OBJECTIVE: To analyze the clinical phenotype and pathogenic mechanism of the ARSL gene variant in a fetus with nasal bone aplasia. METHODS: A 34-year-old pregnant woman who attended Quzhou Maternal and Child Health Care Hospital on January 3, 2023 was selected as the study subject. Whole exome sequencing (WES) was performed on the fetus. Bioinformatics analysis was carried out to identify and prioritize candidate gene variants, followed by Sanger sequencing for familial validation. A mutant plasmid expression vector was constructed and subsequently transfected into HEK293T cells to preliminarily investigate the pathogenetic mechanism of the identified variant. Additionally, a comprehensive review of literature was conducted to systematically summarize the associated clinical phenotypes. This study was approved by the Medical Ethics Committee of Quzhou Maternal and Child Health Care Hospital (Ethics No.: KY-2023-11). RESULTS: WES revealed that the fetus harbored a c.827del (p.L276Rfs*48) variant of the ARSL gene, for which its mother was heterozygous. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic(PVS1+PM2_Supporting). In vitro cellular function studies demonstrated that this variant can result in a substantial decrease in the expression of mutant mRNA, thereby preventing the production of normal ARSL protein. Clinical phenotypes resulting from ARSL gene variants exhibited considerable diversity, with nasal hypoplasia being the most common manifestation. CONCLUSION The c.827del (p.L276Rfs*48) variant of the ARSL gene can lead to degradation of mRNA via the nonsense-mediated mRNA decay pathway, resulting in reduced levels of ARSL protein. The pathogenetic mechanism underlying the ARSL gene variant may be associated with its haploinsufficiency effect.
Humans ; Female ; Pregnancy ; Adult ; Frameshift Mutation ; HEK293 Cells ; Nasal Bone/abnormalities* ; Fetus/abnormalities* ; Exome Sequencing

ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

AIM: To analysis the correlation between extraocular muscle thickness measured by quantitative CT analysis of orbital structures and clinical activity score(CAS)of thyroid-associated ophthalmopathy(TAO).METHODS:This was a retrospective analysis, selecting clinical data of TAO patients admitted to the hospital from October 2020 to February 2025. Healthy individuals were chosen from hospital's physical examination as the control group. All participants underwent CT examination, the superior rectus muscle, inferior rectus muscle, medial rectus muscle, lateral rectus muscle, orbital area, protrusion degree, and total cross-sectional area of extraocular muscles/total orbital area ratio(OM/TOA)from the two groups of participants were compared. CAS was used to evaluate TAO patients, and the correlation between CAS score and quantitative analysis indicators of CT orbital structure was analyzed. Quantitative analysis indicators for CT orbital structure in TAO patients at different stages of activity were compared, and the predictive value of these indicators for TAO patients at different activity stages was investigated.RESULTS:A total of 77 TAO patients were enrolled in this study, including 38 males and 39 females, with ages ranging from 28 to 70 y(mean age 49.5±6.9 y). There were 77 cases in the control group, including 40 males and 37 females, with ages ranging from 26 to 70 y(mean age 49.0±7.3 y). There was no significant difference in gender and age between the two groups(both P>0.05). The quantitative analysis of left eye, right eye, and binocular CT orbital structure in TAO group patients showed significantly higher indicators than the control group(all P<0.001), and the CAS score of TAO group was 3.94±1.51 points. The CAS score was positively correlated with various indicators of CT orbital structure quantitative analysis(all P<0.05). According to the CAS score results, 14 cases(28 eyes)of TAO patients with a CAS score<3 were classified as inactive phase, including 8 males and 6 females, with an average age of 43.79±9.58 y. A total of 63 cases(126 eyes)with a CAS score of ≥3 was classified as active phase, including 30 males and 33 females, with an average age of 50.78±5.47 y. There was no significant difference in gender among TAO patients with different active phases(P=0.519), but there was a significant difference in age(P<0.001). The quantitative indicators of CT orbital structure in inactive patients were significantly lower than those in active patients(P<0.05). Finally, the superior rectus muscle, age, and degree of protrusion were selected to be included in the Logistic regression model. The analysis results showed that there was a correlation between the superior rectus muscle index, degree of protrusion and TAO activity phase(P<0.05), while age, and TAO activity phase showed no significant correlation(P>0.05). The ROC curve analysis results showed that the area under the curve(AUC)was 0.863, the standard error was 0.063, P<0.001, and the 95% confidence interval(95% CI)of AUC was 0.740-0.985. The sensitivity of the model prediction was 73.0%, the specificity was 92.9%, and the Youden index was 0.659. The prediction accuracy was 97.9%, the recall rate was 73.0%, and the F1 value was 0.836. The predicted optimal critical value was 0.857. The predicted probability was 0.74.CONCLUSION:Quantitative CT analysis of orbital structures can be used to assess disease severity in TAO patients.

