ObjectiveTo analyze the causes of occupational acute 1,2-dichloroethane (1,2-DCE) poisoning accident during the use of polyurethane grouting materials for waterproof plugging operation in the construction industry. Methods By combining the clinical symptoms of the patient, worksite survey of occupational health and workplace occupational hazards monitoring method, the cause of an occupational acute 1,2-DCE poisoning accident was investigated at a construction site during the use of polyurethane grouting material for waterproofing and plugging operations. Results The patient was engaged in waterproof grouting work using polyurethane grouting material. The main volatile organic components in the raw materials were 1,2-DCE, with traces of dichloromethane, methyl acetate and others. The result of post-incident on-site investigation showed that the short-term exposure concentration of 1,2-DCE in the workplace air was 578.70 mg/m³, which was more than 30 times higher than the national occupational health standard limit. The mass concentration of 1,2-DCE in the patient's blood was 230 μg/L. Combined with the patient's occupational hazard exposure history, clinical manifestations, worksite survey of occupational health, and laboratory test results, according to GBZ 39-2016 Diagnosis of Occupational Acute 1,2-Dichloroethane Poisoning, this incident was diagnosed as a severe occupational acute 1,2-DCE poisoning event caused by the use of inferior polyurethane grouting material. Conclusion The excessive concentration of 1,2-DCE in the workplace air is the main cause of this poisoning accident. Construction sites with confined space operations should improve various occupational health management systems, occupational health engineering protective facilities, and personal protective equipment must be provided for workers.

Objective:To screen and verify the key radioresistance genes regulated by m6A methylation in nasopharyngeal carcinoma (NPC) based on the chip data and cell experiments.Methods:The microarray data of NPC radioresistance genes, m6A regulated genes and mRNA expression profiles of NPC genes were downloaded from Gene Expression Omnibus (GEO) database. The differential genes were screened and statistically analyzed by R software. The biological processes, signal pathways and interaction networks of these genes were analyzed by bioinformatics. The m6A regulatory factors were knocked down and the radioresistant strains were constructed. The above m6A differential radioresistant genes of NPC were screened and verified by real-time reverse transcription PCR (qRT-PCR) and Western blot. The m6A modification of screened genes and their direct binding ability with methyltransferase 3 (METTL3) were verified by methylated RNA immunoprecipitation qPCR (MeRIP-qPCR). The siRNA of selected genes was transfected into NPC cells, and after treatment with ionizing radiation, cell proliferation was detected by CCK-8 assay and EdU, apoptosis and cell cycle were detected by flow cytometry, and radiosensitivity was detected by clone formation assay. The trend of differences in the abundance of Fe 2+ and lipid peroxidation between the control and EGLN3 knockdown groups after ionizing radiation treatment was compared by paired t-test. Results:Chip data GSE48501 intersected with GSE200792 and GSE53819 to obtain 6 differential genes, including EGLN3, FOSL2, ADM, JUN, VEGFA and PRDM1. The target genes of EGLN3 and FOSL2 were further screened by TNMplot and KMplot, etc. The mRNA of the target genes directly bound to METTL3 and were subjected to its mediated modification of m6A. The target genes were up-regulated in the parental cells after irradiation in a dose and time gradient manner, which were also significantly up-regulated in radioresistant cells. After EGLN3 and FOSL2 were down regulated, the proliferation activity of NPC cells was more significantly decreased after irradiation, and the radiosensitization ratio was statistically significant compared with that of NPC cells without EGLN3 and FOSL2 down-regulation. After irradiation, EGLN3 down-regulated NPC cells significantly down-regulated glutathione peroxidase 4 (GPX4) expression, increased the abundance of Fe 2+ and lipid peroxidation, which played a role in radiosensitization by inducing ferroptosis. Conclusions:EGLN3 and FOSL2 play a role in radioresistance in NPC through METTL3 mediated m6A methylation. Down-regulation of EGLN3 combined with ionizing radiation can increase the intracellular Fe 2+ abundance and lipid peroxidation and down-reuglate the expression of GPX4 in NPC cells, which can enhance radiosensitization for NPC radiotherapy by the ferroptosis pathway.

