Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

Objective:To study the effects of L-T4 gel combined with metformin on Ach and MCT8 content in hippocampus of hypothyroidism model rats.Methods:40 rats were randomly divided into 5 groups, normal control group (CON group) , hypothyroidism group (Hypo group) , L-T4 replacement group (L-T4 group) , metformin treatment group (MET group) and combined treatment group (L-T4+MET group) by random number table. Rats in CON group were given normal drinking water, and rats in the other four groups were given drinking water containing 0.05% propylthiouracil for 6-week hypothyroidosis modeling. At the 5th week of modeling, rats in MET group were given 1ml/100g metformin solution by intragastric administration, and rats in L-T4 group were applied with L-T4 gel agent at a dose of 0.1g/100g. L-t4+MET group were treated with L-T4 gel and metformin solution. At the end of 6-week modeling, the blood of abdominal aorta was collected, and the hippocampal tissue of the brain was quickly separated on an ice platform. Meanwhile, the trachea and thyroid were cut out and photographed to record their size. They were stored in a -80℃ refrigerator or soaked in 4% paraformaldehyde for fixation and used for immunohistochemical staining. T-test was used to confirm the difference between the data of each group, one-way analysis of variance was used to compare the means between multiple groups, and chi-square test was used when the count data were expressed as percentage ( χ2) . P<0.05 was used to indicate statistical significance between the data, and the difference was statistically significant. Results:Nishner staining showed that the optical density of the Hypo group was lower than that of the CON group ( t=8.944, P<0.001) , the optical density of the MET group was higher than that of the Hypo group ( t=4.472, P<0.001) , and the optical density of the L-T4 group was higher than that of the Hypo group ( t=4.472, P<0.001) . The optical density of rats in the combined treatment group was higher than that in the Hypo group ( t=8.944, P<0.001) , and recovered to the level of the CON group ( P=1.000) . After 2 weeks of treatment, the total thyroxine level (TT4) of the Hypo group was lower than that of the CON group ( t=14.536, P<0.001) , and the TT4 level of the MET group was higher than that of the Hypo group ( t=6.924, P<0.001) . TT4 level of L-T4 group was higher than that of Hypo group ( t=4.892, P<0.001) , TT4 level of combined treatment group was higher than that of Hypo group ( t=12.890, P<0.05) , and recovered to the level of CON group ( t=0.494, P=0.709) . After the study, the thyroid tissue of each group was collected. The thyroid tissue weight of the Hypo group was higher than that of the CON group ( t=7.906, P<0.001) , the thyroid tissue weight of the MET group and L-T4 group was lower than that of the Hypo group (MET: t=2.000, P<0.001; L-T4: t=3.000, P<0.001) , but higher than that of the CON group (MET: t=3.000, P<0.001; L-T4: t=2.000, P<0.001) . The thyroid weight of L-T4+MET group was similar to that of CON group ( P=1.000) . HE staining showed that the size of thyroid follicles was different in the combined treatment group, and the number of glial and absorbed vacuoles basically recovered similar to that of CON. After treatment, the Ach level in the Hypo group was lower than that in the CON group ( t=3.618, P<0.001) , the Ach level in the MET group was higher than that in the Hypo group ( t=3.121, P=0.016) , the Ach level in the L-T4 group was higher than that in the Hypo group ( t=3.321, P=0.027) , and the Ach level in the combined treatment group was higher than that in the Hypo group ( t=3.202, P=0.001) . And recovered to the level of CON group ( t=3.362, P=0.605) . After treatment, the MCT8 level in the Hypo group was higher than that in the CON group ( t=11.254, P<0.001) , the MCT8 level in the MET group was lower than that in the Hypo group ( t=5.679, P<0.001) , and the MCT8 level in the L-T4 group was lower than that in the Hypo group ( t=5.813, P<0.001) . The MCT8 level of the combined treatment group was lower than that of the Hypo group ( t=8.624, P<0.001) , and recovered to the level of the CON group ( t=0.587, P=0.477) . Conclusion:L-T4 gel combined with metformin has a good therapeutic effect on hypothyroidism, which can increase the level of Ach and decrease the level of MCT8 in hippocampus.

