Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

Pediatric acute liver failure (PALF) is a rare and critical clinical syndrome with a poor prognosis. Its etiology is complex, with a significant proportion of cases having remained classified as indeterminate or cryptogenic PALF. With the application of high-throughput sequencing technologies, a spectrum of disorders caused by specific genetic metabolic defects and characterized by stress-sensitive Recurrent acute liver failure (RALF) has been gradually unveiled, collectively termed Infantile liver failure syndrome (ILFS). Although the molecular mechanisms underlying the subtypes ILFS1, ILFS2, and ILFS3 differ by involving aminoacyl-tRNA synthetase defects, vesicular transport disorders, and autophagy abnormalities, respectively, they share a common clinical phenotype of RALF triggered by fever or infection. This article has systematically reviewed the clinical phenotypic spectrum, molecular genetic characteristics, differential diagnosis strategies, and therapeutic advances of the three ILFS subtypes, with the goal of improving early clinical recognition and precise intervention, and providing an important reference for evaluating the prognosis of different subtypes.
Humans ; Liver Failure, Acute/therapy* ; Infant ; Diagnosis, Differential

Objective To analyze the characteristic influencing factors for enlarged perivascular spaces(EPVS)in different regions of acute ischemic stroke(AIS)patients and explore their un-derlying pathogenesis.Methods A total of 172 AIS patients admitted to our department from September 2020 to September 2023 were consecutively enrolled.According to the distribution of EPVS,they were divided into basal ganglia EPVS group(n=103)and non-basal ganglia EPVS group(n=69),as well as centrum semiovale EPVS group(n=77)and non-centrum semiovale EPVS group(n=95).General information,NIHSS score at onset,TOAST classification,fasting blood glucose,liver function,coagulation function,and homocysteine(Hcy)level were collected in all the patients.Multivariate logistic regression analysis was used to identify independent influen-cing factors for EPVS in different regions.Results The basal ganglia EPVS group had significant-ly advanced age and larger proportion of hypertension than the non-basal ganglia EPVS group,while the centrum semiovale EPVS group had smaller proportion of hyperhomocysteinemia,and larger ratios of smoking and alcohol consumption,higher alanine aminotransferase(ALT)level,and longer thrombin time than the non-centrum semiovale EPVS group(P＜0.05,P＜0.01).Mul-tivariate logistic regression analysis showed that hypertension(OR=2.093,95％CI:1.045-4.192,P=0.037)and age(OR=1.071,95％CI:1.016-1.130,P=0.011)were independent influ-encing factors for basal ganglia EPVS,while alcohol consumption(OR=2.418,95％CI:1.097-5.330,P=0.029)and thrombin time(OR=1.593,95％CI:1.129-2.249,P=0.008)were inde-pendent influencing factors for centrum semiovale EPVS.Conclusion EPVS in different regions of AIS patients are associated with distinct risk factors.Age and hypertension are primary influen-cing factors for basal ganglia EPVS,while alcohol consumption and prolonged thrombin time are significant factors for centrum semiovale EPVS.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

ObjectiveTo understand the epidemic characteristics of influenza in Beijing from 2023 to 2024, and to provide a scientific basis for the prevention and control of influenza. MethodsData on influenza-like illness (ILI) from secondary level and above hospitals, etiology surveillance data, and influenza clusters outbreaks data from 2023‒2024 were used to analyze the epidemic trend and pathogenic characteristics of influenza. Furthermore, an influenza comprehensive index was used to categorize the epidemic intensity at the severity level. ResultsA total of 2 065 857 ILI cases were reported in 2023‒2024 epidemic season, and the percentage of ILI was 3.67%. The age group of 5‒14 years accounted for the highest proportion of ILI (30.48%). A total of 41 766 throat swabs from ILI were detected, with a positive rate of 17.28%.A (H3N2) (51.86%) and B Victoria (41.93%) were the most prevalent subtypes of influenza virus. Clustered influenza outbreaks occurred mainly in primary schools (57.78%) and middle schools (35.55%), mainly caused by the influenza A (H3N2) subtype (85.93%). According to the influenza comprehensive index (I), the period of influenza activity and above (I>0.5) lasted for a total of 37 weeks, accounting for 71.15% of the entire influenza season. ConclusionCompared with previous years, the epidemic level of influenza in Beijing was increased in 2023‒2024, and the peak time became earlier. The comprehensive index method can objectively evaluate the level of influenza epidemic and provide suggestions for the future prevention and control of influenza in Beijing.

