Point-of-care analysis of levodopa (l-dopa) in patients' blood is crucial yet challenging for the scientific management of Parkinson's disease (PD). In this study, inspired by the catalytic mechanism of tyrosinase, we developed a biomimetic smartphone sensor for point-of-care monitoring of l-dopa. This sensor employs a copper-based biomimetic recognition layer, synthesized via one-step electrochemical polymerization of l-serine (L-Ser), l-histidine (L-His), and copper ions, which forms binuclear copper complexes mimicking the active site of tyrosinase, thereby enabling specific recognition and catalysis of l-dopa. A comprehensive anti-interference analysis was conducted by using 30 potential interferents that may be present in serum. The results confirmed its robust anti-interference performance against coexisting interferents, thereby addressing a significant shortcoming of previous methods. Additionally, the sensor exhibits excellent stability. It maintains stable performance after more than 35 repeated tests. It retains 98.61% of its initial activity after stored at room temperature for one week, effectively reducing analytical costs. Systematic validation experiments confirmed that the constructed copper-based biomimetic sensor exhibits excellent accuracy and precision, with a detection limit as low as 1.32 nM. Integrated with a smartphone via Bluetooth, this sensor enables rapid point-of-care testing of l-dopa, allowing the entire workflow to be completed within 10 min. Its successful application in the analysis of multiple PD patients' serum samples further validates the application potential of the developed biomimetic smartphone sensor in PD population.
OBJECTIVE:To systematically evaluate the efficacy and safety of different antithrombotic regimens for preventing portal vein system thrombosis (PVST) formation in patients with cirrhosis and portal hypertension undergoing splenectomy using a network meta-analysis method based on published literature. METHODS:A comprehensive search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, and three Chinese databases (CBM, CNKI, and Wanfang Data) from inception to June 2025. Studies involving different prophylactic antithrombotic regimens for patients with cirrhosis and portal hypertension who underwent splenectomy were included. Literature screening and assessment of the methodological quality of the included studies were performed using the Cochrane systematic review method, and characteristic information was extracted for network meta-analysis. The clinical outcomes included the incidence of PVST at postoperative month 1 (POM 1), postoperative month 3 (POM 3), and postoperative month 6 (POM 6), the incidence rate of bleeding and the course of antithrombotic prophylaxis. RESULTS:A total of 19 studies involving 1968 patients were included. Nine different prophylactic antithrombotic regimens were analyzed, including antiplatelet therapy (APT) alone; anticoagulation alone, including low-molecular-weight heparin (LMWH) + warfarin, LMWH + rivaroxaban, and rivaroxaban alone; anticoagulation combined with APT, including LMWH + APT, LMWH + warfarin + APT, LMWH + apixaban + APT, and rivaroxaban + APT; and placebo. The results of the network meta-analysis and direct meta-analysis revealed that rivaroxaban + APT had the best efficacy in reducing PVST-POM 1, PVST-POM 3, and PVST-POM 6, followed by LMWH + warfarin + APT. The efficacy of APT alone and placebo was relatively poor. The incidence rate of bleeding was similar among the different prophylactic antithrombotic regimens. Three months of postoperative prophylactic antithrombotic therapy could significantly reduce the incidence of PVST, whereas extending the course to 6 months provided no further reduction of the incidence of PVST. CONCLUSION:For patients with cirrhosis and portal hypertension undergoing splenectomy and with Child‒Pugh class A-B liver function, prophylactic antithrombotic regimens combining anticoagulation and APT, especially rivaroxaban + APT, show the best efficacy, significantly reducing the incidence of PVST without increasing the risk of bleeding. A 3-month postoperative prophylactic antithrombotic therapy may be the optimal preventive course.
ObjectiveTo analyse the use of prophylactic proton pump inhibitors (PPIs) and their benefits for the prevention of gastrointestinal injury and to determine the optimal course of preventive use among patients with minor ischaemic stroke (IS) and transient ischaemic attack (TIA) at low risk of gastrointestinal bleeding (GIB) treated with short-term dual-antiplatelet therapy (DAPT).MethodsWe retrospectively collected clinical data from the hospital information system (HIS) from January 2022 to December 2023. The data were collected from patients who were admitted to a tertiary hospital with a first occurrence of minor IS/TIA diagnosed within 14 days and treated with short-term DAPT. Univariate and multivariate logistic regression analyses were used to explore the correlations between the use of PPIs, different treatment durations, and the incidence rates of GIB, gastrointestinal discomfort, other types of bleeding, and pneumonia in these patients.ResultsA total of 220 patients were included, with 52 in the PPI group (23.64%) and 168 in the non-PPI group (76.36%). The results showed that PPI use did not significantly reduce the incidence of GIB (P = 0.059) or other types of bleeding (P = 0.916) in patients who were treated with DAPT and were at low risk of GIB. The incidence of pneumonia in the PPI group was higher than that in the non-PPI group, but the difference was not statistically significant (42.86% vs. 23.00%, P = 0.840). However, PPI use significantly reduced the occurrence of gastrointestinal discomfort (P = 0.033, OR: 0.448; 95% CI: 0.215–0.935), with no significant difference based on treatment duration (≤7 days vs. >7 days, P = 0.520).ConclusionRegular use of PPIs within the first 7 days of initiating DAPT in patients with minor IS/TIA at low risk of GIB significantly reduces symptoms of gastrointestinal discomfort while minimizing adverse effects due to overuse of PPIs.
