Objective To establish and verify a time-resolved fluorescence immunochromatographic assay for the detection of S100B protein content based on double-antibody sandwich method,so as to provide a reliable method for the auxiliary diagnosis of neurological disorders and tumors.Methods Time-resolved fluorescent microspheres were used to label mouse anti-human S100B protein IgG2a monoclonal antibody(labeled antibody,clone number 22G7-3) and goat anti-chicken IgY antibody,respectively,and NC membranes were coated with mouse anti-human S100B protein IgG2a monoclonal antibody(coating antibody,clone number 5H2-3) and chicken IgY antibody as detection line(T line) and quality control line(C line),respectively,to prepare fluorescent immunochromatographic test strips.The coating antibody concentration(0.5,1,1.5,2 mg/mL),labeled antibody concentration(5,10,15,20 μg/mL) and detection time(5,8,10,12,15,18,20,22 min) were optimized.Serum and EDTA anticoagulated plasma from the same donor were used as samples to analyze the matrix effects.The linear range,limit of blank,precision,accuracy,anti-interference capability and stability of the method were verified.In addition,the established method and electrochemiluminescence method were used to detect 30 serum samples respectively,and the results were compared.Results The optimal conditions were coating antibody concentration of 2 mg/mL,labeled antibody concentration of 15 μg/mL,and detection time of 12 min.There was a significant matrix effect between serum and EDTA plasma,and plasma T/C was significantly lower than serum(t = 5.075,P < 0.01).Adding 2.5,5,and 10 mmol/L Ca~(2+) could improve the consistency of the two detection results,with R~2 of 0.846 0,0.724 1,and 0.723 9,respectively,while R~2 was 0.154 8 when Ca~(2+) was not added.There was a good linear relationship between S100B antigen concentration and T/C in the range of 0.01-10 ng/mL,and the linear equation was y = 3.857 81 x + 0.483 37,R~2 = 0.997 4.The limit of blank was 0.003 ng/mL.The coefficients of variation(CVs) of precision verification were less than 10%,and the relative deviations of accuracy verification were also less than 10%.Compared with the corresponding control group,bilirubin,hemoglobin,lipids,neuron specific enolase(NSE),glial fibrillary acid protein(GFAP) and ubiquitin carboxyl-terminal hydrolase isozyme L1(UCHL1) exhibited no significant effect on the test results(t = 0.660,0.141,1.691,1.875,0.091 and 0.274,respectively,each P > 0.05).Compared with 0 d,there was no significant difference in the test results of the test strips stored at 37 ℃ for 7,14,21,28,35 and 42 d(t = 0.197,0.451,0.199,1.506,0.074 and 0.768,respectively,each P > 0.05).There was no significant difference in the results of the 30 serum samples detected by the established method and electrochemilumine-scence method(difference range was-0.93-0.88,W =-2.000,P > 0.05).Conclusion The established time-resolved fluorescence immunochromatography method based on the double-antibody sandwich method has good linearity,precision,accuracy,anti-interference ability and stability,which has good correlation with commonly used clinical methods and can be used for the rapid quantitative detection of S100B protein in serum samples.

To analyze global trends and research hotspots in exercise intervention for overweight and obesity from 2010 to 2024, to provide novel perspectives for comprehensive management research on overweight and obesity.

Objective To explore a new training strategy suitable for clinical education and talent cultivation in gy-necologic oncology.Methods Ninety undergraduates from each of the two grades of clinical medicine curriculum at Kunming Medical University were randomly divided into control group(n=40)and research group(n=50).The"4+3"teaching model of plan-do-check-action(PDCA)cycle integrated with TBL were adopted,whereas the control group was educated with classic methods.Two groups of students were evaluated with quantitative assessments and anonymous questionnaire surveys.Results Multidimensional questionnaire surveys indicated that the teaching model of the test group provided a better learning experience than classic teaching methods as proved by significant improvements in educational reform(58％),learning interest(64％),skill development(72％),capacity building of learning(66％)and satisfaction with the new model of training(70％)(P＜0.05,＜0.01).Further-more,the PDCA cycle can address the short-comings of the previous teaching iteration.In written exams,the class-room quiz scores,regular grades,and comprehensive scores of the research group were(18.38±5.81),(29.09±0.29),and(82.38±4.03)points respectively all higher than those of the control group(P＜0.01).Conclusions The PDCA cycle and the TBL-embedded teaching model promote the standardization of gynecologic oncology teach-ing procedures,thereby enhancing teaching quality and achieving precise alignment between student satisfaction and assessment performance.

