Abstract: Objective 　To clarify the similarities and differences between two models simulating estrogen deficiency by comparing cardiovascular indicators of Ovariectomized (OVX) and Old animals, and to provide evidence to study the myocardial protective mechanism of estrogen receptor G protein-coupled estrogen receptor 30 (GPR30) in selected animal models. Methods　OVX and Old animal models were established. Echocardiography, ELISA, Western blot, morphology, and transmission electron microscopy were used to compare the cardiac functions, estrogen level, estrogen receptor protein level in myocardial tissue, myocardial fibrosis, and mitochondrial changes in myocardial tissue. Results　The cardiac functions, estrogen level, and estrogen receptor protein level in the OVX group were dependent on time. Cardiac functions in the OVX-8W group were significantly lower than those in the control group, and the estrogen and estrogen receptor protein levels were decreased continuously. Cardiac functions in the Old model group were significantly lower than those in control and OVX groups, and the levels of estrogen and estrogen receptor protein were significantly lower than those in control and OVX-4W groups. In the Old model group, obvious myocardial fibrosis was observed, and myocardial cells were significantly enlarged. The heart-to-body ratio was significantly increased, and the mitochondrial structure in myocardial cells was swollen and deformed. Mitochondrial cristae were broken, and vacuolation was observed. Conclusions　Both OVX and Old animal models successfully simulate the decrease in the estrogen level. To study fibrosis related to myocardial infarction and heart failure, and conduct research related to mitochondria and other energy metabolism, it is recommended to choose the Old animal model. If the OVX model is selected, it is recommended that the experimental observation endpoint is more than 4 weeks after OVX. Studies on estrogen, blood pressure, obesity, ischemia and reperfusion should use the OVX model.

Abstract: Objective　To investigate pathological damage and functions after subchronic exposure to sodium fluoride (NaF) on the heart, liver, kidneys, and testes of male rats, and to explore the possible mechanism. 　 Methods Thirty-two Wistar male rats were randomly divided into control, and low, medium, and high dose groups with eight rats in each group. NaF at doses of 0, 12, 24, and 48 mg / kg body weight was applied by intragastric administration once a day at 6 days per week and for 16 weeks. The occurrence of dental fluorosis and body mass in each group of rats was recorded, and the organ coefficients of the heart, liver, kidneys, and testes of rats were calculated. Serum levels of SOD, CAT, GSH-Px, and MDA were measured by ELISA. Pathological changes of the heart, liver, kidneys, and testes were observed by HE staining. Biochemical method were used to determine the myocardial enzyme profile, liver functions, and kidney functions in rats, and analyze the sperm quality of rats. Results　Compared with rats in the control group, rats in low, medium, and high dose groups showed different degrees of fluorosis changes in maxillary and mandibular incisors, indicating successful modeling. The body weight of rats in the high dose group was lower than that in the other three groups (P<0. 05). The renal organ coefficient in low and high dose groups was higher than that in the control group (P<0. 05). Compared with that in the control group, CAT and GSH-Px activity was decreased in medium and high dose groups (P<0. 05). The serum level of MDA in in the high dose group was increased (P<0. 05). Compared with the findings in the control group, HE staining showed different degrees of pathological damage in the heart, liver, kidneys, and testes of low, medium, and high dose groups. Compared with those in the control group, LDH and CK-MB levels were increased in each dose group (P<0. 05). The serum levels of ALT and AST were increased in medium and high dose groups (P<0. 05), and the serum level of GGT was increased in the high dose group (P<0. 05). Serum levels of BUN and Scr were increased in low, medium, and high dose groups (P<0. 05). The sperm count of rats was decreased in low, medium, and high dose groups, and sperm motility and the sperm malformation rate were increased ( P< 0. 05). Conclusions 　Subchronic exposure to sodium fluoride damages multiple organs in rats, and the mechanism may be related to oxidative stress induction.

