The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Effects of Methionine Restriction on Proliferation, Cell Cycle, and Apoptosis of Human Acute Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells.@*METHODS@#Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay.@*RESULTS@#Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells.@*CONCLUSION@#Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

Anatomy and imaging of abdominal aorta and its branches in Southwestern China population / 解剖学报

Objective To investigate the normal reference values of abdominal aorta and its branches in Southwest China, so as to provide basis for clinical diagnosis and treatment of abdominal aortic aneurysm. Methods The length, diameter and angle of the abdominal aorta and its branches were measured in 20 cadavers. At the same time, 300 cases without obvious pathological changes in four urban populations were selected for abdominal CT angiography (CTA) to measure the length, diameter and angle of abdominal aorta and its branches. Results Display rate of abdominal aorta was 100%,the average length of abdominal aorta was (12.96±0.81) cm, the diameter of abdominal aorta was (1.93±0.28) cm, (1.55±0.23) cm, (1.61±0.19) cm in renal artery plane (Ⅰ), inferior mesenteric artery plane (Ⅱ) and lower edge plane of lumbar vertebrae (Ⅲ), and the average value on image was (2.17 ± 0.42) cm, (1.81 ± 0.40) cm, (1.99 ± 0.53) cm; Display rate of common iliac artery was 100%, the angle between left and right common iliac artery was (59.80± 4.66) ° and the diameter of the end was (1.16±0.33) cm and (1.12±0.11) cm; Display rate of celiac trunk on cadaver was 100%, the average length was (1.61±0.27) cm, the average diameter on cadaver was (0.78±0.71) cm, the image was (0.88± 0.31) cm; Display rate of renal artery was 100%, the average length of the left renal artery was (2.58 ± 0.50) cm, that of the right was (4.26±0.65) cm, the initial average diameter of the left renal artery was (0.55±0.24) cm, and the right renal artery was (0.62±0.20) cm; Display rate of the superior mesenteric artery was (100%), that of the on cadaver was (4.56 ± 0.29) cm, that of the image was (4.93 ± 0.84) cm, and that of the angle between the abdominal aorta was (38.05±5.99)°; Display rate of the inferior mesenteric artery was (100%),the average length of the inferior mesenteric artery was (6.57±0.79) cm on the cadaver, the image was (6.70±0.76) cm, and that of the angle between the abdominal aorta was (73.79 ± 9.62) ° and the initial diameter was (0.48 ± 0.29) cm. Conclusion The normal reference values of abdominal aorta and its visceral branches in Southwest China population were measured. CTA has a special advantage in showing the lesions of abdominal aorta and its branches in lumen, extraluminal and vascular wall, which can provide anatomical data of patients before operation.

The inhibitory effect of a novel phosphodiesterase 4 inhibitor ZL-n-91 on proliferation of osteosarcoma U20S cells / 中国药理学通报

Aim To explore the anti-cancer effects of ZL-n-91, a novel and highly selective phosphodiesterase 4 inhibitor, on the osteosarcoma U2OS cells.Methods CCK-8 assay was used to detect the inhibitory effect of ZL-n-91 with different concentrations(0, 20, 40, 80, 160, 240, 320, 400, 480 μmol·L-1)and different intervention time(0, 24, 48, 72, 96 h)on the proliferation of U2OS cells.Tablet clone forming experiment was used to detect the effect of ZL-n-91 on the clonality of U2OS cells.Flow cytometry was used to detect the cell apoptosis and cell cycle distribution.Western blot was employed to detect the expression of Bcl-2, CDK2, CDK4, CyclinD1, CyclinE1 protein.Results The inhibitory rate of ZL-n-91 on U2OS cells was concentration- and time-dependent(P<0.05), and its half inhibition rate IC50 was 174.1 μmol·L-1.ZL-n-91 significantly inhibited the clonality of U2OS cells(P<0.01).ZL-n-91 significantly induced cell apoptosis, and caused cell cycle arrest at G0/G1 phase in U2OS cells(P<0.01).The results of Western blot showed that ZL-n-91 significantly down-regulated the expression of Bcl-2, CDK2, CDK4, CyclinD1, CyclinE1 proteins in U2OS cells(P<0.05).Conclusions The novel selective phosphodiesterase 4 inhibitor, ZL-n-91, can significantly inhibit the proliferation of osteosarcoma U2OS cells with induction of cell cycle arrest and cell apoptosis, and may become a potential anti-cancer agent.

