Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

Establishment of a machine learning model for the diagnosis of clinically significant prostate cancer based on transrectal contrast-enhanced ultrasound parameters and clinical data / 中华超声影像学杂志

Objective:To establish a machine learning model for the diagnosis of clinically significant prostate cancer based on transrectal contrast-enhanced ultrasound parameters and clinically relevant data.Methods:A retrospective analysis was performed on 151 patients in Chongqing University Cancer Hospital who underwent transrectal contrast-enhanced ultrasonography and transrectal ultrasound-guided needle biopsy from November 2018 to September 2021. The time intensity curve was drawn using VueBox software and 12 parameters such as rise time, peak time, average transit time, peak intensity, and rising slope were quantitatively analyzed. Age, total prostate-specific antigen, free prostate-specific antigen, free prostate-specific antigen ratio, volume, prostate-specific antigen density, and transrectal contrast-enhanced ultrasonography parameters, a total of 18 characteristic parameters, were analyzed and screened through relevant attribute values and information gain attribute values. The screening features were trained and tested by the machine learning single algorithm and integrated algorithm, and then the model was evaluated by the F1 value and the area under the ROC curve(AUC).Results:Using the related attribute value and the information gain attribute value, 12 variables and 5 variables were screened out respectively to establish a machine learning model. The model established by the ensemble algorithm was better than the single algorithm. For the two variable selection methods, the AUC (0.810 vs 0.789) and F1 values (0.748 vs 0.742) of the Bagging ensemble algorithm model, which basic algorithm was decision tree, were the highest, followed by Logistic regression and support vector machine(SVM) in order of AUC and F1 values.Conclusions:Based on transrectal contrast-enhanced ultrasound parameters and clinical data, the Bagging ensemble model based on decision tree has the best performance in diagnosing clinically significant prostate cancer.

Effect of Jingui Shenqiwan on Diabetic Osteoporosis in Mice via AGEs/RANKL/NF-κB Pathway Based on Theory of "Kidneys Governing Bones" / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis （DOP） in mice by regulating the advanced glycation end products （AGEs）/receptor activator of nuclear factor-κB ligand （RANKL）/nuclear factor-κB （NF-κB） signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific， dominant negative insulin-like growth factor-1 receptor （MKR） mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group， low- and high-dose Jingui Shenqiwan group （1.3， 2.6 g·kg-1）， and an alendronate sodium group （0.01 g·kg-1）， with 10 mice in each group. Additionally， 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period， fasting blood glucose （FBG） measurement and oral glucose tolerance test （OGTT） were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs， phosphorylated NF-κB （p-NF-κB）， and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway， osteoprotegerin （OPG）， and Runt-related transcription factor 2 （RUNX2） proteins in femoral bone tissues. ResultCompared with the normal group， mice in the model group exhibited significantly increased FBG （P<0.01）， trabecular bone degeneration， abnormal bone morphological parameters， significantly increased area under the curve （AUC） of OGTT （P<0.01）， enlarged kidney volume， significantly increased kidney function indicators and kidney index （P<0.01）， disrupted renal glomeruli and renal tubule structures， significantly increased expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues （P<0.05）， and significantly decreased expression of OPG and RUNX2 in femoral bone tissues （P<0.01）. Compared with the model group， mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC （P<0.01）. Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore， the expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues was significantly reduced （P<0.05， P<0.01）， and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased （P<0.05， P<0.01）. ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions， thereby alleviating the symptoms of DOP in mice， demonstrating a therapeutic effect on DOP from the perspective of the kidney.

