Molecular SPECT/CT Profiling of Claudin18.2 Expression In Vivo: Implication for Patients with Gastric Cancer.

Zolbetuximab (IMAB362), a monoclonal antibody targeting Claudin18.2 (CLDN 18.2), demonstrates a significant clinical benefit in patients with advanced gastroesophageal cancers. The noninvasive assessment of CLDN18.2 expression through molecular imaging offers a potential avenue for expedited monitoring and the stratification of patients into risk groups. This study elucidates that CLDN18.2 is expressed at a noteworthy frequency in primary gastric cancers and their metastases. The iodogen method was employed to label IMAB362 with 123I/131I. The results demonstrated the efficient and reproducible synthesis of 123I-IMAB362, with a specific binding affinity to CLDN18.2. Immuno-single-photon emission computed tomography (SPECT) imaging revealed the rapid accumulation of 123I-IMAB362 in gastric cancer xenografts at 12 h, remaining stable for 3 days in patient-derived tumor xenograft models. Additionally, tracer uptake of 123I-IMAB362 in MKN45 cells surpassed that in MKN28 cells at each time point, with tumor uptake correlating significantly with CLDN18.2 expression levels. Positron emission tomography/computed tomography imaging indicated that tumor uptake of 18F-FDG and the functional/viable tumor volume in the 131I-IMAB362 group were significantly lower than those in the 123I-IMAB362 group on day 7. In conclusion, 123I-IMAB362 immuno-SPECT imaging offers an effective method for direct, noninvasive, and whole-body quantitative assessment of tumor CLDN18.2 expression in vivo. This approach holds promise for accelerating the monitoring and stratification of patients with gastric cancer.

[Source Apportionment of Morphine in Wastewater].

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.

Taste traces: Capsaicin and sweeteners as anthropogenic markers in municipal wastewater.

Dietary-derived substances possess significant potential as anthropogenic markers owing to the large consumption and different intake habit. To investigate and evaluate such markers, wastewater samples from 35 wastewater treatment plants across 29 Chinese cities were collected to analyze artificial sweeteners (acesulfame and cyclamate) and natural spicy compounds (capsaicin and dihydrocapsaicin). Acesulfame (mean: 14.6 µg/L), cyclamate (mean: 24.3 µg/L), and capsaicin (mean: 101 ng/L) can be further investigated as anthropogenic markers due to their high detection frequency at high concentrations. Spatial use patterns revealed that acesulfame (5.31 g/d/1000 inhabitants (inh)) and cyclamate (8.16 g/d/1000 inh) use in northern China notably surpassed that in southern China (1.79 g/d/1000 inh and 3.23 g/d/1000 inh, p < 0.05). Conversely, chili pepper use was significantly higher (p < 0.05) in southern China (6702 g/d/1000 inh) than in northern China (2751 g/d/1000 inh), signifying a preference for sweetness in the northern regions and a predilection for spiciness in the southern regions. The total annual use of acesulfame (1842 t), cyclamate (3110 t), and chili (18.4 million tonnes) in China was estimated by this study, which was close to the national statistical production. In addition, sweetener use was negatively associated with the elderly population ratio, suggesting that the elderly population might not consume sweet foods. This study reveals the dietary sources of anthropogenic markers, highlighting the need for further research on the environmental implications of such markers.

A Novel Risk Score Model for the Differential Diagnosis of Type 2 Diabetic Nephropathy: A Multicenter Study.

Introduction: DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. Methods: A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients "ß" to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. Results: Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m2, 24 h UTP ≥ 3 g, and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. Conclusion: The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Simulation study of an x-ray sub-picosecond resolution detection system based on time-domain amplification.

This study proposes what we believe to be a novel x-ray detection system that achieves a temporal resolution of 930 fs with photorefractive and four-wave mixing effects. The system comprises two parts: a signal-conversion system and signal-acquisition system. The signal-conversion system is based on the photorefractive effect, which converts x-ray evolution into the variation of infrared interference intensity. The signal-conversion sensor consists of ultra-fast response LT-GaAs and a high-resolution interference cavity, achieving a resolution of  767 fs. The signal-acquisition system consists of a time-domain amplification system based on four-wave mixing and a high-resolution signal-recording system with a resolution of 21 ps, providing a temporal resolution of 525 fs.

Catalytic Oxidation of Acetone on SmMn2O5: Effect of Acid Etching and Loading Treatment.

