Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

OBJECTIVE To summarize the clinical data of 2 cases of multiple organ dysfunction syndrome(MODS)induced by infection with renal leptospira so as to provide bases for prevention and control of severe dis-eases.METHODS The clinical data of the 2 patients with leptospirosis were retrospectively analyzed after the super typhoon'Yagi'on Sep.6,2024.The cases of leptospirosis that were reported at home and abroad in recent 5 years were retrieved.The epidemiological characteristics,clinical manifestations and treatment outcomes of the cases were observed.RESULTS The 2 patients began to have symptoms on the nineth day after the typhoon,both cases presented with the manifestation such as fever,pain and fatigue,shortness of breach and cough,jaundice and anu-ria,with the blood culture negative;the definite diagnosis was mased by blood metagenomic capture method(MetaCAP).The poultry was considered as the infection source,and the illness condition progressed to sepsis and MODS.Case 1 was complicated with empsyxis,jaundice hemorrhage and renal failure and finally died.Case 2 was also detected with leptospira from cerebrospinal fluid and was complicated with renal failure and meningoencephal-itis but was cured.Among 17 cases of leptospirosis from the literatures,the male and peasants were dominant,the infected water was the major infection factor(at least 7 cases);fever,pain and fatigue,shortness of breath and cough as well as hemoptysis were the major symptoms.There were at least 12 cases with the decline of plate-lets counts,10 cases complicated with empsyxis,11 cases complicated with shock and MODS and 10 cases treated with invasive mechanical ventilation.The misdiagnosis rate was up to 76.47％,and the mortality rate was 29.41％.CONCLUSIONS The leptospirosis is a severe disease,early precise antimicrobial treatment and timely or-gan function support are the crucial to the improvement of prognosis.The health care workers should attach great importance to inquiry for diagnosis,maintain vigilant to the disease for the people with fever of unknown ori-gin,shortness of breath,pain and fatigue by combining the epidemiological history,and make an early definite di-agnosis based on novel molecular diagnosis technique so as to avoid the progression to sepsis and MODS.

Objective:To evaluate the real-world safety and preliminary clinical outcomes of Nirsevimab in preterm infants.Methods:This descriptive study retrospectively enrolled 111 preterm infants who voluntarily received respiratory syncytial virus (RSV) monoclonal antibody at Tianjin Central Hospital of Gynecology Obstetrics between October 1, 2024, and June 30, 2025. Data collection included baseline characteristics, comorbidities, Nirsevimab administration details, and telephone follow-up for RSV-related infections, hospitalizations, and serious adverse events. Descriptive statistics were applied.Results:(1) The cohort had a mean gestational age of (30.9±2.8) weeks (range 24 +3-36 +6 weeks) and birth weight (1 479±475) g (range 680-2 720 g). (2) Comorbidities included retinopathy of prematurity (29.7%, 33/111), bronchopulmonary dysplasia (22.5%, 25/111), congenital heart disease (3.6%, 4/111), and necrotizing enterocolitis (0.9%, 1/111). (3) Median age at Nirsevimab administration was 46 d (range 3-121 d), with median corrected gestational age of 37 +5 weeks (range 33 +5-49 +6 weeks) and median weight 2 300 (range 1 680-4 870) g. (4) No adverse reactions occurred within one week post-injection. Twenty-six infants (23.4%) received Nirsevimab on the same day as other vaccines. Among the 50 cases with complete blood count and C-reactive protein testing within one week before and after Nirsevimab injection, only one (2.0%) showed elevated C-reactive protein levels post-injection; increased eosinophil percentages were observed in 24 cases (48.0%), while the remaining 26 cases (52.0%) showed decreased percentages. Administration of Nirsevimab occurred during the RSV epidemic season in 79 infants (71.2%), with the remaining 32 cases (28.8%) vaccinated outside the epidemic season. (5) During follow-up to median age 171 d (range 84-380 d), no mortality, RSV-related lower respiratory infections, hospitalizations, or intensive care unit admissions occurred. Nineteen cases (17.1%) required outpatient/emergency visits for acute respiratory infections without wheezing, including nine pneumonia (8.1%) and two otitis media (1.8%) cases. Fifteen (13.5%) were hospitalized, one (0.9%) required intensive care unit care, and none needed mechanical ventilation. Conclusion:Nirsevimab demonstrated favorable safety profiles for preventing RSV in preterm infants with no confirmed RSV cases during follow-up.