Objective To explore the mediating effects of potential mediating factors on occur-rence of stroke-associated pneumonia(SAP)in patients with varying degrees of neurological deficit based on real-world case data.Methods A total of 902 hospitalized patients in the acute phase of stroke were selected as study subjects.Clinical characteristics were compared among patients with dif-ferent degrees of neurological deficit and those with SAP.R studio was employed to generate a correla-tion heatmap of potential mediating factors,enabling the identification of primary potential mediating factors.Multivariate logistic regression analysis was conducted to assess the impact of the degree of neurological deficit,potential mediating factors,and stroke-associated pneumonia.R studio was also used to analyze the interaction between the degree of neurological deficit and potential mediating factors,as well as the mediating role of potential mediating factors in the association between neurological deficit and SAP.Results Based on the results of the correlation heatmap,this study screened out five major potential mediating factors,namely consciousness level,neutrophil-to-lymphocyte ratio(NLR),chlorine(Cl),fasting blood glucose(FBG)and albumin(ALB).Multivariate logistic re-gression analysis revealed that the degree of neurological deficit was significantly associated with the level of consciousness,NLR,Cl,FBG levels and the occurrence of SAP.Interaction analysis dem-onstrated an interaction between the degree of neurological deficit and FBG levels.Mediation analy-sis indicated that the total effect of the association between neurological deficit and SAP was 0.302.Both the level of consciousness and NLR exhibited partial mediating effects in the association be-tween neurological deficit and SAP,with mediating effect proportions of 25.92％and 15.15％,re-spectively.Conclusion Consciousness level and NLR have partial mediating effects in the occur-rence of SAP in patients with different neurological deficits.There is an interaction between the de-gree of neurological deficit and the level of FBG.

Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8(ANGPTL8)by endothelial cells(HPAECs)of human pulmonary artery,and the role and mecha-nism of ANGPTL8 in pulmonary hypertension(PH).Methods HPAECs were treated under hypoxic and hyperoxic conditions,and the expression level of ANGPTL8 was detected using Western blot and PCR.The changes in endo-thelial-mesenchymal transition(EndMT)and ERK signaling pathway activity were analyzed.Simultaneously,new-born rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia(BPD)model.The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed.Results Under hypoxic condition,the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway.ANGPTL8 promoted the EndMT process induced by hypoxia(P<0.05)and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT.The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P<0.05).Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway.This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Didangtang is a classic formula for treating blood stasis and heat， as recorded in the Treatise on Febrile Diseases， and it has been highly praised by medical practitioners throughout history. It has been recorded in many traditional Chinese medical texts and used to this day. This article comprehensively examined the records of Didangtang in different ancient versions of Treatise on Febrile Diseases by excavating and sorting out related ancient medical books and modern literature. It also investigated the dosage unit measurement， preparation method， and content of the formula in medical books throughout history. The article provided a detailed summary and exploration of the origins and processing methods of rhubarb， peach kernels， leeches， and flies in the formula. At the same time， it reviewed the clinical practice of Didangtang by medical practitioners throughout history in relevant medical books， mainly including the adjustment of dosage forms， the increase or decrease in medicinal taste and dosage， the expansion of clinical application， and the creation and elucidation of similar formulas. Although there may be differences in the above information among medical practitioners throughout history， the basic idea of attacking blood stasis and heat is consistent. In addition， based on clinical practice， the author adhered to the principle of treating stasis and heat disease as the first reference when using Didangtang. It was suggested that blood should be circulated instead of stopping in the treatment of stasis and heat accumulation syndrome. At the same time， it was believed that the use of the method of attacking stasis and heat to regulate brain diseases and mental illnesses derives from the fact that removing stasis and generating new energy can nourish the heart and mind， providing ideas for the treatment of such diseases with Didangtang. On this basis， modern clinical and animal experiments have shown that Didangtang has certain effects in improving microcirculation disorders， regulating blood rheology and hemodynamics， enhancing insulin resistance， and inhibiting inflammatory reactions. This may be an important mechanism for the formula to ''conquer blood stasis and heat''. This article explored the textual research and clinical mechanism of Didangtang， presenting facts and evidence， so as to provide a reference for the clinical application of Didangtang and the research on other prescriptions.