Childhood obesity has become a global public health issue. Current research indicates that early life obesogen exposure has emerged as a significant risk factor for childhood obesity. While obesogens have been confirmed to influence the development and progression of childhood obesity through mechanisms such as endocrine disruption and epigenetic programming, controversies remain regarding the establishment of causal relationships, assessment of combined exposures, and validation of transgenerational effects in humans. In recent years, novel approaches including multi-omics technologies, exposome-based analysis, and multigenerational cohort studies have integrated dynamic biomarker monitoring with analyses of social-environmental interactions, offering new perspectives and methodologies for constructing a systematic "exposure-mechanism-outcome" research framework. This article reviews literature from PubMed and Web of Science up to August 2025 on the association between early life obesogen exposure and childhood obesity, summarizing evidence on the health effects of early life obesogen exposure, major exposure pathways and internal exposure assessment, interactions and amplifying effects of social and environmental factors, as well as the biological mechanisms underlying obesogen action. It further examines current research frontiers and challenges, aiming to provide a theoretical foundation for early prevention and precision intervention of childhood obesity.

Objective:To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease (AD) which was named with senescence accelerated mouse-prone 8(SAMP8), as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase (p38MAPK) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathways.Methods:Seven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group) using a random number table: model group, low-dose Huanshaodan group(1.17g/kg, twice daily via gavage), and high-dose Huanshaodan group(2.34g/kg, twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1, SAMR1)were designated as the normal control group( n=6).The mice in control group and the model group received 0.9% NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP) and ionized calcium-binding adaptor molecule-1(Iba1) as markers for astrocytes and microglial cells in the hippocampus, respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison. Results:Morris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice( F=3.787, P<0.05).From the 5th to 6th day, the escape latencies of the low- and high-dose Huanshaodan groups were lower than those of the model group(both P<0.05).On the 4th to 6th day, the escape latencies of the high-dose Huanshaodan group were lower than those of the low-dose group(all P<0.05).Significant differences were observed in the residence time in the target quadrant and the number of crossing the platform among the four groups of mice( F=8.587, 12.633, both P<0.05).The residence time in the target quadrant of the model group((17.8±3.4)s) and the number of crossing the platform((1.6±0.6)times)were less than those of the control group((40.6±3.7)s, (4.6±0.6)times) and high-dose Huanshaodan group(31.8±4.0)s, (2.8±0.8)times), all P<0.05).Western blot results indicated significant differences in the expression of iNOS, COX-2, p-p38MAPK/p38MAPK, and p-ERK1/2/ERK1/2 in the hippocampal tissues of the four groups of mice( F=207.516, 10.627, 108.497, 34.330, all P<0.05) and the indexes in model group were all higher than those of control group and high-dose Huanshaodan group(all P<0.05).ELISA results revealed significant differences in the levels of IL-6, TNF-α and IL-1β in the serum of the four groups of mice( F=66.790, 82.424, 42.919, all P<0.05), and the indexes of model group were higher than those of the other three groups(all P<0.05).Immunofluorescence results showed significant differences in the relative fluorescence intensity of GFAP and Iba1 in the hippocampal tissues of the four groups of mice( F=20.269, 56.437, both P<0.05).The relative fluorescence intensity values of GFAP and Iba1 in the hippocampal tissues of the high-dose Huanshaodan group were lower than those of the model group(both P<0.05), while the expression level of Iba1 in high-dose group was lower than that in the low-dose group( P<0.05). Conclusion:High-dose Haunshaodan may inhibit the activation of hippocampal glial cells by blocking the p38MAPK and ERK1/2 pathways, reducing neuroinflammation, then improving learning and memory disorders in SAMP8 mice.