Protective Effects of Hu-Lu-Ba-Wan () against Oxidative Stress in Testis of Diabetic Rats through PKCα/NAPDH Oxidase Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan (, HLBW) on the testis of diabetic rats.@*METHODS@#Twenty-four male Wistar rats (160-180 g) were randomly divided into 3 groups according to a random number table, including a control group (n=8), diabetic group (n=8), and HLBW group (n=8). Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin (26 mg/kg). Then HLBW granule was administrated for 12 weeks. Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined. Oxidative stress markers in both serum and testis were tested. Meanwhile, testicular morphology was observed under hematoxylin and eosin (HE) and the ultrastructure of Leydig cell was observed by electron microscope. The superoxide anion level was detected by DHE, and TUNEL-positive cells of testis was evaluated by TUNEL assay. The gene and protein expression of protein kinase C (PKCα), phosphorylated PKCα (P-PKCα) and P47phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis.@*RESULTS@#Compared with the diabetic group, HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum (P<0.01). HLBW administration also reduced the levels of reactive oxygen species (ROS) in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats. Additionally, HLBW down-regulated the protein and mRNA levels of PKCα, P-PKCα and P47phox in testicular tissues.@*CONCLUSION@#HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα /NAPDH oxidase signaling pathway.

Jiao-tai-wan Up-regulates Hypothalamic and Peripheral Circadian Clock Gene Cryptochrome and Activates PI3K/AKT Signaling in Partially Sleep-deprived Rats / 华中科技大学学报（医学）（英德文版）

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Jiao-tai-wan Up-regulates Hypothalamic and Peripheral Circadian Clock Gene Cryptochrome and Activates PI3K/AKT Signaling in Partially Sleep-deprived Rats / 华中科技大学学报（医学）（英德文版）

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Application of reverse molecular docking technology in target prediction, active ingredient screening and action mechanism exploration of traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicine(TCM) modernization has gradually become a worldwide trend. Reverse docking technology has also gradually become a useful tool for TCM modernization. It involves docking a small-molecule drug in the potential binding cavities of a set of clinically relevant macromolecular targets. Detailed analysis of the binding characteristics was used for the ranking of the targets according to the tightness of binding. This process can be used to potentially identify the novel molecular targets for the drug which may be relevant to its mechanism of action or side effect. In order to explore the action mechanism, screen the active ingredients and seek the treating target of TCM, reverse molecular docking technology has been widely used and has achieved remarkable results in recent years. In this review, we summarized the application of reverse molecular docking technology in the target seeking, active ingredients screening and potential mechanism exploration of TCM, which may provide more scientific basis for the clinical research and development of new herbal drugs.

Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD).</p><p><b>METHODS</b>Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined.</p><p><b>RESULTS</b>The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine.</p><p><b>CONCLUSIONS</b>JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.</p>

Effects of berberine and cinnamic acid on palmitic acid-induced intracellular triglyceride accumulation in NIT-1 pancreatic β cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells.</p><p><b>METHODS</b>Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction.</p><p><b>RESULTS</b>PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study.</p><p><b>CONCLUSION</b>It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.</p>

Pharmacokinetic and pharmacodynamic characteristics of berberine and jateorhizine in Coptidis Rhizoma powder and their monomeric compounds in type 2 diabetic rats / 中国中药杂志

This article focused on a comparative analysis on the pharmacokinetic and pharmacodynamic characteristics of berberine (BER) and jateorhizine(JAT) in Coptidis Rhizoma powder (HL-P) and their monomeric compounds (BER + JAT, BJ) in type 2 diabetic (T2D) rats to explore the beneficial. effect of HL-P in the treatment of T2D. The T2D rats were treated with HL-P, BER, JAT and BJ, respectively for 63 d. The pharmacokinetic parameters, dynamic changes in blood glucose level and blood lipid values were measured. The results showed that, compared with other corresponding group, t(max), T(½ka) of BER and JAT in HL-P group were reduced, while C(max), AUC(inf), AUC(last), V(L)/F were significantly increased; compared with model group, blood glucose levels were decreased significantly in HL-P group since the 18th day, while those in BER or BJ group were reduced since the 36th day, however, blood glucose levels showed no obvious changes in JAT group; compared with model group, FFA values in all treatment group were decreased significantly. Moreover, TG, HDL and LDL value in HL-P group, LDL value in BER group and HDL value in BJ group were improved significantly. The above results showed that Coptidis Rhizoma powder showed excellent pharmacokinetic characteristics and excellent activity of lowering blood glucose and lipid. It provided a scientific basis for oral application of Coptidis Rhizoma powder in the treatment of T2D.

