Effect of South African Herb Hoodia gordonii on Liver Glucolipid Metabolism and PI3K/Akt/FoxO1 Signalling Pathway in db/db Mice / 中国实验方剂学杂志

ObjectiveTo observe the effects of the South African herb Hoodia gordonii （HG） on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase （PI3K）/protein kinase B （Akt）/factor forkhead protein O1 （FoxO1） signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose： model group， metformin group （0.195 g·kg-1）， and low dose （0.39 g·kg-1）， medium dose （0.78 g·kg-1）， and high dose （1.56 g·kg-1） HG groups， with six m/m mice in each group， and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg-1 by gavage. Body weight， water intake， and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration， serum insulin （FINS）， low-density lipoprotein cholesterol （LDL）， total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine （CREA） were measured， and liver sections were embedded and stained with hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and oil red O. Protein expression of PI3K p85， p-Akt， and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K， Akt， and FoxO1 in liver tissue was detected by real-time polymerase chain reaction （Real-time PCR）. ResultAfter six weeks of administration intervention， it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups （P<0.05）. The level of islet resistance index was significantly reduced in both the low and medium dose HG groups （P<0.05）. The expression levels of TC， TG， and LDL were reduced in all HG groups （P<0.05， P<0.01）. Pathologically， HG could alleviate hepatocyte steatosis， reduce the volume and content of lipid droplets in liver， and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low， medium， and high dose HG groups compared with the model group （P<0.01）. p-Akt protein expression was significantly increased in the medium and high dose HG groups （P<0.05， P<0.01）. p-FoxO1 protein expression was significantly increased in the low， medium， and high dose HG groups （P<0.05， P<0.01）. Compared with the model group， PI3K mRNA was increased in low dose， medium dose， and high dose HG groups （P<0.05）， and Akt mRNA was increased in high dose HG group （P<0.05）. FoxO1 mRNA was decreased in low dose， medium dose， and high dose HG groups （P<0.05）. ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice， which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

Discussion on the Diagnosis and Treatment of Thyroid Nodules Based on the Theory of"One Qi Peripheral Flow" / 世界科学技术-中医药现代化

The concept of"one qi peripheral flow"originates from the ancient Chinese philosophy of"qi monism"and the theory of yin and yang chi chemistry in the Yellow Emperor's Classic of Internal Medicine,and was formally proposed in Huang Yuanyu's The Origin of the Four Sacred Hearts,which elaborates on the theory of one qi circumference in which the earth pivots on four signs and the left rises and the right descends.Based on this theory,this paper discusses the diagnosis and treatment of thyroid nodules,believes that the development of thyroid nodules is closely related to the deficiency of the earth and qi,and the disorder of the liver and lungs,and combines the evidence of modern research to argue that the deficiency of the earth and qi,and the disorder of the liver and lungs are the important pathomechanisms of the thyroid nodules,proposes to refer to the results of ultrasound elasticity imaging of the thyroid gland for staging and typing treatment of thyroid nodules.It also summarizes the clinical use of medicines in different stages and types,aiming at estoring the"one qi peripheral flow"in the body,and provides a new diagnostic and therapeutic idea for the clinical diagnosis and treatment of thyroid nodules.

Effect of remimazolam combined with desflurane and flumazenil antagonism for anesthesia during ophthal-mic day surgery / 实用医学杂志

Objective To evaluate the effect of remimazolam combined with desflurane and flumazenil antagonism for anesthesia during ophthalmic day surgery.Methods This is a prospective randomized controlled trial.A total of 64 patients undergoing elective general anesthesia with laryngeal mask during ophthalmic day surgery were selected and randomly assigned to propofol group(n = 32)and remimazolam group(n = 32).The propofol group was given propofol anesthesia induction and propofol combined with diflurane anesthesia maintenance;the remazolam group was given remazolam anesthesia induction and remazolam combined with diflurane anesthesia maintenance,and flumazenil antagonism was given intravenously at the end of the operation.Continuous intravenous infusion of remifentanil was administered during surgery in both groups.The primary outcome was emergence time.The secondary outcome included changes in intraoperative hemodynamic parameters,extubation time,time to leaving the operating room,duration of postoperative recovery room(PACU)stay,and the occurrence of other perioperative adverse reactions.Results Emergence time,extubation time,and time to leaving the operating room in remimazolam group were significantly shorter than those in group propofol(P<0.05)[(4.11±1.17)vs.(8.64±2.77)min,(4.61±1.11)vs.(9.90±2.81)min and(6.60±2.01)vs.(11.74±3.11)min,respectively].The incidences of intraopera-tive hypotension and bradycardia in the remimazolam group were significantly lower than that in the propofol group(P<0.05);There was no statistically difference in the duration of PACU stay and the incidence of postoperative complications between the two groups(P>0.05).Conclusion Remimazolam combined with desflurane general anesthesia and flumazenil antagonism for anesthesia management in ophthalmic day surgery could significantly shorten the time of emergence and extubation,help to maintain hemodynamic stability with fewer adverse reactions,and improve the safety of ophthalmic daytime surgery,which is worthy of clinical promotion and application.

