This study aimed to explore the effects of akebiaquinata and dandelion extracts in impro-ving intestinal redox homeostasis in weaned rabbits.In the trial,120 35-day-old Ira rabbits weig-hing(1.22±0.08)kg were randomly divided into 4 groups according to the two-factor design,namely group C(basal diet),group D(basal diet+0.5％dandelion extract),group A(basal diet+0.5％akebiaquinata extract),and group DA(basal diet+0.5％dandelion extract+0.5％akebia-quinata extract),with 10 replicates in each group.The adapt period was one week and the experi-mental period was four weeks.At the last day,serum,liver tissue,jejunum and ileal mucosa samples were collected and stored for measurement.The results showed that:(1)First week,the average daily weight gain of group C was significantly lower than that of group D and group A(P＜0.05),and the feed weight ratio was significantly higher than that of group D and group A(P＜0.05).(2)The content of reactive oxygen species(ROS)in liver and serum was significantly reduced in akebiaquinata extract(P＜0.01),and the content of serum ROS in dandelion extract was significantly reduced(P＜0.01),and there were significant and extremely significant interac-tions in liver and serum,respectively.Extracts of akebiaquinata and dandelion were effective in re-ducing the levels of oxidative damage markers in tissues and serum,but increasing the content of malondialdehyde in liver tissues.(3)Akebiaquinata extract significantly increased the activity of glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)in serum(P＜0.01),and significantly reduced the activity of T-AOC in liver(P＜0.01)and superoxide dismutase in je-junum and liver(P＜0.05).Dandelion extract significantly increased the activity of T-AOC in ser-um and GSH-Px in jejunum(P＜0.05).The extracts of akebiaquinata and dandelion had a signifi-cant interaction effect on peroxidase in serum(P＜0.05).(4)The expression of Kelch-like ECH-as-sociated protein 1(Keap1)and NAD(P)H:quinone oxidoreductase 1(NQO1)genes in the jejunum was significantly and extremely significantly reduced by akebiaquinata extract.The extracts of ake-biaquinata and dandelion had significant interaction effects on ileal NQO1,Heme oxygenase1 and Superoxide dismutase 2(P＜0.05)and Keap1(P＜0.01).The expression of NQO1 gene in liver tis-sue was significantly reduced by akebiaquinata extract(P＜0.05).Dandelion and Akebiaquinata ex-tracts can reduce the content of reactive oxygen species in vivo and alleviate oxidative damage.At the same time,dandelion and akebiaquinata extract can work together to regulate antioxidant gene expression and antioxidant enzyme activity through the Nrf2-Keap1 signaling pathway to maintain intestinal redox homeostasis and relieve intestinal oxidative stress.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

ObjectiveTo discuss the origin of rare abnormal karyotypes of fetuses with high risk of trisomy 18 revealed by non-invasive prenatal testing （NIPT） and its impact on fertility. MethodsThe cytogenetic and molecular genetic analyses were performed on the abnormal chromosomes of a prenatally diagnosed fetus with rare complete translocation trisomy 18. Using the keywords “translocation trisomy 18” or “trisomy 18 translocation” in both Chinese and English， we searched PubMed， CNKI， SinoMed， WanFang Data， CQ VIP and the Chinese Medicine database. The relevant case series were retrieved and critically appraised. ResultsG-banded karyotype analysis showed that the maternal karyotype was 46，XX，t（9；18）（q31.2；q23） and the fetal karyotype was 47， XN， t （9； 18） （q31.2；q23）mat， +18， which was a rare complete translocation type of trisomy 18. The SNP array revealed the fetus had increased copy number of chromosome 18 and two complete chromosome 18 inherited from the mother with balanced chromosomal translocation. Literature search found two children with complete translocation trisomy 18 reported abroad. Both of them had trisomy 18 phenotype and originated from the balanced translocation between parental chromosome 18 and other chromosomes. ConclusionNIPT gives an effective advance warning of trisomy 18. SNP array not only improves the detection rate of chromosomal abnormalities， but also helps identify the origin. The karyotype is still the gold standard for prenatal diagnosis.

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
Humans ; Lectins ; Candida ; Candidemia ; Reproducibility of Results ; Polymerase Chain Reaction ; Nucleic Acids ; Magnetic Phenomena

Objective: To determine the causal association between long-term Nitrogen dioxide (NO₂) exposure and the risk of cardiovascular hospitalization. Methods: Based on a sub-cohort of a community-based prospective cohort study, a total of 36 271 participants were recruited from 35 communities randomly selected in Guangzhou in 2015. The annual average exposure of NO₂, demographic characteristics, lifestyle factors, and information on the causes of hospitalization was collected. We applied marginal structural Cox models to investigate the effect of NO₂ on cardiovascular hospitalization. Demographic and behavioral factors also stratified results. Results: The mean age of participants in the present study was (50.9±17.8) years, and the cardiovascular admission rate was 8.7%, with 203 822 person-years of follow-up. The annual mean NO₂ concentration was 48.7 μg/m³ during 2015-2020. For each 10 μg/m³ increase in NO₂ concentrations, the HRs (95%CIs) of total cardiovascular hospitalization, cardiovascular hospitalization, and cerebrovascular hospitalization were 1.33 (1.16-1.52), 1.36 (1.16-1.60) and 1.25 (1.00-1.55), respectively. Participants who were never married/married, with secondary education, high exercise frequency, or non-smokers/current smokers may be more susceptible than their counterparts. Conclusion: Long-term exposure to NO₂ significantly increased hospitalization risk for cardiovascular disease.
Humans ; Adult ; Middle Aged ; Aged ; Nitrogen Dioxide ; Prospective Studies ; Cardiovascular Diseases/epidemiology* ; Causality ; Hospitalization