The anti-inflammatory effect of simplified Zhiqin Decoction was observed by using lipopolysaccharide (LPS)-induced inflammation mouse model. The main chemical constituents and the main mechanism of action of simplified Zhiqin Decoction were predicted by network pharmacology. Animal experiments verified the anti-inflammatory mechanism of simplified Zhiqin Decoction (this experiment was approved by the Animal Experiment Ethics Committee of Southwest University, approval number: IACUC-20210825-02). Simplifying Zhiqin Decoction has a significant anti-inflammatory effect on inflammatory mice, can significantly improve the overall macro shape of mice, reduce body temperature, water intake, increase the number of autonomous activities; alleviate liver, lung, spleen, thymus inflammation and pathological damage; decrease tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, nitric oxide (NO), prostaglandin E₂ (PGE₂) content in serum and urine. The contents of serum immune factors IgG, IgA and IgM were increased. Network pharmacology predicted 66 potential anti-inflammatory active components of simplified Zhiqin Decoction involving 132 inflammatory targets, and the key anti-inflammatory signaling pathway involved PI3K/AKT, TNF, JAK-STAT, etc. Animal experiments show that simplified Zhiqin Decoction can significantly reduce the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway related proteins in lung tissue of inflammatory mice. The results of this study showed that simplified Zhiqin Decoction had significant anti-inflammatory effects, and its main anti-inflammatory components were quercetin, β-sitosterol, kaempferol, wogonin, stigmasterol, luteolin, neobaicalein, etc. The main mechanism of its anti-inflammatory action is that it significantly inhibits the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway protein.

Objective To investigate the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament on postoperative analgesia and inflammation response in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 60 elderly patients who had undergone robot-assisted laparoscopic radical prostatectomy from June 2022 to June 2023 were randomly divided into a group of ultra-sound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament combined with general anesthesia(observation group,n = 30)and a general anesthesia group(control group,n = 30).Both groups received patient-controlled intravenous analgesia after surgery.The first compression time of an analgesic pump and the numbers of effective compression and remedial analgesia were recorded.The VAS scores at postsurgical hours 2,12,24,and 48 during rest and coughing were recorded.Interleukin-6(IL-6)and systemic immunoinflammatory index(SII)at one day before surgery and two hours,one day and three days after surgery were recorded.Anal exhaust time,length of postoperative hospital stay and occurrence of adverse reactions were recorded.Results The observation group,as compared with the control group,had significantly longer first compression time of an analgesic pump and had fewer numbers of effective compressions and remedial analgesic administrations(P<0.05).The VAS scores during rest and coughing in the observation group were lower than those in the control group at postsurgical hours 2,12,24,and 48(P<0.05).As compared with one day before surgery,both IL-6 and SII in the two groups increased at 2 hours,1,and 3 days after surgery,but the changes in the observation group were lower than those in the control group(P<0.05).As compared with the control group,the observation group had shorter anal exhaust time and length of postoperative hospital stay,and a lower incidence of adverse reactions(P<0.05).Conclusions Ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament can provide better postoperative analgesia,reduce inflammatory response and accelerate postoperative recovery in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.

Objective:To evaluate the effect of anterior quadratus lumborum block at the lateral supra-arcuate ligament on the postoperative pulmonary function in patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.Methods:Seventy-two American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 50-80 yr, with body mass index of 18.5-27.9 kg/m 2, scheduled for elective robot-assisted laparoscopic radical prostatectomy under general anesthesia, were divided into 2 groups ( n=36 each) using a random number table method: control group and observation group. After induction of general anesthesia, observation group underwent anterior quadratus lumborum block at the lateral supra-arcuate ligament under ultrasound guidance, with 20 ml of 0.375% ropivacaine administered on each side. Control group only received total intravenous anesthesia. Postoperative analgesia was provided by patient-controlled intravenous analgesia until 48 h after operation, and intravenous dezocine was administered as rescue analgesic when the visual analogue scale score at rest≥4. Pulmonary function was assessed at 1 day before surgery and 1-7 days after surgery. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), maximal mid-expiratory flow rate (FEF 25%-75%), and time to recovery of 80% predicted pulmonary function were recorded. Arterial blood gas analysis was performed at 1 day before surgery and 1-3 days after surgery, and SpO 2, PaO 2 and PaCO 2 were recorded. The consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were recorded. Postoperative pulmonary complications within 7 days after operation and re-hospitalization within 30 days were recorded. The time to first flatus, postoperative length of hospital stay and occurrence of adverse reactions (dizziness, nausea, vomiting) within 3 days after surgery were also recorded. Results:Compared with control group, FVC, FEV 1 and FEF 25%-75% were significantly increased postoperatively, the time to recovery of 80% FVC, FEV 1 and FEF 25%-75% was shortened, postoperative SpO 2 and PaO 2 were increased, postoperative PaCO 2 was decreased, the consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were reduced, the postoperative time to first flatus and length of hospital stay were shortened, and the incidence of adverse reactions and pulmonary complications was decreased ( P<0.05). Conclusions:Anterior quadratus lumborum block at the lateral supra-arcuate ligament can improve postoperative pulmonary function, reduce adverse reactions, and promote early recovery for the patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

