Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups： blank group， model group， low-， medium-， and high-dose Anmeidan groups， and the Suvorexant group， with 10 rats in each group. Except for the blank group， the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution （30 mg·kg^-1·d^-1） by gavage， while the low-， medium-， and high-dose Anmeidan groups received Anmeidan decoction （4.55， 9.09， 18.18 g·kg^-1·d^-1） by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor （EGF）， brain-derived neurotrophic factor （BDNF）， and vasoactive intestinal peptide （VIP） were measured using enzyme-linked immunosorbent assay （ELISA）. Untargeted metabolomics was employed to identify differential metabolites in rat serum， and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group， the model group exhibited significant reductions in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.01）， along with significant decreases in VIP， EGF， and BDNF levels （P<0.05，P<0.01）. A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group， the low-， medium-， and high-dose Anmeidan groups showed significant increases in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.05，P<0.01）， as well as a significant increase in VIP levels （P<0.05，P<0.01）. Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan， with network topology analysis suggesting that Caspase-3， B-cell lymphoma 2 （Bcl-2）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， matrix metalloproteinase-9 （MMP-9）， and Toll-like receptor 4 （TLR4）， among others， may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis revealed major enriched pathways， including the cyclic adenosine monophosphate （cAMP） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment， with its mechanisms of action potentially involving the regulation of immune-inflammatory responses， energy metabolism， and apoptosis-related pathways.

OBJECTIVE To investigate the efficacy and safety of ropivacaine combined with oxycodone for the analgesia of iliac fascia nerve block in patients undergoing hip replacement. METHODS Sixty-six patients who underwent hip replacement at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2023 to April 2024 were selected and randomly divided into observation group and control group， with 33 cases in each group. Before induction of anesthesia， ultrasound-guided iliac fascial nerve block was performed. Patients in the observation group were treated with 0.33% ropivacaine+0.1 mg/kg oxycodone injection mixture 30 mL， and patients in the control group were treated with 0.33% ropivacaine injection 30 mL. The time of first postoperative rescue analgesia， 24 h postoperative analgesic drug consumption， sensory block and motor block effective and maintenance time， satisfaction degree， numerical rating scale （NRS） pain score， Ramsay sedation score， muscle strength score， heart rate （HR）， mean arterial pressure （MAP）， oxygen saturation（SpO2）， sleep score， anxiety score， and the occurrence of adverse reactions in the two groups were all recorded. RESULTS Compared with the control group， the first rescue analgesia time after operation was significantly prolonged in the observation group， and 24 h postoperative analgesic drug consumption after operation decreased； the effective time of sensory block was significantly shortened， and the maintenance time of sensory block was significantly prolonged， and the satisfaction score was higher； the NRS pain score after iliac fascia nerve block was lower， HR and MAP were lower， and the anxiety score and sleep score 24 and 48 h after operation were lower （P＜0.05）. In terms of safety， patients in both groups had adverse reactions after operation， such as hypertension， nausea， vomiting， and dizziness， but there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Oxycodone combined with ropivacaine shows good efficacy and safety for iliac fascial nerve block analgesia in patients undergoing hip replacement， can significantly prolong the analgesic time of ropivacaine， reduce postoperative analgesic drug consumption， improve the sleep quality of patients， and promote the rapid recovery of patients.

AIM: To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics.METHODS: Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf). Larvae were randomized into four groups: control group(CG; aquaculture water), model group(MG; 130 mmol/L glucose), low-dose HXMMT treatment group(L-HX; 130 mmol/L glucose +7.5 mg/L HXMMT), and high-dose HXMMT treatment group(H-HX; 130 mmol/L glucose +75 mg/L HXMMT), with a 3-day intervention period until 6 dpf. The area and length of eyes, and body length of zebrafish were observed by stereomicroscopy, retinal morphology was observed by hematoxylin-eosin staining(HE), and retinal vessel diameter was observed under fluorescence microscope. Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish, and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS: HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement, widened gaps, and thickened inner nuclear layer(INL)in ganglion cell layer GCL); retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG, and it was significantly changed after the intervention of HXMMT, with significant efficacy in the H-HX(P<0.05); transcriptomics profiling identified 1 470 reversed DEGs, predominantly enriched in the AMPK signaling pathway, FoxO signaling pathway, retinal developmental processes, and tight junction regulation. Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571, P<0.05).CONCLUSION: HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1, pde6c, arr3a, plk1, fbp1b, foxo1a, pcna, and cdk1, as well as synergistically modulating processes such as retinal development in camera-type eyes, visual perception, microtubule cytoskeletal organization, tight junctions, and the AMPK signaling pathway, Foxo signaling pathway.