Abstract: Objective　To investigate whether rapamycin reduces deposition of p-tau protein induced by aluminum through mTOR inhibiton. Methods　The study employed four groups of 24 SD rats: control, low dose aluminum maltol(10 μmol/ kg Al(mal)3), medium dose aluminum maltol(20 μmol/ kg Al(mal)3 ), and high dose aluminum maltol(40 μmol/ kg Al(mal)3), groups. The Morris water maze (MWM) test was used to assess the learning and memory abilities of rats. p-tau, p-mTOR, and PSD95 in the hippocampus were detected by Western blot. PC12 cells were divided into control, aluminum treatment, aluminum+DMSO, aluminum+100 nmol rapamycin, aluminum+300 nmol rapamycin, and divided into Al-treated and Al+rapamycin groups, the MWM test was used to assess learning and memory abilities of rats. p-tau, p-mTOR, and PSD95 in the hippocampus were detected by Western blot. Results　The MWM test showed that the escape latency time of rats in the aluminum-treated group was longer than that in the control group, and that in medium and high dose aluminum mal groups was significantly longer than that in the control group ((35. 24±4. 78) and (25. 92±8. 80)vs (20. 32±6. 04), P<0. 001). The target quadrant residence time and crossing platform times of rats in Al exposure groups were decreased with the increase in the Al exposure dose (P<0. 05). Compared with the findings in the control group, in the aluminum-treated group, p-mTOR/ mTOR and p-tau/ tau levels in the hippocampus of rats were significantly increased (P<0. 05), and PSD95 was significantly decreased (P<0. 05). Compared with the findings in the group exposed to aluminum alone, in rapamycin treatment groups, p-mTOR/ mTOR and p-tau/ tau were decreased, especially in 300 and 500 nmol rapamycin groups, p-tau was restored to the normal level of the control group, and PSD95 was also increased significantly (P<0. 05). Compared with the findings in Al-treated groups, in Al+rapamycin group, learning and memory abilities of rats were improved, p-mTOR/ mTOR and p-tau/ tau in the hippocampus of rats were significantly decreased (P<0. 05), and PSD95 was significantly increased (P<0. 05). Conclusions　Activation of mTOR phosphorylation is involved in excessive deposition of p-tau protein induced by aluminum. Rapamycin inhibits p-tau deposition by inhibiting the phosphorylation activity of mTOR.

Abstract: Objective　To study the effect of tiaoyuansan on autistic rat behavior as well as proinflammatory factors and GABA in brain tissue and its therapeutic effect. Methods　Forty VPA-induced autistic rats were divided into a model control group and three dosage groups of tiaoyuansan (2. 5, 5 and 10 g/ kg). Ten normal rats were used as the normal control group. Tiaoyuansan at various concentrations or water were administered orally to the corresponding groups once a day for 30 days. The open field test and the three chamber social test were performed. The cerebral cortex and hippocampus were collected to determine the contents of GABA, IL-1β and IL-6. Results　Compared with the findings in the normal control group, in the model control group, the percentage of distance and time in the central area were decreased(P=0. 026, P= 0. 044) and the percentage of distance and time in the perimeter area were increased (P= 0. 026, P=0. 044) in the open field test, the times of searching for unfamiliar rats were decreased (phase II: P=0. 011, phase III: P=0. 041) in the three chamber social test, GABA in the cerebral cortex was increased (P=0. 002), and IL-1β and IL-6 in the hippocampus were increased (P=0. 011, P=0. 003). Compared with the findings in the model control group, in the high dosage group, the percentage of distance and time in the central area were increased (P=0. 007, P=0. 021) and the percentage of distance and time in the perimeter area were decreased (P= 0. 007, P= 0. 021) in the open field test, the times of searching for unfamiliar rats were increased (phase II: P=0. 032, phase III: P=0. 000) in three chamber social test, GABA in the cerebral cortex was decreased (P=0. 006), and IL-1β and IL-6 in the hippocampus were decreased (P=0. 001, P=0. 002). Conclusions　Tiaoyuansan reduces stereotypical behavior and increases the social times of VPA-induced autistic rats. Therefore, it has certain therapeutic effect on autism.

