Mitochondrial and peroxisome fission deficiency-related encephalopathy caused by DNM1L gene mutation is a rare and fatal epileptic encephalopathy, with clinical phenotype and genetic heterogeneity. The acute stage is drug-resistant epilepsy with poor prognosis and serious neurological sequelae. A case of genetically confirmed encephalopathy related to mitochondrial and peroxisome fission defects is reported, the clinical data, treatment process are summarized, and the previous literature is reviewed to improve the understanding of the rare disease.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Objective:To compare gene expression profiles in normal human cervical epithelial cells (HcerEpic) before and after Chlamydia trachomatis ( Ct) infection. Methods:HcerEpic cells that were pretreated with DEAE-D were infected with Ct serotype E standard strain and then cultured for 44 h. Uninfected HcerEpic cells were used as the control group. Total RNA was extracted from the cells in each group and reverse transcribed to construct a cDNA library. Differences in gene expression profiles between the two groups were analyzed by high-throughput sequencing and the representative genes were selected for verification by qPCR. Results:A total of 23 997 genes were detected, including 125 differentially expressed genes. Among the 125 genes, 119 were up-regulated and six were down-regulated. GO analysis showed that the differentially expressed genes were enriched in several biological processes including defense response to virus, typeⅠinterferon signaling pathway and cellular responses to typeⅠinterferons. KEGG enrichment analysis showed the differentially expressed genes were mainly enriched in the pathways related to virus infections, such as influenza A virus, herpes simplex virus, EB virus and HPV, and NOD-like receptor pathway.Conclusions:There were significant differences in transcriptome profiles of HcerEpic cells before and after Ct infection. The differentially expressed genes were mainly enriched in the interferon pathway, which was closely related to the antiviral processes in cells. qPCR verified the differentially expressed genes and the genes closely related to the interferon pathway, such as ISG15, IFIT2, OASL and UBE2L6.

Objective To explore the effect of circadian rhythm genes on flavonoids biosynthesis in safflower and its molecular mechanism. Methods Based on the transcriptome and metabolomic database of safflower corolla, we screened the circadian rhythm genes that correlate with biosynthesis of flavonoids in safflower. qPCR was used to quantify the expressions of circadian rhythm genes in different flowering stages at different time points in a single day. LC-MS was performed to determine the accumulation of flavonoids. The correlation between them was analyzed as well. Yeast Two-Hybrid experiment was used to verify the interactive proteins of these genes. Results Seven circadian rhythm genes PRR1, PRR2, ELF3, FT, PHYB, GI and ZTL were obtained. PRR1 gene was positively correlated with flavonoids accumulation (r≥0.7). The full length of PRR1 is 3 201 bp, encoding 421 amino acids, which is highly homologous with rice OsPRR73 gene and named as CtPRR1 (GenBank accession number: MW492035). CtPRR1 was mainly expressed in flowers, and the expression level increased in the daytime and declined in the evening gradually. Correspondingly, the content of flavonoids showed an opposite variation. Both of them displayed a circadian rhythm with a negative correlation (r≥−0.7). In addition, 2 heat shock proteins along with 3 AP2 transcription factors interacting with CtPRR1 protein were obtained via Yeast Two-Hybrid experiment. Conclusion CtPRR1 negatively regulated the safflower flavonoids accumulation in a circadian rhythm way, which may be affected by these interacting proteins.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

OBJECTIVE：To establish QAMS method for simultaneou s determination of 7 effective components in Yao medicine Yueli yaomi spray ，such as α-cyperone，α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide ， so as to provide method reference for the quality control of the preparation. METHODS ：GC method was adopted. The determination was performed on DB- 1701P capillary column ，using nitrogen as carrier gas. The temperature of the hydrogen flame ion detector was 240 ℃. The temperature was programmed ，the inlet temperature was 240 ℃，the injection volume was 1 μL and the split ratio was 20 ∶ 1. Using limonene as internal reference ，the relative correction factors of other 6 components were calculated，the contents of them were calculated with relative correction factors ，and then compared with the results of internal standard method （using naphthalene as internal standard ）. RESULTS ：The mass concentration linear range of α-cyperone， α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide were 0.008 9-1.110 0，0.028 3-3.540 0，0.020 5- 2.560 0，0.023 0-2.880 0，0.016 3-2.035 0，0.013 1-1.640 0，0.008 3-1.040 0 mg/mL（all r＞0.999 0）；the limits of quantification were 0.005 6，0.013 1，0.011 4，0.018 6，0.010 8，0.008 9，0.004 5 mg/mL；the detection limits were 0.001 9，0.004 1，0.003 7， 0.006 2，0.003 5，0.002 9，0.001 5 mg/mL；RSDs for precision ，stability（24 h），and repeatability tests were all less than 2％ （n＝5 or n＝6）； the average recoveries were 98.48％ ， 014） 101.37％，97.96％，99.80％，102.79％，97.77％，102.14％， and RSDs were all lower than 2％（n＝9），respectively. The average relative correction factors of α-cyperone，α-pinene， β-pinene，β-elemene，caryophyllene oxide and ligustilide were 1.045 8，0.621 0，0.488 5，0.382 9，0.708 9，0.956 9 respectively，and the RSDs were all lower than 2％（n＝6）. There wa s no statistical significance in contents of 7 components between QAMS method and internal standard method （P＞0.05）. CONCLUSIONS ：The established QAMS method is simple ， accurate，stable and reproducible ，and can be used for simultaneous determination for 7 components in Yueli yaomi spray.