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing. METHODS: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan. RESULTS: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent. CONCLUSION Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.
Chromosome Deletion ; Chromosomes ; Female ; Fetus ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Objective:To investigate the protective effect of hyperbaric oxygen preconditioning on intestinal ischemia-reperfusion injury (IRI) in rats.Methods:Thirty male SD rats were randomly divided into sham-operated group ( n=10), ischemia-reperfusion injury group (I/R, n=10) and hyperbaric oxygen preconditioning group (HBO, n=10). In the HBO group, the rats were exposed to hyperbaric oxygen for 60 min every time, twice a day for two days. Twenty-four hours after the last exposure, the rats were undergone IRI (ischemia 45 min/reperfusion 60 min). The jejunum was taken out for paraffin section. HE staining was used to detect the histopathological change. The malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the jejunum were measured with the tissue homogenization. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Results:In I/R group, HE staining showed obvious exfoliation of jejunum villus, significant inflammatory cellular infiltration, and massive separation of epithelial layer and lamina propria. In HBO group, after HBO preconditioning, the damage of intestinal mucosa was significantly reduced, and the structure of villus was intact with only a small amount of inflammatory cellular infiltration. Compared with the sham-operated group, the MDA content (1.46±0.14 nmol/mg protein) and MPO activity (0.190±0.018 U/g tissue) in the jejunum of the I/R group were significantly higher after IRI. HBO preconditioning could significantly reduce the MDA content (0.84±0.09 nmol/mg protein) and MPO activity (0.097±0.011 U/g tissue), as compared with I/R group. All those differences were statistically significant ( P<0.05). In addition, compared with I/R group, the number of positive cells of HBO group was significantly lower as determined by TUNEL ( P<0.01). Conclusion:The HBO preconditioning had a protective effect on intestinal IRI, and the mechanism may be related to anti-oxidation, anti-inflammation, and anti-apoptosis.

Objective:To investigate the protective effect of hyperbaric oxygen preconditioning on intestinal ischemia-reperfusion injury (IRI) in rats.Methods:Thirty male SD rats were randomly divided into sham-operated group ( n=10), ischemia-reperfusion injury group (I/R, n=10) and hyperbaric oxygen preconditioning group (HBO, n=10). In the HBO group, the rats were exposed to hyperbaric oxygen for 60 min every time, twice a day for two days. Twenty-four hours after the last exposure, the rats were undergone IRI (ischemia 45 min/reperfusion 60 min). The jejunum was taken out for paraffin section. HE staining was used to detect the histopathological change. The malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the jejunum were measured with the tissue homogenization. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Results:In I/R group, HE staining showed obvious exfoliation of jejunum villus, significant inflammatory cellular infiltration, and massive separation of epithelial layer and lamina propria. In HBO group, after HBO preconditioning, the damage of intestinal mucosa was significantly reduced, and the structure of villus was intact with only a small amount of inflammatory cellular infiltration. Compared with the sham-operated group, the MDA content (1.46±0.14 nmol/mg protein) and MPO activity (0.190±0.018 U/g tissue) in the jejunum of the I/R group were significantly higher after IRI. HBO preconditioning could significantly reduce the MDA content (0.84±0.09 nmol/mg protein) and MPO activity (0.097±0.011 U/g tissue), as compared with I/R group. All those differences were statistically significant ( P<0.05). In addition, compared with I/R group, the number of positive cells of HBO group was significantly lower as determined by TUNEL ( P<0.01). Conclusion:The HBO preconditioning had a protective effect on intestinal IRI, and the mechanism may be related to anti-oxidation, anti-inflammation, and anti-apoptosis.