Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.
Mice ; Animals ; Antioxidants/analysis* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Paeonia/chemistry* ; Glutathione/analysis*

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.
Angioedemas, Hereditary/genetics* ; Asian People ; Female ; Humans ; Male ; Mutation ; Pedigree ; Retrospective Studies

The structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia was investigated. Animal experiments strictly follow the regulations of Medical Laboratory Animal Ethics Committee of Qinghai University, School of Medicine. SD rats were randomly divided into a control group, a moderate altitude hypoxia group, and a high altitude hypoxia group. The pH value of the feces was measured and histopathological changes in the small intestine were determined by HE staining, and the intestinal flora were characterized by 16S rDNA high throughput sequencing technology on the 3rd, 7th, 15th, and 30th day of hypoxia exposure. Compared with the control group, the fecal pH value of rats in the moderate altitude hypoxia group and the high altitude hypoxia group was decreased significantly. The lamina propria and submucosa capillaries were slightly dilated and congested on the 3rd day in the moderate altitude hypoxia group. In the high altitude hypoxia group the submembrane capillaries were dilated and congested, the lamina propria of the mucosa showed mild edema, and the lymphatic vessels were dilated on the 7th day. The composition and diversity of intestinal flora in these rats changed significantly with prolonged exposure to the high altitude hypoxic environment. A total of 35 phyla, 87 classes, 205 orders, 337 families, 638 genera, and 256 species were annotated in the three groups of rats, including Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Akkermansia, and Lactobacillus_murinus. Compared with the control group, the intestinal flora of the hypoxic groups showed the most significant changes by the 15th day. There were 9 microbiota of gut microorganisms with relative abundance in the moderate altitude hypoxia group, of which Rikenellaceae_RC9_gut_group bacteria was the most common, there were 19 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group, of which Ruminococcaceae bacteria was the most common. The results of this study indicate significant changes in the intestinal flora with high altitude hypoxia, and establish a foundation for further research on the initiation and development of diseases and drug metabolism in high altitude hypoxia.

The combination of ginkgo ketoester tablet - donepezil (GD) is a popular combination commonly used in clinic for the treatment of Alzheimer's disease. To evaluate the learning and memory improving ability of different proportions of the two drugs. We optimized the ratio of GD for treatment of dementia using a mouse model. Dementia was induced by multiple neuronal damages in mice. The experimental protocols were approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine and all the procedures were strictly conducted in accordance with ethical principle of animal use and care. Morris water maze, brain hematosylin-eosin staining and the changes of the neurotransmitters and related enzymes in the plasma or brain tissues were tested to determine the effect of GD on dementia mice. The results showed that the dementia mice were significantly different from the normal group in terms of behavior, pathological sections and related indicators. Compared to the dementia mice, partial administration groups could improve learning and memory ability as well as indexes in the blood and brain tissues. Both the principal component analysis and multi-attribute comprehensive index methods were used to comprehensively evaluate the total effect of GD on anti-dementia. The results showed that the combination of two drugs at the dose of 0.5 to 1 times was in a dose-effect relationship, and the dose of 1 (the clinical equivalent) had the best treatment effect. Then based on the optimal dose, GD 1∶1 had best effect, which was consistent with the clinical use of two drugs. This provides scientific basis for more effective application of the compatibility between ketoester tablet and donepezil for modern clinic medicine.

OBJECTIVE: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes. METHODS: The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes. RESULTS: The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%. CONCLUSION The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.
Chromatography, High Pressure Liquid ; Liposomes ; Magnetic Resonance Spectroscopy ; Taxoids

BackgroundThe effectiveness of the combination of electroacupuncture (EA) and behavioral training (BT) for mid/advanced cerebral infarction (M/ACI) and related mechanisms remains unclear. This study aimed to investigate the combined effects on the learning-memory ability and event-related potential P300 in rats with M/ACI.

MethodsEighty rats with M/ACI were divided into Group Model (M), Group EA, Group BT, and Group EA-BT (n = 20) according to the random number with five healthy rats in Group Control (CON). On the 6 week after modeling, EA, BT, and EA-BT were given to Group EA, Group BT, and Group EA-BT, respectively, whereas Group M and Group CON were not given any intervention. Y-maze test and P300 were recorded before and after the intervention.

