Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective:To introduce the stereotactic cardiac radioablation (SCRA) based on the stereotactic body radiotherapy (SBRT), and comprehensively evaluate the new approach by short-term effectiveness and safety.Methods:Patients with ventricular arrhythmia (VA) were evaluated and included in this clinical trial, who were immobilized by vacuum bag and performed simulation with 4-dimensional computed tomography (4DCT). In this study, the planning target volume (PTV) was set as the target to design a SBRT plan using volumetric modulated arc therapy (VMAT), which was evaluated by dose parameters such as R 50%, homogeneity index and conformity index, etc. The results of Holter and echocardiography were monitored during the follow-up and compared with the data before treatment. Results:Three subjects with ventricular tachycardia (VT) and one with premature ventricular contraction (PVC) received the same prescription of 25 Gy in a single fraction. The average volume of PTV was 71.4 cm 3(60.3-89.4 cm 3). The average time of beam delivery was 12.0 min (4.5-21.0 min). And the short-term follow-up lasted for an average of 18 weeks (14-25 weeks), which showed significant decrease in both VT and PVC load without complications. Conclusion:This study reports the implementation method of SCRA and proves its short-term effectiveness and safety, but the effects and standards of the key radiotherapy techniques still need to be explored.

ObjectiveTo investigate the causes of discontinuation of subcutaneous allergen immunotherapy （SCIT） in patients with allergic rhinitis （AR） and / or bronchial asthma （BA） in the Pearl River Delta region， and to improve the compliance of these patients. MethodsIt was a retrospective， multi-center real world study. Patients with AR and / or BA receiving SCIT in six hospitals in the Pearl River Delta region from January 2015 to December 2020 were recruited. The clinical data of all patients were collected， and the patients with abscission were followed up by telephone. ResultsIn this study， 1 244 patients who received SCIT were included. A total of 427 patients stopped SCIT before 3 years （34.3%）. Children， married patients and patients with positive family history of allergy and total immunoglobulin E （tIgE） > 200 U / mL showed relatively good compliance （P<0.05）， while more patients of AR alone stopped SCIT before 3 years than patients of AR complicated with BA （P<0.05）. Patients with high symptom score and drug score before treatment had better compliance （P<0.001）. A total of 279 cases （65.3%） of the non-adherence group were followed by telephone. The first three reasons for discontinuing treatment were the treatment did not achieve the expected effect （115 cases， 41.2%）， factors pertaining to learning and daily life （74 cases， 26.5%） and adverse reactions （29 cases， 10.4%）. The number of patients stopping SCIT decreased gradually with time； the proportion of patients who discontinued treatment due to adverse reactions in the first year of treatment was higher than that in the second and third years （P<0.05）. ConclusionFailure to achieve the expected effect was the primary reason for poor compliance of patients receiving SCIT and discontinuation mainly occurred on the early stage of the treatment. The supervision from family members is helpful to improve the compliance， suggesting that individualized measures need to be taken to reduce the loss of SCIT.

ObjectiveTo investigate the effects of gene polymorphism on the pharmacokinetics of sufentanil （SUF） in children with congenital heart disease undergoing interventional cardiac surgery. MethodsA total of 168 ASA grade Ⅱ patients aged 6~72 months and scheduled for interventional cardiac surgery were enrolled into the study. Anesthesia was induced by using propofol 2 mg·kg^-1， SUF 0.3 μg·kg^-1 and cisatracurium besilate 0.2 mg·kg^-1. Propofol 8 mg·kg^-1·h^-1 was administered to maintain anesthesia. Blood samples were collected at 5， 10， 20， 30， 45， 60， 75， 90 min after administration of SUF by dilution sampling method. Plasma concentration of sufentanil was determined by UHPLC-MS/MS method and pharmacokinetic parameters were calculated by Phoenix Winnonlintm^TM software. The genotypes were detected by matrix-assisted laser desorption ionization-time of flight mass spectrometry （MALDI-TOF MS）. The genotypes and pharmacokinetic data were analyzed by SNPStats software and the model with the smallest value of Akaike information criterion was chosen as the best model. ResultsThirty single nucleotide polymorphisms （SNPs） in 9 genes possibly involved in pharmacokinetics， pharmacodynamics related targets， metabolic enzymes， transporters and pathways of SUF were examined. ABCG2 rs2054576 and OPRM1 rs4870266 were found to be related to area under the curve （AUC） （P<0.05）. OPRM1 rs2236257 was correlated with the apparent volume of distribution （V_d） （P<0.05）. CYP3A4 rs2246709， OPRM1 rs2236257 and rs4870266 were associated with the drug clearance rate （CL） （P<0.05）. ConclusionGene polymorphisms of ABCG2 rs2054576，CYP3A4 rs2246709 and OPRM1 rs2236257， rs4870266 could significantly affect the pharmacokinetics of SUF in children undergoing interventional cardiac surgery.

