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.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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.

Objective:To explore the relationship between hemoglobin variability (Hb-var) and risk of all-cause death and cardiovascular death in patients with peritoneal dialysis (PD), and to provide basis for reducing the risk of death in PD patients.Methods:It was a multicenter retrospective cohort study. The clinical data of regular PD patients from Nanfang Hospital of Southern Medical University, Shunde Hospital of Southern Medical University, Foshan First People's Hospital and Ganzhou People's Hospital from July 1, 2008 to December 31, 2019 were collected. Hb-var was calculated based on hemoglobin at baseline before PD and in the first year after PD. The patients were divided into low Hb-var group, moderate Hb-var group and high Hb-var group according to the tertiles of first year Hb-var, and the differences of baseline clinical data among three groups were compared. Follow-up endpoints included death, transfer to hemodialysis, transfer to kidney transplantation, transfer to other centers, loss of follow-up, or on December 31, 2021. Cox regression analysis model was used to analyze the association of the first-year Hb-var with all-cause death and cardiovascular death. Fine-Gray competitive risk regression model was used to evaluate the impact of competitive events on mortality risk.Results:A total of 1 562 patients with PD were included in the study, aged (47.6±13.8) years old, with 821 males (52.6%) and baseline hemoglobin of 81 (69, 94) g/L. Hb-var in the first year of PD was 26.6 (16.7, 40.3) g/L. There were statistically significant differences in age, body mass index, serum albumin, hemoglobin, serum creatinine, serum calcium, serum phosphorus, intact parathyroid hormone and the proportion of renin-angiotensin system inhibitors among low Hb-var group (<20.0 g/L), moderate Hb-var group (20.0-35.5 g/L) and high Hb-var group (≥35.5 g/L, all P<0.05). The follow-up time was 33 (19, 51) months, and 208 patients (13.3%) died, among which 111 patients (53.4%) died of cardiovascular death. Multivariate Cox regression analysis showed that the higher Hb-var in the first year, the lower the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.018) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) in PD patients. Compared with low Hb-var group, the risk of all-cause death ( HR=0.56, 95% CI 0.37-0.82, P=0.003) and cardiovascular death ( HR=0.54, 95% CI 0.31-0.95, P=0.032) was lowest in the high Hb-var group. The competitive risk regression model analysis showed that Hb-var in the first year was still negatively correlated with the risk of all-cause death ( HR=0.98, 95% CI 0.97-0.99, P=0.041) and cardiovascular death ( HR=0.98, 95% CI 0.97-0.99, P=0.039). Conclusion:High Hb-var in the first year is associated with low risk of all-cause death and cardiovascular death in PD patients with severe anemia at baseline.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.

ObjectiveTo observe the effect of Xiaoyaosan on the expression of RAS homologous gene family member A （RhoA） and Rho-related coiled protein kinase 1 and 2 （ROCK1 and ROCK2） in gastric tissues of rats with liver depression and spleen deficiency syndrome and to explore its mechanism of regulating gastrointestinal motility in rats with liver depression and spleen deficiency syndrome. MethodSeventy-two male SD rats were randomly divided into 6 group， namely the normal group， the model group， the fluoxetine group （0.001 8 g·kg^-1）， the Xiaoyaosan high （16.7 g·kg^-1）， medium （8.35 g·kg^-1） and low-dose （4.175 g·kg^-1） group， with 12 rats in each group. In addition to the normal group， the rats in other groups were used to establish the model of liver depression and spleen deficiency syndrome by chronic restraint stress. At the same time， the rats in the normal group and the model group were given normal saline （10 mL·kg^-1）， and the rats in each drug group were given corresponding doses of drugs once a day for 21 d. After modeling， the gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The mRNA and protein expressions of RhoA， ROCK1， and ROCK2 in gastric tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAs compared with the normal group， the gastric emptying rate， intestinal propulsion rate， and the mRNA and protein expressions of RhoA， ROCK1， and ROCK2 in gastric tissues in the model group were lower （P<0.05， P<0.01）. The abnormal changes in the above indexes in the Xiaoyaosan high， medium， and low-dose groups were all improved in varying degrees as compared with the model group （P<0.05， P<0.01）. ConclusionXiaoyaosan improves gastrointestinal motility in rats with liver depression and spleen deficiency syndrome， which may be related to the up-regulation of the RhoA/ROCK signal pathway in gastric tissues.

A 69-year-old man was treated with adalimumab 80 mg subcutaneously for psoriasis for the first time. Two days later, the patient developed diffuse erythema with pruritus. Because the active stage of psoriasis was not excluded, adalimumab 40 mg subcutaneous injection was continued once a week for 4 times. The patient′s skin erythema and pruritus continued to worsen. After intravenous infusion of methylprednisolone sodium succinate 40 mg/d for 1 week, the systemic erythema and pruritus were slightly relieved, but the condition was repeated after stopping the drug. Urine routine and sediment analysis showed urinary occult blood (+++), 190 red blood cells/μl, urinary protein (+) , and serum creatinine 80 μmol/L. Renal biopsy and skin histopathology suggested IgA nephropathy and psoriasiform dermatitis, respectively. After consultation with dermatologists, erythroderma caused by deterioration of psoriasis was considered. Excluding other factors, it is considered that IgA nephropathy and erythroderma were probably induced by adalimumab. Methotrexate 10 mg per week was given orally and halometasone ointment was used externally. The skin damage in the patient was gradually improved. Hematuria and proteinuria were self-relieved slowly.At one-year of follow-up, the patient′s renal function and urine routine remained normal, and nephropathy and rash did not recur.

A 69-year-old man was treated with adalimumab 80 mg subcutaneously for psoriasis for the first time. Two days later, the patient developed diffuse erythema with pruritus. Because the active stage of psoriasis was not excluded, adalimumab 40 mg subcutaneous injection was continued once a week for 4 times. The patient′s skin erythema and pruritus continued to worsen. After intravenous infusion of methylprednisolone sodium succinate 40 mg/d for 1 week, the systemic erythema and pruritus were slightly relieved, but the condition was repeated after stopping the drug. Urine routine and sediment analysis showed urinary occult blood (+++), 190 red blood cells/μl, urinary protein (+) , and serum creatinine 80 μmol/L. Renal biopsy and skin histopathology suggested IgA nephropathy and psoriasiform dermatitis, respectively. After consultation with dermatologists, erythroderma caused by deterioration of psoriasis was considered. Excluding other factors, it is considered that IgA nephropathy and erythroderma were probably induced by adalimumab. Methotrexate 10 mg per week was given orally and halometasone ointment was used externally. The skin damage in the patient was gradually improved. Hematuria and proteinuria were self-relieved slowly.At one-year of follow-up, the patient′s renal function and urine routine remained normal, and nephropathy and rash did not recur.