A machine learning model predicts stroke associated with blood cadmium level.

Stroke is the leading cause of death and disability worldwide. Cadmium is a prevalent environmental toxicant that may contribute to cardiovascular disease, including stroke. We aimed to build an effective and interpretable machine learning (ML) model that links blood cadmium to the identification of stroke. Our data exploring the association between blood cadmium and stroke came from the National Health and Nutrition Examination Survey (NHANES, 2013-2014). In total, 2664 participants were eligible for this study. We divided these data into a training set (80%) and a test set (20%). To analyze the relationship between blood cadmium and stroke, a multivariate logistic regression analysis was performed. We constructed and tested five ML algorithms including K-nearest neighbor (KNN), decision tree (DT), logistic regression (LR), multilayer perceptron (MLP), and random forest (RF). The best-performing model was selected to identify stroke in US adults. Finally, the features were interpreted using the Shapley Additive exPlanations (SHAP) tool. In the total population, participants in the second, third, and fourth quartiles had an odds ratio of 1.32 (95% CI 0.55, 3.14), 1.65 (95% CI 0.71, 3.83), and 2.67 (95% CI 1.10, 6.49) for stroke compared with the lowest reference group for blood cadmium, respectively. This blood cadmium-based LR approach demonstrated the greatest performance in identifying stroke (area under the operator curve: 0.800, accuracy: 0.966). Employing interpretable methods, we found blood cadmium to be a notable contributor to the predictive model. We found that blood cadmium was positively correlated with stroke risk and that stroke risk from cadmium exposure could be effectively predicted by using ML modeling.

Targeted Delivery of Gemcitabine for Precision Therapy of Cholangiocarcinoma Using Hyaluronic Acid-Modified Metal-Organic Framework Nanoparticles.

Chemotherapy is widely recognized as an important approach for the treatment of cholangiocarcinoma. Gemcitabine (GEM) has been considered a first-line drug for treating cholangiocarcinoma due to its ability to effectively inhibit the proliferation, migration, and invasion of liver cancer cells. However, the systemic toxicity, premature degradation, and lack of tumor-targeting properties of GEM limit its application in cholangiocarcinoma chemotherapy. Additionally, precise targeted delivery of GEM is necessary to align with the current concept of precision medicine. In this study, considering the overexpression of hyaluronic acid (HA) receptors (CD44) on cholangiocarcinoma cells, we designed GEM@ZIF-67-HA NPs by loading GEM onto ZIF-67 and modifying its surface with HA. The structure, size, morphology, and elemental composition of GEM@ZIF-67-HA were analyzed using transmission electron microscopy, Fourier transform infrared spectroscopy, ζ-potential, and isothermal adsorption. Cell toxicity experiments demonstrated that GEM@ZIF-67-HA NPs not only reduced cytotoxicity to normal cells but also effectively inhibited the viability of two types of cholangiocarcinoma tumor cells. In a subcutaneous tumor model, GEM@ZIF-67-HA significantly suppressed tumor growth. The tumor-targeting and controllable properties of GEM@ZIF-67-HA NPs hold promise for further development in the strategy of precise targeted therapy for cholangiocarcinoma.

The cerebral mechanism underlying the acupoints with specific effect for gallbladder stone disease: protocol for a randomized controlled task-fMRI trial.

BACKGROUND: As it has been recorded in ancient Chinese classics, Yanglingquan (GB34) and Dannangxue (EX-LE6) are two important acupoints that can regulate the function of the gallbladder. Acupuncture at these two acupoints is considered particularly effective for gallbladder disease treatment, especially for alleviating gallbladder stone disease (GSD) symptoms that can be aggravated after intaking high-fat food. However, the superior effect between the two acupoints still needs to be further explored, as well as the underlying central mechanism has never been investigated to date. METHODS AND DESIGN: Ninety participants diagnosed with GSD will be randomly divided into group A (acupuncture at GB34), group B (acupuncture at EX-LE6), and group C (acupuncture at non-acupoint) in a ratio of 1:1:1. All of them will receive a 30-min acupuncture treatment with fatty-food cues being presented before and after acupuncture. During the task, participants will be scanned by MRI and required to rate their desire for high-/low-fat food with an 11-point Likert scale. Additionally, the participants' pain/discomfort sensation will be evaluated using the Numeric Rating Scale (NRS) at four timepoints, including before the 1st task fMRI scan, before and after acupuncture, and after the 2nd task fMRI scan. For both behavior and fMRI data, the ANOVA analysis will be conducted among three groups to testify the immediate effect of GB34 and EX-LE6. The post hoc t-test will be employed to further explore the superiority between acupuncture with GB34 and EX-LE6. Furthermore, correlation analyses will be conducted to investigate a possible correlation between neural changes and clinical data. DISCUSSION: In comparison to the non-acupoint, the results will firstly explore the superior effect between acupuncture with GB34 and EX-LE6 on GSD patients by observing their behavioral and neural response change to fatty-food cue, and then to investigate the underlying central mechanism. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000034368 . Registered on 3 July 2020.

