italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective To establish a liquid chromatography tandem mass spectrometry(LC-MS/MS)method for the determination of polymyxin B and tigecycline in rat plasma and to study the pharmacokinetic profile in rats.Methods Rat plasma was treated with 3％trichloroacetic acid-methanol solution(50∶50)for protein precipitation on a Symmetry C18(150.0 mm × 4.6 mm,3.5 μm)column,with mobile phase:0.1％formic acid in water-0.1％formic acid in acetonitrile at a flow rate of 0.6 mL·min-1,the column temperature was 40 ℃,and the ionization source was electrospray ionization,positive ion detection mode:multiple reaction detection.The method was investigated for its specificity,standard curve and lower limit of quantification,precision and recovery,stability and reproducibility.Results The linear range of tigecycline was 25-2 500 ng·mL-1,the lower limit of quantification was 25 ng·mL-1,and the extraction recovery was 95.89％-107.90％;the linear range of polymyxin B,was 82-8 200 ng·mL-1,the lower limit of quantification was 80 ng·mL-1,and the extraction recovery was 93.84％-97.70％;the linear range of polymyxin B2 was 9-900 ng·mL-1,the lower limit of quantification was 9 ng·mL-1,the extraction recovery was 96.41％-104.80％;the intra-day and inter-day relative standard deviations of each substance were 96.41％-104.80％.The linear range was 9-900 ng·mL-1,the lower limit of quantification was 9 ng·mL-1,and the extraction recoveries were 96.41％-104.80％.The intra-day and inter-day relative standard deviations of each substance were less than 10％,and the stability and reproducibility were good.Conclusion This method is simple,sensitive,and has a short analytical time,and is suitable for the determination of the blood concentration of polymyxin B and tigecycline in rat plasma as well as for pharmacokinetic studies.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

Objective:To analyze epidemiological characteristics and spatiotemporal clustering of hepatitis A in China from 2005 to 2023.Methods:The incidence data of hepatitis A in China during 2005-2023 were collected from the China Disease Control and Prevention Information System .Results:From 2005 to 2023, a total of 605 509 cases of hepatitis A were reported in China. The average annual reported incidence rate was 2.32/100 000, the incidence was 2.85/100 000 in men and 1.81/100 000 in women, and the incidence was 3.25/100 000 in age group 0-14 years, 2.10/100 000 in age group 15-64 years and 2.49/100 000 in age group ≥65 years , respectively. The case count in farmers was highest (40.57%, 245 639/605 509). The proportion of the cases in jobless or the unemployed increased most obviously (347.32%), and the proportion of the cases in students decreased most significantly (90.27%). The average annual reported incidence rate in the western China was highest (4.45/100 000), followed by that in northeastern China (2.02/100 000), central China (1.89/100 000) and eastern China (1.16/100 000). From 2020 to 2023, the incidence of hepatitis A showed no spatial clustering. From 2005 to 2019, the obvious hot spots and high-high clustering areas mainly distributed in provinces, such as, Sichuan, Qinghai, Xinjiang, Xizang and Gansu. The low-low clustering areas were mainly distributed in Beijing, Tianjin, Hebei, Shandong, Jiangsu, Shanghai, Zhejiang, Fujian, Henan, Anhui, Jiangxi, Jilin and Liaoning. An independent high-low clustering was found in Shanxi during 2014-2019. A total of 5 high incidence clustering areas were detected through spatiotemporal scanning analysis.Conclusions:The incidence rate of hepatitis A in China declined significantly from 2005 to 2023. The reported incidence rate in the elderly showed no obvious decrease, and the reported cases accounted for the highest proportion in the whole population. Before 2020, the reported incidence rate of hepatitis A showed high-high clustering in western China, the spatiotemporal clustering disappeared from 2020 to 2023, but the reported incidence rate of hepatitis A in western China was still high. It is suggested to pay attention to the prevention and control of hepatitis A in populations at high risk and areas with high incidence of hepatitis A.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To explore the influence factors and predictors of treatment response after adrenocorticotropic hormone(ACTH)in infantile epileptic spasms syndrome(IESS).Methods A retrospective analysis was conducted on 80 cases of IESS infants(50 males and 30 females)who were diagnosed and treated with ACTH in Chengdu Women's and Children's Central Hospital from January 2016 to December 2020.Patients were divided into effective group(n=39)and ineffective group(n=41)based on their response of ACTH treatment after 28 days,and their clinical data including the patients'basic information,etiology,treatment programmer,per-and post-treatment Kramer scores of electroencephalogram(EEG)hypsarrhythmia severity and so on,were collected to compare and analyze between the two groups.A modified Poisson regression model was constructed to discover predictors of outcome,and the receiver operating characteristic(ROC)curves were used to assess the prognosis evaluation of the positive predictive value.Results The ages at seizure onset ranged from one month and seven days to one year and nine months.Seizure types included simple epileptic spasms in 66 cases and combined with other types(focal and secondarily generalized seizures)in 14 cases.Thirty-two cases had been given anti-seizure medications(ASMs)before ACTH treatment.The median Kramer scores per-treatment and at 14 days post-treatment were 10.0(8.3,12.0)and 6.0(4.0,7.0),respectively.After ACTH treatment,39(48.8%)cases were effective.Compared with the effective group,the ineffective group had significantly higher proportion of abnormal perinatal conditions,unknown aetiology with normal development,ASMs given before ACTH treatment,the dosages of ACTH greater than 2 U/(kg·d),combinations of two or more ASMs,poor control,and still seizure attack after ACTH treatment of 14 days(P<0.05).Additionally,the Kramer scores after ACTH treatment of 14 days in the ineffective group were also significantly higher(P<0.05).The modified Poisson regression model showed that there were significant statistic differences between the two groups on ASMs given before ACTH treatment(RR=0.546,95%CI 0.357-0.833,P=0.005)and Kramer scores of hypsarrhythmia severity(RR=0.701,95%CI 0.620-0.792,P<0.001),while there were no significant differences between the two groups in term of ages,gender,perinatal conditions,etiologies,seizure types,Kramer scores before treatment,time lag between onset and treatment,duration of ACTH treatment,kinds of ASMs combination.ROC curve analysis showed that only Kramer scores at 14 days after ACTH treatment could predict the treatment response with sensitivity and specificity of 92.7%and 84.6%,respectively,with Youden index of 0.773.The area under the ROC curve was 0.930(95%CI 0.873-0.987,P<0.001)and the cut-point of the score was 6,indicating that the higher the Kramer scores at 14 days after ACTH treatment,the worse the treatment response.The treatment response rate would reduce by about 30.0%if the Kramer score increased by one point.Conclusion ASMs given before ACTH treatment may influence the treatment response.Kramer scores greater than 6 at day 14 after ACTH treatment may be used as a predictor of treatment response after ACTH in IESS patients.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.