The impact of vitamin D levels on glycemic control and lipid metabolism in diabetic patients has received widespread attention. However, currently, there was no unified standard for vitamin D supplementation dosages, with significant variations among guideline recommendations. For instance, the 2022 ESPEN Guidelines recommended a daily supplementation of 1,500–5,000 International Units (IU) for patients at risk of vitamin D deficiency or who repeatedly experience vitamin D deficiency; however, guidelines from Italy suggested a daily supplement dose of 800–1,000 IU for patients with vitamin D deficiency. In this study, we searched the PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, and Wanfang databases from their inception to 31 May 2024 for literature. The effects of different supplementation levels on vitamin D levels, glycosylated hemoglobin (HbA1c) levels and total cholesterol (TC) levels were analyzed using random-effects and fixed-effects models, respectively, and we applied the Modified Jadad Scale and the Newcastle-Ottawa Scale (NOS) score to evaluate the quality of the RCT studies and retrospective analyses, respectively. We included a total of seven papers involving 468 patients with a follow-up period of 3 to 6 months. The results of the study showed that vitamin D levels were significantly higher in the high-dose group than in the low-dose group at both 3 and 6 months of treatment [mean difference (MD) = −12.48, 95% confidence interval (CI): −15.25 to −9.72 and MD = −28.22, 95% CI (−40.92, −15.72), both p < 0.05], and the effect of prolonged treatment was more significant. HbA1c levels were significantly lower in the high-dose group than in the low-dose group [MD = 0.41, 95% CI (0.14, 0.67), p = 0.003], and TC levels were not significantly different between the two groups [MD = 1.84, 95% CI (−8.07, 0.67), p = 0.72]. Therefore, in patients with diabetes mellitus complicated by vitamin D deficiency, higher-dose supplementation (>4,000 IU/day) might have had potential advantages in increasing vitamin D levels and improving glycemic control. However, further studies were still needed to clarify the long-term safety and risk–benefit ratio of higher-dose supplementation.
High-dose methotrexate(HD-MTX) has been used in clinical treatment of hematological malignancies and toxicity appeared at the same time. Gene polymorphisms may participate in the activity of MTX-related enzymes and induce drug-related toxicity. The influence of MTHFR C677T, MTHFR A1298C and ABCB1 C3435T polymorphisms on the MTX-related toxicity and delay elimination in adult with hematological malignancies is controversial. Here, a total of 111 patients were analyzed. MTHFR C677T, MTHFR A1298C and ABCB1 C3435T gene polymorphisms are related to MTX-related toxicity in adults with hematological malignancies. Age(≥ 60 years) and MTHFR 1298AC were identified as independent risk factors for delayed elimination of MTX. This reminds us that the MTHFR C677T, MTHFR A1298C and ABCB1 C3435T gene polymorphisms are expected to be a useful tool in reducing toxicity and improving outcome in personalized HD-MTX therapy for patients with hematological malignancies.
Background: Kawasaki disease is a primary cause of pediatric cardiac issues, with the risk of coronary artery complications, heart attacks, and untreated death. Approximately 10% of patients do not respond to initial high dose intravenous immunoglobulin treatment. Our unique model aimed to explore high resolution small animal ultrasound for coronary imaging and its correlation with histopathology and clinical progression. Methods: Eighteen BALB/c mice were divided into Kawasaki disease and control groups. Kawasaki disease was induced with a single intraperitoneal injection of Lactobacillus casei cell wall extract. High resolution small animal ultrasound monitored coronary changes on multiple days, and histopathological analysis covered various organs. Results: The findings reveal significant changes in coronary artery diameter, with both the left and right coronary arteries expanding considerably during the experiment. By day 21, the model group exhibited marked coronary artery widening. Ejection fraction and fractional shortening deteriorated significantly by day 14 compared to the baseline. The histopathology report offers a comprehensive timeline of cardiac involvement. Conclusion: Our model uniquely illustrates coronary arteritis and cardiac lesions in Kawasaki disease mice, emphasizing progressive coronary dilation, notably by day 21. Correlation with pathology supports our findings, shedding light on disease progression in this mouse model, suggesting a delayed course compared to human Kawasaki disease, with potential severe myocarditis.