Abstract: Objective　To investigate various ischemia times of myocardial ischemia-reperfusion injury (MI/ RI) in Chinese miniature swine and provide the basis to establish the optimal model of MI/ RI in Chinese miniature swine. Methods　Twenty-nine Chinese miniature swine were randomly divided into a sham group (n=6), 30 min ischemia group (n=7), 60 min ischemia group (n=7), and 90 min ischemia group (n=9). After pentobarbital sodium anesthesia, left coronary angiography was performed in each model group, and a balloon was exchanged into the middle of the left anterior descending branch through a wire. We elevated the ST segment on a body surface electrocardiogram and the numbers of ventricular fibrillations and defibrillations during the operation. Left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS) were recorded before the operation, before reperfusion, and at 1, 2 and 3 h of reperfusion. Serum levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured at the same time. The area of myocardial infarction was observed by double staining with TTC/ Evans blue. The non-reflowed area after reperfusion was observed by thioflavin S staining. Results Mortality was the highest in the 90 min ischemia group. The numbers of ventricular fibrillations and defibrillations were increased significantly with increasing ischemia time (P<0. 05, P<0. 01). Ejection fraction and fractional shortening were obviously lower after 90 min of ischemia and ay 3 h of reperfusion compared with those in the other groups (P<0. 05, P<0. 01). No significant differences were found in the electrocardiogram, areas of myocardial infarction and non-reflow, myocardial tissue staining, or serum levels of CK-MB, LDH, SOD, and MDA among model groups. Conclusions　A swine model of MI/ RI with 90 min of ischemia had strong arrhythmias and high mortality, whereas models established under ischemia for 30 min with reperfusion for 3 h replicated the characteristic lesions of clinical disease with low mortality and are suitable for studies of pathogenesis and drug actions.

Abstract: Objective 　To investigate the effect of methyltransferase-like 3 ( METTL3)-mediated N6 methyladenosine (m6A) modification on oxidized low-density lipoprotein (ox-LDL)-induced mouse monocyte-macrophage leukemic cell (RAW264. 7) pyroptosis. Methods　RAW264. 7 cells were treated with 50 μg/ mL ox-LDL for 24 h, and then METTL3 overexpression and knockdown experiments were conducted, and RNA m6A methylation levels were analyzed. Fluorescence quantitative PCR and Western blot were used to measure mRNA and protein expression levels of METTL3, NLRP3, NF-κB p65, GSDMD-N and Caspase-1. Lactate dehydrogenase (LDH) cytotoxicity was used to detect LDH release. Enzyme-linked immunosorbent assays (ELISA) to measure the levels of inflammatory cytokines IL-1β, IL-6, TNF-α, IL-10 and IL-18. Results　After ox-LDL stimulation, METTL3 expression and the RNA m6A methylation level were upregulated. Secreted IL-1β, IL-6, IL-18 and TNF-α were significantly increased, while IL-10 expression was decreased after ox-LDL stimulation of RAW264. 7 macrophages (P< 0. 05). On the basis of ox-LDL induction, after METTL3 overexpression, the RNA m6A methylation level was increased, mRNA and protein expression of NLRP3, NF-κB p65, GSDMD-N and Caspase-1 were significantly increased, the levels of proinflammatory cytokines IL-6, TNF-α, IL-1β and IL-18 were increased, the level of anti-inflammatory cytokine IL-10 was decreased, and LDH release was increased. METTL3 knockdown the showed the opposite trends. Conclusions 　METTL3-mediated m6A modification promotes ox-LDL-induced macrophage pyroptosis and inflammatory responses.

Abstract: Objective　To explore the effects of Gancao Xiexin decoction(GXD)on aquaporin(AQP)3 and AQP4 in rats with ulcerative colitis(UC). Methods　Thirty-two clean SD rats, eight SD rats were used as the blank group, the remaining 24 rats were used to replicate the UC model with 4% dextran sulfate sodium. After the model was successful, the rats were divided into model, Western medicine(slow-release mesalazine granules), and Chinese medicine(Gancao Xiexin decoction)groups, eight rats in each group and then gavaged continuously for 2 weeks once a day. Body mass, disease +activity index, colon length, colonic mucosa damage index, histopathological changes, histological damage index, serum tumor necrosis factor-α (TNF-α), interleukin-(IL)-1β, IL-6 and colonic AQP3 and AQP4 were assessed. Results Compared with the blank group, serum levels of TNF-α, IL-1β, and IL-6 in model and administration groups were increased(P<0. 05), colonic AQP3 and AQP4 levels in model and administration groups were decreased(P<0. 05), and colonic AQP3 mRNA levels in model and administration groups, and AQP4 mRNA levels in model and Western medicine groups were declined(P< 0. 05). There was no remarkable difference in mRNA expression of colonic AQP4 between Chinese medicine and blank groups(P>0. 05). Compared with the model group, serum levels of TNF-α, IL-1β, and IL-6 in Western and Chinese medicine groups were decreased(P<0. 05), serum levels of TNF-α, IL-1β and IL-6 in the Chinese medicine group were lower than those in the Western medicine group(P<0. 05), colonic AQP3 and AQP4 protein and mRNA levels in administration groups were increased(P<0. 05), the colonic AQP4 protein level in the Chinese medicine group was higher than that in the Western medicine group(P<0. 05), and colonic AQP3 and AQP4 mRNA levels in the Chinese medicine group were higher than those in the Western medicine group(P<0. 05). Conclusions　GXD effectively improves the body weight, disease activity index, colonic mucosa damage index, and histological damage index of UC rats, which may regulate serum TNF-α, IL-1β, and IL-6 levels by improving AQP3 and AQP4 protein and mRNA levels in the colon, which may be the mechanism of GXD in for UC treatment.

