Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.@*METHODS@#Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.@*RESULTS@#The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).@*CONCLUSIONS@#EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

Impairment of superovulation on the establishment of pregnancy in mice / 解剖学报

Objective To explore whether superovulation impairs the process of pregnancy establishment in mice by changing the intrauterine environment. Methods The implantation and pregnancy of superovulated and normal mice were compared. The superovulated mice were subjected to unilateral tubal ligation on day 0. 5 and blastocysts were transplanted to the other uterine horn on day 2. 5. The number of implantation sites of bilateral uterine horn was compared. The differences between preimplantation uteri of superovulated and normal pseudopregnancy mice were compared by tissue sections and high-throughput sequencing. Bioinformatics analysis was performed on the differentially expressed genes in two groups. Results Compared with the control group, the pregnancy rate of mice in the superovulation group decreased significantly. The number of implantation sites in the superovulation group was higher than the control. There was no significant difference in the pregnancy rate of the uterine horn between the control side and the transplanted side of the superovulated mice. The endometrium was thinned and the number of glands was reduced in superovulated pseudopregnancy mice. The gene expression patterns of preimplantation uterus in superovulation pseudopregnancy and normal pseudopregnancy mice were different. There were 1097 significantly differentially expressed genes, including 752 up-regulated genes and 345 down-regulated genes. Bioinformatics analysis showed that differentially expressed genes are mainly involved in biological processes, such as decidualization, response to progesterone, positive regulation of angiogenesis. They were mainly enriched in FoxO signaling pathway, cell cycle pathway and steroid biosynthesis pathway. Conclusion Superovulation impaired the process of establishing pregnancy and altered the gene expression patterns of biomarker of uterine receptivity in mice.

Femtosecond laser-assisted cataract phacoemulsification combined with goniosynechialysis in the treatment of primary acute angle-closure glaucoma with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in the treatment of acute angle-closure glaucoma complicated with cataract.METHODS: A total of 53 patients(60 eyes)with primary acute angle closure glaucoma complicated with cataract admitted to our hospital from April 2020 to February 2021 were selected. They were divided into two groups according to the surgical method, with 28 cases(30 eyes)who were treated with femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in group A, and 25 cases(30 eyes)who were treated with traditional cataract phacoemulsification combined with goniosynechialysis in group B. The effective phacoemulsification time(EPT)and cumulative dissipated energy(CDE)during surgery in two groups were recorded. Patients were followed up to 3mo after surgery, and the intraocular pressure, anterior chamber depth(ACD), best corrected visual acuity, corneal endothelial cell loss rate(ECL)and surgical complications were observed in both groups.RESULTS: The postoperative intraocular pressure was significantly decreased and ACD was significantly increased(all P&#x003C;0.05), and there was no difference between the two groups(all P&#x003E;0.05). The postoperative best corrected visual acuity of the two groups was significantly better than that before surgery(P&#x003C;0.05), and group A was significantly better than group B at 1d after surgery(P&#x003C;0.05). The EPT, CDE, ECL and incidence of complications(7% vs. 27%)in group A were significantly lower than those in group B(all P&#x003C;0.05).CONCLUSION: Femtosecond laser-assisted cataract phacoemulsification combined with goniosynechialysis in the treatment of primary acute angle-closure glaucoma combined with cataract has a significant therapeutic effect, which can effectively improve surgical safety, reduce the rate of corneal endothelial cell loss, and have fewer complications.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice / 中国针灸

OBJECTIVES@#To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy.@*METHODS@#A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.@*RESULTS@#Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.@*CONCLUSIONS@#Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter / 中华创伤杂志(英文版)

PURPOSE@#High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances.@*METHODS@#Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA).@*RESULTS@#In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results.@*CONCLUSION@#The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.