Acupuncture for biliary colic: a systematic review protocol.

INTRODUCTION: Biliary colic (BC) is a severe pain associated with nausea and vomiting, which is the most common symptom among the gallstone population. This protocol proposes a methodology for conducting a systematic review and meta-analysis that aims to assess the benefits and safety of acupuncture in patients with BC. METHODS AND ANALYSIS: Clinical trials will be identified through nine databases from inception to December 2020, using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Database and Wanfang Database. Search words will be used for the BC and acupuncture. The analysis would include randomised, controlled, clinical trials of adults with BC that were published in either Chinese or English. The primary outcome is to measure pain relief. Two or three reviewers should be in charge of study selection, data extraction and evaluating the risk of bias. RevMan software (V.5.4) will be used to perform the assessment of the risk of bias and data synthesis. ETHICS AND DISSEMINATION: Ethics approval will not be required for this review, as it will only involve the collection of literature previously published. The results of this meta-analysis will be disseminated in a peer-reviewed journal or relevant conference, through publication. TRIAL REGISTRATION NUMBER: CRD42020167510.

Anatomic Variation of the Cystic Artery: New Findings and Potential Implications.

Purpose: To determine the anatomy of the cystic artery by dual-source CT, and correlate imaging findings with those patients who had laparoscopic cholecystectomy (LC). Materials and Methods: Following institutional review board approval, a total of 289 consecutive patients (204 men and 85 women) were evaluated with CT for abdominal pain, including 55 patients subsequently underwent LC. Location of the cystic artery termination, distance between the cystic artery origin and the gallbladder, and angle between the cystic artery and its parent artery were evaluated by two radiologists. The laparoscopic surgical video record (gold standard) was similarly evaluated by a surgeon. Results: A total of 256 cystic arteries in the 247 patients were included. Cystic artery terminations are predominately found in ventral Calot triangle plane (50.8%, type II). Cystic artery origin immediately adjacent to the gallbladder surface was seen in 11/256 (4.3%). Zero angle between the cystic artery and its parent artery was found in 17 of 256 cystic arteries (6.6%). The cystic arteries and the Calot triangle were depicted in 49 patients (95% confidence interval: 85%, 97%). For all 49 patients, CT imaging findings were consistent with surgical video records. No case involved vascular and biliary injury occurred. Conclusions: Given the large number of LC performed each year, better knowledge of anatomic variation of the cystic artery could potentially prevent arterial injury and bile duct injury, particularly for patients with unusual anatomy.

Anti-PD-1, anti-VEGF, and temozolomide therapy in a patient with recurrent glioblastoma: a case report.

BACKGROUND: Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months.Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. RESULTS: The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. CONCLUSION: The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.

A Protective Role for RHOJ in NonSmall Cell Lung Cancer Based on Integrated Bioinformatics Analysis.

RHOJ is a small G protein characterized by its abundant expression in endothelial cells. Existing research has documented a link between abnormal RHOJ expression and carcinogenesis. This research aims to investigate the protective role of RHOJ in nonsmall cell lung cancer (NSCLC). In this study, Cancer Genome Atlas database and Gene Expression Omnibus were collected to analyze RHOJ expression and gene regulation networks in NSCLC. Oncomine™ and Gene Expression Profiling Interactive Analysis tools were first utilized to analyze RHOJ expression, and then cBioPortal was employed for identification of RHOJ alterations and associated functional networks. To identify differential RHOJ expression, LinkedOmics was used, which also served to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Besides, the target networks of kinases factors were explored using gene enrichment analysis. Our results suggested that lower expression of RHOJ was observed in patients with NSCLC compared with normal people. Low expression of this gene is linked to functional networks involving cytoskeleton, adhesion, infection, and Ras signaling pathways. Functional network analysis suggested that RHOJ regulates the Staphylococcus aureus infection, AGE-RAGE signaling pathway, and DNA and RNA damage. In conclusion, the results in this study demonstrated that data mining is an effective approach that can uncover information about RHOJ expression and potential regulatory networks in NSCLC, thus laying the groundwork for future studies of a similar kind.

