R-/-)were used in the Hargreaves test to evaluate their basal pain threshold,with the paw withdrawal latency(PWL)as the observation index.② WT and D3R-/-mice were divided into control groups and model groups,respectively.On the training day(the first day,D 1),the model groups received inescapable electric shocks(1.5 mA,10 s,10 s interval,15 cycle)while the control groups did not.Contextual fear tests were conducted on D2,D7,D10,D14,and D16 after training,with the percentage of freezing time(FT)as the observation index to evaluate fear memory acquisition induced by contextual cues.On D17,after the model groups showed no more fear responses to contex-tual cues,they were re-stimulated with low-intensity current(0.5 mA,10 s,10 s interval,15 cycle)to evoke fear memory.The two control groups did not receive any shocks.Contextual fear tests were conducted on day 18,and the FT%of each group was observed to evaluate fear memory retrieval induced by contextual cues.③ Another cohort of WT and D3R-/-mice was used to further investigate the underlying neural mechanism,with the same grouping and treatment as in ②.Real-time dynamic changes in calcium signals of dopamine(DA)neurons in the ventral tegmental area(VTA)of WT and D3R-/-mice were detected using fiber photometry during electric shocks.The fluorescence area under the curve(AUC)was used as the indicator to quantify the excitability of DA neurons.RESULTS ① In the Hargreaves test,there was no significant difference in PWL between D3R-/-mice and WT mice,indi-cating the two genotype mice had no significant differences in the basal pain threshold.② Compared with the WT control group,the percentage of FT of the WT model group significantly increased on D2,D7,D10,and D14(P<0.05).Compared with the D3R-/-control group,the percentage of FT of the D3R-/-model group significantly increased only on D2 and D7(P<0.01).Meanwhile,the percentage of the FT of D3R-/-model group was significantly lower than in the WT control group on D2,D7,D10,and D14(P<0.05,P<0.01).During memory recall(D18),the percentage of FT of the WT model and D3R-/-model groups significantly increased compared to their respective control groups(P<0.01,P<0.05),while the percentage of FT of D3R-/-model mice was significantly lower than that of WT model mice(P<0.01).③ In the fiber photometry test,during the shock period,the calcium signals of DA neurons in the VTA of WT model and D3R-/-model mice rapidly increased within the first 2 s,and then gradually decreased between 2 to 10 s.The AUC within the 2 to 10 s interval was significantly lower in D3R-/-model mice compared to WT model mice(P<0.05),indicating that the excitability of DA neurons in the VTA of D3R-/-model mice was significantly lower than that of WT-model mice.CONCLUSION D3R knockout inhibits the acquisition and recall of long-term fear memory in mice,and its neurobiological mechanism may be related to the decreased excitability of DA neurons during electric shock.

BACKGROUND:Pyroptosis,as a unique form of inflammatory cell death,plays an important role in the instability of atherosclerotic lesions.OBJECTIVE:To explore the action mechanism of recombinant B-cell lymphoma 2-related protein A1(BCL2A1)in atherosclerosis.METHODS:(1)Human umbilical vein endothelial cells were treated with 200 μg/mL oxidized low-density lipoprotein for 24 hours to induce endothelial injury.Subsequently,50 nmol/L BCL2A1 interfering plasmid(BCL2A1 short hairpin RNA,sh-BCL2A1)and 1.5 μg/mL histone deacetylase 1 gene(HDAC1)overexpression vector(pcDNA-HDAC1)was transfected into human umbilical vein endothelial cells,or both pcDNA-HDAC1 and BCL2A1 overexpression vector(pcDNA-BCL2A1)were transfected simultaneously.After 48 hours of cell culture,the expression levels of BCL2A1 and HDAC1,cell viability,cell pyroptosis level,and BCL2A1 acetylation level were detected.(2)The atherosclerosis mouse model was constructed by high-fat feeding APOE-/-mouse for in vivo verification.500 μL of BCL2A1 and HDAC1 lentiviral overexpression vectors were injected into mice via tail vein,respectively or simultaneously.The expression levels of BCL2A1 and HDAC1 and the damage of arterial tissue in mice were detected.RESULTS AND CONCLUSION:The expression of BCL2A1 was upregulated in human umbilical vein endothelial cells induced by oxidized low-density lipoprotein.Interference of BCL2A1 improved cell viability and inhibited pyroptosis and inflammatory response.In addition,HDAC1 was down-regulated in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells.Cell viability was elevated and pyroptosis and inflammatory response were inhibited by promoting BCL2A1 deacetylation.In vivo experiments showed that BCL2A1 was highly expressed in arterial tissues of mice fed with high-fat diet,while HDAC1 was lowly expressed.Additionally,HDAC1 alleviated high-fat diet-induced arterial tissue lesions in ApoE-/-mice by promoting the deacetylation of BCL2A1.It is concluded that HDAC1 may inhibit pyroptosis of human umbilical vein endothelial cells by deacetylating BCL2A1 to reduce atherosclerosis and inflammatory response.