The key of catalytic oxidation technology is to develop a stable catalyst with high activity. It is still a serious challenge to achieve high conversion efficiency of acetone with an integral catalyst at low temperature. In this study, the SmMn2O5 catalyst after acid etching was used as the support, and the manganese mullite composite catalyst was prepared by loading Ag and CeO2 nanoparticles on its surface. By means of SEM, TEM, XRD, N2-BET, XPS, EPR, H2-TPR, O2-TPD, NH3-TPD, DRIFT, and other characterization methods, the related factors and mechanism analysis of acetone degradation activity of the composite catalyst were discussed. Among them, the CeO2-SmMn2O5-H catalyst has the best catalytic activity at 123 and 185 °C for T50 and T100, respectively, and shows excellent water and thermal resistance and stability. In essence, the surface and lattice defects of highly exposed Mn sites were formed by acid etching, and the dispersibility of Ag and CeO2 nanoparticles was optimized. Highly dispersed Ag and CeO2 nanoparticles have a highly synergistic effect with the support SmMn2O5, and the reactive oxygen species provided by CeO2 and the electron transfer brought by Ag further promote the decomposition of acetone on the carrier SMO-H. In the field of catalytic degradation of acetone, a new catalyst modification method of high-quality active noble metals and transition metal oxides supported by acid-etched SmMn2O5 has been developed.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.

Evaluation of eight psychoactive drugs used in Chinese cities by wastewater-based epidemiology.

With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.

An Electrochemical-Based Point-of-Care Testing Methodology for Uric Acid Measurement.

Point-of-care technology (POCT) is an important method in clinical testing in the future, which can achieve the purpose of rapid analysis. In this work, we assembled an electrochemical POC sensor for uric acid (UA) by surface modification of a screen-printed electrode. Copper nanowires were used as electrode modifiers to achieve high-performance electrochemical oxidation of UA. This electrochemical sensor can achieve linear detection of UA in the range of 10 µM to 2 mM. The detection limit of the sensor was calculated to be 2 µM. Although the detection performance of this sensor is not competitive with high-performance electrochemical sensors, it has been able to meet the needs of POC detection. At the same time, the sensor has excellent anti-interference performance. It has also been used successfully to test urine and serum samples from healthy and gout patients.

Research Progress of a Composite Metal Oxide Catalyst for VOC Degradation.

Volatile organic compounds (VOCs) are atmospheric pollutants that have been of concern for researchers in recent years because they are toxic, difficult to remove, and widely sourced and easily cause damage to the environment and human body. Most scholars use low-temperature plasma biological treatment, catalytic oxidation, adsorption, condensation, and recovery techniques to treat then effectively. Among them, catalytic oxidation technology has the advantages of a high catalytic efficiency, low energy consumption, high safety factor, high treatment efficiency, and less secondary pollution; it is currently widely used for VOC degradation technology. In this paper, the catalytic oxidation technology for the degradation of multiple types of VOCs as well as the development of a single metal oxide catalyst have been briefly introduced. We also focus on the research progress of composite metal oxide catalysts for the removal of VOCs by comparing and analyzing the metal component ratio, preparation method, and types of precursors and the catalysts' influence on the catalytic performance. In addition, the reason for catalyst deactivation and a correlation between the chemical state of the catalyst and the electron distribution are discussed. Development of a composite metal oxide catalyst for the catalytic oxidation of VOCs has been proposed.