Objective To study the epidemiological characteristics of special pathogenic infection in Wenchang area following the super typhoon"Yagi"disaster,and provide basis for the diagnosis,treatment,prevention and control of infectious diseases in disaster-affected areas.Methods Clinical characteristics and pathogenic data of 7 groups of patients infected with 9 species of zoonotic pathogens and opportunistic pathogens were analyzed retrospectively.The 7 groups included:pre-typhoon landfall group(August 6 to September 5,2024),post-typhoon landfall group(September 6 to October 5,2024),and groups in the past years of the same period(A2023,B2022,C2021,D2020,E2019,September 6 to October 5 of each year in 2019-2023).Epidemiological characteristics of patients as well as distribution and resistance of pathogens were compared and analyzed.Results In post-typhoon landfall group,26 patients were infected.The overall infection rate of the post-typhoon landfall group was higher than all groups except B2022 group(all P＜0.05).The infected cases mainly distributed in coastal areas.The main route of infection was outside the hospital(88.5％).Male accounted for 80.8％,agricultural workers accounted for 53.9％,and 69.2％of the cases occurred within 10 days after the typhoon.The major infection sites were multiple site co-infection,bloodstream infection,and soft tissue infection.The main pathogens maintained high sensitivity to commonly used antimicrobial agents.The accuracy of clinical initial empirical antimicrobial use was relatively low(45.5％in post-typhoon landfall group vs 62.8％in the groups of the same period in the past).The clinical cure rate decreased to 76.9％,and mortality increased to 7.7％.The mortality of patients infected with Burkholderia pseudomallei and kidney infected with Leptospira were 25.0％and 50.0％,respectively.Conclusion After ty-phoon disaster,special pathogen infection significantly increases and the prognosis is poor.It is recommended to emphasize blood culture and molecular biology testing to facilitate early diagnosis and precise treatment,optimize prevention and control measures,and enhance the accuracy of clinical empirical medication.

Objective:To evaluate the real-world safety and preliminary clinical outcomes of Nirsevimab in preterm infants.Methods:This descriptive study retrospectively enrolled 111 preterm infants who voluntarily received respiratory syncytial virus (RSV) monoclonal antibody at Tianjin Central Hospital of Gynecology Obstetrics between October 1, 2024, and June 30, 2025. Data collection included baseline characteristics, comorbidities, Nirsevimab administration details, and telephone follow-up for RSV-related infections, hospitalizations, and serious adverse events. Descriptive statistics were applied.Results:(1) The cohort had a mean gestational age of (30.9±2.8) weeks (range 24 +3-36 +6 weeks) and birth weight (1 479±475) g (range 680-2 720 g). (2) Comorbidities included retinopathy of prematurity (29.7%, 33/111), bronchopulmonary dysplasia (22.5%, 25/111), congenital heart disease (3.6%, 4/111), and necrotizing enterocolitis (0.9%, 1/111). (3) Median age at Nirsevimab administration was 46 d (range 3-121 d), with median corrected gestational age of 37 +5 weeks (range 33 +5-49 +6 weeks) and median weight 2 300 (range 1 680-4 870) g. (4) No adverse reactions occurred within one week post-injection. Twenty-six infants (23.4%) received Nirsevimab on the same day as other vaccines. Among the 50 cases with complete blood count and C-reactive protein testing within one week before and after Nirsevimab injection, only one (2.0%) showed elevated C-reactive protein levels post-injection; increased eosinophil percentages were observed in 24 cases (48.0%), while the remaining 26 cases (52.0%) showed decreased percentages. Administration of Nirsevimab occurred during the RSV epidemic season in 79 infants (71.2%), with the remaining 32 cases (28.8%) vaccinated outside the epidemic season. (5) During follow-up to median age 171 d (range 84-380 d), no mortality, RSV-related lower respiratory infections, hospitalizations, or intensive care unit admissions occurred. Nineteen cases (17.1%) required outpatient/emergency visits for acute respiratory infections without wheezing, including nine pneumonia (8.1%) and two otitis media (1.8%) cases. Fifteen (13.5%) were hospitalized, one (0.9%) required intensive care unit care, and none needed mechanical ventilation. Conclusion:Nirsevimab demonstrated favorable safety profiles for preventing RSV in preterm infants with no confirmed RSV cases during follow-up.