Electroacupuncture for acute exacerbation of chronic obstructive pulmonary disease complicated with gastrointestinal dysfunction: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of electroacupuncture (EA) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with gastrointestinal dysfunction.@*METHODS@#A total of 100 patients with AECOPD complicated with gastrointestinal dysfunction were randomly divided into an EA group (50 cases, 2 cases dropped off, 1 case excluded) and a medication group (50 cases). Both groups were treated with symptomatic and supportive treatment such as low flow oxygen, nebulized inhalation of short-acting β2 agonist (SABA) or short-acting muscarinic antagonist (SAMA) combined with inhaled corticosteroid (ICS). The EA group was treated with EA at Zusanli (ST 36), Yinlingquan (SP 9), Zhongwan (CV 12), Shuifen (CV 9), Tianshu (ST 25), Chize (LU 5) and Lieque (LU 7), with discontinuous wave, 2 Hz in frequency, 30 min each time, once a day. In the medication group, oral mosapride citrate tablets were given, 3 times a day, 5 mg each time. Both groups were treated for 5 d. Before and after treatment, the gastrointestinal symptom rating scale (GSRS) score was observe, serum procalcitonin (PCT), C-reactive protein (CRP), and plasma oxygenation index (PaO2/FiO2) were detected, and patient satisfaction degree was evaluated in the two groups.@*RESULTS@#Compared with before treatment, except for diarrhea dimension in the medication group, the total scores and each dimension scores of GSRS were decreased (P<0.05), serum PCT and CRP were decreased (P<0.05), plasma PaO2/FiO2 was increased (P<0.05) in the two groups after treatment. After treatment, in the EA group, the total score and abdominal pain, dyspepsia, constipation and diarrhea scores of GSRS were lower than those in the medication group (P<0.05), meanwhile serum PCT and CRP were lower and plasma PaO2/FiO2 was higher than those in the medication group (P<0.05). The improvement of gastrointestinal symptoms, life quality and overall satisfaction degree in the EA group were superior to those in the medication group (P<0.05).@*CONCLUSION@#EA could improve the symptoms of patients with AECOPD complicated with gastrointestinal dysfunction, reduce inflammatory response, improve oxygenation and patient satisfaction degree.

Influencing factors of negative conversion time of nucleic acid detection in 228 patients infected with Omicron variant of SARS-CoV-2 in Shanghai / 中国热带医学

@#Abstract: Objective To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods　The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (≤18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results　The mean nucleic acid conversion time of 228 patients was (18.7±12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2±2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8±1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P>0.05); however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P<0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P<0.05). Conclusions The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.

Dajianzhong decoction in treating visceral pain of irritable bowel syndrome based on ERK 1/2/nuclear factor kB signal pathway / 解剖学报

Objective To investigate whether Dajianzhong decoction can treat visceral pain of irritable bowel syndrome (IBS) by interfering with ERK1/2/nuclear factor kB (NF-kB) pathway and its downstream molecules.Methods The IBS visceral pain rat model was prepared by method such as mother-infant separation, acetic acid enema, and intraperitoneal injection of chicken ovalbumin. Rats were randomly divided into normal control group (normal saline), model group (normal saline), Dajianzhong decoction (10.8 g/kg) treatment group, and the control group of pinaverium bromide (45 mg/kg). Eight rats in each group were given intragastrically for 14 days. To evaluate the visceral sensitivity of rats, abdominal withdrawal reaction (AWR) was used ; the expression of ERK1/2 mRNA, NF-kB mRNA, cyclooxygenase-2 (COX-2)mRNA, and matrix metalloproteinase 9 (MMP-9) mRNA in colon tissue of rats in each group were detected by Real-time PCR; Immunohistochemistry staining method was used to detect the expression of NF-kB and COX-2 in the colon tissue of each group. Results Compared with the normal rats, AWR scores of model rats increased significantly at 60, 40 and 20 mmHg pressure (P0.05). Conclusion Dajianzhong decoction can play a role in treating visceral pain of irritable bowel syndrome ( IBS) by interfering ERK1/2/NF-kB pathway and its downstream molecules..

Research progress on hypoxia-induced imbalance of calcium homeostasis in pulmonary artery smooth muscle cells and its treatment / 中国药理学通报

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

Research progress on therapeutic strategies for improving pulmonary vascular remodeling in pulmonary hypertension / 中国药理学通报

Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure. All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death. The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues. These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor. Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH. In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of "lung distension";(4)research into monomers of traditional Chinese medicine; and(5)research into new targets.