IL-10 in vitro could enhance IFNγ expression and suppress PD-1 expression in CD8 T cells from esophageal cancer patients.

IL-10 is commonly regarded as an immunoregulatory cytokine, but accumulating evidence suggests that IL-10 may promote CD8 T cell expansion and proliferation. In this study, tumor infiltrating (TI) and peripheral blood (PB) CD8 T cells were collected from esophageal cancer patients. Interestingly, IL-10 concentration in the tumor microenvironment increased with advancing tumor stage, while TI CD8 T cell-mediated IL-10 production decreased with advancing tumor stage. By flow cytometry, three distinctive subsets, including IL-10+IFNγ-, IL-10+IFNγ+, and IL-10-IFNγ+, could be observed in TI CD8 T cells. The former two subsets were present at much higher frequency in stage I and stage II patients than in stage III patients. IL-10+IFNγ+ TI CD8 T cells presented significantly higher IFNγ and lower PD-1 expression than the IL-10-IFNγ+ TI CD8 T cells. PB CD8 T cells, on the other hand, produced little IL-10 but potent IFNγ upon stimulation. Interestingly, intermediate level of exogenous IL-10 could significantly elevate the expression of IFNγ by PB CD8 T cells, while high level of exogenous IL-10 resulted in reduced expression of IFNγ by PB CD8 T cells. Exogenous IL-10 could not significantly reduce the frequencies of PD-1+ PB CD8 T cells, but significantly reduced the MFI of PD-1 in the PB CD8 T cells, especially in stage III patients. Together, this investigation demonstrated that IL-10 enhanced IFNγ expression and suppressed PD-1 expression in PB and TI CD8 T cells; however, the frequency of IL-10-expressing TI CD8 T cells decreased with increasing severity in esophageal cancer.

Effects of pilose antler peptide on bleomycin-induced pulmonary fibrosis in mice.

The aim of present study was to evaluate the effects of the pilose antler peptide (PAP) on bleomycin (BLM)-induced lung fibrosis. The lung wet-to-dry weight (W/D) ratio and myeloperoxidase (MPO) activity were measured. The serum levels of super-oxide dismutase (SOD), malondialdehyde (MDA) were examined. Then the contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 were determined using ELISA method. Furthermore, the protein expressions of Rho, ROCK1, p-IκB, IκB, p-NF-κB, NF-κB in lung tissues were detected by western blot analysis. As a result, PAP markedly decreased pulmonary W/D ratio, lung MPO activity and relieved lung histopathological changes. In addition, PAP increased the level of SOD and reduced the levels of MDA, TNF-α, IL-1ß, IL-6 in serum of BLM-stimulated mice. In addition, PAP remarkably inhibited the protein levels of ROCK/NF-κB pathway. In conclusion, our results showed that PAP exhibited protective effects on pulmonary fibrosis via the regulation of ROCK/NF-κB pathway.

A Police and Insurance Joint Management System Based on High Precision BDS/GPS Positioning.