ObjectiveTo analyze the epidemiological characteristics of influenza-like illness (ILI) cases and the distribution patterns of influenza virus types in Xiaogan City from 2020 to 2024, and to provide a scientific basis for local influenza prevention and control. MethodsData on ILI surveillance reported by two national sentinel hospitals in Xiaogan City and influenza virus detection data reported by the network laboratory of Xiaogan Center for Disease Control and Prevention during 2020‒2024 were collected. All data were stratified and statistically analyzed by time, age and gender. Inter-group differences were compared using the chi-square (χ²) test, and statistical analyses were performed with SPSS 27.0 software. ResultsA total of 781 528 outpatient and emergency cases were reported by two sentinel hospitals in Xiaogan City from 2020 to 2024, among which 34 078 were ILI cases, with an ILI proportion (ILI%) of 4.36%. The highest proportion of ILI cases was observed in the 0‒<5 years age group, accounting for 28.62% (9 754/34 078). A total of 11 000 surveillance samples were tested, and 1 515 were positive for influenza virus, with an overall positive rate of 13.77%. Among the positive samples, 724 (47.79%) were influenza A (H3N2) subtype, 232 (15.31%) were influenza A (H1N1) subtype, 554 (36.57%) were influenza B (Victoria lineage), and 5 (0.33%) were mixed infections. A statistically significant difference was found in the seasonal distribution of influenza virus positivity rate (χ²=9 120.63, P<0.001). Epidemic peaks mainly occurred in winter and spring, with positivity rates ranging from 42.22% to 76.62%, while summer epidemic peaks were observed only in 2021 and 2022 (positivity rate was 21.48% and 43.03%, respectively). A statistically significant difference was also observed in influenza virus positivity rate among different age groups (χ²=846.61, P<0.001), with the highest influenza positive rate in the 5‒<15 years age group. No statistically significant difference was found in gender distribution (χ²=2.43, P=0.650). ConclusionThe influenza epidemic season in Xiaogan City is mainly in winter and spring, with occasional summer peaks. Prevention and control efforts should focus on children and adolescents aged 5 to <15 years, and targeted measures should be adopted in key settings such as schools. It is necessary to continuously strengthen influenza surveillance to provide a scientific basis for formulating prevention and control strategies.