Mechanism of pulmonary artery remodeling induced by calcium overload induced by hypoxia / 药学学报

Patients with hypoxia pulmonary hypertension (HPH) are often accompanied by dyspnea, fatigue, and headache. With the development of the disease, the right ventricle gradually collapses and eventually leads to death. Hypoxic pulmonary vascular remodeling is an important pathological basis of HPH, and the remodeled pulmonary vessels will form permanent thickening. The mechanism of hypoxic pulmonary vascular remodeling is relatively complex. At present, there are few studies on drugs for pulmonary vascular remodeling on the market, mainly focusing on the alleviation of pulmonary vasoconstriction. It was found that hypoxia induces calcium overload in pulmonary artery smooth muscle cells (PASMCs), resulting in the proliferation of PASMCs. The main mechanisms include: ① abnormal expression of calcium pumps; ② abnormal calcium channels in the plasma membrane of pulmonary artery smooth muscle cells; ③ overexpression of calcium-sensitive receptors in cells; ④ the expression of Na+/Ca2+ exchanger type-1 was abnormal. This review summarized several mechanisms of hypoxia induced calcium overload leading to pulmonary artery remodeling, hoping to provide a new idea for the treatment of HPH.

Decidualization induced by mouse tetraploid embryos / 解剖学报

Objective To investigate the role of inner cell mass (ICM) in decidualization using decidua induced by two-cell embryos or tetraploid embryos through tubal embryo transfer. Methods Tetraploid embryo, as the inner cell mass-deficient embryo, were produced by electrofusion of mouse 2-cell embryos. Decidua was induced by 2-cell embryos or tetraploid embryos through tubal embryo transfer. Decidua induced by 2-cell embryos was employed as a control. Morphologic and implantation site of decidua were compared between two-cell embryo-induced decidua and tetraploid embryo-induced decidua. The differentially expressed microRNA ( miRNA ) was screened by high-throughput sequencing. The target genes of differentially expressed miRNA in two groups were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Tetraploid embryo-induced decidual tissue and 2-cell embryo- induced decidual tissue were very similar at the implantation site, but there were significant differences in decidual morphology. There were 16 miRNAs differentially expressed in decidua of the two groups, of which 11 miRNAs (miR-466f- 3p, miR-302 d-3p, miR-466i-5p, miR-465c-5p, miR-302a-5p, miR-7068-3p, miR-741-3p, miR-302a-3p, miR-433-5p, miR-144-5p, miR-878-5p) were up-regulated in tetraploid embryo-induced decidua and 5 miRNAs (miR-690, miR-193b- 5p, miR-147-3p, novel_327, miR-363-3p) were down-regulated in tetraploid embryo-induced decidua. Bioinformatics analysis showed that the target genes played function such as protein binding and ion binding, and mainly involved in cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway, estrogen signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and so on. Conclusion ICM plays an important role in decidualization.

Mechanism of insulin-like growth factor 2 regulating human ovarian granulosa cell proliferation through the phosphatidylinositol 3-kinase/ protein kinase B signaling pathway / 解剖学报

Objective To explore the effect and mechanism of insulin-like growth factor 2 ( IGF2 ) on the proliferation of human ovarian granulosa cells ( KGN ). Methods KGN cells cultured in vitro and treated with different concentrations of IGF2 were divided into control group and IGF2 group (25 μg/L, 50 μg/L, 100 μg/L), and then cells were divided into control group, 100 μg/L IGF2 group, LY294002 group, and IGF2 +LY294002 group after intervened the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway with LY294002. MTS and 5-ethynyl-2'- deoxyuridine (EdU) method was used to detect the effect of IGF2 on KGN cell proliferation, and enzyme linked immunosorbent assay was used to detect the contents of estrogen and progesterone in cell culture supernatant. The expressions of insulin like growth factor 1 receptor (IGF1R), protein kinase B (Akt), phosphorylated protein kinase B(p-Akt) and CYP19A1 protein in each group were detected by Western blotting. Results With the concentration gradient of IGF2, the proliferation rate of KGN cells and the secretion of estrogen and progesterone gradually increased. The cell proliferation rate and hormone level in the group treated with lOOfig/L IGF2 were the highest (P<0.01), while the PI3K/Akt signaling pathway was inhibited, and the cell proliferation rate and hormone secretion decreased significantly (P<0.01). The protein expression levels of IGF1R, p-Akt and CYP19A1 in different concentration groups increased significantly (P<0.05). While the expression of the above proteins were affected by intervened the PI3K/Akt signaling pathway. Compared with the control group, the protein expression of IGF1R and p-Akt increased significantly in IGF2 group and IGF2 +LY294002 group(P<0.01), CYP19A1 increased significantly in IGF2 group(P<0.01), the protein expression of p-Akt and CYP19A1 decreased significantly in LY294002 group (P<0.05), there was no significant difference in the protein expression of IGF 1R. Compared with the IGF2 group, the protein expression of p-Akt and CYP19A1 decreased in IGF2 +LY294002 group (P<0.01), there was no statistically significant difference in the protein expression of IGF1R, and the expression levels of IGF1R, p-Akt and CYP19A1 were significantly reduced in LY294002 group (P<0.01). Conclusion IGF2 may promote the proliferation and secretion of human ovarian granulosa cells through the PI3K/Akt signaling pathway mediated by IGF1R.

