Arsenic is a widely occurring metalloid element in the natural environment and is one of the primary carcinogens identified by the World Health Organization (WHO), but the specific carcinogenic mechanism is currently unclear. In recent years, through toxicological studies on arsenic, it has been found that exposure to arsenic can affect cellular metabolism in the body, which may be closely related to the carcinogenic mechanism of arsenic. Therefore, the authors review the research progress on arsenic exposure-induced effects on glucose metabolism, lipid metabolism, and amino acid metabolism, with a view to providing a theoretical basis for the study of the mechanism of arsenic carcinogenesis.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the impact of a history of atopy on the value of fractional exhaled nitric oxide (FENO) for predicting sputum eosinophils in patients with chronic cough. METHODS: A total of 868 patients with persistent cough lasting more than 3 weeks without pulmonary infection were enrolled, including 119 patients with subacute cough (defined as cough lasting 3-8 weeks) and 749 with chronic cough (longer than 8 weeks). The predictive value of FENO level for sputum eosinophilia was analyzed using receiver-operating characteristic (ROC) curve analysis, and the area under the curve (AUC) was calculated. The atopy status of the patients was determined by screening for history of allergy, hay fever, or animal or food allergies. RESULTS: Of the 868 patients enrolled, 173 patients (19.9%) had eosinophilic airway inflammation (EAI). In the overall patients, the median (Q1, Q3) FENO level was 18 (12, 35) ppb, ranging from 5 to 300 ppb. The patients with chronic cough and a positive history of atopy had a higher median FENO level than those without atopy (24 [13, 50] vs 18 [11, 34]; Z=2.25, P= 0.029), and FENO level was significantly correlated with EAI (r=0.281, P < 0.001). The AUCs of FENO for diagnosis of airway eosinophilia in patients with atopy and those without atopy were 0.677 (95% CI: 0.548-0.806) and 0.708 (95% CI: 0.660-0.756), respectively. The optimal cut-off value of FENO for diagnosing EAI was higher in patients with atopy than in those without atopy (72 vs 28.5 ppb). CONCLUSION A history of atopy reduces the predictive value of FENO level for EAI in patients with chronic cough, suggesting the importance of examining the atopic status when interpreting test results of FENO.
Humans ; Cough/diagnosis* ; Exhalation ; Fractional Exhaled Nitric Oxide Testing ; Nitric Oxide/analysis* ; Eosinophilia ; Chronic Disease ; Inflammation

OBJECTIVE: To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. METHODS: Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. RESULTS: TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). CONCLUSION Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.
Animals ; Asthma/chemically induced* ; Inflammation ; Macrophages ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases ; Respiratory System ; Toluene 2,4-Diisocyanate/adverse effects*

Objective:To evaluate the clinical efficacy of Zhiwei pill for bile reflux gastritis （BRG） with symptoms of disharmony of liver and stomach， evaluate the safety after treatment by three-arm study， and investigate the regulatory action to gastrointestinal hormones. Method:One hundred and eighty patients were randomly divided into placebo group （60 cases）， control group （60 cases） and observe group （60 cases） by random number table. Patients in three groups got lifestyle intervention of non-drug therapy. Patients in control group got hydrotalcite tablets 1-2 hours after meal or untimely bedtime or in case of stomach pain， 2 tablets/time， 3 times/day. Patients in placebo group got simulated medicine of Zhiwei pill 1 hour after meal， 6 g/time， 3 times/day. Patients in observe group got Zhiwei pill 1 hour after meal， 6 g/time， 3 times/day. The treatment continued for 4 weeks in all 3 groups. Before and after treatment， scores were graded for symptoms of disharmony of liver and stomach and patient reported outcome （PRO） scale for patients with chronic gastrointestinal diseases. Gastroscopy was taken to grade the scores of bile reflux and mucosa under gastroscope. Levels of gastrin （GAS）， motilin （MTL）， cholecystokinin （CCK）， substance P （SP） and gastrointestinal hormones were detected. Efficacy for traditional Chinese medicine（TCM） syndrome and efficacy under gastroscope were compared， and safety after treatment was evaluated. Result:After treatment， the total scores of the main symptoms and 7 secondary symptoms of disharmony of liver and stomach in observe group were all lower than those in placebo group and control group （P<0.01）， and scores of symptoms of disharmony of liver and stomach and PRO were all lower than those in control group and placebo group （P<0.01）. After treatment， scores of degree of bile reflux and mucosa under gastroscope in observe group were all lower than those in placebo group and control group （P<0.01）. Level of CCK was lower than that in placebo group and control group （P<0.01）， while levels of MTL， GAS and SP were higher than those in placebo group and control group （P<0.01）. Total effective rate of TCM syndrome was 91.38%（53/58）， higher than 71.93%（41/57） in control group and 34.62%（18/52） in placebo group. The total effective rate in gastroscopy was 93.10%（54/58）， higher than 78.95%（45/57） in control group and 28.85%（15/52） in placebo group （P<0.05 or P<0.01）. No adverse reactions related to Zhiwei pill were found. Conclusion:Zhiwei pill can improve bile reflux， promote the healing of mucosa under gastroscope， regulate gastrointestinal hormones， improve gastrointestinal motor function， significantly alleviate clinical symptoms， and improve quality of life， with better efficacy for TCM syndrome and efficacy in gastroscopy， and it is safe for clinical use.