Objective To study the epidemiological characteristics of special pathogenic infection in Wenchang area following the super typhoon"Yagi"disaster,and provide basis for the diagnosis,treatment,prevention and control of infectious diseases in disaster-affected areas.Methods Clinical characteristics and pathogenic data of 7 groups of patients infected with 9 species of zoonotic pathogens and opportunistic pathogens were analyzed retrospectively.The 7 groups included:pre-typhoon landfall group(August 6 to September 5,2024),post-typhoon landfall group(September 6 to October 5,2024),and groups in the past years of the same period(A2023,B2022,C2021,D2020,E2019,September 6 to October 5 of each year in 2019-2023).Epidemiological characteristics of patients as well as distribution and resistance of pathogens were compared and analyzed.Results In post-typhoon landfall group,26 patients were infected.The overall infection rate of the post-typhoon landfall group was higher than all groups except B2022 group(all P＜0.05).The infected cases mainly distributed in coastal areas.The main route of infection was outside the hospital(88.5％).Male accounted for 80.8％,agricultural workers accounted for 53.9％,and 69.2％of the cases occurred within 10 days after the typhoon.The major infection sites were multiple site co-infection,bloodstream infection,and soft tissue infection.The main pathogens maintained high sensitivity to commonly used antimicrobial agents.The accuracy of clinical initial empirical antimicrobial use was relatively low(45.5％in post-typhoon landfall group vs 62.8％in the groups of the same period in the past).The clinical cure rate decreased to 76.9％,and mortality increased to 7.7％.The mortality of patients infected with Burkholderia pseudomallei and kidney infected with Leptospira were 25.0％and 50.0％,respectively.Conclusion After ty-phoon disaster,special pathogen infection significantly increases and the prognosis is poor.It is recommended to emphasize blood culture and molecular biology testing to facilitate early diagnosis and precise treatment,optimize prevention and control measures,and enhance the accuracy of clinical empirical medication.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

OBJECTIVE To summarize the clinical data of 2 cases of multiple organ dysfunction syndrome(MODS)induced by infection with renal leptospira so as to provide bases for prevention and control of severe dis-eases.METHODS The clinical data of the 2 patients with leptospirosis were retrospectively analyzed after the super typhoon'Yagi'on Sep.6,2024.The cases of leptospirosis that were reported at home and abroad in recent 5 years were retrieved.The epidemiological characteristics,clinical manifestations and treatment outcomes of the cases were observed.RESULTS The 2 patients began to have symptoms on the nineth day after the typhoon,both cases presented with the manifestation such as fever,pain and fatigue,shortness of breach and cough,jaundice and anu-ria,with the blood culture negative;the definite diagnosis was mased by blood metagenomic capture method(MetaCAP).The poultry was considered as the infection source,and the illness condition progressed to sepsis and MODS.Case 1 was complicated with empsyxis,jaundice hemorrhage and renal failure and finally died.Case 2 was also detected with leptospira from cerebrospinal fluid and was complicated with renal failure and meningoencephal-itis but was cured.Among 17 cases of leptospirosis from the literatures,the male and peasants were dominant,the infected water was the major infection factor(at least 7 cases);fever,pain and fatigue,shortness of breath and cough as well as hemoptysis were the major symptoms.There were at least 12 cases with the decline of plate-lets counts,10 cases complicated with empsyxis,11 cases complicated with shock and MODS and 10 cases treated with invasive mechanical ventilation.The misdiagnosis rate was up to 76.47％,and the mortality rate was 29.41％.CONCLUSIONS The leptospirosis is a severe disease,early precise antimicrobial treatment and timely or-gan function support are the crucial to the improvement of prognosis.The health care workers should attach great importance to inquiry for diagnosis,maintain vigilant to the disease for the people with fever of unknown ori-gin,shortness of breath,pain and fatigue by combining the epidemiological history,and make an early definite di-agnosis based on novel molecular diagnosis technique so as to avoid the progression to sepsis and MODS.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.