Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

Objective:To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT).Methods:The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed.Results:(1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ ( HR=4.555, 95% CI: 1.525-13.607; P=0.007) and micropapillary subtype ( HR=2.396, 95% CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions:Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

Objective To observe the clinical effect of osteoporotic vertebral compression fracture(OVCF)and analyze the value of magnetic resonance imaging(MRI)and bone metabolism indexes in predicting the poor prognosis.Methods A total of 258 OVCF patients admitted to Hangzhou Ninth Peopl's Hospital from March 2021 to March 2023 were selected as study objects.After percutaneous kyphoplasty(PKP)or percutaneous vertebroplasty(PVP),visual analogue scale(VAS)score and Cobb angle were collected.The patients were divided into poor prognosis group and good prognosis group according to whether the fracture was repeated after surgery.MRI and bone metabolism indexes of patients were collected,and the influencing factors of prognosis were analyzed.Results The VAS scores of OVCF patients decreased with the extension of time(P<0.05).One month and three months after surgery,the Cobb angle of injured vertebrae in OVCF patients was significantly lower than that before surgery(P<0.05).The proportion of vertebral fluid signs in poor prognosis group was significantly higher than that in good prognosis group(P<0.05),and N-terminal midragment of osteocalcin(N-MID)and 25-hydroxyvitamin D[25(OH)D]in poor prognosis group were lower than those in good prognosis group(P<0.05).Vertebral fluid signs,N-MID and 25(OH)D were all associated with poor prognosis in OVCF patients(P<0.05).The area under the curve(AUC)of vertebral fluid signs,N-MID and 25(OH)D alone for predicting poor prognosis of OVCF was 0.744,0.872 and 0.822,the sensitivity was 56.5%,87.0%and 73.9%,and the specificity was 92.3%,74.5%and 80.9%,respectively.Above indicators combined AUC,sensitivity and specificity were 0.967,95.7%and 80.9%.Conclusion PKP/PVP can reduce pain and improve function in OVCF patients.MRI vertebral fluid signs,N-MID and 25(OH)D are all factors affecting the poor prognosis of OVCF patients,and the combination of three factors can predict the poor prognosis of OVCF patients.

ObjectiveTo explore the correlation among knee hyperextension angle, lower limb joints kinematics parameters and the activation of main muscles of lower limb in stroke hemiplegic patients with knee hyperextension during walking. MethodsFrom August, 2020 to September, 2021, 24 stroke hemiplegic patients with knee hyperextension and 24 healthy subjects matched with sex, age, height and body mass with knee hyperextension were analyzed with three-dimensional gait analysis system and the wireless surface electromyography acquisition system, to record the range of motion of pelvis, hip, knee and ankle joints in sagittal plane, and the activation of bilateral gluteus maximus, biceps femoris, vastus medialis and gastrocnemius medialis. ResultsAs the maximum of knee hyperextension, range of motion of the joints in sagittal plane and the activation of the muscles were different between the patients and the healthy subjects during the single-support phase of walking (|t| > 3.080, P < 0.01), and the maximum of knee hyperextension correlated with the activation of gluteus maximus in the patients (r = -0.532, P < 0.01), and the range of motion of ankle plantar flexion in both the patients and the healthy subjects (r > 0.686, P < 0.001). ConclusionThe correction for knee hyperextension gait in stroke hemiplegic patients may not only need to pay attention to knee joint control, but also need further treatment of ankle control and hip muscle function.

