Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

Objective To investigate the effect and mechanism of zanthoxylum bungeanum seed oil on autophagy and apoptosis of laryngeal cancer cells.Methods Human bronchial epithelial cells BEAS-2B and human laryngeal cancer cells Hep-2 were treated with different volume fractions(v/v)of Zanthoxylum bungeanum seed oil(0,0.02%,0.04%,0.06%,0.08%,0.10%),respectively,cell viability was detected by cell counting kit-8 method(CCK-8).Hep-2 cells in logarithmic growth phase were randomly divided into control group,Zanthoxylum bungeanum seed oil low,medium and high dose groups and Zanthoxylum bungeanum seed oil high dose+insulin-like growth factor 1(IGF-1)(PI3K agonist)group,cell apoptosis and cell cycle progression were detected by flow cytometry(FCM)assay,the formation of autophagic vesicles was detected by monodansyl cadaverine(MDC)staining,the expression of apoptosis,autophagy and phosphatidylinositide 3-kinases(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)pathway-related proteins were detected by Western blotting(WB).Results Compared with the control group Hep-2(99.03%±0.82%),treatment with zanthoxylum bungeanum seed oil(0.02%,0.04%,0.06%,0.08%,0.10%)(v/v)could reduce cell survival rate(84.63%±0.73%,57.34%±0.84%,19.76%±0.62%,17.22%±0.72%,12.19%±0.81%),and the differences were statistically significant(t=22.718～133.559,all P<0.001),while it has no inhibitory effect on BEAS-2B activity(t=0.283～1.980,all P>0.05).Compared with the control group,the Hep-2 apoptosis rate,G1/G0 phase cell proportion,autophagic vesicle integrated optical density(IOD)value,Cleaved-caspase-3,Bcl-2 associated X protein(Bax),microtubule-associated protein 1A/1B 1ight chain 3I/Ⅱ(LC 3I/Ⅱ)and Beclin-1 expression were all increased in the low,medium,and high-close groups of zantheoxylum bungeanum seed oil(t=4.270～58.425);the proportion of G2/M phase cells,ubiquitin-binding protein P62,Bcl-2 expression and p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR expression were all decreased(t=3.041～58.765),and the differences were statistically significant(all P<0.05).Compared with the high-dose zanthoxylum bungeanum seed oil group,the apoptosis rate of Hep-2,the proportion of G1/G0 phase cells,the expression of Cleaved-caspase-3,Bax,LC3Ⅱ/I and Beclin-1,the IOD value of autophagic vesicles(t=4.931～39.507),the expression of Bcl-2 and ubiquitin-binding protein P62,the proportion of G2/M phase cells,the ratio of p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR in the high-dose zanthoxylum bungeanum seed oil+IGF-1 group were decreased(t=3.402～14.207),and the differences were statistically significant(all P<0.05).Conclusion Zanthoxylum bungeanum seed oil can promote autophagy and apoptosis of Hep-2 cells,and its mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway activation.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