Effects and mechanisms of ferroptosis on high glucose-induced retinal pigment epithelial cells injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effects and mechanisms of ferroptosis on high glucose(HG)-induced retinal pigment epithelium(RPE)cells injury, and to provide new ideas for the treatment of diabetic retinopathy(DR).METHODS: The ARPE-19 cell lines cultured in vitro were divided into normal control group(NC group), high glucose group(HG group), and high glucose+Ferrostatin-1 group(Fer-1 group). The cell viability of each group was detected by CCK-8 assay. The expressions of interleukin 6(IL-6), IL-1β and monocyte chemotactic protein-1(MCP-1)were detected using ELISA kits. The levels of malondialdehyde(MDA), glutathione(GSH), glutathione peroxidase 4(GPX4)and iron content were detected using the corresponding assay kits. The mitochondrial changes in ARPE-19 cells were observed by transmission electron microscopy. The expressions of ferroptosis-related proteins including long-chain lipoyl CoA synthase 4(ACSL4)and GPX4, as well as vascular endothelial growth factor(VEGF)were detected by Western blotting and immunofluorescence staining.RESULTS: Compared with NC group, the cell viability of HG group decreased significantly, the expression levels of inflammatory factors in cell supernatant increased, the contents of MDA and iron significantly increased, GSH and GPX4 significantly decreased(all P&#x003C;0.01), the mitochondria of ARPE-19 cells shrunk, the expression of proteins ACSL4 and VEGF increased, while the expression of GPX4 decreased(all P&#x003C;0.01). Compared with HG group, the cell viability of Fer-1 group significantly increased, the expression levels of inflammatory factors in cell supernatant decreased, MDA and iron contents significantly decreased, GSH contents and GPX4 viability significantly increased(all P&#x003C;0.05), the morphology of mitochondria in ARPE-19 cells improved, the expression of ACSL4 and VEGF decreased, while the expression of GPX4 increased(all P&#x003C;0.05).CONCLUSION: Ferroptosis is involved in the injury of RPE induced by HG. Inhibiting ferroptosis can improve cell viability, reduce inflammation and oxidative stress, and alleviate HG-induced RPE cells injury.

Animal Modeling of Diabetic Nephropathy：A Study Based on Literature / 中国实验方剂学杂志

ObjectiveTo summarize the modeling elements， evaluation indicators， characteristics， and drawbacks of the animal models of diabetic nephropathy， and thus provide guidance for the standardized modeling and rational application of these models. MethodThe articles about the animal experiments of diabetic nephropathy published in the last decade were retrieved from China National Knowledge Infrastructure， Wanfang Data， and PubMed. The data of animal species， sex， modeling techniques， modeling criteria， and evaluation indicators were analyzed in Excel. ResultA total of 287 publications were included in this study. Male SD rats were mainly used for the modeling of diabetic nephropathy. The animal models of type 1 diabetes were mainly established by intraperitoneal injection of streptozotocin （STZ） at 60-69 mg·kg-1 once or 50 mg·kg-1 for 5 continuous days， and those of type 2 diabetes by intraperitoneal injection of STZ at 30-39 mg·kg-1 once or 30 mg·kg-1 for 2 continuous days combined with 4 weeks of high-fat and high-sugar diet. Blood glucose and 24-hour urine protein were mainly used to determine whether the modeling was successful. The evaluation indicators of the animal models mainly included basic indicators， glucose and lipid metabolism indicators， and renal function indicators. ConclusionAnimal models are commonly used in the research on diabetic nephropathy， while there is no unified standards for the preparation or evaluation of the animal models. Moreover， Chinese medicine is rarely considered in the modeling. Through literature review and data analysis， this paper summarizes the modeling elements and standards， key evaluation indicators， characteristics， and shortcomings， aiming to build the animal models of diabetic nephropathy with a high success rate and with the characteristics in line with the clinical pathogenesis and syndromes.

Application of ZHANG Zhongjing，s Jizihuang （Egg Yolk） Prescriptions in Type 2 Diabetes Mellitus based on the Theory of “Yin Restricts Fire” and “Many Different Diseases can be Treated in the Same Way” / 中医杂志

Type 2 diabetes mellitus （T2DM） can be categorized into “xiao ke （消渴）” in traditional Chinese medicine （TCM）. The theory of “yin restricts fire” originates from Inner Canon of Yellow Emperor （《黄帝内经》） which states that “yin essence restricts chief fire”， and the crucial pathogenesis and treatment of xiao ke coincide with this theory. ZHANG Zhongjing，s three prescriptions of Jizizhuang （egg yolk） are Baihe Jizizi Decoction （百合鸡子汤）， Huanglian Ejiao Decoction （黄连阿胶汤） and Painong Powder （排脓散）， which are scattered in different chapters of Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）. By analyzing and summarizing the mechanism and characteristics of the three prescriptions， it is found that the three prescriptions are in line with the characteristics of “yin restricts fire” and the pathogenesis of T2DM. These three prescriptions are composed of Jizizhuang and different medicinals. Baihe Jizizi Decoction is composed of Jizizhuang and Baihe （Bulbus Lilii）， and can be used to treat T2DM and mental diseases. Huanglian Ejiao Decoction is composed of Jizihuang， Ejiao （Colla Corii Asini）， Shaoyao （Radix Paeoniae Alba seu Rubra）， Huanglian （Rhizoma Coptidis） and Huangqin （Radix Scutellariae）， which could be used to treat T2DM and cardiorenal system diseases. Painong Powder is composed of Jizizhuang， Shaoyao， Jiegeng （Radix Platycodonis） and Zhishi （Fructus Aurantii Immaturus）， which can be used to treat T2DM and carbuncle. Therefore， based on the theory of “yin restricts fire” and “many different diseases can be treated in the same wa”， this paper propose that the three Jizihuang prescriptions could be used in T2DM， which could provide ideas for clinical treatment.