Hemophilia is a hereditary coagulation disorder, in which patients often suffer from joint dysfunction due to recurrent joint bleeding, with the knee joint being particularly susceptible to involvement, thereby significantly impairing their ability to walk.Gait analysis, as an objective, quantitative, and comprehensive assessment tool, can be employed to accurately evaluate the walking function of patients and provide a scientific basis for the rehabilitation management of individuals with hemophilia.With the deepening of medical research, the role of gait analysis in the rehabilitation management of hemophilia is increasingly being recognized.This review article summarizes the application of gait analysis in the rehabilitation management of hemophilia, including changes in gait parameters, kinematic and kinetic characteristics of joints in patients with hemophilia, as well as the relationships between these parameters and the severity of the disease and treatment outcomes in hemophilia patients, exploring the role of gait analysis in the rehabilitation management of hemophilia to better apply it in clinical practice.

Objective:To assess the effects of recognition function of four-lead electrocardiogram(ECG)synchronization technique and multi-parameter fusion technique in reducing the number of false alarms and improving the quality of alarms in intensive care units(ICU).Methods:Four-lead ECG synchronization technique and multi-parameter fusion technique were used to strengthen the monitoring and assessment for the alarm of clinical monitors,and reduce the false alarm rate of monitors.The clinical alarm data of bed units corresponding to 48 monitors in clinical use of ICU,cardiovascular intensive care unit(CCU)and neurosurgery intensive care unit(NICU)of Hainan General Hospital from October 14 to December 27,2024 were selected.According to the opening and close of the four-lead ECG synchronization and multi-parameter fusion technique algorithm of the monitors,they were divided into group A(opened four-lead ECG synchronization and multi-parameter fusion),group B(opened four-lead ECG synchronization,but closed multi-parameter fusion),group C(closed four-lead ECG synchronization,but opened multi-parameter fusion)and group D(closed four-lead ECG synchronization and multi-parameter fusion),with 12 units in each group.The numbers of total alarms and false alarms generated by monitor of each bed unit among different optimization strategies were compared.Results:The numbers of average daily alarm of the monitors in groups A,B and C were respectively(134.2±32.4)cases,(392.5±68.2)cases and(583.4±126.5)cases,which were lower than those in group D(1 073.2±168.6),with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).The optimization rates of the alarm numbers in groups A,B and C were increased by 87.51%,63.47%and 45.67%,respectively.The rates of average false alarm of the monitors in groups A,B and C were respectively(1.04±0.15)%,(1.73±0.12)%and(2.07±0.08)%,which were lower than(3.76±0.2)%in group D,with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).Conclusion:Four-lead ECG synchronization technique and multi-parameter fusion technique can effectively optimize the number of alarms in ICU,and reduce the proportion of false alarms of monitors in department,and decrease fatigue of medical staffs for alarm.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
Humans ; Parkinson Disease/drug therapy* ; Diabetes Mellitus, Type 2/pathology* ; Signal Transduction/physiology* ; Receptor, Insulin/metabolism* ; Animals ; Insulin Resistance/physiology* ; Insulin/metabolism*