Car ownership in China reached 194 million vehicles at the end of 2016. The traffic congestion index (TCI) exceeds 2.0 during rush hour in some cities. Inefficient processing for minor traffic accidents is considered to be one of the leading causes for road traffic jams. Meanwhile, the process after an accident is quite troublesome. The main reason is that it is almost always impossible to get the complete chain of evidence when the accident happens. Accordingly, a police and insurance joint management system is developed which is based on high precision BeiDou Navigation Satellite System (BDS)/Global Positioning System (GPS) positioning to process traffic accidents. First of all, an intelligent vehicle rearview mirror terminal is developed. The terminal applies a commonly used consumer electronic device with single frequency navigation. Based on the high precision BDS/GPS positioning algorithm, its accuracy can reach sub-meter level in the urban areas. More specifically, a kernel driver is built to realize the high precision positioning algorithm in an Android HAL layer. Thus the third-party application developers can call the general location Application Programming Interface (API) of the original standard Global Navigation Satellite System (GNSS) to get high precision positioning results. Therefore, the terminal can provide lane level positioning service for car users. Next, a remote traffic accident processing platform is built to provide big data analysis and management. According to the big data analysis of information collected by BDS high precision intelligent sense service, vehicle behaviors can be obtained. The platform can also automatically match and screen the data that uploads after an accident to achieve accurate reproduction of the scene. Thus, it helps traffic police and insurance personnel to complete remote responsibility identification and survey for the accident. Thirdly, a rapid processing flow is established in this article to meet the requirements to quickly handle traffic accidents. The traffic police can remotely identify accident responsibility and the insurance personnel can remotely survey an accident. Moreover, the police and insurance joint management system has been carried out in Wuhan, Central China's Hubei Province, and Wuxi, Eastern China's Jiangsu Province. In a word, a system is developed to obtain and analyze multisource data including precise positioning and visual information, and a solution is proposed for efficient processing of traffic accidents.

Pregnane X receptor is associated with unfavorable survival and induces chemotherapeutic resistance by transcriptional activating multidrug resistance-related protein 3 in colorectal cancer.

BACKGROUND: Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood. METHODS: Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays. Luciferase reporter, Chromatin-immunoprecipitation and Site-directed mutagenesis were evaluated the mechanisms. The PXR and multidrug resistance-related protein 3 (MRP3) expressions were examined by western blot, RT-PCR or immunohistochemistry of TMA. Kaplan-Meier and Cox regression were adopted to analyze the prognostic value of PXR in colorectal cancer (CRC). RESULTS: PXR over-expression significantly increased oxaliplatin (L-OHP) transport capacity with a reduction of its content and repressed the effects of L-OHP on tumour cell proliferation and apoptosis. Conversely, PXR knockdown augments L-OHP-mediated cellular proliferation and apoptosis. Moreover, PXR significantly reduced the therapeutic effects of L-OHP on tumor growth in nude mice. Further studies indicated a positive correlation between PXR and MRP3 expression and this finding was confirmed in two independent cohorts. Significantly increased MRP3 expression was also found in PXR over-expressing cell lines. Mechanistically, PXR could directly bind to the MRP3 promoter, activating its transcription. The PXR binding sites were determined to be at -796 to -782bp (CTGAAGCAGAGGGAA) and the key binding sites were the "AGGGA" (-787 to -783bp) on the MRP3 promoter. Accordingly, blockade of MRP3 diminishes the effects on drug resistance of PXR. In addition, PXR expression is significantly associated with poor overall survival and represents an unfavorable and independent factor for male or stage I + II CRC patient prognosis. CONCLUSIONS: PXR is a potential biomarker for predicting outcome and activates MRP3 transcription by directly binding to its promoter resulting in an increased L-OHP efflux capacity, and resistance to L-OHP or platinum drugs in CRC. Our work reveals a novel and unique mechanism of drug resistance in CRC.

Decreased expression of C10orf10 and its prognostic significance in human breast cancer.

Breast cancer is a common malignant tumor, which severely threatens the health of women with an increasing incidence in many countries. Here, we identified C10orf10 as a novel differentially expression gene using expression microarray screening. The expression analysis indicated that C10orf10 was frequently decreased in human breast cancers compared to noncancerous breast tissues (81/95, P = 0.0063). Kaplan-Meier analysis indicated that patients with low C10orf10 expression showed a poorer prognosis both in mRNA (n = 1115, P = 0.0013) and protein (n = 100, P = 0.003) levels. Univariate and multivariate analysis showed that the C10orf10 expression was an independent prognostic factor for overall survival of breast cancer patients. Further analysis revealed that low expression of C10orf10 was an unfavorable factor for the prognosis of the patients who were luminal A, luminal B, Her2+ subtypes, at histological grade 2, lymph node negative and ER positive. Our data provided the first evidence that C10orf10 expression was frequently decreased in breast cancer tissues, and low expression of C10orf10 may be an important prognostic factor for poorer survival time of breast cancer patients.