ResultsAfter intervention, the P300 latency was lower and the amplitude was higher in the Group EA-BT, Group EA, and Group BT than before (for latency, t = -7.638, -4.334, and -5.916; for amplitude, t = 8.125, 3.846, and 5.238; P < 0.01), with Group EA-BT superior to Group EA (for latency, t = -3.708; for amplitude, t = 3.653; P < 0.01) and Group BT (for latency, t = -2.067; for amplitude, t = 2.816; P < 0.05), with no significant difference between Group BT and EA (for latency, t = -1.439; for amplitude, t = 1.075; P > 0.05). While the performances of Y-maze tests in the Group EA-BT, Group EA, and Group BT were all better than before (t = 10.359, 4.520, and 7.791, P < 0.01), with Group EA-BT better than Group EA (t = 5.627, P < 0.01) and Group BT (t = 2.913, P < 0.01) respectively, and Group BT better than Group EA (t = 2.912, P < 0.01).

ConclusionEA or BT can affect P300 in rats with M/ACI, and the combination of these two methods can significantly improve the learning-memory ability.

Acupuncture Points ; Animals ; Cerebral Infarction ; Disease Models, Animal ; Electroacupuncture ; Evoked Potentials ; Humans ; Rats ; Rats, Inbred ACI ; Rats, Sprague-Dawley

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Objective:To investigate the clinical biological characteristics of EVI1 positive acute myeloid leukemia (AML) and its effect on early chemotherapy.Methods:The clinical and biological characteristics of 33 AML patients with EVI1 positive were retrospectively analyzed in 361 AML patients who were diagnosed and treated in our institute from March 2015 to July 2016,and the clinical and biological features,and rates of the induced remission were compared between the intermediate risk and poor risk with EVI1 positive AML,moreover,the influential factors on complete remission (CR) were analyzed.The expression of EVI1/ABL was tested in 32 healthy donors to confirm the abnormal threshold of EVI1 expression.Results:The definition of EVI1 positive was that the quantitative expression of EVI1/ABL was more than 8.0％.The 33 AML patients with EVI1 positive were found in 361 newly diagnosed AML patients,in which the female and male patients were 17 and 16 respectively,the median age was 45 (18-67) years,with a median follow-up of 6.6 (0.7-13.2) months.Intermediate karyotype was found in 17 patients (including 9 patients with normal karyotypes,1 patient with + 8);unfavorable karyotype was found in 14 patients [including 7 patients with-7/7q-,4 patients with t (v;11q23),3 patients with inv (3)/t (3;3),and 2 patients without mitotic figures].The rate of CR in the first induction chemotherapy was 42.4％,and the rate of total CR was 60.6％.According to the NCCN,16 intermediate risk patients and poor risk patients were divided,without favorable risk patients.The rate of CR in the first induction chemotherapy were 68.8％ and 17.6％ (P =0.005) in the intermediate risk and poor risk respectively,that of total CR were 81.3％ and 41.2％ (P =0.032),and the rates of relapse were 7.7％ and 14.3％.Univariable analysis revealed that unfavorable karyotype could affect the rate of CR in the first reduction chemotherapy and that of total CR (P =0.004,0.029).The poor risk patients had higher mortality (41.2％ vs.6.3％,P =0.039) and lower overall survival (OS) (P =0.012).Conclusion:EVI1 may be not an independent prognostic factor for the AML patients considering the appearance in the intermediate and poor risk patients.It predicts poor outcome in the EVI1 positive AML patients who have unfavorable karyocytes,such as-7/7q-,t (v;11 q23),and inv (3)/t (3;3),and also a low rate of both CR in the first induction chemotherapy and total CR.It also has a low rate of long-term survival and high mortality in the AML patients with EVI1 positive,who may benefit from allogeneic bone marrow transplantation as soon as possible.

Objective To research whether the polyunsaturated fatty acids (PUFAs) level in prenatal and postpartum women af‐fect the incidence of postpartum depression .Methods 102 eligible and voluntary parturients of full‐term normal delivery were se‐lected and the serum specimens before labor and on postpartum 3 ,42 d were respectively collected for detecting serum PUFAs lev‐els .The perinatal depression related factors questionnaire and the Edinburgh Postnatal Depression Scale (EPDS) were filled in and the scores were evaluated for analyzing the incidence of postpartum depression .Results Among 102 pregnant women and parturi‐ents ,the postputum depression appeared in 28 cases with the positive rate of 27 .5% .The incidence rate of postpartum depression in the eicosapentaenoic acid (EPA) low values group and the docosahexaenoic acid (DHA) low and medium values groups was higher than that in the high values groups ;the incidence rate of postpartum depression in the arachidonic acid (AA) high value group was the higher than that in the low value group .Conclusion The lower the EPA and DHA levels ,the easier to develop depression .