Objective:To discuss the inhibitory effects of combined application of chlorogenic acid(CA),procyanidin(PC),and paeoniflorin(PF),the active components of Paeoniae Radix Rubra,on Enterococcus faecalis(E.faecalis)and its biofilm,and to clarify the mechanism.Methods:The minimal inhibitory concentration(MIC)and minimal bactericidal concentration(MBC)of CA,PC,and PF against E.faecalis were detected by microdilution method;the fractional inhibitory concentration index(FICI)and fractional bactericidal concentration index(FBCI)of the three active components of Paeoniae Radix Rubra in combination were detected by checkerboard dilution method.The experiment was divided into control group,high concentration of single-drug groups(PF-10 group,PC-6 group,and CA-10 group),and drug combination groups(CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group).Crystal violet staining was used to detect the biofilm formation of E.faecalis in various groups after treated with three active components in combination;scanning electron microscope(SEM)was used to observe the morphology of E.faecalis biofilm in various groups after treated with three active components in combination;spot assay was used to detect the inhibitory effects of three active components in combination on E.faecalis planktonic bacteria and biofilm in various groups;SEM was used to observe the damage to E.faecalis cell membrane in various groups after treated with three active components in combination;kit was used to detect the adenosine triphosphate(ATP)levels in E.faecalis planktonic bacteria and biofilm in various groups after treated with three active components in combination.Results:Among the three active components of Paeoniae Radix Rubra,the MIC of PC was 4 g·L?1 and the MBC was 6 g·L?1;the MIC of CA was 8 g·L?1 and the MBC was 10 g·L?1;the MIC and MBC of PF were both>10 g·L?1,and the concentration of PF was selected as 10 g·L?1.The combination of PC and CA showed synergistic effects,the combination of PC and PF showed additive effects,and the combination of CA and PF showed additive effects.The crystal violet staining results showed that compared with control group,the biofilm formations of E.faecalis in PF-10 group,PC-6 group,CA-10 group,and drug combination groups were significantly decreased(P<0.05);compared with PF-10 group,the biofilm formations of E.faecalis in PC-6 group,CA-10 group,CA-2+PC-1 group,CA-2+PC-2 group,PF-4+PC-2 group,PF-6+PC-2 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01).The SEM results showed that in control group,the E.faecalis biofilm was thick,with tightly connected bacteria,regular morphology,and intact cell membranes;in PF-10 group,PC-6 group,and CA-10 group,the thickness of E.faecalis biofilm was significantly reduced,and the arrangement of bacteria became relatively loose;in all drug combination groups,the E.faecalis biofilm was significantly reduced or even completely disappeared,and under high magnification,the biofilm structure was completely absent,with bacterial fragments adhering and aggregating,losing their original bacterial morphology.The spot assay results showed that compared with control group,the colonies of E.faecalis planktonic bacteria in PF-10 group,PC-6 group,and CA-10 group were significantly reduced after treated for 5,10,and 30 min,indicating gradually enhanced bactericidal effects;among drug combination groups,the combination of CA and PC significantly reduced the colonies of E.faecalis planktonic bacteria within 5 min,showing strong bactericidal effects.Compared with CA group and PC group,the colonies of E.faecalis planktonic bacteria in all drug combination groups showed no significant reduction after treated for 5,10,and 30 min;compared with control group,the colonies of E.faecalis biofilm in PF-10 group,PC-6 group,and CA-10 group were gradually decreased after the treated for 30 and 60 min,suggesting that the high concentration of single-drug groups exhibited gradually enhanced bactericidal effects on E.faecalis in biofilm.Among them,the biofilm-killing effect of PC-6 group was the most significant,with no colony formation observed after treated for 30 min;in drug combination groups,only a few colonies of E.faecalis biofilm were observed in CA-2+PC-2 group after treated for 30 min,indicating effective killing of bacteria in biofilm;compared with PC-6 group and CA-10 group,all drug combination groups achieved the bactericidal effects of high concentration of single-drug groups at low concentrations.The SEM results showed that in control group,E.faecalis exhibited an oval shape with intact cell membranes;in PF group,bacterial morphology was altered,and cell membrane integrity was damaged;in CA group,most bacterial cell membranes remained relatively intact,but the bacterial surface showed shrinkage and depression,with a few bacteria exhibiting disrupted cell membrane integrity;in PC group,the integrity of bacterial cell membranes was most severely damaged,leading to leakage of cellular contents and aggregation of cell fragments into flocculent structures;in all drug combination groups,E.faecalis exhibited ruptured cell membranes,leakage of contents,and aggregation of bacterial debris,especially in the combination of CA and PC,where the most severe disruption of bacterial cell membrane integrity and complete leakage of contents were observed;in the combination of PF and CA,bacterial surface pits and shrinkage were observed,with occasional cell membrane rupture.The kit results showed that compared with control group,the ATP levels in E.faecalis planktonic bacteria and biofilm in various groups were significantly decreased(P<0.01);compared with PF-10 group,the ATP levels in E.faecalis planktonic bacteria in CA-10 group,CA-2+PC-2 group,PF-4+CA-4 group,and PF-6+CA-4 group were significantly decreased(P<0.05 or P<0.01),and the ATP levels in E.faecalis biofilm in CA-10 group and CA-2+PC-2 group were significantly decreased(P<0.05 or P<0.01).Conclusion:The combined application of PF,PC,and CA,the active components of Paeoniae Radix Rubra,exhibits significant inhibitory effects on E.faecalis and its biofilm formation.The pairwise combinations of three active components show synergistic or additive effects,with the combination of CA and PC demonstrating the most significant synergistic effect.The underlying mechanism may be related to the disruption of E.faecalis cell membrane integrity and inhibition of bacterial ATP levels.