OBJECTIVE: This study was designed to provide the evidences on the toxicokinetics of microplastics (MPs) and nanoplastics (NPs) in the bodies of mammals. METHODS: 100 nm, 3 μm, and 10 μm fluorescent polystyrene (PS) beads were administered to mice once by gavage at a dose of 200 mg/kg body weight. The levels and change of fluorescence intensity in samples of blood, subcutaneous fat, perirenal fat, peritesticular fat, cerebrum, cerebellum, testis, and epididymis were measured at 0.5, 1, 2, and 4 h after administration using an IVIS Spectrum small-animal imaging system. Histological examination, confocal laser scanning, and transmission electron microscope were performed to corroborate the findings. RESULTS: After confirming fluorescent dye leaching and impact of pH value, increased levels of fluorescence intensity in blood, all adipose tissues examined, cerebrum, cerebellum, and testis were measured in the 100 nm group, but not in the 3 and 10 μm groups except in the cerebellum and testis at 4 h for the 3 μm PS beads. The presence of PS beads was further corroborated. CONCLUSION After a single oral exposure, NPs are absorbed rapidly in the blood, accumulate in adipose tissues, and penetrate the blood-brain/testis barriers. As expected, the toxicokinetics of MPs is significantly size-dependent in mammals.
Male ; Animals ; Mice ; Microplastics ; Plastics ; Genitalia ; Adipose Tissue ; Polystyrenes/toxicity* ; Nerve Tissue ; Mammals

This paper clarified the scientific connotation of the changes in cold and heat properties of Arisaematis Rhizoma and Arisaema Cum Bile through investigating the changes of substance and energy metabolism after drug intervention in the rats with normal and cold/heat syndrome, so as to improve the method of evaluating the drug properties of Chinese medicine. After one week of adaptive feeding, healthy male SD rats were randomly divided into three parts: normal rats, heat syndrome rat models, and cold syndrome rat models. Through ice water bath and oral euthyrox(120 μg·kg~(-1)), the models of cold syndrome and heat syndrome were induced, respectively. The models were made at 9:00 am. and administrated by gavage at 3:00 pm. every day. All administration groups were administrated with Arisaematis Rhizoma and Arisaema Cum Bile decoction, respectively, and the blank group was given the same dose of normal saline. After continuous administration for 15 d, the rats were anesthetized by chloral hydrate, blood was taken from abdominal aorta, and the hearts and livers were removed and stored at-80 ℃. The changes in the body weight and anal temperature of rats during administration were detected, and the liver coefficient of rats was detected after removing the liver. Enzyme-linked immunosorbent assay(ELISA) was adopted to detect the expression level of the indexes related to substance and energy metabolism in liver and heart of rat, and Western blot was used to detect the expression of key proteins in AMPK/mTOR signaling pathway for further verification. The results showed that Arisaematis Rhizoma enhanced the expression level of enzymes related to substance and energy metabolism in the normal and cold and heat syndrome rat models, and increased anal temperature, which exhibited warm(hot) drug property. Arisaema Cum Bile inhibited the level of substance and energy metabolism in rats, and reduced anal temperature, which showed cold(cool) drug property. Chinese Pharmacopoeia has recorded "Arisaematis Rhizoma has warm property and Arisaema Cum Bile has cool property", which is consistent with the phenomenon in this study. Therefore, it is feasible to evaluate the drug properties of Chinese medicine based on the substance and energy metabolism of normal and cold/heat syndrome model rats, which completes the method of evaluating drug properties of Chinese medicine.
AMP-Activated Protein Kinases ; Animals ; Arisaema/chemistry* ; Bile ; Chloral Hydrate ; Cold-Shock Response/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism ; Heat Stroke/therapy* ; Hot Temperature ; Male ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; Syndrome ; TOR Serine-Threonine Kinases ; Thyroxine ; Water

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (P_non-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q₂ subgroup of mtDNAcn, those in the Q₁ subgroup (HR=2.00,95%CI:1.08-3.70) and Q₄ subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q₃ subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (P_interaction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
Cohort Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics* ; Female ; Humans ; Liver Neoplasms/genetics* ; Male ; Mitochondria

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
Aged ; Anxiety ; Cross-Sectional Studies ; Depression ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rectum ; Surveys and Questionnaires