Zuogui Jiangtang Qinggan Formula improves glucolipid metabolism in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating FoxO1/MTP/APOB signaling pathway / 中国中药杂志

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.

Influence of nonylphenol on cytoactive and the expression of G protein-coupled estrogen receptor in human colon cancer SW480 cells / 中华消化外科杂志

Objective:To investigate the influence of nonylphenol (NP) on cytoactive and the expression of G protein-coupled estrogen receptor 30 (GPR30) in human colon cancer SW480 cells.Methods:The experimental study was conducted. The human colon cancer SW480 cells were cultured in vitro. The influence of NP on proliferation, cell cycle, apoptosis and the expression of GPR30 in human colon cancer SW480 cells were analyzed by cell proliferation, cell cycle detection, cell apoptosis and gene expression and protein expression experiments. Cell grouping: SW480 cells cultured with medium were set as the control group, cultured with medium+1×10 ?8 mol/L estradiol were set as the estradiol group, cultured with medium+1×10 ?8 mol/L NP were set as the NP group, cultured with medium+1×10 ?8 mol/L NP+1×10 ?7 mol/L GPR30 specific antagonist G15 were set as the NP+G15 group, respectively. Observation indicators: (1) proliferation index of human colon cancer SW480 cells in the 4 groups; (2) cycle proportion of human colon cancer SW480 cells in the 4 groups; (3) apoptosis index of human colon cancer SW480 cells in the 4 groups; (4) GPR30 messenger RNA(mRNA) expression of human colon cancer SW480 cells in the 4 groups; (5) GPR30 protein expression of human colon cancer SW480 cells in the 4 groups. Measurement data with normal distribution were represented as Mean± SD and one way ANOVA was used for comparison between groups. The least significant difference method was used to test the pairwise comparison. Results:(1) Proliferation index of human colon cancer SW480 cells in the 4 groups. Results of the cell proliferation experiments showed that the proliferation indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 100.00±0.00, 89.19±4.86, 148.96±6.04 and 120.40±3.39, respectively, showing a significant difference among the 4 groups ( F=21.45, P<0.05). There was a significant difference between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the estradiol group, between the control group and the NP+G15 group ( P>0.05). (2) Cycle proportion of human colon cancer SW480 cells in the 4 groups. Results of the cell cycle detection experiments showed that the proportions of human colon cancer SW480 cells in the S phase of the cell cycles in the control group, the estradiol group, the NP group and the NP+G15 group were 39.96%±2.02%, 36.67%±0.62%, 43.85%±1.02% and 38.29%±1.42%, respectively, showing a significant difference among the 4 groups ( F=10.08, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (3) Apoptosis index of human colon cancer SW480 cells in the 4 groups. Results of the cell apoptosis experiments showed that the apoptosis indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 1.67±0.18, 4.80±0.31, 0.75±0.11 and 2.20±0.19, respectively, showing a significant difference among the 4 groups ( F=136.79, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (4) GPR30 mRNA expression of human colon cancer SW480 cells in the 4 groups. Results of quantitative real-time polymerase chain reaction detection showed that the relative expression rates of GPR30 mRNA in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.00±0.00, 0.86±0.05, 1.89±0.27 and 0.64±0.12, respectively, showing a significant difference among the 4 groups ( F=26.61, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). (5) GPR30 protein expression human colon cancer SW480 cells in the 4 groups. Results of Western blot detection showed that the relative expression rates of GPR30 protein in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.83±0.16, 1.68±0.15, 3.10±0.30 and 1.26±0.11, respectively, showing a significant difference among the 4 groups ( F=34.05, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). Conclusion:Low dose of NP can increase the proliferation index and the proportion of cells in the S phase of the cell cycles, decrease the apoptosis index, and promote the mRNA and protein expression of GPR30 in human colon cancer SW480 cells.