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; physiopathology ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; epidemiology ; physiopathology ; therapy ; Retrospective Studies ; Young Adult

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

OBJECTIVE: To explore the application value and clinical effect of three-dimensional printing combined with composite plate internal fixation in the treatment of old acetabular posterior wall fracture. METHODS: From May 2010 to October 2016, Mimics 19.0 software was used to plan preoperatively according to a 1:1 print pelvic 3D model. At the same time, 23 patients with old acetabular posterior wall fractures were treated with combined plate internal fixation, including 15 males and 8 females, aged 20 to 63 (43.0±5.1) years old, and the time from injury to operation was 23 to 101(47.0±10.5) days. According to Letournel-Judet classification, 11 cases were posterior wall fracture, 7 cases were transverse with posterior wall fracture, and 5 cases were posterior column with posterior wall fracture. All patients were treated with single Kocher-Langenbeck approach combined plate internal fixation, and the evaluation indexes were recorded during operation, after operation and during follow-up. RESULTS: The operation time of 23 patients was (113.5±11.5) min, bleeding was (550.0±104.7) ml and fluoroscopy was (12.7±0.8) s. Matta radiographic reduction criteria were used: excellent in 14 cases, good in 7 cases and poor in 2 cases; 23 patients were followed up for 10 to 24 (16.0±5.6) months. The hip function was evaluated according to the modified Merle d'Aubingne and Postal scoring system at the last follow-up: excellent in 11 cases, good in 8 cases, fair in 3 cases and poor in 1 case. There were 3 cases of traumatic arthritis, 1 case of femoral head necrosis, 2 cases of heterotopic ossification and 5 cases of sciatic nerve irritation. CONCLUSIONS 3D printing technique is an effective and fast method for the treatment of old acetabular posterior wall fractures. In addition, the printing model can provide three-dimensional morphological structure for the operator, combined with preoperative simulation, facilitate intraoperative reduction, and effectively improve the efficiency of surgery.
Acetabulum ; Adolescent ; Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; Humans ; Male ; Printing, Three-Dimensional ; Treatment Outcome ; Young Adult

AIM:To investigate the effect of toosendanin(TSN)on invasion and migration abilities of human ovarian cancer cells and the related mechanism.METHODS:The human ovarian cancer cell lines CAVO-3 and SKVO-3 were treated with TSN at different concentrations.The cell viabilty at 12,24,48,72 and 96 h after TSN treatment was measured by CCK-8 assay.Scratch wound healing assay and Transwell assay were employed to measure the invasion and migration abilities of CAVO-3 cells.The protein expression of nuclear factor-κB(NF-κB)p65,E-cadherin,N-cadherin,vimentin and Snail was determined by Western blot.RESULTS:TSN significantly inhibited the viability of CAVO-3 and SKVO-3 cells(P<0.05 ).Compared with control group ,the migration and invasion abilities of CAVO-3 cells in TSN group decreased significantly(P<0.05).In addition,the expression of NF-κB p65 and E-cadherin protein increased no-tably,followed with N-cadherin,vimentin and Snail protein decreased significantly(P<0.05).However,the inhibitor of NF-κB BAY11-7082 reversed the impact above.Compared with TSN group ,the migration and invasion abilities in TSN +BAY11-7082 group increased significantly(P<0.05).The protein expression of E-cadherin also decreased notably ,fol-lowed with the protein expression of N-cadherin,vimentin and Snail increased significantly(P<0.05).CONCLUSION:TSN inhibits the invasion and migration abilities of human ovarian cancer cells ,which is related to the inhibition of epitheli-al-mesenchymal transition process mediated by NF-κB/Snail signaling pathway.