ObjectiveTo observe the effects of Xiere Xingpi Yin （XRXPY） on the body mass and body fat distribution in patients with simple obesity， and to preliminarily explore whether the mechanism involves the regulation of specific obesity-related microRNAs （miRNAs）. MethodsA randomized controlled trial design was employed to recruit patients with simple obesity diagnosed with the traditional Chinese medicine （TCM） syndrome of dampness-heat accumulating in the spleen. Using a randomized controlled trial design， 95 patients with simple obesity of dampness-heat encumbering the Spleen syndrome were recruited， after 3 were excluded， 92 were randomly assigned in a 1∶1 ratio by means of a random number table. On the basis of lifestyle intervention， the observation group received XRXPY granules， while the control group received a placebo. Serum samples and TCM symptom scores were collected before and after the 12-week observation period. Differences in body mass loss， body composition， lipid metabolism， and TCM symptom scores were compared between the groups. An obesity-related miRNA dataset was constructed by searching the Human MicroRNA Disease Database. Library construction， sequencing， and quality control were performed on 6 selected patients from each group to screen the differentially expressed miRNAs. The intersection of these miRNAs with the obesity-related miRNAs was verified by bioinformatics and correlation analysis. ResultsBaseline characteristics were comparable between the two groups before treatment. A total of 86 patients completed the study （42 cases in the observation group and 44 cases in the control group）. The proportion of patients achieving ≥5% body weight reduction was significantly higher in the observation group than in the control group 81.0% （34/42） vs. 43.2% （19/44） （χ²=12.963， P<0.01）. Compared with baseline within the observation group， body weight， waist circumference， and TCM syndrome score were significantly decreased （P<0.01）， as were body fat percentage （P<0.01） and serum triglyceride level （P<0.05）. Compared with the control group after treatment， waist circumference and TCM syndrome score were significantly lower in the observation group （P<0.01）， and body weight showed a trend toward reduction. When changes from baseline were compared between the two groups， the magnitudes of decrease in body weight， waist circumference， and TCM syndrome score were all significantly greater in the observation group than in the control group （P<0.01）. With respect to safety， no serious adverse events occurred in either group and no participant discontinued the study because of adverse events. Compared with baseline， alanine aminotransferase levels decreased significantly in both the control and observation groups （P<0.01）， and urea decreased significantly in the observation group （P<0.01）， indicating a favorable safety profile. Sequencing identified nine differentially expressed miRNAs. After intersecting with the obesity-related miRNA dataset （187 miRNAs）， 3 miRNAs were identified： miR-221 （log₂FC=-6.62， P=0.009）， miR-29a （log₂FC=6.33， P=0.016）， and miR-10b （log₂FC=-5.91， P=0.029）. A total of 262 target genes of the 3 miRNAs were identified， which were significantly enriched in 67 pathways， including the lysine degradation pathway （P=0.001）. Correlation analysis revealed a positive correlation between miR-221 and triglycerides （r=0.46， P=0.027）， a negative correlation between miR-29a and waist-to-hip ratio （r=-0.41， P=0.047）， and positive correlations of miR-10b with body fat percentage （r=0.49， P=0.014） and waist circumference （r=0.44， P=0.032）. ConclusionXRXPY combined with lifestyle intervention can effectively reduce the body mass and improve body composition. The underlying mechanism may involve the regulation of the lysine degradation pathway via miR-221， miR-29a， and miR-10b， though further verification is required.

ObjectiveTo observe the effects of Xiere Xingpi Yin （XRXPY） on the body mass and body fat distribution in patients with simple obesity， and to preliminarily explore whether the mechanism involves the regulation of specific obesity-related microRNAs （miRNAs）. MethodsA randomized controlled trial design was employed to recruit patients with simple obesity diagnosed with the traditional Chinese medicine （TCM） syndrome of dampness-heat accumulating in the spleen. Using a randomized controlled trial design， 95 patients with simple obesity of dampness-heat encumbering the Spleen syndrome were recruited， after 3 were excluded， 92 were randomly assigned in a 1∶1 ratio by means of a random number table. On the basis of lifestyle intervention， the observation group received XRXPY granules， while the control group received a placebo. Serum samples and TCM symptom scores were collected before and after the 12-week observation period. Differences in body mass loss， body composition， lipid metabolism， and TCM symptom scores were compared between the groups. An