Inhibition of proprotein convertase subtilisin/kexin type 9: a novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats.</p><p><b>METHODS</b>A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA), apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in liver tissues were determined by Western blot analysis.</p><p><b>RESULTS</b>Compared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues (P<0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins (P<0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P<0.01). These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.</p><p><b>CONCLUSIONS</b>Hdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.</p>

Intestinal absorption of berberine and 8-hydroxy dihydroberberine and their effects on sugar absorption in rat small intestine / 华中科技大学学报（医学）（英德文版）

The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes / 中国中药杂志

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

Intestinal absorption of berberine and 8-hydroxy dihydroberberine and their effects on sugar absorption in rat small intestine / 华中科技大学学报（医学）（英德文版）

The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

Effects of Chinese Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats / 华中科技大学学报（医学）（英德文版）

The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.

Jiaotai Pill enhances insulin signaling through phosphatidylinositol 3-kinase pathway in skeletal muscle of diabetic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats.</p><p><b>METHODS</b>The rat model of type 2 diabetes mellitus (T2DM) was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method.</p><p><b>RESULTS</b>All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β (InsRβ) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect.</p><p><b>CONCLUSION</b>JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.</p>

Effects of Chinese Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats / 华中科技大学学报（医学）（英德文版）

The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.

Multivariate analysis of hepatic encephalopathy occurrence in patients with liver failure / 中华肝脏病杂志

To investigate the risk factors of hepatic encephalopathy in patients with liver failure. Nine-hundred-and-seventy-six hepatitis B virus (HBV) patients with liver failure were retrospectively analyzed. Clinical data (sex, age, family history, liver cirrhosis, diabetes, celiac infection, pulmonary infection, liver kidney syndrome, upper gastrointestinal hemorrhage) and laboratory findings (albumin, globulin, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyl transferase, alkaline phosphatase, cholesterol, cholinesterase, K+, Na+, creatinine, international normalized ratio (INR), alpha-fetoprotein, HBV DNA, white blood cell, hemoglobin, platelet) were collected and used to screen the risk factors for hepatic encephalopathy by univariate and multiple regress analyses. Multiple logistic regression analysis indicated that upper gastrointestinal hemorrhage [risk (R) = 0.993, relative hazard (RH) = 2.699, 95% confidence interval (CI): 1.567-4.651], pulmonary infection [R = 1.043, RH = 2.839, 95% CI: 1.680-4.797], INR [R = 0.257, RH = 1.293, 95% CI: 1.220-1.370], AST level [R = 0.001, RH = 1.001, 95% CI: 1.000-1.001], and cirrhosis [R = 0.569, RH = 1.815, 95% CI: 1.112-2.965] were closely correlated with hepatic encephalopathy. HBV-infected patients presenting with upper gastrointestinal haemorrhage, pulmonary infection, prolonged INR, elevated AST, or liver cirrhosis should be carefully monitored for indications of hepatic encephalopathy to initiate timely therapeutic interventions.

Polymerase region mutations and hepatitis B virus genotypes in chronic hepatitis B patients with poor response to lamivudine / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the mutations in Polymerase region and hepatitis B virus (HBV) genotypes in chronic hepatitis B patients with poor response to Lamivudine treatment.</p><p><b>METHODS</b>631 chronic hepatitis B patients with poor response to Lamivudine were recruited in this study. Real-time PCR and DNA sequencing were used to determine HBV genotypes; direct sequencing was performed to detect mutations, and real-time PCR was used to quantify HBV DNA load. Mutations in polymerase region were investigated in different HBV genotypes.</p><p><b>RESULTS</b>272 patients were infected with HBV of genotype B, and 359 patients were infected with HBV of genotype C. The mean age of patients infected with HBV of genotype C (39.1+/-11.4 years old) were significant higher than that of patients infected with HBV of genotype B (33.7+/-9.7 years old) (t = -6.55, P less than 0.01). The patients infected with HBV of genotype C had relatively higher HBV DNA load [(5.96+/-1.22) log10 copies/ml] than the patients infected with HBV of genotype B [(5.58+/-1.21) log10 copies/ml] (t = -2.01, P less than 0.05). The overall incidence rate of A181V/T mutation in genotype C (5.3%) was significantly higher than that in genotype B (0.4%) (x2=12.23, P less than 0.01), but the incidence rate of M204I/V, L180M, T184A/G/I/S, S202G/I and V173L mutations was not significantly different between genotype B and C (each P more than 0.05). M204I mutation in genotype B (20.6%) was more frequent than that in genotype C (13.9%) (x2=4.91, P less than 0.05). The Lamivudine resistance mutations were not significantly different between genotype B and genotype C (x2 = 0.00, P more than 0.05).</p><p><b>CONCLUSIONS</b>The incidence rate of lamivudine resistance mutation is not significantly different between genotype B and genotype C, but patients infected with HBV of genotype C have higher HBV DNA load than patients infected with HBV of genotype B.</p>