: To explore the relationship between metal exposure level and blood pressure, so as to provide a scientific basis for verifying the relationship between metal exposure and elevated blood pressure among primary school students. Methods: In July 2022, a total of 555 students of second to sixth grade were selected by cluster random sampling method from two primary schools in Zhuxi County, Shiyan City, Hubei Province. A questionnaire survey was conducted to obtain the socio demographic characteristics and living habits of the participants. The height, weight, body mass index(BMI) and blood pressure were obtained by physical examination. At the same time, the urine of the subjects was collected, and the metal mass fraction in urine was detected by inductively coupled plasma mass spectrometry. The relationship between metal mass fraction in urine and blood pressure was analyzed by generalized linear regression. Results: The detection rate of elevated blood pressure in primary school students was 15.86% , and there was a statistically significant difference in the detection rate of elevated blood pressure among obese primary school students (yes:37.25%,no:13.69%, χ 2=19.28, P <0.01).There were statistically significant differences in BMI[15.80( 14.69 ， 17.92 )，17.87(15.49，20.89)kg/m 2] between the non elevated blood pressure group and the elevated blood pressure group of elementary school students ( Z =-4.67, P <0.01). The geometric mean mass fraction of zinc in urine was the highest ( 6 942.86 μg/g), titanium was the lowest (2.20 μg/g). Zinc and lead were positively correlated with elevated systolic blood pressure( β = 0.054 , 0.014), zinc and cadmium were positively correlated with elevated diastolic blood pressure ( β =0.038,0.029) ( P <0.05). Conclusions Metal zinc, lead and cadmium concentration are associated with elevated blood pressure. It is necessary to intervene and control the exposure of zinc, lead and cadmium in the environment to promote the blood pressure health of primary school students.

Objective To analyze the prevalence, annual trends, and co-morbidity trends of common chronic diseases among workers in a large automotive industry from 2019 to 2021, and to provide a scientific basis for the health management of workers in the automotive industry. Methods The health examination data of workers in a large automotive industry from 2019-2021 were analyzed. Trends in the prevalence of chronic diseases and co-morbidities were analyzed using Join Point software and trend χ² test. Results The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in the 2019 – 2021 health checkups of workers in this enterprise increased at an average rate of 9.27%, 11.35%, and 3.99% per year, respectively. The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in male workers showed an increasing trend at an average rate of 7.05%, 9.25%, and 2.91% per year, respectively. The prevalence of metabolic syndrome in female workers showed an increasing trend at an average rate of 20.76% per year. The prevalence of metabolic syndrome, hyperuricemia and fatty liver was on the rise in the age groups ≤ 29 years old and 40 – 49 years old. The proportion of metabolic syndrome and its co-morbidity with one or two common chronic diseases showed an increasing trend. Conclusion The prevalence and co-morbidity of common chronic diseases in this enterprise are generally on the rise. The enterprise should focus on health education and preventive care for chronic diseases among workers aged ≤ 29 and 40 – 49 years old and male workers and control the annual increasing trend of metabolic syndrome among female workers and workers in the age group ≤ 29 years.

Objective To investigate the effect of dihydroartemisinin (DHC) on the proliferation capacity of human oral squamous carcinoma cells and its mechanism of action. Methods The viability and colony formation ability of CAL27 cells treated with different concentrations of dihydroartemisinin was measured by CCK-8 and colony formation assay. The expression of proteins related to proliferation and autophagy was determined by Western blot. Potential targets for DHA inhibition of the biological behavior of oral cancer were screened based on network pharmacology and bioinformatics. Measurement was conducted after the cells were cotreated with autophagy blocker 3-methyladenine and autophagy inducers rapamycin and dihydroartemisinin. Results Dihydroartemisinin significantly reduced the proliferation viability and clone formation ability of CAL27 cells in a concentration-dependent manner. The PCNA expression level also decreased substantially. DHA suppressed oral cancer targets involving autophagy-related pathways. DHA intervention increased the expression of intracellular autophagy-related proteins Beclin-1 and LC3. After co-treatment of DHA combined with autophagy blocker, the proliferation viability and clone formation ability of CAL27 cells decreased. The expression of PCNA increased, and the expression of Beclin-1 and LC3 decreased. Conclusion Dihydroartemisinin could inhibit the proliferative capacity of oral squamous carcinoma cells in vitro, and its effect may be correlated with the induction of autophagy.