Objective:To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease (AD) which was named with senescence accelerated mouse-prone 8(SAMP8), as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase (p38MAPK) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathways.Methods:Seven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group) using a random number table: model group, low-dose Huanshaodan group(1.17g/kg, twice daily via gavage), and high-dose Huanshaodan group(2.34g/kg, twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1, SAMR1)were designated as the normal control group( n=6).The mice in control group and the model group received 0.9% NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP) and ionized calcium-binding adaptor molecule-1(Iba1) as markers for astrocytes and microglial cells in the hippocampus, respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison. Results:Morris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice( F=3.787, P<0.05).From the 5th to 6th day, the escape latencies of the low- and high-dose Huanshaodan groups were lower than those of the model group(both P<0.05).On the 4th to 6th day, the escape latencies of the high-dose Huanshaodan group were lower than those of the low-dose group(all P<0.05).Significant differences were observed in the residence time in the target quadrant and the number of crossing the platform among the four groups of mice( F=8.587, 12.633, both P<0.05).The residence time in the target quadrant of the model group((17.8±3.4)s) and the number of crossing the platform((1.6±0.6)times)were less than those of the control group((40.6±3.7)s, (4.6±0.6)times) and high-dose Huanshaodan group(31.8±4.0)s, (2.8±0.8)times), all P<0.05).Western blot results indicated significant differences in the expression of iNOS, COX-2, p-p38MAPK/p38MAPK, and p-ERK1/2/ERK1/2 in the hippocampal tissues of the four groups of mice( F=207.516, 10.627, 108.497, 34.330, all P<0.05) and the indexes in model group were all higher than those of control group and high-dose Huanshaodan group(all P<0.05).ELISA results revealed significant differences in the levels of IL-6, TNF-α and IL-1β in the serum of the four groups of mice( F=66.790, 82.424, 42.919, all P<0.05), and the indexes of model group were higher than those of the other three groups(all P<0.05).Immunofluorescence results showed significant differences in the relative fluorescence intensity of GFAP and Iba1 in the hippocampal tissues of the four groups of mice( F=20.269, 56.437, both P<0.05).The relative fluorescence intensity values of GFAP and Iba1 in the hippocampal tissues of the high-dose Huanshaodan group were lower than those of the model group(both P<0.05), while the expression level of Iba1 in high-dose group was lower than that in the low-dose group( P<0.05). Conclusion:High-dose Haunshaodan may inhibit the activation of hippocampal glial cells by blocking the p38MAPK and ERK1/2 pathways, reducing neuroinflammation, then improving learning and memory disorders in SAMP8 mice.

To summarize the perioperative nursing experience of a premature infant with ABO hemolytic disease who underwent resection of giant Altman type Ⅰ sacrococcygeal teratoma at 43 hours after birth.Key points of preoperative nursing care include the cooperative blood transfusion to correct anemia,and the protection of tumor body,the prevention of rupture and bleeding.Key points of intraoperative nursing care include the personalized postural safety management,the target-oriented fluid therapy to maintain circulation stability,and composite insulation measures to prevent hypothermia.Key points of postoperative nursing care include sequential fluid replenishment to treat neonatal capillary leakage syndrome;protective ventilation strategies to maintain effective breathing;precision wound care,prevention and control of postoperative infection;progressive mixed feeding;to empower family members and improve the quality of continuous rehabilitation.After careful treatment and nursing care,the patient was discharged 18 days after surgery.During the 7-month follow-up,the growth and development were normal.

Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective To investigate the diagnostic value of serum human β-defensin 2(HBD2)and soluble growth stimulating gene 2(sST2)levels in pediatric refractory Mycoplasma pneumonia.Methods A total of 145 children diagnosed with Mycoplasma pneumonia were recruited,and divided into refractory pneumonia group(n=53)and common pneumonia group(n=92)based on whether they had refractory or common pneumonia.General data were compared between the two groups.Ser-um HBD2 and sST2 levels were measured using enzyme-linked immunosorbent assay(ELISA).Multi-variate logistic regression analysis was used to identify influencing factors for the occurrence of refracto-ry Mycoplasma pneumonia.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum HBD2 and sST2 levels in refractory Mycoplasma pneumonia.Results The proportion of lung consolidation and pleural effusion in refractory pneumonia group was significantly higher,and the fever time was significantly longer than that in common pneumonia group(P＜0.05).Serum HBD2 and sST2 levels in the refractory pneumonia group were signifi-cantly higher than those in the common pneumonia group(P＜0.05).Multivariate Logistic regres-sion analysis indicated that lung consolidation,pleural effusion,high serum HBD2 level and high serum sST2 level were risk factors for pediatric refractory Mycoplasma pneumonia(P＜0.05).The area under the curve and Youden's index for diagnosing pediatric refractory Mycoplasma pneumonia were 0.817 and 0.557 for serum HBD2 level,and 0.841 and 0.607 for serum sST2 level,respec-tively.Combined diagnosis using both markers resulted in an area under the curve of 0.916 and a Youden's index of 0.721.Conclusion The combined detection of serum HBD2 and sST2 levels holds significant diagnostic value for pediatric refractory Mycoplasma pneumonia.

To summarize the perioperative nursing experience of a premature infant with ABO hemolytic disease who underwent resection of giant Altman type Ⅰ sacrococcygeal teratoma at 43 hours after birth.Key points of preoperative nursing care include the cooperative blood transfusion to correct anemia,and the protection of tumor body,the prevention of rupture and bleeding.Key points of intraoperative nursing care include the personalized postural safety management,the target-oriented fluid therapy to maintain circulation stability,and composite insulation measures to prevent hypothermia.Key points of postoperative nursing care include sequential fluid replenishment to treat neonatal capillary leakage syndrome;protective ventilation strategies to maintain effective breathing;precision wound care,prevention and control of postoperative infection;progressive mixed feeding;to empower family members and improve the quality of continuous rehabilitation.After careful treatment and nursing care,the patient was discharged 18 days after surgery.During the 7-month follow-up,the growth and development were normal.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

Objective:To explore the safety and reliability of retrosigmoid approach BONEBRIDGE implantation in patients with auricle reconstruction using skin expansion flap.Methods:A retrospective analysis was conducted on 43 congenital aural atresia cases (43 ears) who underwent BONEBRIDGE implantation from September 2019 to January 2023 in Beijing Tongren Hospital. 30 males and 13 females were included in this work. The implantation age was 9-36 years old (median age=10 y/o). All cases underwent auricle reconstruction surgery using the posterior ear flap expansion method, with 36 cases using the single expanded postauricular flap method and 7 cases using two-flap method. BONEBRIDGE implant surgery was performed during the third stage of auricle reconstruction or after all stages. The hearing improvements were evaluated by comparing the changes in pure tone hearing threshold and speech recognition rate of patients before and after BONEBRIDGE implantation. Routine follow-up was conducted to observe the hearing results and complications. SPSS 14.0 software was applied for data statistical analysis.Results:All 43 patients healed well and had no surgical complications when discharge. The average bone conduction hearing threshold after surgery was (8.2±6.6) dBHL, and there was no statistically significant difference compared to the preoperative [(8.1±5.7) dBHL] ( P=0.95). After surgery, the threshold of hearing assistance with power on was significantly lower than that without hearing assistance [(32.8±4.6) dBHL vs (60.5±5.5) dBHL], and the difference was statistically significant ( P<0.001). The speech recognition rate of monosyllable words, disyllabic words and short sentences in quiet environment increased to 72%, 84%, and 98% respectively. The differences were statistically significant ( P<0.001). The speech recognition rate of monosyllabic words, disyllabic words, and short sentences in noise environment was significantly increased by 70%, 80%, and 92% respectively ( P<0.001). After a follow-up of 4 to 47 months (median=24 months), the hearing results were stable and the aesthetic outcomes were satisfying. One patient had delayed hematoma around coil of the implant. After aspiration and compressed dressing for one week, hematoma was not recurrent. Conclusion:For patients after auricle reconstruction using expanded postauricular flap, the preference of retrosigmoid approach is a good choice in terms of safety and reliability of operation, as well as aesthetic appearance.

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.