In this study, Au nanoparticles were introduced to functionalize hydrogen-terminated diamond (H-diamond) to optimize surface modification and improve the performance of diamond sensor for trace detection of SARS-CoV-2 N-protein. The Au nanoparticles were obtained by an electron beam evaporation system and annealing. Atom force microscope and scanning electron microscope were utilized to characterize the structure, morphology, and distribution of fabricated Au nanoparticles. The concentration of SARS-CoV-2 N-protein was determined by the investigation of transfer characteristics of a diamond solution gate field effect transistor. Sensitivity of this sensor was obtained as 27.43 mV/lg (N-protein concentration), which was higher than a regular H-diamond sensor. In addition, it had a wider linear detection range of 10−15–10−5 mg/ml and a lower limit of detection of 10−15 mg/ml. Accordingly, the detection performance of diamond sensor has been greatly improved due to the functionalization of Au nanoparticles.
Assessment of glucose concentration is vital for diagnosis and treatment of diabetes mellitus. Since the electrochemical advantages of diamond for biosensing, we introduced partly-oxygen-diamond solution-gate field-effect transistor (SGFET) to detect glucose. Partly-O-diamond was obtained from H-diamond by ultraviolet ozone treatment. Then, 1-pyrenebutyric acid–N-hydroxy succinimide ester and glucose oxidase were modified on diamond surface. At last, shifts of transfer characteristics were applied to determine glucose concentration. The as-prepared biosensor exhibited a wide linear response from 10−5 to 10−1 M with high sensitivity of −53 mV/log10 [glucose concentration]. Furthermore, this biosensor showed good repeatability and stability in multiple detections.
AimsTo systematically evaluate the efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition (TPN)-associated hyperglycemia based on published literature and the data of completed clinical trials using a network meta-analysis.MethodsA comprehensive search of PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED) up to December 15, 2022, was performed to collect information on different insulin infusion methods used for the treatment of TPN-associated hyperglycemia, and the Cochrane systematic review method was used to screen the literature, evaluate the quality of the included literature, and extract clinical characteristics for a network meta-analysis. Clinical outcomes included mean blood glucose (MBG), hypoglycemia, hospital length of stay, hyperglycemia, surgical site infection (SSI) and mean total daily insulin.ResultsA total of 21 articles, including 1,459 patients, were included to analyze 6 different routes of insulin infusion, including continuous intravenous insulin infusion (CVII), continuous subcutaneous insulin infusion (CSII), subcutaneous glargine insulin (s.c. GI), the addition of regular insulin to the PN mixture (RI-in-PN), multiple subcutaneous insulin injections (MSII) and 50% of insulin administered as RI-in-PN + 50% of insulin administered as s.c. GI (50% RI-in-PN + 50% s.c. GI). The results of the network meta-analysis showed that MSII was the least effective in terms of MBG, followed by CVII. The 6 interventions were basically equivalent in terms of the hypoglycemia incidence. In terms of the length of hospital stay, patients in the CVII group had the shortest hospital stay, while the MSII group had the longest. CVII was the best intervention in reducing the incidence of hyperglycemia. The incidence of SSI was the lowest in the CSII and CVII groups, and the mean daily insulin dosage was the lowest in the CVII group.ConclusionCurrent literature shows that for the treatment of TPN-associated hyperglycemia, CVII is the most effective, reducing the incidence of hyperglycemia and shortening the length of hospital stay without increasing the incidence of hypoglycemia. MSII has the worst efficacy, leading to a higher MBG and longer hospital stay, and RI-in-PN, CSII, s.c. GI and 50% RI-in-PN + 50% s.c. GI are better in terms of efficacy and safety and can be substituted for each other.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifierCRD42023439290.
In this study, we introduced H-terminated diamond solution-gate field-effect transistor (H-diamond SGFET) to detect trace SARS-CoV-2 N-protein, which plays an important role in replication and transcription of viral RNA. 1-Pyrenebutyric acid-N-hydroxy succinimide ester (Pyr-NHS) was modified on H-diamond surface as linker, on which the specific antibody of SARS-CoV-2 N-protein was catenated. Fourier transform infrared spectrum, scanning electron microscope and energy dispersive spectrum were utilized to demonstrate the modification of H-diamond with Pyr-NHS and antibody. Shifts of IDS(max) at VGS =-500 mV in transfer characteristics of H-diamond SGFET was observed to determine N-protein concentration in phosphate buffer solution. Good linear relationship between IDS(max) and log10(N-protein) was observed from 10-14 to 10-5 g/mL with goodness of fit R2 = 0.90 and sensitivity of 1.98 mu A/Log10 [concentration of N-protein] at VDS =-500 mV, VGS =-500 mV. Consequently, this prepared H-diamond SGFET biosensor may provide a new idea for diagnosis of SARS-CoV-2 due to a wide detection range from 10-14 to 10-5 g/mL and low limit of detection 10-14 g/mL.