Abstract: Objective　An miR-100 knockout mouse model was established to preliminarily explore the effect of miR-100 gene deletion on the development of the mouse hematopoietic system. Methods　By putting EIIa-Cre^- ; miR-100^{fl/ fl} mice and EIIa-Cre⁺ ;miR-100^{+/ +} mice were bred to produce EIIa-Cre⁺ ; miR-100^{fl/ fl} (miR-100^{-/ -} ) mice, that is, miR-100 knockout mice. The genotype of mice was identified by PCR and q-PCR, and the knock-out efficiency of miR-100 gene in mouse bone marrow and spleen was verified. Peripheral blood, bone marrow, and spleen were isolated, and single-cell suspensions were prepared. The effect of gene deletion on the hematopoietic system of mice was analyzed by blood count, flow cytometry, and methylcellulose colony formation experiments. The relationship between miR-100 and Mospd2 was verified by q-PCR and RNA-binding protein immunoprecipitation (RIP). Results　The PCR and q-PCR result showed that miR-100-knockout mice were successfully constructed. The result of the blood count, flow cytometry, and methylcellulose blood cell colony formation experiments showed that the proportion of peripheral blood myeloid cells in miR-100 gene-deficient mice increased, but mouse bone marrow and spleen myeloid cells, T/ B lymphocyte, and the proportional and absolute cell counts of lymphocytes and erythrocytes were unchanged, and deleting miR-100 had no effect on the proportion or number of bone marrow hematopoietic stem progenitor cells or the ability of bone marrow mononuclear cells to form colonies. The q-PCR result showed that miR-100 deletion promoted the expression of Mospd2 in mouse bone marrow cells. RIP experiments showed that miR-100 binds to Mospd2 in the form of an AGO2 protein complex and thereby regulates the expression of Mospd2. Conclusions　A miR-100-knockout mouse model was successfully established in this study, and the gene deletion affected the proportion of peripheral blood myeloid cells, which verified the relationship between miR-100 and Mospd2. This study has provided further information on the role of this gene in the regulation of hematopoiesis in mice.

Abstract: Objective　To investigate the effects of trigonelline (TRG) on lipid metabolism and insulin resistance in gestational diabetes mellitus (GDM) rats. Methods 　Eight female Wistar rats were randomly selected for normal feeding, and the remaining rats were fed a high fat diet for 8 weeks. After cage mating to confirm pregnancy, normal fed rats were used as the control group, and the high fat fed rats were intraperitoneally injected with 35 mg/ kg streptozotocin to induce the GDM model. Model rats were randomly divided into model, TRG low-dose (15 mg/ (kg·d)), TRG high-dose(45 mg/ (kg·d)) and metformin hydrochloride (MH) (200 mg/ (kg·d)) groups with eight rats in each group. Control and model groups were treated with the same amount of normal saline by intragastric administration for 14 consecutive days. Weigh and the fasting blood glucose (FBG) were measured. BM and the contents of 24 h Alb, AST, ALT, BUN, and SCr, serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol(TC), and triglyceride (TG) were measured. Fasting insulin (FINS) content was measured in each group. Insulin resistance index (HOMA-IR) and insulin sensitivity index (HOMA-ISI) were calculated. Histopathological changes of the pancreas in rats were observed. Levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) in pancreatic tissues were measured. Results　The GDM rat model was successfully established. Compared with the findings in the control group, FBG, serum LDL-C, TC and TG, FINS, HOMA-IRI, MDA, and TNF-α and IL-6 levels in pancreatic tissue were increased, serum HDL-C content, HOMAISI, and SOD and CAT activities in pancreatic tissue were decreased in model, TRG low-dose, TRG high-dose, and MH groups (P<0. 05), and pathological changes of various degrees were found in pancreatic tissue. Compared with the findings in the model group, in TRG low-dose, TRG high-dose, and MH groups, FBG, serum LDL-C, TC and TG, FINS, HOMAIRI, MDA, and TNF-α and IL-6 levels in pancreatic tissue were decreased, serum HDL-C content, HOMA-ISI, and SOD and CAT activities in pancreatic tissue were increased ( P< 0. 05), and pathological injury of pancreatic tissue was gradually decreased. The effect of TRG in low-dose, high-dose, and MH groups was gradually enhanced (P<0. 05). Conclusions　Trigonelline reduces the blood glucose level, improves liver and kidney functions, and abnormal blood lipid metabolism, reduces insulin resistance and improves insulin sensitivity in GDM rats. Its effect may be related to reducing inflammation and oxidization.