Effects of mangiferin on obesity complicated with type 2 diabetes in MKR mice / 中国药理学通报

Aim To investigate the mechanism of the effect of mangiferin on obesity complicated with type 2 diabetes mellitus in MKR transgenic mice. Methods MKR mice were randomly divided into model group,metformin group(0.11 g·kg-1),mangiferin low-dose group(25 mg·kg-1),mangiferin medium-dose group(50 mg·kg-1),and mangiferin high-dose group(100 mg·kg-1); FVB/N mice of the same age were used as control group. The mice were given intragastric administration for five weeks,the body weight and fasting glucose of mice were measured every week,the oral glucose tolerance(OGTT)was detected on 30th day of administration,and the insulin tolerance(ITT)was detected on 33rd day,and serum metabolic indexes were detected after administration. HE staining,oil-red O staining and Masson staining were used to observe the changes of liver morphology in mice. HE staining was used to observe the changes of fat morphology in mice. Western blot was used to detect the protein expression changes of TNF-α,IL-6,IL-1β in adipose tissues. Results High-dose mangiferin significantly reduced body weight,decreased fasting blood glucose,increased insulin content,and improved OGTT and ITT; it decreased serum triglyceride,alanine aminotransferase and aspartate aminotransferase levels; it also decreased the expression of serum IL-6 and TNF-α; it significantly reduced the expression of inflammatory factors in adipose tissues. Conclusions Mangiferin has therapeutic effects on obese MKR mice with type 2 diabetes,which is related to reducing the inflammatory response in adipose tissues.

Down-regulation of SIK2 expression alleviates myocardial ischemia-reperfusion injury in rats by inhibiting autophagy through the mTOR-ULK1 signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the role of salt-inducible kinase 2 (SIK2) in myocardial ischemia-reperfusion (IR) injury in rats.@*METHODS@#Fifteen male SD rats were randomized equally into sham operation group, myocardial IR model group, and SIK2 inhibitor group (in which the rats were treated with intravenous injection of 10 mg/kg bosutinib via the left femoral vein 24 h before modeling). Ultrasound was used to detect the cardiac function of the rats, and myocardial pathologies were observed with HE staining. Transmission electron microscopy was used to observe autophagy of myocardial cells, and Western blotting was performed to detect the contents of the autophagy-related proteins SIK2, LC3B, Beclin-1, p62 and the expressions of p-mTOR, mTOR, p-ULK1, and ULK1 in myocardial tissue.@*RESULTS@#Myocardial IR injury significantly increased the number of autophagosomes (P < 0.05) and the expression of SIK2 protein (P < 0.01) in the myocardial tissues. Treatment with bosutinib before modeling obviously lowered the expression of SIK2 protein (P < 0.01), alleviated myocardial pathologies, and reduced the number of autophagosomes (P < 0.05) in the myocardial tissue. The rats with myocardial IR injury showed obviously lowered LVEF and FS values (P < 0.001), which were significantly improved by bosutinib treatment (P < 0.05); no significant difference was detected in IVSDd or LVPWDd among the 3 groups (P > 0.05). Myocardial IR injury obviously increased the expressions of LC3-II/LC3-I and Beclin-1 proteins and lowered the expression of p62 protein (P < 0.01), and these changes were significantly rescued by bosutinib treatment (P < 0.05). The rat models of myocardial IR injury showed significantly increased expression of p-ULK1 (Ser757) (P < 0.01) and lowered expression of p-mTOR protein (P < 0.0001) in the myocardium, and these changes were obviously reversed by bosutinib (P < 0.01 or 0.05); there was no significant difference in mTOR and ULK1 expressions among the 3 groups (P > 0.05).@*CONCLUSION@#SIK2 may promote autophagy through the mTOR/ULK1 signaling pathway, and inhibiting SIK2 can reduce abnormal autophagy and alleviate myocardial IR injury in rats.