Detection of carbohydrate antigen 19-9 (CA19-9) via hydrogen-terminated diamond (H-diamond) solution-gate field-effect transistor (SGFET) sensor had been carried out for the first time. Linker molecule 1-pyrenebutyric acid-N-hydroxy succinimide ester (Pyr-NHS) was fixed on the surface of H-diamond by pi-pi bonding. Then, anti-CA19-9 antibody was immobilized with Pyr-NHS. After specific binding of CA19-9 and antibody, transfer characteristics of H-diamond SGFET exhibited a gate voltage shift in negative direction at the same output current. The sensitivity of sensor was obtained as -50.98 mV/Log(10)[antigen concentration]. The minimum detection concentration was 0.001 U/mL. This article illustrated a potential application of H-diamond SGFET sensor in CA19-9 detection.
The concentration of glucose was detected using an H-terminated diamond solution-gate field-effect transistor (H-diamond SGFET). The linker molecular 1-pyrenebutyric acid–N-hydroxy succinimide ester (Pyr-NHS) was introduced to modify the H-diamond surface. Then, glucose oxidase (GOD) was immobilized on the diamond surface by linker Pyr-NHS. Atomic force microscope and scanning electron microscope measurements confirmed the successful immobilization of Pyr-NHS and GOD enzyme on the H-diamond surface. The concentration of glucose was determined by the shift of gate voltage ( ${V}_{\text {GS}}$ ) in transfer characteristics of H-diamond SGFET. Also, the sensitivity of sensor for glucose detection was obtained as −58.69 mV/ ${\text {log}}_{{10}}$ (glucose concentration) by the slope of fitting curve, which represented the relationship between ${\Delta {V}}_{\text {GS}}$ and logarithmic of glucose with concentration increasing from 1 $\times 10^{-{3}}$ to 1 M. The reusability of device was characterized by the transfer properties and small standard deviation (SD) of maximum output current ( ${I}_{\text {DS(max)}}$ ) in four tests, indicating excellent reusability for detection of glucose.
BACKGROUND:Suppurative arthritis induced by Scedosporium apiospermum (S. apiospermum) or Mycobacterium fortuitum (MF) was rare, and even more so when caused by a mixed infection of the two. In this paper, we report the rare case of suppurative arthritis induced by S. apiospermum and MF.METHODS:A 46-year-old patient whose left knee was accidentally injured by a rotary tiller. His left knee joint was clearly swollen although debridement and suturing had been performed twice at a local hospital. Bacterial culture result was MF and S. apiospermum after admission. Definitive therapy (debridement combined with treatment using three antibiotics) was initiated.RESULTS:Although the fungus reappeared when he tried to discontinue the drug, after the third debridement combined with treatment using three antibiotics for 8 months, the infection was controlled and did not recur.CONCLUSIONS:This demonstrates that early bacteriological examination is essential. Treatment of fungus generally requires a long course. However, course of medication should be related to the patient's specific conditions and the implementation of the operation.
Software defined networking (SDN) reshapes the ossified network architectures, by decoupling the control plane and data plane. Due to such a decoupling, SDN assumes that rules issued by the control plane are always correctly enforced by the data plane. However, this assumption breaks as an adversary can prevent the data plane from enforcing the rules, by exploiting the vulnerabilities of switch OS and control channel. The serious consequence is that packets may deviate from their original paths, thereby violating critical security policies like access control. To this end, this paper introduces rule enforcement verification (REV), which enables the controller to check whether switches have correctly enforced the rules that it issues. Since using message authentication code (MAC) can incur heavy switch-to-controller traffic, we propose the compressive MAC, which lets switches compress MACs before reporting to the controller, thereby significantly reducing the bandwidth cost. Finally, we propose a heuristic flow selection algorithm, which allows the controller to verify much less flows for rule coverage. We implement REV based on Open vSwitch with DPDK, and use experiments to show: (1) by using compressive MAC, REV achieves a 97% reduction in switch-to-controller traffic, and an $8\times $ increase in verification throughput; (2) by using the heuristic flow selection algorithm, REV can reduce the number of flows to verify by 40%-60%.