Abstract: Objective 　To establish an improved method for chromosome aberration testing in mouse spermatogonia, obtain large amounts of constant and clear metaphase chromosomes for reading, and apply the improved method to assess the mutagenic effect of Maca. Methods　Thirty male ICR mice were randomly divided into six groups with five mice in each group. Seminiferous tubules were minced for spermatogonial cell enrichment. The fragments were treated with a 1. 5 mg/ mL collagenase solution (in serum-free culture medium at 35℃ for 15 minutes with intermittent agitation (3 minute intervals). After routine hypotonic treatment, fixation, and cell smearing, slides were observed under a microscope and compared with those prepared by the conventional method. Results 　A large number of well-dispersed metaphase phase spermatogonium with a clear background and compact chromosome structure were prepared and observed by our method, and the chromosome slides prepared by this method were easy to read. Compared with the result with the conventional method, the number of high magnification fields required for observation was significantly decreased (P<0. 01) and the mitotic index was obviously increased ( P< 0. 01 ). The chromosomal aberration rate of the cyclophosphamide-positive control group was significantly higher than that of the control group (P<0. 01). No significant differences were found in the chromosome aberration rate between the Maca groups of various dosages and the control group(P>0. 05). Conclusions　The enrichment efficiency of spermatogonial cells and the success rate of experiments were improved by the modified method, and this method was significantly better than conventional method. Maca had no effect on the chromosomes of mouse spermatogonial cells under the experimental conditions.

Abstract: Objective　To explore the therapeutic effect of Hypericum japonicum on the hyperuricemia rat model. Methods　Seventy-two SD rats were randomly divided into six groups: a blank group, model group, low, medium, and high dose groups of Hypericum japonicum, and a Febrista group. Except in the blank group, the hyperuricemia model was established by intraperitoneal injection of 250 mg/ (kg·d) potassium oxonate. The blank group was administered the same volume of normal saline as the control. After 4 weeks of continuous modeling, the Febrista group was treated at 0. 01 g/ (kg·d) administered by gavage, and the low, middle and high dose groups of Hypericum japonicum were treated at 0. 16, 0. 22, and 0. 27 g/ (kg·d) by gavage, respectively. Changes in general living conditions and the appearance of rats, serum biochemical indicators (UA, BUN, Cre, ALT, and AST) and serum proinflammatory factors (TNF-α, IL-17, and IL-18) were observed and compared. Changes in the renal pathology of rats were also observed and compared. Results Each dose of Hypericum japonicum improve a series of symptoms, such as a poor mental state and slow movement of rats. Hypericum japonicum also significantly reduced the serum levels of uric acid, creatinine, and urea nitrogen in the model group, and the improvement was dependent on dose. IL-17, IL-18 and TGF-α levels in medium and high dose groups of Hypericum japonicum were decreased significantly. Pathological observations also showed that Hypericum japonicum improved atrophy of the glomerulus and swelling of the renal tubular lumen, and renal interstitial fibrosis was significantly improved with only a small number of infiltrating inflammatory cells. The improvement of the renal status was dependent on dose. Conclusions　Hypericum japonicum reduces blood uric acid and may elicit protective and therapeutic effects in the kidney of hyperuricemia model rats by inhibiting inflammatory reactions.