Calcium signal transduction in mitochondria in hypoxic pulmonary hypertension / 中国药理学通报

Hypoxic pulmonary hypertension (HPH) is characterized by hypoxic pulmonary vasoconstriction (H P V) and hypoxic pulmonary vascular remodeling(HPVR). Previous studies have shown that intracellular Ca

Research progress in lipid-drug conjugates / 药学学报

The technology of lipid-drug conjugates is developed on the basis of prodrug principle, which overcomes some drawbacks of drugs via increasing the lipophilicity of hydrophilic or poorly soluble drugs to promote the absorption of drugs and enhance the curative effect. This article sums up the research progress of lipid-drug conjugates from the chemical synthesis methods of conjugates, the types of conjugates, the influence on biological activity of drugs, the application in nanoparticles for drug delivery and the mechanism of absorption and degradation.

Changes in Cold and Hot Syndrome and Gastrointestinal Bacterial Community Structure in Mice by Intervention with Food of Different Nature / 中国结合医学杂志

OBJECTIVE@#To reveal the effect of foods with different natures on cold or hot syndrome and gastrointestinal bacterial community structure in mice.@*METHODS@#Forty-five 6-week-old male ICR Kunming mice of clean grade were divided into 5 groups, 9 per group, including the control (CK), hot nature herbs (HM), Hong Qu glutinous rice wine (RW), tea rice wine (TW), and cold nature herbs (CM) groups. Distilled water or corresponding herbs were administered to mice (0.01 mL/g body weight) in the 5 groups by gastric infusion respectively, once daily for 28 d. Appearance, behavior, and serum biochemical indicators, including 5-hydroxytryptamine (5-HT), thyroid stimulating hormone (TSH), noradrenaline (NE), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), the hot nature index, as well as the gastrointestinal bacterial community structure were analyzed in all groups after treatment.@*RESULTS@#After supplementation for 28 d, CM and TW mice showed different degrees of cold syndrome, and HM and RW mice showed different degrees of hot syndrome. Compared with the HM and RW mice, the TSH, NE, cAMP levels and hot nature indices in the CM and TW mice were significantly decreased and 5-HT and cGMP levels were significantly increased (P<0.05). There was no obvious change in appearance or behavior in CK mice. Results of clustering analysis showed that the gastrointestinal bacterial community structures were highly similar in TW and CM mice as well as in RW and HM mice, and that they were from the same branch, respectively, when the distance was 0.02. The key microbes associated with cold syndrome were Lachnospiraceae uncultured, Lactococcus, etc., and the key microbes associated with hot syndrome were S24-7 norank, Ruminococcaceae uncultured, etc. CONCLUSION: The interventions with different nature foods could change cold or hot syndrome in mice, leading to changes in gastrointestinal bacterial community structure.

Effect of Total Alkaloids from Nandina domfestica in Attenuating Arsenic Trioxide and Its LC-MS / 中国实验方剂学杂志