obesity-related miRNA dataset was constructed by searching the Human MicroRNA Disease Database. Library construction， sequencing， and quality control were performed on 6 selected patients from each group to screen the differentially expressed miRNAs. The intersection of these miRNAs with the obesity-related miRNAs was verified by bioinformatics and correlation analysis. ResultsBaseline characteristics were comparable between the two groups before treatment. A total of 86 patients completed the study （42 cases in the observation group and 44 cases in the control group）. The proportion of patients achieving ≥5% body weight reduction was significantly higher in the observation group than in the control group 81.0% （34/42） vs. 43.2% （19/44） （χ²=12.963， P<0.01）. Compared with baseline within the observation group， body weight， waist circumference， and TCM syndrome score were significantly decreased （P<0.01）， as were body fat percentage （P<0.01） and serum triglyceride level （P<0.05）. Compared with the control group after treatment， waist circumference and TCM syndrome score were significantly lower in the observation group （P<0.01）， and body weight showed a trend toward reduction. When changes from baseline were compared between the two groups， the magnitudes of decrease in body weight， waist circumference， and TCM syndrome score were all significantly greater in the observation group than in the control group （P<0.01）. With respect to safety， no serious adverse events occurred in either group and no participant discontinued the study because of adverse events. Compared with baseline， alanine aminotransferase levels decreased significantly in both the control and observation groups （P<0.01）， and urea decreased significantly in the observation group （P<0.01）， indicating a favorable safety profile. Sequencing identified nine differentially expressed miRNAs. After intersecting with the obesity-related miRNA dataset （187 miRNAs）， 3 miRNAs were identified： miR-221 （log₂FC=-6.62， P=0.009）， miR-29a （log₂FC=6.33， P=0.016）， and miR-10b （log₂FC=-5.91， P=0.029）. A total of 262 target genes of the 3 miRNAs were identified， which were significantly enriched in 67 pathways， including the lysine degradation pathway （P=0.001）. Correlation analysis revealed a positive correlation between miR-221 and triglycerides （r=0.46， P=0.027）， a negative correlation between miR-29a and waist-to-hip ratio （r=-0.41， P=0.047）， and positive correlations of miR-10b with body fat percentage （r=0.49， P=0.014） and waist circumference （r=0.44， P=0.032）. ConclusionXRXPY combined with lifestyle intervention can effectively reduce the body mass and improve body composition. The underlying mechanism may involve the regulation of the lysine degradation pathway via miR-221， miR-29a， and miR-10b， though further verification is required.

Objective To propose a lung artery segmentation method that integrates shape and position prior knowledge, aiming to solve the issues of inaccurate segmentation caused by the high similarity and small size differences between the lung arteries and surrounding tissues in CT images. Methods Based on the three-dimensional U-Net network architecture and relying on the PARSE 2022 database image data, shape and position prior knowledge was introduced to design feature extraction and fusion strategies to enhance the ability of lung artery segmentation. The data of the patients were divided into three groups: a training set, a validation set, and a test set. The performance metrics for evaluating the model included Dice Similarity Coefficient (DSC), sensitivity, accuracy, and Hausdorff distance (HD95). Results The study included lung artery imaging data from 203 patients, including 100 patients in the training set, 30 patients in the validation set, and 73 patients in the test set. Through the backbone network, a rough segmentation of the lung arteries was performed to obtain a complete vascular structure; the branch network integrating shape and position information was used to extract features of small pulmonary arteries, reducing interference from the pulmonary artery trunk and left and right pulmonary arteries. Experimental results showed that the segmentation model based on shape and position prior knowledge had a higher DSC (82.81%±3.20% vs. 80.47%±3.17% vs. 80.36%±3.43%), sensitivity (85.30%±8.04% vs. 80.95%±6.89% vs. 82.82%±7.29%), and accuracy (81.63%±7.53% vs. 81.19%±8.35% vs. 79.36%±8.98%) compared to traditional three-dimensional U-Net and V-Net methods. HD95 could reach (9.52±4.29) mm, which was 6.05 mm shorter than traditional methods, showing excellent performance in segmentation boundaries. Conclusion The lung artery segmentation method based on shape and position prior knowledge can achieve precise segmentation of lung artery vessels and has potential application value in tasks such as bronchoscopy or percutaneous puncture surgery navigation.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.