Abstract: Objective　To investigate the role and underlying mechanism of circular RNA tousled-like kinase 1(circTLK1) in myocardial ischemia/ reperfusion injury (MIRI). Methods　Forty-eight C57BL/6 mice were divided into a sham operation group (Sham), MIRI group, sh-NC group, sh-circTLK1 group, sh-circTLK1+antagomir-NC group, and sh-circTLK1+antagomir-miR-26a-5p group with eight mice per group. The MIRI mouse model was established by ligation of the left anterior descending coronary artery. Left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic diameter, and end-systolic diameter were measured by echocardiography to assess cardiac functions. Serum levels of lactate dehydrogenase, cardiac troponin I and creatine kinase isoenzyme were measured by ELISA. Histopathological changes of myocardial tissue were assess by hematoxylin-eosin staining. Cardiomyocyte apoptosis was detected by TUNEL staining. mRNA and protein expression of circTLK1, miR-26a-5p, and YES1 in myocardial tissue were measured by real-time quantitative PCR and Western blot. An interaction between circTLK1/ YES1 and miR-26a-5p was verified by dual luciferase reporter assays and RNA-binding protein immunoprecipitation. Results　Compared with the findings in the Sham group, the ejection fraction, fractional shortening, and the level of myocardial tissue miR-26a-5p in the MIRI group were significantly decreased, the left ventricular end-diastolic diameter, end-systolic diameter, activities of serum lactate dehydrogenase and creatine kinase isoenzyme, the level of cardiac troponin I, myocardial cell apoptosis rate, and mRNA and protein levels of circTLK1 and YES1 in myocardial tissue were significantly increased (all P<0. 05). Moreover, cardiomyocytes were disordered, and inflammatory cell infiltration was observed among interstitial cells. circTLK1 knockdown significantly upregulated miR-26a-5p expression, inhibited YES1 expression, improved the changes in the above indicators (all P<0. 05), and reduced myocardial injury. Inhibition of miR-26a-5p significantly attenuated the protective effect of circTLK1 knockdown against MIRI by upregulating YES1 expression. Dual luciferase reporter assays and RNA-binding protein immunoprecipitation confirmed the direct interaction between circTLK1 and miR-26a-5p, and YES1 was a target of miR-26a-5p. Conclusions　Knockdown of circTLK1 may exert a protective effect against MIRI by regulating the miR-26a-5p / YES1 axis, and circTLK1 may be a potential therapeutic target for MIRI.

Abstract: Objective　Metformin(Met)is a commonly used hypoglycemic drug in clinical practice. Regulation of energy metabolism is one of the main mechanisms of its pharmacological action. In this study, we investigated the antidepressive effect of metformin on the basis of mitochondrial oxidative respiratory chain-related genes and explored the related mechanism of its antidepressive effect from the perspective of energy metabolism. Methods 　ICR mice were injected subcutaneously with corticosterone(20 mg/ kg)for 3 weeks to induce a mouse model of depression-like behaviors. One week after injection, metformin ( 200, 100 and 50 mg/ kg) was administered by gavage for 2 weeks. During administration, the preference rate of sucrose was measured. At the end of administration, an open field test was conducted, and the times and duration of mice traveling in the central area and the distance traveled in the peripheral area were recorded. qPCR and Western blot were used to detect the mRNA and protein expression of mitochondrial respiratory chain related genes NADH dehydrogenase ubiquinone (Nduf), mitochondrial ribosomal protein (Mrp), brain-derived neurotrophic factor(BDNF), cAMP response element-binding protein(CREB), and postsynaptic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR), and N-methyl-d-aspartic acid receptor(NMDAR) in the hippocampus. The effects of metformin(administration for 1 week)on normal mice were also observed. Results　Metformin did not affect the weight of normal or model mice. The sucrose preference rate was enhanced after metformin administration in normal and model mice. In the open field test, metformin increased the number of entrances to the central area in normal and model mice, and increased the distance traveled in the peripheral area in model mice. Additionally, metformin upregulated the mRNA expression of most Nduf subtypes(except for Ndufa8 and Ndufa13)and Mrp, the mRNA expression of Creb, Ampar, Nmdar and protein expression of BDNF, CREB, AMPAR, NMDAR in the hippocampus of normal mice, while antagonizing downregulation of Bdnf, Creb mRNA expression and BDNF, CREB protein expression in model mice. Conclusions　Metformin improves depression-like behavior induced by corticosterone in mice. Its mechanism is related to regulating the expression of genes and proteins related to the mitochondrial oxidative respiratory chain and neural plasticity in the hippocampus.