Objective To quantitatively assess the correlation between the skeletal muscle index(SMI)of patients and the occur-rence of anastomotic leakage(AL)in rectal cancer patients after surgery,and to analyze the risk factors for AL in rectal cancer patients and the influencing factors of sarcopenia.Methods The clinical,pathological,and related imaging data of 362 patients who under-went radical surgery for rectal cancer were retrospectively analyzed.All patients underwent pelvic MRI and abdominal CT scans(plain/enhanced)within one month before surgery,and the third lumbar vertebra skeletal muscle area(L3-SMA)was measured from the images.All patients were divided into AL group(56 cases)and control group(306 cases)based on the presence or absence of postoperative complications.The differences in clinical characteristics and imaging parameters between the two groups were analyzed.A logistic risk prediction model was established.Results Significant differences were observed between the two groups in sarcopenia,type of surgery,surgical approach,serum albumin level,operation duration,stoma type,and extramural vascular invasion(EMVI)(P＜0.05).These factors were incorporated in a multivariate logistic regression analysis model,the area under the curve(AUC)of receiver operating characteristic(ROC)curve of the model was 0.810[95％confidence interval(CI)0.743-0.876,P＜0.001],with a sensitivity of 0.865 and specificity of 0.669.Conclusion Sar-copenia is a significant risk factor for AL after rectal cancer surgery.It enhances the predictive efficacy for postoperative AL and serves as a basis for identifying high-risk populations for AL in clinical practice.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Objective To investigate the effect and mechanism of zanthoxylum bungeanum seed oil on autophagy and apoptosis of laryngeal cancer cells.Methods Human bronchial epithelial cells BEAS-2B and human laryngeal cancer cells Hep-2 were treated with different volume fractions(v/v)of Zanthoxylum bungeanum seed oil(0,0.02%,0.04%,0.06%,0.08%,0.10%),respectively,cell viability was detected by cell counting kit-8 method(CCK-8).Hep-2 cells in logarithmic growth phase were randomly divided into control group,Zanthoxylum bungeanum seed oil low,medium and high dose groups and Zanthoxylum bungeanum seed oil high dose+insulin-like growth factor 1(IGF-1)(PI3K agonist)group,cell apoptosis and cell cycle progression were detected by flow cytometry(FCM)assay,the formation of autophagic vesicles was detected by monodansyl cadaverine(MDC)staining,the expression of apoptosis,autophagy and phosphatidylinositide 3-kinases(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)pathway-related proteins were detected by Western blotting(WB).Results Compared with the control group Hep-2(99.03%±0.82%),treatment with zanthoxylum bungeanum seed oil(0.02%,0.04%,0.06%,0.08%,0.10%)(v/v)could reduce cell survival rate(84.63%±0.73%,57.34%±0.84%,19.76%±0.62%,17.22%±0.72%,12.19%±0.81%),and the differences were statistically significant(t=22.718～133.559,all P<0.001),while it has no inhibitory effect on BEAS-2B activity(t=0.283～1.980,all P>0.05).Compared with the control group,the Hep-2 apoptosis rate,G1/G0 phase cell proportion,autophagic vesicle integrated optical density(IOD)value,Cleaved-caspase-3,Bcl-2 associated X protein(Bax),microtubule-associated protein 1A/1B 1ight chain 3I/Ⅱ(LC 3I/Ⅱ)and Beclin-1 expression were all increased in the low,medium,and high-close groups of zantheoxylum bungeanum seed oil(t=4.270～58.425);the proportion of G2/M phase cells,ubiquitin-binding protein P62,Bcl-2 expression and p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR expression were all decreased(t=3.041～58.765),and the differences were statistically significant(all P<0.05).Compared with the high-dose zanthoxylum bungeanum seed oil group,the apoptosis rate of Hep-2,the proportion of G1/G0 phase cells,the expression of Cleaved-caspase-3,Bax,LC3Ⅱ/I and Beclin-1,the IOD value of autophagic vesicles(t=4.931～39.507),the expression of Bcl-2 and ubiquitin-binding protein P62,the proportion of G2/M phase cells,the ratio of p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR in the high-dose zanthoxylum bungeanum seed oil+IGF-1 group were decreased(t=3.402～14.207),and the differences were statistically significant(all P<0.05).Conclusion Zanthoxylum bungeanum seed oil can promote autophagy and apoptosis of Hep-2 cells,and its mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway activation.

Objective To quantitatively assess the correlation between the skeletal muscle index(SMI)of patients and the occur-rence of anastomotic leakage(AL)in rectal cancer patients after surgery,and to analyze the risk factors for AL in rectal cancer patients and the influencing factors of sarcopenia.Methods The clinical,pathological,and related imaging data of 362 patients who under-went radical surgery for rectal cancer were retrospectively analyzed.All patients underwent pelvic MRI and abdominal CT scans(plain/enhanced)within one month before surgery,and the third lumbar vertebra skeletal muscle area(L3-SMA)was measured from the images.All patients were divided into AL group(56 cases)and control group(306 cases)based on the presence or absence of postoperative complications.The differences in clinical characteristics and imaging parameters between the two groups were analyzed.A logistic risk prediction model was established.Results Significant differences were observed between the two groups in sarcopenia,type of surgery,surgical approach,serum albumin level,operation duration,stoma type,and extramural vascular invasion(EMVI)(P＜0.05).These factors were incorporated in a multivariate logistic regression analysis model,the area under the curve(AUC)of receiver operating characteristic(ROC)curve of the model was 0.810[95％confidence interval(CI)0.743-0.876,P＜0.001],with a sensitivity of 0.865 and specificity of 0.669.Conclusion Sar-copenia is a significant risk factor for AL after rectal cancer surgery.It enhances the predictive efficacy for postoperative AL and serves as a basis for identifying high-risk populations for AL in clinical practice.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.