Effect of Huangqi Guizhi Wuwutang on Diabetic Peripheral Neuropathy in MKR Mice via Regulating Endoplasmic Reticulum Stress / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang （HQGZWWT） in the treatment of diabetic peripheral neuropathy （DPN） in MKR mice via regulating endoplasmic reticulum （ER） stress. MethodThirty-two 8-week-old MKR mice （half were male and half were female） were fed with a high-fat diet for four weeks， and then 1% streptozotocin （STZ） was injected intraperitoneally for five days. After the blood glucose was stabilized， the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose （FBG） value ≥11.1 mmol·L-1 were randomly divided into model group ， Huangqi Guizhi Wuwutang in original dosage group （30 g·kg-1·d-1）， Huangqi Guizhi Wuwutang in formula dosage group （6.25 g·kg-1·d-1）， and positive drug group （mecobalamin tablets， 0.17 mg·kg-1·d-1）. Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group， the change in FBG was tested， and hematoxylin and eosin （HE） staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition， the expression of c-Jun N-terminal kinase （JNK）， phosphorylated c-Jun N-terminal kinase （p-JNK） and inositol requiring enzyme 1α （IRE1α） proteins was determined by immunohistochemical test and Western blot （WB）. ResultCompared with the conditions in the normal group and blank group， the time of paw withdrawal， paw licking and tail flick in the model group was shortened （P<0.01）， and the conduction velocity of sciatic nerve was decreased （P<0.01）. Compared with the conditions in the model group， the behavioral and functional indicators were improved by HQGZWWT （P<0.05，P<0.01）. The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group （P<0.05）， while that was lowered by HQGZWWT compared with the condition in the model group （P<0.05）. However， there was no difference among the treatment groups. According to the WB， the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group （P<0.05，P<0.01）， while that was decreased by HQGZWWT compared with the condition in the model group （P<0.05，P<0.01）. No difference was observed between the HQGZWWTO and HQGZWWTF groups. ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve， which may be related to its delaying the ER stress response of sciatic nerve.

Fruit variation and geographical distribution of citron / 中国中药杂志

The ripe dried fruit of citron(Citrus medica) is one of the important sources of Chinese herb Citri Fructus. At the same time, it is also grown for edible and ornamental uses. There are many species and abundant genetic variation. To clarify the intraspecific variation and resource distribution of citron, this study investigated the variation in 11 citron fruits, basically covering the main species in China, including Xiaoguo citron(C. medica var. ethrog), Goucheng(C. medica var. yunnanensis), Muli citron(C.medica var. muliensis), Dehong citron(C.medica×Citrus spp.), Fuzhou citron(C.medica×C.grandis?), Mawu(C.medica×C.grandis?), Cangyuan citron, Binchuan citron, Sweet citron, Big citron, and Small citron. The natural communities of citron were proved to be mainly distributed in the southwestern and western Yunnan and southeastern Tibet of China, with Yunnan, Sichuan, Guangxi, Chongqing, Hubei, and Zhejiang identified as the main production areas. Citron has also been widely grown in India, the Mediterranean region, and the Caribbean coast countries. The field investigation revealed the large-scale intraspecific variation of citron fruits. Most of the fruits are oval-like or sphere-like in shape. The fruits are green when raw and yellow when ripe, with oil cell dots on the skin, stripe-likes running from top to bottom, and bulge at the top. Usually, in the smaller citron fruits, the pulp and juice vesicles are better developed and the central columella is tighter. By contrast, the juice vesicles and central columella in larger fruits became more vacant, with carpels visible, and the apex segregation and development of the carpels is one of the reasons for variation. These variations should be given top priority in the future variety selection and breeding, and the quality differences of different citron species and their mechanisms should be further studied. In particular, variety selection and classification management according to their medicinal or edible purposes will provide scientific and technological supports for the orderly, safe, and effective production of citron products consumed as food and medicine.

Effect of Huluan Decoction on SIRT1/NF-κB/p53/p21 Pathway in Model Mice with Premature Ovarian Insufficiency / 中国实验方剂学杂志