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

OBJECTIVE: To analysis the dynamic change of cytokines in patients with occupational trichloroethylene-induced medicamentosa-like dermatitis(OMDT) at the initial stage of treatment. METHODS: Twenty-two cases of early onset OMDT with no glucocorticoid treatment history were selected as the research subjects by judgment sampling method. Blood samples were collected on the 1 st, 2 nd, 3 rd, 4 th and 5 th weeks after admission and on the day of hospital discharge. The levels of tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), interleukin(IL)-5, IL-6 and IL-10 in plasma samples were measured by the enzyme linked immunosorbent assay. RESULTS: The five cytokines in patients with exfoliative dermatitis showed an increasing trend at the initial stage of treatment. Among them, the levels of TNF-α, IL-5 and IL-10 reached a peak and then dropped rapidly to form a plateau, and the levels of IFN-γ and IL-6 were slightly increased and the duration of increase was shorter than that of other cytokines. The levels of TNF-α, IFN-γ, IL-5 and IL-6 in patients with erythema multiforme remained within the detection limits in the detection process. Only a few patients showed a short-term increase, the IL-10 level showed a slight increase at the initial stage and then decreased to the plateau stage. The levels of TNF-α, IFN-γ and IL-6 in patients with bullous epidermal necrolysis increased rapidly at the initial detection stage for a short period of time, and then decreased sharply. The level of IL-5 remained at the detection limit, and the IL-10 level showed alternative rising and falling pattern. Part of the dynamic change of cytokines in patients with exfoliative dermatitis and bullous epidermal necrolysis was similar. CONCLUSION: The levels of TNF-α, IFN-γ, IL-5, IL-6, and IL-10 in OMDT patients changed with the progression of the disease at the early treatment stage, and the degree of change was related to the type of rash. Among them, the levels of TNF-α and IL-10 showed dynamic changes due to the progression of the disease, which could be considered as effect biomarkers to evaluate the severity and progression of the disease, and provide a reference for the rational treatment of patients.

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards

OBJECTIVE: To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage Ⅱ DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance. METHODS: We collected fresh stage Ⅱ colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR. The apoptosis rates of HCT116 cells with and without siRNA- mediated transient SFRP4 knockdown were determined using flow cytometry. We further investigated the expression pattern of Ki-67 and its correlation with SFRP4 expression. RESULTS: Compared with pMMR colon cancer tissues or cells, both dMMR colon cancer tissues (=0.014) and cells (=0.0079) showed significantly increased expression of SFRP4, which was in negative correlation with Ki-67 (=0.041). In HCT116 cells, transient SFRP4 knockdown resulted in decreased cell apoptosis, including both early apoptosis (=0.003) and late apoptosis (=0.024). CONCLUSIONS Up-regulation of SFRP4 in dMMR stage Ⅱ colon cancer promotes apoptosis and inhibits proliferation of the cancer cells, and may improve the prognosis of dMMR colon cancer.
Apoptosis ; Cell Proliferation ; Colon ; metabolism ; pathology ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; DNA Mismatch Repair ; Gene Knockdown Techniques ; HCT116 Cells ; Humans ; Ki-67 Antigen ; metabolism ; Prognosis ; Proto-Oncogene Proteins ; genetics ; metabolism ; Up-Regulation

Objective To analyze the clinical characteristics of patients with metastatic carcinoma of bone. Methods The clinical data of 217 patients with metastatic carcinoma of bone was retrospectively analyzed. The clinical features were summarized,including primary tumor,age distribution,first symptom,time of onset and bone metastatic site. Visual analogue scale(VAS)was used to evaluate the difference of pain in patients with bone metastases before and after zoledronic acid treatment. Results The bone metastasis occurred more frequently in men(male:female = 1.28:1). The majority of primary tumors were lung cancer(51.61％)and breast cancer (15.67％),respectively. The peak ages of the patients with metastatic carcinoma of bone were between 50 and 70 years old. Most of the patients with metastatic carcinoma of bone initially showed varying degrees of pain ,some of the patients with dysfunction,pathological fracture,or local lumps as the initial symptoms,only a tiny minority of patients were inadvertently found. Onset time was often within 3 months ,which accountings for 54.84％. Bone metastases were mostly in the spine,pelvis,femur and ribs,and most of the bone metastases were multiple. The VAS score of 108 patients who with bone metastases pain treated by zoledronic acid was 0～4(1.31 ± 1.07),with statistically significant differences compared with pretherapy(P<0.01). Conclusion In order to reduce the pain of patients,and to improve the quality of life and prolong the survival time,bone metastases should be diagnosed early and given comprehensive treatment.