Methotrexate ( MTX) is administered at a high dose for the treatment of diseases such as leukemia and malignant lymphoma. However, it will cause serious adverse reactions such as acute kidney injury,myelosuppression, and mucositis. On the basis of hydration alkalization and high-dose leucovorin rescue in children with high risk of MTX poisoning,blood purification should be performed as soon as possi-ble to clear MTX. The number and frequency of hemodialysis should be determined according to the general condition of the child,the degree of renal injury and the concentration of MTX,and high-throughput hemodi-alysis can be selected if available. Continuous renal replacement therapy is suitable for children with hemodynamic instability. When the MTX concentration is extremely high, it is recommended to combine hemoperfusion and hemodialysis to achieve better clearance.

Objective To analyze the clinical characteristics of fatal cases with confirmed influenza A ( H1N1) in children in order to improve the diagnosis and treatment. Methods The fatal cases of influenza A (H1N1) admitted to Pediatric Intensive Care Unit of Beijing Children′s Hospital from December 2017 to March 2018 were collected,whose clinical features,diagnosis,treatment,and the causes of death were ana-lyzed retrospectively. Results A total of eight children were enrolled. The age ranged from 3 months to 9 years,and six cases were less than 5 years old. Four cases had underlying diseases. All patients had fever, cough,dyspnea,cyanosis,flaring nares and three depressions sign. Four cases had coma. On admission,the average score of pediatric index of mortality was 58. 8％. Blood routine test showed that lymphocyte predomi-nance in six cases, three cases had leukopenia. C-reactive protein elevated in five patients. Procalcitonin increased in all cases. P/F ratio (PaO2/FiO2) were less than 100 mmHg(1 mmHg =0. 133 kPa) in four cases who were diagnosed as severe acute respiratory distress syndrome. The pulmonary imaging showed mul-tiple parenchymal or mixed lesions. Three cases had air leakage syndrome,and one had pleural effusion. Bac-terial culture was performed on the day of admission. Four cases were complicated with bacterial infection. Three cases had Gram-positive cocci infection,and multidrug-resistant bacteria were predominant. The aver-age time from onset to definitive diagnosis was 8 days. Neuraminidase inhibitors were used in all patients,and the average time from onset to the first dose was 8 days. Mechanical ventilation were performed in all patients in this group. Extracorporeal membrane oxygenation was applied in one case. Four cases in this group died of severe acute respiratory distress syndrome. Three cases died of influenza associated encephalopathy,and one died of septic shock with multiple organ failure. Conclusion Fatal influenza A (H1N1) mostly appeares in children under 5 years old or with underlying diseases. Acute respiratory distress syndrome and influenza associ-ated encephalopathy are the main causes of death. Delayed diagnosis and delayed use of anti-influenza drugs may be an important factors leading to death,and bacteria infection may be another important cause of death.

Objective: To evaluate the effect of prophylactic nimodipine in vasospasm prevention and outcome improvement in children with subarachnoid hemorrhage (SAH). Methods: A prospective, randomized controlled clinical trial which enrolled children with SAH who were admitted to pediatric intensive care unit (PICU) of Beijing Children′s Hospital from January 2015 to October 2018 was conducted. A total of 43 patients were randomly divided into nimodipine group (24 patients) and control group (19 patients) according to random number table. Transcranial Doppler (TCD) was used to dynamically monitor blood flow velocity and spectrum monography of bilateral middle cerebral artery (MCA) for vasospasm evaluation. Pediatric cerebral performance category (PCPC) scale was used to evaluate patients′ brain function on 28^th day after discharge. Data were analyzed by t test, Mann-Whitney U test, χ² test. Results: Except heart rate ((157±26) vs. (137±34) beats/min, t=2.079, P=0.045), no significant differences existed between the two groups in basic demographic characteristics, primary diseases, and clinical manifestations (all P>0.05). The peak velocities of bilateral MCA on the 5^th day after admission were significantly lower in nimodipine group (left MCA (136±34) vs. (158±23) cm/s, t=-2.890, P=0.006; right MCA (129±34) vs. (176±27) cm/s, t=-3.717, P=0.001). Likewise, a lower peak velocity of left MCA was observed on the 7^th day after admission in nimodipine group ((127±45) vs. (152±13) cm/s, t=-2.903, P=0.007), but no significant difference existed in that of right MCA ((131±48) vs. (150±22) cm/s, t=-1.760, P=0.090). Eleven patients suffered from vasospasm, 25% (6/24) in nimodipine group and 26% (5/19) in control group (χ²=0.010, P=1.000), within whom 8 patients had complete remission after continuing nimodipine treatment, one died in hospital and the other two′s vasospasm still existed at the time of discharge. No significant differences were found between the two groups in mean length of hospitalization, proportion of mechanical ventilation, Glasgow coma scale at discharge, survival rate at discharge or survival rate on 28^th day after discharge (all P>0.05). However, nimodipine group had a higher proportion of favorable PCPC brain function (92% (22/24) vs. 63% (12/19), χ²=5.208, P=0.030). No side effects such as hypotension, rash or injection site erythema were observed. Conclusion Prophylactic nimodipine cannot reduce vasospasm incidence in children with SAH but may improve short-term brain function, without any significant safety issues.