ObjectiveTo explore the possible mechanism of the treatment of dry eye with liver-meridian constraint-heat syndrome by Runmu Xiaoyao Powder （润目逍遥散） by miR-146a-5p and interleukin-1 receptor-associated kinase 1/tumour necrosis factor receptor associated factor 6/nuclear factor-κB （IRAK1/TRAF6/NF-κB） signalling pathway. MethodsEighty C57BL/6J mice were randomly divided into normal group， model group， agonist group， inhibitor group， sodium hyaluronate group， and Runmu Xiaoyao Powder high-， medium-， and low-dose groups， with 10 mice in each group. Except for the normal group， the mice of dry eye with liver-meridian constraint-heat syndrome were modeled by using benzalkonium chloride solution eye drops combined with chronic pain stimulation. Beginning on the 30th day of modelling， mice in Runmu Xiaoyao Powder high-， medium-， and low-dose groups were given 29， 14.5， and 7.25 g/kg of Runmu Xiaoyao Powder respectively twice daily by gavage； mice in sodium hyaluronate group were given 5 μl of sodium hyaluronate drops twice daily； mice in the agonist group were given 2 nmol of agomir-146a-5p drops in each eye at a time， and those in the inhibitor group were given 5 nmol of antagomir-146a-5p drops in each eye， with every other day， 3 times per week； mice in the normal and model groups were gavaged with deionised water at 1 ml/（100 g·d）. The intervention was continued for 14 days in each group， and mice in each group were examined for tear secretion， tear film rupture time， corneal fluorescein staining， and irritability scores on the day following the last intervention； HE staining was used to observe the pathological conditions of the cornea and lacrimal glands in each group； corneal and lacrimal gland inflammatory factors， such as interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， miR-146a-5p expression， were examined； matrix metalloproteinase 3 （MMP-3） and matrix metalloproteinase 9 （MMP-9） expression in cornea， IRAK1， TRAF6， nuclear factor κB p65 （NF-κB p65） protein and mRNA expression in cornea and lacrimal gland， and phosphorylated nuclear factor κB p65 （p-NF-κB p65） protein expression were detected. ResultsCompared with the normal group， mice in the model group showed reduced tear secretion， shorter tear film rupture time， higher irritability score （P＜0.05）， and pathological examination showed staining in the centre of the cornea， obvious corneal damage， increased volume of lacrimal gland follicular cells， disordered arrangement， a large number of inflammatory cell infiltration， and increased neovascularisation； corneal and lacrimal gland tissues showed elevated expression of IL-1β and TNF-α， decreased expression of miR -146a-5p， elevated expression of IRAK1， TRAF6， NF-κB p65， p-NF-κB p65 protein and IRAK1， TRAF6， NF-κB p65 mRNA， and elevated expression of MMP-3， MMP-9 protein in the cornea （P＜0.05）. Compared with the model group， all of the above indexes were significantly improved in high-dose group of Runmu Xiaoyao Powder， while some indexes were improved in the sodium hyaluronate group and the middle- and low-dose Runmu Xiaoyao Powder groups （P＜0.05）. Compared with the model group， corneal and lacrimal IRAK1 and TRAF6 mRNA and IRAK1， TRAF6 and p-NF-κB p65 protein expression decreased in the agonist group； compared with the inhibitor group， IRAK1， TRAF6， NF-κB p65 mRNA and protein expression in the cornea and lacrimal gland in the Runmu Xiaoyao Powder groups decreased （P＜0.05）. ConclusionRunmu Xiaoyao Powder can negatively regulate the IRAK1/TRAF6/NF-κB signalling pathway in the cornea and lacrimal gland of mice with dry eye of liver-meridian constraint-heat syndrome by up-regulation of miR-146a-5p， so as to inhibit inflammatory response and reduce the damage of the ocular surface tissues， and the high doses group showed the best effect.