Objective:To observe the effects of Huluan decoction on the expression of apoptosis-related protein silence information regulator 1 （SIRT1）， tumor suppressor gene （p53）， acetylated p53 （Ac-p53）， cyclin-dependent kinase inhibitor （p21）， and nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） p65 and changes in ovarian tissue structure of a mouse model with premature ovarian insufficiency （POI） induced by tripterygium glycosides. Method:Fifty female C57BL/6J mice were randomly divided into the blank group， model group， low- and high-dose Huluan decoction groups， and western medicine （estradiol valerate） group. After intragastric administration of tripterygium glycosides at 80 mg·kg^-1·d^-1 for 14 successive days， mice in the low- and high-dose Huluan decoction groups and western medicine group were treated with Huluan decoction at 1.6 g·kg^-1·d^-1 and 6.2 g·kg^-1·d^-1 and estradiol valerate at 0.13 mg·kg^-1·d^-1， respectively， by gavage since the 15^th day， while those in the blank group were provided with an equal amount of distilled water for 21 consecutive days. Following the last administration， the blood was sampled for detecting the levels of serum anti-Müllerian hormone （AMH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） by ELISA and the ovary was harvested for observing the morphological changes by HE staining. The mRNA expression levels of p53 and p21 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of SIRT1， p53， p21， Ac-p53， NF-<italic>κ</italic>B were assayed by Western blot. Result:Compared with the blank group， the model group exhibited a disordered estrous cycle， diminished ovarian volume， decreased number of follicles at various developmental stages， reduced AMH， and elevated FSH and LH， and elevated p53，p21，Ac-p53，NF-<italic>κ</italic>B protein expression and p53，p21 mRNA， reduced SIRT1 protein expression（<italic>P</italic><0.01）. As revealed by the comparison with the model group， each medication group displayed an increased number of follicles， elevated AMH， reduced FSH and LH （<italic>P</italic><0.01）， up-regulated SIRT1 protein expression （<italic>P</italic><0.01）， and significantly down-regulated mRNA and protein expression of aging-related genes p53， p21， and down-regulated Ac-p53，NF-<italic>κ</italic>B protein expression （<italic>P</italic><0.01）. Conclusion:Huluan decoction significantly reverses the aging process and improves ovarian function possibly by boosting the activity of SIRT1/NF-<italic>κ</italic>B/p53/p21 pathway in ovarian cells， changing the apoptotic state， increasing the growing and mature follicles， and reducing the atretic follicles.

Effect of Yinchenhao Tang on Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease in MKR Mice / 中国实验方剂学杂志

Objective:To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） in MKR mice. Method:Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group，original Yinchenhao Tang （17.16 g·kg^-1） group，Yinchenhao Tang group at a specified dose （4.68 g·kg^-1） in teaching materials，and positive drug ［metformin + simvastatin， （65+2.6）×10^-3 g·kg^-1］ group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group，the liver wet weight，oral glucose tolerance test （OGTT），serum inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>），and changes in blood lipid and liver function were determined. Hematoxylin-eosin （HE） staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope，followed by the detection of Toll-like receptor 4 （TLR4），myeloid differentiation factor 88 （MyD88），and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） protein expression by Western blot. Result:Compared with the model group，the medication groups exhibited significantly reduced liver wet weight index （<italic>P</italic><0.01），improved OGTT result （<italic>P</italic><0.05），and down-regulated serum IL-6 and TNF-<italic>α</italic> levels （<italic>P</italic><0.01）. In terms of morphological changes，Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover， Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4，MyD88，and NF-<italic>κ</italic>B in liver tissue of MKR mice with T2DM combined with NAFLD （<italic>P</italic><0.05），and the down-regulation of TLR4 and NF-<italic>κ</italic>B in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials （<italic>P</italic><0.05）. Conclusion:Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4，MyD88，and NF-<italic>κ</italic>B expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.

Network Meta-analysis of acupuncture and moxibustion for allergic rhinitis / 中国针灸

OBJECTIVE@#To review the therapeutic effect of acupuncture and moxibustion on allergic rhinitis based on the network Meta-analysis.@*METHODS@#The randomized controlled trials of acupuncture and moxibustion for allergic rhinitis were retrieved from the databases, starting from the date of establishment to August 17, 2020, i.e. the PubMed, EMbase, Cochrane Library, CNKI, Wanfang and VIP. The traditional Meta-analysis and network Meta-analysis were performed by RevMan5.3 and GeMTC0.14.3.@*RESULTS@#A total of 50 RCTs were included, including 4260 patients, involving 5 kinds of acupuncture and moxibustion therapies, such as acupuncture, moxibustion, acupoint application, acupoint thread-embedding and auricular point therapy.①In term of total effective rate, acupuncture, moxibustion and acupoint thread-embedding were superior to western medication and auricular point therapy (@*CONCLUSION@#The therapeutic effect of acupuncture and moxibustion on allergic rhinitis is better than western medication, and acupoint thread-embedding has the best curative effect.

