OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

OBJECTIVES: To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells. METHODS: The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both. RESULTS: LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown. CONCLUSIONS LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Cell Proliferation ; Cell Movement ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung ; Neoplasm Invasiveness ; A549 Cells ; Adenocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective:To summarize the experience of designing hair transplantation for post-cleft lip repair moustache defects based on the morphological and tissue characteristics of the upper lip.Methods:A retrospective analysis was conducted on the clinical data of male patients treated at the Hair Transplantation Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2011 to July 2024. Based on the morphology and tissue texture of the upper lip after cleft lip repair, the position and shape of the moustache were designed. Hair follicles were harvested from the mid-occipital region and/or the jaw shadow area using either the strip harvesting method or the follicular unit excision (FUE) technique. Needles of 21 or 22 gauge were used to create incisions in the recipient sites down to the superficial subcutaneous layer. The hair shafts were clamped with micro-forceps and then transplanted into the recipient sites to restore the moustache shape. Postoperatively, the density, shape, direction of the moustache, and the condition of the donor site scars were observed and followed up.Results:A total of 47 male patients, aged 23-43 years (mean 28.7 years), were included. Among them, 29 had undergone lower triangular flap repair, 13 received the Millard technique, and 5 were treated with other surgical methods for cleft lip repair. For hair follicle extraction, the strip method was used in 7 cases, and FUE in 40 cases. The donor sites included the jaw shadow area (9 cases), mid-occipital region (23 cases), and a combination of both (15 cases). The number of transplanted follicular units ranged from 33 to 500 (mean 217). Follow-up duration ranged from 9 months to 10 years (mean 3.5 years). Postoperative complications included folliculitis in 6 cases, and 4 cases required additional transplantation due to insufficient density after one year. The remaining patients exhibited satisfactory hair growth, with natural mustache shape and direction. The graft survival rate was approximately 80%, and donor site scarring was minimal.Conclusion:When performing hair transplantation to treat post-cleft lip repair moustache defects, the design should prioritize the morphological and tissue characteristics of the upper lip, followed by consideration of overall position and bilateral symmetry of the moustache. Only by fully considering the characteristics of the recipient area can optimally repair outcomes be achieved.

Objective:To investigate the effects of a low-energy balanced diet combined with exercise intervention on glycolipid metabolism levels in children with simple obesity.Methods:A prospective randomized controlled trial was performed in this study. Forty children with simple obesity who attended the pediatric outpatient department of Tangshan Maternal and Child Health Care Hospital in Hebei Province from January 2022 to January 2024 were selected and randomly divided into two groups using a random number table: an observation group ( n=22) and a control group ( n=18). No weight-loss products were used by any children in either group. The control group received exercise intervention alone, while the observation group received a combined intervention of exercise and a low-energy balanced diet. The intervention lasted for 8 weeks for both groups. The differences in energy intake during the intervention, as well as body weight, body mass index (BMI), waist circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), and adiponectin levels before and after the intervention were compared between the two groups. Measurement data with normal distribution were expressed as Mean±SD, inter-group comparisons were performed by independent samples t-test, and within-group comparisons before and after treatment were performedby paired t-test. Counting data were expressed as case (%), and inter-group comparisons were performed by χ2 test. Results:The energy intake during the intervention was lower in the observation group than in the control group [(1 450±180) kcal/d vs. (1 780±205) kcal/d, t=-5.35, P<0.001]. Before the intervention, there were no statistically significant differences in body weight, BMI and waist circumference between the two groups (all P>0.05). After 8 weeks of intervention, body weight, BMI, and waist circumference decreased significantly compared to pre-intervention levels in both groups [Control group: (62±12) kg vs. (64±13) kg, (26.4±2.9) kg/m 2 vs. (27.9±3.4) kg/m 2, (85±7) cm vs. (91±7) cm, t=7.23, 9.07, 12.31, respectively, all P<0.001; Observation group: (59±16) kg vs. (65 ± 17) kg, (23.3±4.3) kg/m 2 vs. (28.5±4.1) kg/m 2, (82±9) cm vs. (92±10) cm, t=24.90, 17.93, 21.40, respectively, all P<0.001]. Furthermore, the post-intervention values for body weight, BMI, and waist circumference were significantly lower in the observation group than in the control group ( t=-10.89, -18.92, -5.16, respectively, all P<0.001). Before the intervention, there were no statistically significant differences in FBG, FINS, TG, TC, or adiponectin levels between the two groups (all P>0.05). After 8 weeks of intervention, FBG, FINS, TG, and TC levels decreased significantly compared to pre-intervention levels in both groups [Control group: (4.99±0.26) mmol/L vs. (5.22±0.27) mmol/L, (24±6) mU/L vs. (26±8) mU/L, (1.3±0.5) mmol/L vs. (1.5±0.4) mmol/L, (4.3±0.6) mmol/L vs. (4.5±0.6) mmol/L, t=19.75, 6.69, 7.64, 18.27, respectively, all P<0.001; Observation group: (4.64±0.34) mmol/L vs. (5.31±0.26) mmol/L, (16±5) mU/L vs. (21±10) mU/L, (1.0±0.3) mmol/L vs. (1.4±0.5) mmol/L, (4.0±0.8) mmol/L vs. (4.5±0.8) mmol/L, t=19.66, 8.82, 11.26, 22.68, respectively, all P<0.001]. Adiponectin levels increased significantly in both groups [Control group: (8.0±1.2) mg/L vs. (6.8±1.1) mg/L , t=8.38, P<0.001; Observation group: (8.8±1.1) mg/L vs. (6.8±1.2) mg/L, t=23.78, P<0.001], while the improvements in all these glycolipid metabolic parameters were significantly greater in the observation group than in the control group ( t=3.70, 2.76, 2.42, 2.22,2.14, P=0.001, 0.009, 0.020, 0.027, 0.039). Conclusion:The combined intervention of a low-energy balanced diet and exercise can reduce body weight, blood glucose, and blood lipid levels in obese children, thereby improving their glycolipid metabolism.