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.

BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Objective:To compare the active respiratory circulation technique (ACBT) with the oscillatory positive pressure expiration technique (OPEP) in terms of their ability to improve pulmonary function and minimize complications after cardiac surgery, seeking to define an airway management strategy for such patients.Methods:A total of 101 patients who had undergone cardiac surgery were randomly divided into an ACBT group ( n=50) and an OPEP group ( n=51). On the 1st day after the operation, in addition to conventional medical treatment and early rehabilitation, the subjects were additionally provided with daily 20-minute sessions of ACBT or OPEP training for seven consecutive days. Before the operation, and on the 3rd and 7th day afterward, lung function was assessed using a pulmonary edema imaging assessment system (RALE), computed tomography and pulmonary function indexes. Any complications were also noted. Six-minute walking distance and the Barthel index quantified exercise endurance and ability in the activities of daily living, respectively. Turbidimetry was used to determine the levels of C-reactive protein in the blood. The duration of mechanical ventilation required, ICU stay time, length of postoperative and total hospital stays were also recorded. Results:On day seven after the operation, the average RALE scores of the ACBT and OPEP groups were (12.40±4.37) and (10.20±4.66), respectively—a significant difference. At the same time point, the incidence of atelectasis in the OPEP group was significantly lower than in the ACBT group. The OPEP group′s average maximum inspiratory pressure was a greater percentage of the predicted value, and its average 6-minute walk and BI score were also better. On the 3rd day after the operation, the incidence of lung consolidation in the ACBT group was significantly lower than that in the OPEP group, on average.Conclusions:The curative effect of ACBT is better than that of OPEP in the first few days after such an operation, but after a week OPEP more effectively restores respiratory muscle strength and relieves pulmonary complications. It is recommended to apply these two techniques in stages to optimize postoperative airway management. RALE scoring is an ideal tool for dynamic monitoring of pulmonary complications after cardiac surgery.

Objective:To investigate risk factors for permanent hypoparathyroidism (PHPP) after total thyroidectomy in patients with differentiated thyroid carcinoma (DTC).Methods:The clinical data of 316 DTC patients who underwent total thyroidectomy at our hospital from Jan 2020 to Jan 2023 were retrospectively analyzed. Patients were divided into normal parathyroid function group (284 cases) and hypoparathyroidism group (32 cases) according to whether parathyroid function was decreased. The clinical examination, intraoperative conditions and postoperative pathological data of the two groups were statistically analyzed.Results:Logistic regression analysis showed that: serum calcium on the first postoperative day ( OR=0.163, P<0.05), parathyroid hormon (PTH) on the first postoperative day ( OR=0.958, P<0.05), bilateral lymph node dissection ( OR=3.138, P<0.05), accidental resection of parathyroid (PG) ( OR=2.614, P<0.05), posterior capsule tumor invasion ( OR=3.336, P<0.05) and multiple cancer foci ( OR=2.664, P<0.05) were independent risk factors for PHPP after total thyroidectomy. Conclusion:Postoperative day 1 serum calcium, postoperative day 1 PTH, bilateral lymph node dissection, accidental resection of PG, posterior capsule invasion and multiple cancer foci are independent risk factors for PHPP after total thyroidectomy.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.

Autism spectrum disorder（ASD）is a multifactorial，pervasive neurodevelopmental disorder.As the morbidity rate of ASD in children increases year by year，feeding and eating behaviors，as an important and common clinical problem in children with ASD，are gaining more and more attention.Many children with ASD often have food selection issues，chewing problems，food allergy and related gastrointestinal symptoms，and even serious diseases such as eating disorders，which negatively impact on their growth and development.There are many factors affecting feeding and eating behavior problems in children with ASD，such as sensory processing，ritualistic eating behavior，gastrointestinal symptoms，age，and parenting pressure.There are also a variety of interventions that can help to improve feeding and eating behavior problems in children with ASD.Strengthening the understanding of these influencing factors and intervention treatment methods is beneficial for improving the quality of life in children with ASD.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.

Objective To investigate the spatial distribution patterns and environmental determinants of Lagotis brachystachya Maxim.,a keystone species in Tibetan medicine("Zhi Da Sa Zeng"),under contemporary climatic conditions in China;To provide references for the sustainable utilization of its resources and the ecological protection of alpine grassland areas.Methods Based on the maximum entropy model,the selected species distribution data and environmental factors were added to MaxEnt 4.3.1 software for modeling.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of grassland within the potential suitable areas for Lagotis brachystachya Maxim..Results Under the current climatic conditions,dominant environmental drivers included elevation,monthly average temperature difference between day and night,average precipitation in June,wind speed in September,solar radiation in August,average precipitation in May,average precipitation in October,among which elevation demonstrated the strongest explanatory power(q=0.37)in habitat suitability analysis.The model prediction results showed that the potential suitable area for Lagotis brachystachya Maxim.was 5.31×105 km2.Considering the type of surface coverage,the main suitable habitat for Lagotis brachystachya Maxim.was grassland,with an area of 4.34×105 km2.The high suitable grassland of areas were mainly distributed in Qinghai Province(Yushu Tibetan Autonomous Prefecture,Huangnan Tibetan Autonomous Prefecture,Golog Tibetan Autonomous Prefecture,Hainan Tibetan Autonomous Prefecture,Haibei Tibetan Autonomous Prefecture),Sichuan Province(Ganzi Tibetan Autonomous Prefecture,Aba Qiang Autonomous Prefecture),Xizang Autonomous Region(Naqu City,Shigatse City,Changdu City),and Gansu Province(Gannan Tibetan Autonomous Prefecture).Conclusion This study can provide references for the protection of wild resources and the selection of domestication and cultivation areas for Lagotis brachystachya Maxim..