Comparative Efficacy of Tonic Chinese Herbal Injections for Treating Sepsis or Septic Shock: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Sepsis has high mortality and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for sepsis. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of sepsis treatment. Method: Eight databases were searched from their inception up to September 1, 2021. The methodological quality of included study was evaluated by the Revised Cochrane risk-of-bias tool for randomized trials. Then Bayesian network meta-analysis was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Publication bias was reflected by a funnel plot. Results: A total of 50 eligible randomized controlled trials involving 3,394 participants were identified for this analysis. Five CHIs including Shenfu injection, Shenmai injection, Shengmai injection, Shenqifuzheng injection, and Huangqi injection were included. The results of the NMA and sensitivity analysis showed that Shenqifuzheng (MD = -4.48, 95% CI = -5.59 to -3.24), Shenmai (MD = -3.38, 95% CI = -4.38 to -2.39), Shenfu (MD = -2.38, 95% CI = -3.03 to -1.70) and Shengmai (MD = -1.90, 95% CI = -3.47 to -0.31) combined with Western medicine (WM) had a superior effect in improving the APACHE II score. Based on SUCRA values, Shenqifuzheng injection (95.65%) ranked highest in the APACHE II score, followed by Shenmai (74%), Shenfu (47.1%), Shengmai (35.3%) and Huangqi injection (33.2%). Among the secondary outcomes, Shenmai injection was the most favorable intervention in reducing PCT and CRP levels, and Shenqifuzheng injection was the second favorable intervention in reducing CRP level. Shenfu injection combined with WM was more effective than the other treatments in decreasing the serum IL-6 and TNF-α levels and lowering the 28-days mortality. Regarding the improvement of immune function, Shenqifuzheng injections had obvious advantages. Conclusion: In conclusion, Shenqifuzheng injection was the optimum treatment regimen to improve APACHE II score, reduce CRP level, and regulate immune function. Shenfu injection was superior in reducing the expression of inflammatory factors and decreasing 28-days mortality. Nevertheless, more multicenter, diverse, and direct comparisons randomized controlled trials are needed to further confirm the results. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=254531, identifier CRD42021254531.

Clinical features and risk factors analysis of bronchitis obliterans due to refractory Mycoplasma pneumoniae pneumonia in children: a nomogram prediction model.

BACKGROUND: Early prediction of bronchitis obliterans (BO) is of great significance to the improvement of the long-term prognosis of children caused by refractory Mycoplasma pneumoniae pneumonia (RMPP). This study aimed to establish a nomogram model to predict the risk of BO in children due to RMPP. METHODS: A retrospective observation was conducted to study the clinical data of children with RMPP (1-14 years old) during acute infection. According to whether there is BO observed in the bronchoscope, children were divided into BO and the non-BO groups. The multivariate logistic regression model was used to construct the nomogram model. RESULTS: One hundred and forty-one children with RMPP were finally included, of which 65 (46.0%) children with RMPP were complicated by BO. According to the multivariate logistic regression analysis, WBC count, ALB level, consolidation range exceeding 2/3 of lung lobes, timing of macrolides, glucocorticoids or fiber bronchoscopy and plastic bronchitis were independent influencing factors for the occurrence of BO and were incorporated into the nomogram. The area under the receiver operating characteristic curve (AUC-ROC) value of nomogram was 0.899 (95% confidence interval [CI] 0.848-0.950). The Hosmer-Lemeshow test showed good calibration of the nomogram (p = 0.692). CONCLUSION: A nomogram model found by seven risk factor was successfully constructed and can use to early prediction of children with BO due to RMPP.

The efficacy and safety of Huangqi Guizhi Wuwu decoction for rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis has the characteristics of slow progression, long course, and repeated attacks. At present, western medicine commonly used in clinical practice not only reduces pain and improves symptoms, but also has more adverse reactions, affecting the health, and life of patients. In ancient China, Huangqi Guizhi Wuwu decoction was used by doctors to treat rheumatoid arthritis, with remarkable effect. In recent years, many clinical studies have also shown that Huangqi Guizhi Wuwu decoction has reliable effect in treating rheumatoid arthritis, but there is no evidence of evidence-based medicine. Therefore, this study aims to systematically evaluate the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. METHODS: Using computer to retrieve PubMed, The Cochrance Library, Embase, Web of Science, CNKI, VIP and Wanfang database, in addition manually retrieve Google academic and Baidu academic to collect all randomized controlled trials for Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis, including relevant academic journal and conference papers, dissertations, from the establishment of the database to July 2020. After 2 evaluators independently screened the literature, extracted the data, and evaluated the risk of bias included in the study, RevMan5.3 software was used to analyze the data. RESULTS: This research evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction in treating Rheumatoid arthritis from the aspects of clinical efficacy rate, visual analog scale (VAS), swollen joint count (SJC), morning stiffness time, Rrythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and adverse reaction incidence. CONCLUSION: This study will provide reliable evidence for the clinical application of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RZY3V.

PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.

The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry. The concentration of serotonin in plasma was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial remodeling induced by MCT, and this action was associated with accelerated apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study suggests that PCPA protects against the pathogenesis of PAH by suppressing remodeling and inducing apoptosis, which are likely associated with CTGF and downstream ERK signaling pathway in rats.