Influencing factors and strategies of enhancing nanoparticles into tumors

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.

Research on mechanism of abnormal cerebrovascular cell communication and brain diseases / 中国药理学通报

Brain diseases such as stroke, Alzheimer s disease, epilepsy, have always been worldwide problems that endanger human health and are costly disease from societal perspectives. In recent years, more and more attention has been paid to the relationship between components of neurovascular unit (cerebrovascular endothelial cell, microglia, astrocyte and neuron) and brain diseases. Not only have their structures changed during the pathological process, but also coupling communication and functions have changed accordingly. On the basis of summarizing previous studies on the abnormalities in intercellular communication and its mechanism with brain disorders, this review is expected to find novel targets or therapeutic treatment for neuropsychiatric diseases.

Study on active components and targets of Ginseng in Prevention and treatment of PTSD based on Network Pharmacology / 中国药理学通报

Aim To obtain the active components and targets of ginseng in the prevention and treatment of traumatic stress disorder(PTSD) through the method of network pharmacology. Methods The active components and target information of ginseng with medicinal value were obtained by TCMSP research platform, and the gene information closely related to the pathogenesis of PTSD was obtained by searching GeneCard and OMIM database. The two were matched to obtain the medicinal components and target genes of ginseng in the prevention and treatment of PTSD. The drug-dis- ease-target network diagram was drawn by R and Perl computer languages, and the target genes were analyzed by PPI network analysis, gene ontology ( GO ) and signal transduction pathway ( KEGG) enrichment analysis. Results According to the general pharmacological research methods of traditional Chinese medi cine, the screening parameters of active components were set, and nine kinds of high value medicinal ingredients of Panax ginseng were obtained. There was a drug-target relationship between the nine medicinal components and sixteen target genes related to PTSD disease. Through PPI, GO and KEGG analysis, it was found that the target genes were mainly enriched in physiological functions such as neurotransmitters, syn-aptic plasticity, ion channels and so on. Conclusions Ginseng has the pharmacological effect of preventing and treating PTSD, which may play a role in regulating the metabolism and receptor activity of monoamine neurotransmitters.

Effect of Notch signaling pathway on nerve regeneration after cerebral ischemia in rats with neural stem cells transplantation / 解剖学报

Objective To investigate the mechanism of inhibiting the Notch signaling pathway in promoting neural regeneration after neural stem cells (NSCs) transplantation in rats with cerebral ischemia. Methods The model of focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) method . NSCs were cultured in vitro and transplanted into the striatum ischemic area. In the experiment, 40 SD rats were divided into sham operation group, model group, transplantation group (transplanted neural stem cells), and N-[N-(3, 5-difluorohenacetyl )-L-alanyl ]-S-phenylglycinet-butyl ester( DAPT) + transplantation group. The degree of neuronal damage in each group was observed by HE staining. The expressions of Notchl, Hesl and Hes5 in the brain tissue of each group were detected by immunohistochemistry and Western blotting. Results Compared with the sham operation group, the neuron injury in the model group was severe, and nuclear pyknosis and nuclear lysis were observed. The Notchl, Hesl and Hes5 positive cells increased significantly, and the expression of Notchl, Hesl and Hes5 proteins were significantly up-regulated (P<0. 05). Compared with the model group, the neuronal damage in the transplantation group and the DAPT+ transplantation group were all relieved, and the Notchl, Hesl and Hes5 positive cells were partially expressed, and the expression of each protein decreased (P<0. 05). The DAPT+ transplantation group neurons were compared. The damage was obviously restored, and the expression of protein-positive cells and protein further decreased (P<0. 05). Conclusion Inhibition of Notch signaling pathway can promote nerve regeneration after neural stem cell transplantation in rats with cerebral ischemia. The mechanism is mainly related to down-regulation of Notch 1 , Hesl and Hes5 expression.

Effect of decompression combined with curettage and autogenous bone cement implantation on large cysts of the jaw / 华西口腔医学杂志

Decompression and curettage can result are effective as treatments for large jaw cysts, which are common diseases in the clinic. Based on a treatment used in a previous study, this paper proposes a "three-step method" to treat large jaw cyst and repair the bone defect by decompression, curettage, and autologous dental bone powder implantation. This paper introduces the processes and key points of the operation involved in the abovementioned method.