The Ehlers-Danlos syndromes(EDS)are a group of rare hereditary connective tissue disorders characterized by joint hypermobility,skin hyperextensibility,and tissue fragility.The clinical and genetic hetero-geneity of EDS frequently leads to underdiagnosis and misdiagnosis.Genetic testing is an essential approach to clarify the underlying diagnosis.Recent research has preliminarily established genotype-phenotype correlations and introduced the novel concept of"disease spectrum"in some subtypes.These studies deepen our under-standing of EDS etiology and provide important insights into clinical management.Published in 2023,the Chinese Guidelines for Diagnosis and Treatment of the Ehlers-Danlos Syndromes(the Guidelines)recommend performing genetic testing with deep phenotyping for patients who meet the clinical diagnostic criteria or are sus-pected of having EDS.However,it should be noted that the clinical diagnosis might differ from the molecular diagnosis.Furthermore,cutting-edge approaches such as periodic data reanalysis,integration of RNA sequen-cing into family-based whole-genome sequencing,and third-generation sequencing may facilitate the reclassifi-cation of variants of uncertain significance or resolve undiagnosed cases.This article summarizes recent progress in the genetics research of EDS,with the hope of offering a valuable resource for clinical diagnosis,treatment and scientific research to optimize the quality of life of patients with EDS.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To study the role and preliminary molecular mechanism of TRIM24 regulating macrophage polarization in viral myocarditis(VM).Methods:VM mouse model was established by Coxsackie virus B3(CVB3),and expression of TRIM24 in myocardial tissue was detected.Cardiac inflammation level and polarization phenotype of cardiac infiltrating macrophages in a murine model of cardiac TRIM24 inhibition were detected in vivo.A polarization model of mouse bone marrow-derived macrophages(BMDMs)in vitro was established to observe the role of TRIM24 inhibition in polarizing BMDMs to M1 and M2,as well as its effects on phagocy-tosis and bactericidal function of BMDMs.Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investi-gated.Results:TRIM24 was significantly highly expressed in myocardial tissue of VM mice(P<0.001).Inhibition of TRIM24 expres-sion in myocardium had an attenuating effect on VM and promoted polarization of cardiac infiltrating macrophages to M2.TRIM24 was significantly down-regulated in vitro during the polarization of BMDMs toward M2(P<0.01).Inhibition of TRIM24 expression signifi-cantly promoted macrophage polarization toward M2 type and inhibited polarization toward M1 type,accompanied by a significant increase in STAT6 phosphorylation levels(P<0.01).Conclusion:TRIM24 regulates macrophage M2 polarization via activation of STAT6 signaling pathway to attenuate VM.

Objective To investigate the characteristics of corneal nerve fibers in patients with Parkinson disease （PD） and varying degrees of autonomic dysfunction by using corneal confocal microscopy （CCM）. Methods A total of 70 patients with PD and 31 healthy controls were recruited. CCM was performed for all the patients enrolled， and according to the score of the Scale for Outcomes in Parkinson Disease for Autonomic Symptoms， the patients with PD were divided into mild autonomic dysfunction group and moderate to severe autonomic dysfunction group. CCM parameters and clinical data were compared between the two groups and the healthy control group. The receiver operating characteristic （ROC） curve analysis was used to quantify the efficacy of CCM parameters in the diagnosis of PD with varying degrees of autonomic dysfunction. Results The PD patients with mild autonomic dysfunction and those with moderate to severe autonomic dysfunction had significantly lower CNFD and CNFL than the healthy control group（P<0.05）.In addition， the ROC curve analysis showed that CNFD among CCM parameters had a higher diagnostic value in distinguishing PD patients with moderate to severe autonomic nervous dysfunction from the healthy population， with an area under the ROC curve of 0.8224. Conclusion CCM can be used as an effective and objective detection method to investigate the characteristics of corneal nerve fibers in PD with varying degrees of autonomic dysfunction，which supplements the current research on the application of CCM technique in PD with small fiber neuropathy.
Parkinson Disease