Objective::To study the effect of total alkaloids of Nandina domestica in attenuating arsenic trioxide, and analyze chemical constituents of alkaloids extract of Nandina, in order to provide the theoretical basis for studying the effect of N. domestica in attenuating arsenic trioxide with alkaloids extract of N. domestica as effective fraction. Method::The model of acute liver injury induced by arsenic trioxide was used to compare the effects on heart and liver functions of mice between arsenic trioxide alone and total alkaloids of N. domestica combined with arsenic trioxide. The detoxification of total alkaloids on arsenic trioxide was evaluated based on biochemical parameters and pathological report. Peakview (Version1.2, AB SCIEX) software was used to process the mass spectrometry data of total alkaloids of N. domestica. The structures of determined compounds were identified by molecular weight of compound (molecular formula), secondary fragments, chromatographic peak retention and literature information. Result::Among biochemical indicators, creatine kinase(CK), lactate dehydrogenase(LDH), blood urea nitrogen(BUN), malondialdehyde(MDA), alanine aminotransferase(ALT) and amino transferase of aspartate(AST) of the arsenic trioxide group were increased, while elimination rates of Na+ -K+ -adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and serum creatinine(SCr) were decreased, compared with those of the combination group. CK and LDH of the alkaloids extract group were more obviously increased than those of the N. domestica extract group, but with no remarkable difference. In histomorphometric examination, edema of mouse heart cells was improved, and some kidney and liver damages in rats were alleviated. Totally 25 alkaloids of alkaloid extract were identified. Among them, 18 were known, and 7 were unknown, including 3 structural types, in which apomorphine alkaloids were mostly. Conclusion::Heart, kidney and liver damage degrees of the combination group were significantly alleviated compared with the arsenic trioxide group. The total alkaloids fraction extracted and purified have a significant attenuation in arsenic trioxide toxicity. The detoxification of total alkaloids extract was equal to that of N. domestica extract. Furthermore, apomorphine alkaloids, such as nantenine and domesticine, can be used as index components to establish a quality control method for total alkaloids.

Epidemiological Features of Lung Cancer Mortality between 1990 and 2016 in Xuanwei City,Yunnan Province / 中国医学科学院学报

Objective To describe the trend of lung cancer mortality in Xuanwei City,Yunnan Province,from 1990 to 2016 and provide scientific evidence for the prevention and control of lung cancer in Xuanwei.Methods Mortality data from the 2nd(year 1990-1992)and 3rd(year 2004-2005)Retrospective Survey on Causes of Death,and the Routine Death Registration System(year 2011-2013 and 2014-2016)in Xuanwei were used in this study.We calibrated the missing report of the mortality data for the corresponding periods,calculated the crude mortality rates,standardized mortality rates and corresponding 95% of different types of lung cancers in the above four periods.Results The crude mortality rates of all lung cancers in Xuanwei for these four periods(1990-1992,2004-2005,2011-2013,and 2014-2016)were 34.0/100 000,89.8/100 000,102.3/100 000 and 87.2/100 000 respectively.The standardized morality rate of lung cancer remain high in Xuanwei although it has been decreasing since 2004.Morality rates of lung cancer for most age groups showed decreasing trends.The decrease has been statistically significant in the ≤ 40 year group since 2014.Except for Longchang,the standardized mortality rates have decreased in all other townships with high lung cancer prevalence.Conclusions Although the mortality rate of lung cancer remains high in Xuanwei,it has shown a decreasing trend since 2004.The decrease in lung cancer mortality in populations younger than 40 years is statistically significant.

Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway / 中国实验方剂学杂志

Objective:Screen out the antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma base on system pharmacology with chemical constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma as study objects, in order to provide the theoretical basis for the development of antitumor and nontoxic activities of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. Method:The small molecule ligand library of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was built based on Traditional Chinese Medicine Systems Pharmacology(TCMSP), energy of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was matched with the key protein targets of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal pathway by molecular docking (SYBYL2.1, Tripos), the Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma-targets network model was established based on Cytoscape 3.5.1, and the physicochemical properties of the antitumor activity in Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma were predicted by using SwissADME and admetSAR. Result:There were 25 small molecule constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. Through the energy match, key antitumor constituents of Pinelliae Rhizoma were gondoic acid, 10,13-eicosadienoic, baicalin, 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid. Key antitumor constituents of Aconiti Lateralis Radix Praeparata were deltoin, sitosterol, neokadsuranic acid B, 11,14-eicosadienoic acid. Phosphatidylinositol 3-kinase (PI3Kα), phosphatase and tensin homolog deleted on chromosome ten (PTEN), phosphoinositide dependent protein kinase 1 (PDK1) were key antitumor targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. There were 8 key antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma, which had a low CYP450 inhibition and basically followed the Lipinski rule. Conclusion:Antitumor nontoxic constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma and key targets are screened out from the molecular level, which provides the new ideas for the effective use of nontoxic traditional Chinese medicine(TCM) and breaks the restrictions in using nontoxic TCM.