[Abstract] Objective To study the role of hypoxia inducible factor-1α (HIF-1α) / stromal cell-derived factor-1 (SDF-1) pathway in high altitude hypoxia preconditioning in rat. Methods Seventy-six adult male SD rats, which through fed in low-pressure oxygen chamber (altitude 5000 m) and Xining (altitude 2260 m) to establish the rat model of hypoxia preconditioning. Rats randomly divided into 6 groups: control group (Ctrl), high altitude hypoxic preconditioning 1 day group (HHP-1d), high altitude hypoxic preconditioning 4 days group (HHP-4d), high altitude hypoxic preconditioning 15 days group (HHP-15d), high altitude hypoxic preconditioning 30 days group (HHP-30d), medium altitude hypoxic preconditioning group (MHP). 7. 0 T small animal MRI was used to observe the intracranial structure, diameter of basilar artery and cerebral blood flow in the hippocampus and brainstem regions by the sequences of T2 weighted images (T2WI) and arterial spin labeling (ASL) in the groups of Ctrl, HHP-4d, HHP-30d and MHP. In each group, blood routine was tested, the concentrations of HIF-1α, SDF-1 in serum, platelet activating factor (PAF)and P-selectin (SELP) in plasma were detected by the method of ELISA. Results In the hypoxia preconditioning groups, intracranial structure and diameter of basilar artery had no significant difference, while cerebral blood flow in the regions of brainstem and hippocampus increased significantly (P<0. 05). Meanwhile, red blood cell and white blood cell increased significantly, while platelet decreased significantly in the groups of hypoxia preconditioning (P<0. 05). Red blood cell and platelet in MHP group were closer to Ctrl group. The concentrations of HIF-1α and SDF-1 (except HHP-1d group) increased significantly in hypoxia preconditioning groups (P<0. 05).The concentrations of PAF and SELP increased significantly in HHP-1d and HHP-15d groups. The concentration of PAF decreased significantly in the HHP-4d and HHP-30d groups, and SELP decreased significantly in HHP-4d group (P<0. 05). Conclusion Hypoxia preconditioning can increase oxygen storage and immune defense capacity, improve brain reserve capacity and play the effect of brain protection through HIF-1α/ SDF-1 pathway. The best effect preconditioning was feed at medium altitude (altitude 2260 m) for 30 days.

Objective To investigate the effect of plateau hypoxia on the blood-brain barrier after subarachnoid hemorrhage (SAH) in rats. Methods Adult male SD rats (n = 78) were randomly divided into 4 groups: sham group (sham), SAH model group (SAH), plateau hypoxia sham group (Hp sham) and plateau hypoxia SAH model group (Hp SAH). The rat model of plateau hypoxia was established through low-pressure simulation chamber (altitude 5000 m), and the SAH model was established by endovascular perforation method. At 24 hours after SAH, neurobehavior score and SAH grade were assessed. The morphological changes of neurons and apoptosis of nerve cells in the CA1 region of hippocampal were observed by the staining of Nissl and TUNEL. The expression of phosphorylated PI3K (p-PI3K), PI3K, phosphorylated Akt (p-Akt), Akt, phosphorylated nuclear factor κB (p-NF-κB), NF-κB, matrix metalloproteinase-9 (MMP-9), occludin and claudin-5 in hippocampal were detected by the method of Western blotting. The expression of occludin and claudin-5 proteins in the CA1 region of hippocampal were observed by immunofluorescent staining. Results At 24 hours after SAH, the neurobehavior score decreased significantly and SAH grade increased significantly in the SAH and Hp SAH group (P< 0.05). Neurobehavior score decreased significantly in the Hp SAH group compared with the SAH group (P < 0.05). In the SAH group, neurons in the CA1 region of hippocampus were atrophied and deformed, the arrangement were disordered, the number of neurons decreased significantly, and the apoptosis of nerve cells increased significantly(P< 0.05). Plateau hypoxia could aggravate the morphological damage of neurons and apoptosis of nerve cells. The expression of p-PI3K/PI3K, p-Akt/Akt, occludin and claudin-5 proteins decreased significantly, while the expression of p-NF-κB/NF-κB and MMP-9 proteins increased significantly in the SAH and Hp SAH group (P< 0.05). The expression of p-PI3K/PI3K and MMP-9 proteins increased significantly in Hp SAH group compared with the SAH group. The expression of claudin-5 protein increased significantly in Hp sham group compared with the sham group (P < 0.05). Immunofluorescent staining showed that the expression of occludin and claudin-5 proteins in the CA1 region of hippocampus decreased in the SAH group. Plateau hypoxia could further decreased the expression of occludin and claudin-5 proteins. Conclusion Plateau hypoxia aggravates blood-brain barrier disruption after subarachnoid hemorrhage in rats through inhibiting PI3K/Akt/NF-κB pathway.

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.
Humans ; Male ; Fever ; Glycosylphosphatidylinositols/genetics* ; Membrane Glycoproteins/genetics* ; Mutation ; Rare Diseases ; Seizures ; Child