Objective To analyze the characteristics of newly-diagnosed occupational diseases among female workers in Foshan City from 2013 to 2023. MethodsClinical data of newly-diagnosed occupational diseases among female workers in Foshan City from 2013 to 2023 were collected from the "Occupational Disease and Hazardous Detection Information System" subsystem of the "China Disease Prevention and Control Information System", and their distribution characteristics were analyzed using descriptive epidemiology. Results A total of 218 cases of newly-diagnosed occupational diseases among female workers in Foshan City were reported from 2013 to 2023, categorized into seven categories and 17 types. The median age and median length of exposure to occupational hazards among female workers were 45.1 and 7.8 years, respectively. The top three categories of newly-diagnosed cases were occupational diseases of the ear, nose, throat, and oral cavity (90 cases, all related to occupational noise-induced hearing loss), occupational chemical poisoning (61 cases), and occupational pneumoconiosis and other respiratory diseases (51 cases, including 50 cases with occupational pneumoconiosis). The newly-diagnosed cases were concentrated in Nanhai District, Shunde District, and Gaoming District, accounting for 75.2%. The newly-diagnosed cases were found in non-metallic mineral products manufacturing industry, metal products industry, and electrical machinery and equipment manufacturing industry, accounting for 50.9%. Enterprises of newly-diagnosed cases were mainly distributed in private enterprises and foreign-invested enterprises, accounting for 80.3%. The scale of enterprises of newly-diagnosed cases was mainly small- and medium-sized, accounting for 79.4%. Among the 218 cases, there were 21 cluster cases, involving 16 cases of occupational silicosis and five cases of occupational acute n-hexane poisoning, involving six manufacture industries, with 81.3% cases worked in sanitary ceramic products industry. Conclusion Occupational noise-induced deafness should be listed as a key occupational disease for female workers in Foshan City. Attention should be paid to the prevention of occupational diseases among middle-aged female workers in the non-metallic mineral products industry and small and medium-sized enterprises, and the cluster outbreaks of occupational pneumoconiosis.

Objective:To explore the epileptogenic network patterns in 14 patients with mesial temporal lobe epilepsy (mTLE) originating from the amygdala.Methods:A total of 14 patients with mTLE originating from the amygdala underwent preoperative evaluation in Department of Epilepsy, Guangdong Sanjiu Brain Hospital from January 1, 2019 to December 31, 2023 were selected. A retrospective analysis was performed on the clinical data of these patients. Epileptogenic network patterns were further explored based on stereo-electroencephalogram (SEEG) and positron emission tomography-computed tomography (PET-CT).Results:Craniocerebral MRI indicated 12 patients with unilateral amygdala hypertrophy, and 2 with increased T2-FLAIR signal in the amygdala but no obvious volume change. During interictal period, scalp EEG indicated discharges in one or both temporal regions and distinguished at the lesion side. During ictal period, scalp EEG indicated that the initial side is consistent with the lesion side. Three clinical phenotypes and epileptogenic network patterns were summarized: the first type ( n=5) had clinical manifestations as aura→automotor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→preinsula→temporal pole (by SEEG) and low metabolism in the medial structures of the temporal lobe (by PET-CT); the second type ( n=6) had clinical manifestations as aura→hypermotor/complex motor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→temporal pole→frontal orbital gyrus and anterior cingulate cortex→insula (by SEEG) and low metabolism in the medial structures of the temporal lobe, temporal pole, insula, frontal-orbital gyrus, and inner frontal lobe (by PET-CT); the third type ( n=3) had clinical manifestations as aura→bilateral symmetrical dystonia→autonomic symptoms (with or without oral-alimentary automotor), with epileptic seizure starting from amygdala→hippocampus and insula→temporal pole and adjacent temporal neocortex (by SEEG) and low metabolism in the mesial structures of the temporal lobe and the insula (by PET-CT). Conclusion:The different clinical phenotypes of patients with mTLE originating from the amygdala may have equivalent epileptogenic network patterns.

Objective To investigate the relationship between docosahexaenoic acid (DHA) level and the onset of attention deficit hyperactivity disorder (ADHD) based on Mendelian Randomization (MR).Meth-ods The instrumental variables for DHA and ADHD were extracted from the genome-wide association stud-ies (GWAS) data.To ensure the stablity of the study results,the ADHD datasets were selected from two dif-ferent studies.The The dataset for DHA levels included 115,006 individuals,the ADHD1 dataset consisted of 55374 individuals,including 20183 cases and 35191 controls,the ADHD2 dataset consisted of 225534 indi-viduals,including 38691 cases and 186843 controls,the comprehensive MR and sensitivity analyses were per-formed.The MR analyses were performed by the inverse variance weighted (IVW) method,MR-Egger regression analysis and the weighted median method (WM),utilizing the odds ratio (OR) and effect coefficient (β) as evaluation indictors to explore the bidirectional causal relationship between DHA and ADHD.Results There exists a causal link between DHA levels and the onset of ADHD (ADHD1 IVW:OR=0.833,95％CI:0.719-0.964,P=0.014;ADHD2 IVW:OR=0.895,95％CI:0.808-0.992,P=0.034).Additionally,a reverse causal relation-ship between ADHD and DHA levels (IVW:β=-0.073,95％CI:-0.103 to-0.043,P<0.001) was found.Conclusion The potential bidirectional causal relationship exists between DHA level and ADHD.