Abstract: Objective 　To observe the effect of Euphorbia humifusa on expression of nephrin, desmin, and Angptl4 in glomerular podocytes of diabetic kidney disease (DKD) rats, and to clarify the mechanism of its action in DKD treatment. Methods　Eight-week-old male SD rats were randomly divided into normal (N), DKD group (D) and DKD treated with Euphorbia humifusa (E) groups. Rats in D and E groups were treated by a single tail vein injection of 55 mg/kg streptozotocin to induce the DKD model. Rats in the N group were injected with the same volume of citrate buffer. The DKD model was evaluated by 24 h urinary albumin of >5 mg/ d for 3 consecutive detection. After 5 weeks, the DKD model was established in 10 D group rats and nine E group rats. After successfully establishing the DKD model, the E group was administered 300 mg/ (kg·d) Euphorbia humifusa by gavage, and rats in D and N groups were administered the same volume of double distilled water by intragastric administration for 16 weeks. All rats were weighed before death, urine was collected to measure 24 h urinary albumin, and blood was collected for serum albumin, urea nitrogen, creatinine, cholesterol, and albumin measurements. Hematoxylin-eosin and Masson trichromatic staining were used to observe the nephrotic structure. Podocyte morphology was observed by transmission electron microscopy. Podocytes were labeled by WT1 staining and counted by the dissector/ fractionator method. Protein localization of nephrin, desmin, Angptl4, and WT1 was observed by immunohistochemistry. Western blot was used to measure the protein expression levels of nephrin, desmin, Angptl4, and collagen IV. Nephrin, desmin, Angptl4, and collagen IV mRNA expression was measured by qPCR. Results　Compared with the findings in the N group, in the D group, blood glucose, 24-hour urine albumin, urea nitrogen, creatinine, and cholesterol were significantly increased, while albumin was significantly decreased. All indexes in the E group were significantly improved compared with those in the D group (P<0. 05). Hematoxylin-eosin and Masson staining showed that the glomerular structure of rats in the N group was complete without obvious mesangial hyperplasia. In the D group, mesangial hyperplasia and mesangial matrix deposition were observed. In E the group, these conditions were improved by intragastric treatment with Euphorbia humifusa. Transmission electron microscopy showed that glomerular podocytes of the N group were normal, podocytes of the D group were fused or disappeared, and podocytes of the E group were intact. WT1 staining showed that the number of podocytes in the D group was lower than that in the N group, and the podocytes number in the E group was significantly higher than that in the D group (P<0. 05). Immunohistochemistry, western blotting, and qPCR showed that protein and mRNA expression of desmin, Angptl4, and collagen IV in the N group were lower than those in the D group, while protein and mRNA expression of desmin and Angptl4 in the E group were significantly lower than those in the D group (P<0. 05). Nephrin protein and mRNA expression in the D group was significantly lower than that in the N group, and nephrin protein and mRNA expression in the E group was higher than that in the D group (P<0. 05). Conclusions　Euphorbia humifusa treatment significantly reduces the expression of desmin, Angptl4, and collagen IV, and increases the expression of nephrin in DKD rat podocytes. Euphorbia humifusa effectively protected the mechanical and charge barrier of podocytes, inhibits transdifferentiation of podocytes, reduces proteinuria, and improves renal functions.

Abstract: Objective　To evaluate the therapeutic potential of nerve growth factor (NGF) with penetratin on moderate traumatic brain injury (TBI). Methods　The effect of various cell-penetrating peptides combined with NGF on membrane penetration was analyzed by fluorescence immunocytochemistry in cells in vitro, and the optimal molar ratio was selected. Subsequently, rotarod performance and Morris water maze tests were performed to analyze behavioral changes of the moderate TBI mouse model in each group after administration, including coordinative motor ability and the spatial memory function. GFAP and NeuN protein expression was observed by immunohistochemistry. Results 　Fluorescence immunocytochemistry showed that the content of NGF protein in cells of the NGF/ penetratin group was significantly higher than that in the other groups, and the fluorescence intensity was the highest at a molar ratio of 20 ∶ 1 (penetratin:NGF). Behavioral test showed that the coordination motor function and spatial memory ability of mice in the NGF/ penetratin group were significantly better than those in TBI and NGF groups. Additionally, NeuN protein expression in brain tissue of mice in the NGF/ penetratin group were also significantly higher than that in TBI and NGF groups, while GFAP protein expression in brain tissue was significantly lower than that in the two groups (P<0. 05). Conclusions　Penetratin as a drug delivery carrier promotes NGF to cross the blood-brain barrier and enter damaged brain tissue, which has a good therapeutic effect on moderate TBI mice.