Objective:To investigate the clinical phenotype and genetic characteristics of developmental epileptic encephalopathy 18 (DEE18) caused by SZT2 gene variants. Methods:Clinical data of 2 children with SZT2 related DEE18 who visited the Department of Pediatric Neurology, Linyi People′s Hospital in March 2020 and July 2023 were collected. The whole exome sequencing (WES) and Sanger sequencing were applied to verify the child and their parents. SWISS-MODEL software was used to perform protein 3D modeling for the selected SZT2 gene variants. Results:Both of the 2 cases showed severe global developmental delay, epileptic seizures, autism, megacephaly, facial deformity, hypotonia, corpus callosum malformation, persistent cavum septum pellucidum, and slow background activity and focal discharge in video electroencephalography. Case 1 was easy to startle and thin in stature; case 2 had immune deficiency and clustered seizures. WES results showed that case 1 carried a compound heterozygous variant of c.5811G>A (p.W1937X) (paternal) and c.9269delG (p.S3090Ifs *94) (maternal), while case 2 carried a compound heterozygous variant of c.6302A>C(p.H2101P) (paternal) and c.7584dupA (p.E2529Rfs *20) (maternal), the parents of both patients with normal clinical phenotypes. The 4 mutations mentioned above were novel variations that had not yet been reported domestically or internationally. According to the American College of Medical Genetics and Genomics variant classification criteria and guidelines, the p.S3090Ifs *94 variant was interpreted as pathogenic; p.W1937X variant was interpreted as pathogenic; p.E2529Rfs *20 variant was interpreted as likely pathogenic; p.H2101P variant was interpreted as uncertain significance. 3D modeling showed that the variant of p.H2101P resulted in a significant change in the hydrogen bond around the 2 101st amino acid encoded, leading to a decrease in protein stability. The other 3 variants led to early truncation of peptide chain and obvious changes in protein structure. Conclusions:DEE18 caused by SZT2 gene mutation is mainly an autosome recessive genetic disease, and its clinical manifestations include global developmental delay, epileptic seizures, autism, craniofacial malformation, hypotonia, epileptic discharge, corpus callosum malformation, persistent cavum septum pellucidum, shock, small and thin stature, and immune deficiency. Four novel variants related to the SZT2 gene may be the genetic etiology of DEE18 patients in this study.

Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

Objective:To explore the developmental characteristics of event-related potential(ERP) in cognitive function of recognition memory in children aged 6-12.Methods:A total of 130 normal children were divided into seven age groups (6 ( n=20), 7 ( n=17), 8 ( n=23), 9 ( n=24), 10 ( n=19), 11 ( n=15), and 12 years old ( n=12)) to perform a picture study-recognition task and record the reaction time, accuracy, and ERP components of all participants. SPSS 22.0 software was used for data analysis. Single factor analysis of variance and trend of variance were used to compare the response time and accuracy of 7 groups of children during the recognition stage. Pearson correlation analysis was used to study the correlation between the amplitude of the central midline N2 component and age. Paired t-test was used to examine the old/new effects of the amplitude of midfrontal N2 and midparietal P3 waves. Results:(1) The differences of recognition ability ( F(6, 123)=2.476, P<0.05), old picture reaction time ( F(6, 123)=6.461, P<0.001), and new picture reaction time ( F(6, 123)=4.163, P<0.001) among 7 age groups of children were statistically significant. Recognition ability of children aged 6 (0.61±0.24) was lower than those of 8-12 years old children((0.76±0.27), (0.76±0.10), (0.73±0.11), (0.75±0.10), (0.70±0.17) respectively)(all P<0.05). The reaction time of the old picture showed no difference among the children aged 6-9 (all P>0.05), and the reaction time of old picture of children aged 12 was shorter than those of 6-10 years old children (all P<0.01). There was no significant difference in the reaction time of new pictures among the children aged 6-10 (all P>0.05), and which in children aged 12 was shorter than those in 6-10 years old children(all P<0.01). (2) Age was positively correlated with the amplitude of the N2 component in the central region under the new ( r=0.488, P<0.001) and old picture( r=0.452, P<0.001) conditions. (3)At 6 years old, children showed old/new effects on the mid-frontal electrodes. At 7 years old, there were no old/new effects in either the mid-frontal or mid-parietal regions. From 8 to 9 years old, old/new effects appeared in the mid-parietal lobe. At 10 years old, old/new effects were present in both the mid-frontal and mid-parietal regions. At 11 years old, the mid-parietal lobe showed old/new effects. Finally, at 12 years old, negative old/new effects could be observed in both the mid-frontal and mid-parietal regions. Conclusion:There are three periods of changes in the behavior of picture recognition memory in school-age children. At ages 6-7, the accuracy rate is relatively low; at ages 8-9, it improves; and between ages 10-12, the accuracy rate stabilizes while also enabling faster judgments.Children's recognition memory retrieval process is more complex than their behavioral performance. Children have different tendencies toward strategies, but strategic transitions in recognition processing are not always beneficial for performance.