Objective To explore the effect and safety of right unilateral modified electroconvulsive therapy(RUL-MECT)for major depressive disorder patients(MDD).Methods A randomized controlled trial was conducted on 70 patients with MDD who were randomly divided into a study group and a control group.The study group underwent age-based RUL-MECT,while the control group underwent bitemporal MECT.The participants were evaluated using the 17-item Hamilton depression scale(HAMD-17),MATRICS consensus cognitive battery(MCCB)and orientation recovery tests(ORT).Any adverse reactions that occurred during each intervention process were recorded.Results Before treatment,there were no significant differences in the HAMD-17(32.89±5.68 vs.33.54±4.78)between the two groups(P>0.05).The HAMD-17 score of the intervention group was 6.83±4.68,while the control group was 7.20±4.60 after 8 interventions,repeated measures analysis of variance showed the time effect(P<0.001)was significant.The intergroup effect and interaction effect was not significant(P>0.05).In terms of MCCB scores,there were significant main effect(P<0.001)in connectivity tests,symbol coding,language memory,spatial breadth,number sequence,maze test,visual memory,emotional management and the duration of continuous operation.The intergroup effects of language memory,number sequence,visual memory,speech fluency,and continuous operation were significant(P<0.05).The interaction effect of language memory and continuous operation were significant(P<0.05).After the intervention,the recovery of orientation time was significantly shorter in the study group than that in the control group[(508.57±104.48)s vs.(631.66±212.27)s](P<0.05).The incidence of adverse reactions between two groups(28.6% vs.40.0% )has no significance(P>0.05).Conclusions Compared with bitemporal MECT,RUL-MECT has comparable efficacy in treating depressant and better performance in improving cognitive function and recovery of orientation.

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.

Objective:To study the changes of serum N-glycan abundance in patients with liver fibrosis at different stages of hepatitis C, and to establish and evaluate the diagnostic model for clinical application value.Methods:Data of 169 hepatitis C virus-infected cases with liver fibrosis were enrolled. Nine kinds of serum N-glycans were detected and analyzed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis technology. A binary logistics regression method was used to establish a diagnostic model based on the changes in the relative content of N-glycans in each stage of liver fibrosis. Receiver operating characteristic curve was used to evaluate and compare the diagnostic efficacy with other liver fibrosis diagnostic models.Results:N-glycan diagnostic model (B and C) had highest AUROC= 0.776, 0.827 for distinguishing fibrosis S1~S2 to S3~S4 and S1~S3 to S4 than GlycoFibroTest (AUROC = 0.760, 0.807), GlycoCirrhoTest (AUROC = 0.722, 0.787), aspartate aminotransferase to platelet ratio index (AUROC = 0.755, 0.751), FIB-4 index (AUROC = 0.730, 0.774), and S-index (AUROC = 0.707, 0.744). However, the diagnostic efficacy of model A (AUROC = 0.752) for distinguishing fibrosis S1 with S2~S4 had lower diagnostic potency than that of the aspartate aminotransferase to platelet ratio index (AUROC = 0.807). Diagnostic efficiency was improved when the N-glycan profiling and the aspartate aminotransferase to platelet ratio index were combined to diagnose liver fibrosis in each stage, and the area under the receiver operating characteristic curve was 0.839, 0.825, and 0.837, respectively.Conclusion:The serum N-glycan profiling diagnostic model has potential clinical application value in the diagnosis of liver fibrosis in patients with hepatitis C.