Abstract:Raising the microbial level of experimental mice by mouse rederivation has become essential in experimental animal research institutions, and it is an important technical method to guarantee the life quality of experimental mice. The current international mouse rederivation protocol is in vitro fertilization and embryo transplantation technology. The technology platform of mouse rederivation is comprehensive, covering various functional areas including a dirty mouse feeding room, mouse embryo operation room, surrogate mouse feeding room, and purified mouse feeding room. Considering the technology platform of mouse rederivation in the Animal Center of Zhejiang University as an example, the design strategies and operation mode were analyzed, and maintenance of the technology platform is discussed from the aspects of mouse microbial quality control, environmental sanitation control, and instrument and equipment maintenance to provide references for construction of the same type of technology platform.

Abstract:Diabetes is a chronic disease with glucose metabolism disorder. Long term hyperglycemia leads to chronic damage of the kidneys, heart, blood vessels, nerves, and other organs. Sodium/ glucose cotransporter 2 (SGLT2) inhibitors are a new type of hypoglycemic drug that reduces the blood glucose level by a new mechanism independent of insulin secretion. Such drugs reduce the renal glucose threshold by inhibiting SGLT2, which is responsible for reabsorption of glucose in urine in the renal tubules of the kidney, and expelling excess glucose, thereby reducing the glucose level in blood circulation. Additionally, SGLT2 inhibitors not only treat diabetes, but can also be used to treat cardiovascular, renal, hypertension, and other diseases caused by diabetes. This article reviews the role and mechanism of SGLT2 inhibitors in diabetes and its complications.

Abstract:Metabolic syndrome (MS) is a group of metabolic disorders that directly increases the risk of obesity, type 2 diabetes mellitus, and cardiovascular disease. The incidence of MS is rising worldwide, the mortality and economic burden of which are increasing each year. miRNAs play a crucial role in various biological processes by regulating gene expression through transcriptional mechanisms, and alterations of gene expression are associated with glucose and lipid metabolic disorders. Therefore, we selected certain MS-related miRNAs and summarized the roles and possible mechanisms of miRNAs in the regulation of MS components to facilitate understanding the mechanism underlying the MS development, explored the potential of miRNAs as MS biomarkers, and provide new ideas for MS treatment.

Abstract:Perimenopausal syndrome is a series of autonomic nervous system dysfunctions caused by decreased levels of steroid hormones such as estrogen and progesterone, which is accompanied by neuropsychological symptoms of a group of syndromes NS seriously affecting women’s physical and mental health as well as quality of life. Establishing a cell model in vitro is an effective method to study PMS. Analyzing and studying a cell model of this disease may provide treatment guidance. In this review, the related literature involving the application of cell models of PMS in recent years in PubMed, Embase and Web of Science databases were searched, and the establishment method, evaluation indicators, and model characteristics of cell models for PMS are summarized and systematically analyzed. The research progress of cell models of PMS was reviewed to provide a reference and ideas for the reasonable establishment and in-depth study of cell models for PMS.

Abstract:Cirrhosis is caused by an imbalance of hyperplasia and extracellular matrix decomposition in the liver for various reasons, and it is a major link between various liver diseases to the development of cirrhosis. The process of liver fibrosis is reversible. Liver injury leads to activation of hepatic stellate cells to form muscle fibrocytes, excessive extracellular matrix deposition in the liver, and then liver fibrosis. Its consequences often lead to irreversible cirrhosis and even liver cancer. The specific pathogenesis and molecular signal transduction mechanism of liver fibrosis are unclear. Therefore, it is important to explore the pathogenesis of hepatic fibrosis and investigate anti-fibrotic target drugs. To this end, this article reviews the pathogenesis of liver fibrosis and the related signal transduction studies.