Objective To evaluate the relationship between the hippocampal neuron-protective mechanism of hydrogen in a rat model of oxygen-glucose deprivation and restoration(OGD/R)and mito-chondrial autophagy.Methods Hippocampal neurons isolated from healthy Sprague-Dawley rats(24 h af-ter birth)were cultured in vitro,seeded in polylysine-coated 6-well plates at a density of 7×105 cells/well and then divided into 5 groups(n＝30 each)using a random number table method: control group(C group),OGD/R group,OGD/R+H2 group,OGD/R plus 3-methyladenine(3-MA)group(OGD/R+3-MA group),and OGD/R plus H2 plus 3-MA group(OGD/R+H2+3-MA group).The cells were cultured for 24 h in normal culture atmosphere(75％N2-20％O2-5％CO2)in group C,and cells were subjected to oxygen-glucose deprivation for 2 h followed by O2-glucose supply for 24 h to establish the model of OGD/R injury in OGD/R,OGD/R+H2,OGD/R+3-MA and OGD/R+H2+3-MA groups.The cells were cultured for 24 h in a hydrogen-rich incubator(60％H2-10％O2-5％CO2-25％N2)after establishing the model in group OGD/R+H2.Autophagy inhibitor 3-MA 10 mmol/L was added,and then cultured for 24 h in normal culture atmosphere after establishing the model in group OGD/R+3-MA.Autophagy inhibitor 3-MA 10 mmol/L was added,and then cultured for 24 h in hydrogen-rich incubator after establishing the model in group OGD/R+H2+3-MA.The cell survival rate was measured using MTT assay.DCFH-DA fluorescent probe was applied for determination of reactive oxygen species(ROS)activity.The mitochondrial membrane potential was measured using a JC-10 assay kit.The neuronal apoptosis was detected by flow cytometry,and apoptosis rate was calculated.The expression of mitophagy-related protein microtubule-associated protein 1 light chain 3(LC3),PINK1 and Parkin was determined by Western blot,and LC3Ⅱ/LC3Ⅰ ratio was calculated.Results Compared with group C,the cell survival rate and MMP were significantly decreased,the apop-tosis rate and ROS activity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰrati-o were increased in OGD/R and OGD/R+H2 groups(P＜0.05).Compared with group OGD/R,the cell survival rate and MMP were significantly increased,the apoptosis rate and ROS activity were decreased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in group OGD/R+H2(P＜0.05),and the cell survival rate and MMP were significantly decreased,the apoptosis rate and ROS activ-ity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in group OGD/R+3-MA(P＜0.05).Compared with group OGD/R+H2,the cell survival rate and MMP were significantly decreased,the apoptosis rate and ROS activity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in OGD/R+3-MA and OGD/R+H2+3-MA groups(P＜0.05).Conclusion Hippocampal neuron-protective mechanism of hydrogen against OGDR injury is relat-ed to promoting mitochondrial autophagy in rats.

Objective: To evaluate the relationship between the hippocampal neuron-protective mechanism of hydrogen in a rat model of oxygen-glucose deprivation and restoration (OGD/R) and mitochondrial autophagy. Methods: Hippocampal neurons isolated from healthy Sprague-Dawley rats (24 h after birth) were cultured in vitro, seeded in polylysine-coated 6-well plates at a density of 7×10⁵ cells/well and then divided into 5 groups (n=30 each) using a random number table method: control group (C group), OGD/R group, OGD/R+ H₂ group, OGD/R plus 3-methyladenine (3-MA) group (OGD/R+ 3-MA group), and OGD/R plus H₂ plus 3-MA group (OGD/R+ H₂+ 3-MA group). The cells were cultured for 24 h in normal culture atmosphere (75%N₂-20%O₂-5%CO₂) in group C, and cells were subjected to oxygen-glucose deprivation for 2 h followed by O₂-glucose supply for 24 h to establish the model of OGD/R injury in OGD/R, OGD/R+ H₂, OGD/R+ 3-MA and OGD/R+ H₂+ 3-MA groups.The cells were cultured for 24 h in a hydrogen-rich incubator (60% H₂-10% O₂-5% CO₂-25% N₂) after establishing the model in group OGD/R+ H₂.Autophagy inhibitor 3-MA 10 mmol/L was added, and then cultured for 24 h in normal culture atmosphere after establishing the model in group OGD/R+ 3-MA.Autophagy inhibitor 3-MA 10 mmol/L was added, and then cultured for 24 h in hydrogen-rich incubator after establishing the model in group OGD/R+ H₂+ 3-MA.The cell survival rate was measured using MTT assay.DCFH-DA fluorescent probe was applied for determination of reactive oxygen species (ROS) activity.The mitochondrial membrane potential was measured using a JC-10 assay kit.The neuronal apoptosis was detected by flow cytometry, and apoptosis rate was calculated.The expression of mitophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), PINK1 and Parkin was determined by Western blot, and LC3Ⅱ/LC3Ⅰ ratio was calculated. Results: Compared with group C, the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in OGD/R and OGD/R+ H₂ groups (P<0.05). Compared with group OGD/R, the cell survival rate and MMP were significantly increased, the apoptosis rate and ROS activity were decreased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in group OGD/R+ H₂(P<0.05), and the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in group OGD/R+ 3-MA (P<0.05). Compared with group OGD/R+ H₂, the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in OGD/R+ 3-MA and OGD/R+ H₂+ 3-MA groups (P<0.05). Conclusion Hippocampal neuron-protective mechanism of hydrogen against OGDR injury is related to promoting mitochondrial autophagy in rats.