Research on reliability management of medical equipment supply in cardiology ward / 中国医学装备

Objective:To construct a reliability management index system of cardiology medical equipment supply,to form a reliability evaluation strategy,and to improve the effectiveness of reliability management.Methods:13 supply management items were decomposed from the three links of spare parts before use,tracking during use and post-use processing of 126 medical equipment,and the probability of work error,probability of quality problems and risk expectation of diagnosis and treatment were evaluated in the whole process management,and the whole-process management countermeasures of grading and stratification,quality standardization and department cooperation was formed.2,000 pieces(sets)of medical equipment used in The People's Hospital of Longhua from 2021 to 2022 were selected by random sampling method,and the department cooperative management[referred to as collaborative management mode,1,000 pieces(sets)times]and reliability evaluation management[referred to as evaluation management mode,1,000 pieces(sets)times]were adopted respectively.The reliability and satisfaction of medical equipment under different management modes were compared.Results:The work error probabilities of pre-use spare parts,in-use tracking,post-use processing and supply of medical equipment adopting evaluation management mode were(4.74±2.19)%,(4.39±1.85)%,(5.75±1.88)%and(8.29±1.30)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=5.367,5.663,5.432,6.847;P<0.05);the probabilities of quality problems were(4.13±1.67)%,(3.89±1.25)%,(5.28±1.84)%and(7.64±1.18)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=6.504,6.229,5.123,6.166,P<0.05);the risk expectations of diagnosis and treatment were(2.74±0.89)%,(2.47±0.96)%,(3.42±0.95)%and(4.02±1.09)%,respectively,which were lower than the collaborative management mode,the difference was statistically significant(t=7.027,6.509,8.915,9.266,P<0.05).The satisfaction of the relevant staff on the performance quality,sterilization specifications,supply timeliness,level of collaboration and safety of the medical equipment adopting the evaluation management mode were(93.54±4.65)%,(91.67±4.11)%,(94.58±4.34)%,(92.39±3.82)%and(90.97±3.76)%,respectively,which were higher than the collaborative management mode,the difference was statistically significant(t=2.809,3.030,2.843,4.939,3.739,P<0.05).Conclusion:The reliability management model can reduce the work errors and security risks in medical equipment supply,improve the reliability of supply and improve the quality of supply service.

Effects of Erxian Decoction （二仙汤） on Choroid Plexus Folate Transport-Hippocampal Neurogenesis in Rat Brain Tissue of Late-Onset Depression Model / 中医杂志

ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction （二仙汤） for late-onset depression （LOD）. MethodsForty Wistar male rats of 7-8 weeks were divided into 20 each of normal group and youth depression group. Sixty Wistar male rats of 20 months were divided into 20 each of elder group， LOD group and Erxian Decoction group. The rats in youth depression group were modelled with chronic unpredictable mild stress （CUMS） for 6 weeks to build a depression model， and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model， with no interventions in the normal group and the elder group. Gastric administration was carried out at the same time of modelling， rats in Erxian Decoction group were given 8 g/（kg·d） of Erxian Decoction by gavage， and rats in the normal group， youth depression group， elder group， and LOD group were given 4 ml/（kg·d） of pure water by gavage， for 6 weeks in each group. Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats， absent field experiment was used to evaluate the spontaneous activity ability of rats， and T-maze experiment was used to evaluate the cognitive function of rats； Western blot assay was used to detect neuronal nuclei （NeuN）， nestin， doublecortin （DCX） in hippocampal tissue， and zonula occludens-l （ZO-1）， folate receptor α （FRα）， reduced folate carrier （RFC）， and protoncoupledfolate transporter （PCFT） protein expression in choroid plexus； immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin， the number of double-positive cells for 5-bromodeoxyuracil nucleoside （BrdU）/DCX in hippocampal dentate gyrus， and the protein expression of ZO-1， FRα， RFC， and PCFT in choroid plexus tissues； ELISA technique was used to detect plasma， cerebrospinal fluid， 5-methyltetrahydrofolate （5-MTHF） in hippocampal tissues； Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues and the expression of nestin， DCX， and NeuN proteins in hippocampal tissues of rats in youth depression group and LOD group. ResultsCompared with normal group， rats in youth depression group and LOD group showed reduced sugar water preference， reduced total distance travelled in the absent field， reduced number of times through the grid， prolonged forced swimming immobilisation， reduced hippocampal NeuN， nestin and DCX protein expression， reduced number of Ki-67/nestin double-positive cells in hippocampal dentate gyrus， reduced number of BrdU/DCX double-positive cells in hippocampal dentate gyrus， and reduced expression of ZO-1 and FRα proteins and fluorescence intensity （P＜0.05 or P＜0.01）； the correct rate of T-maze on days 3 and 4 in the rats of youth depression group and on days 2 to 4 in the rats of LOD group significantly decreased， and the content of 5-MTHF in the cerebrospinal fluid and hippocampal tissues of the rats of LOD group significantly decreased as well （P＜0.05 or P＜0.01）. Compared with youth depression group， rats in LOD group showed a decrease in total distance travelled in absenteeism， number of times through the grid， a significant decrease in the correct rate of the T-maze on day 1-4， a decrease in NeuN， nestin， DCX protein expression of hippocampal tissue and the number of Ki-67/nestin double-positive cells， BrdU/DCX double-positive cells of hippocampal dentate gyrus （P＜0.05 or P＜0.01）. Compared with LOD group， rats in Erxian Decoction group had elevated sugar-water preference and total distance travelled in absenteeism and number of times through the grid， shorter forced swimming immobility time， significantly higher correct rate of the T-maze on day 3-4， elevated expression of NeuN， nestin， and DCX proteins in hippocampal tissues， increased number of Ki-67/nestin double-positive cells and BrdU/DCX double-positive cells in hippocampal dentate gyrus， and increased 5-MTHF content in cerebrospinal fluid and hippocampal， and ZO-1， FRα， RFC， PCFT protein expression and fluorescence intensity increased in choroid plexus （P＜0.05 or P＜0.01）. Correlation analysis showed that there was a positive correlation between 5-MTHF content in cerebrospinal fluid （r = 0.466）， hippocampal tissue （r = 0.522） and nestin expression in hippocampal tissue （P＜0.05）. ConclusionErxian Decoction could improve depressive-like behaviour and cognitive impairment in LOD model rats， and its mechanism may promote hippocampal neurogenesis by alleviating structural damage to the choroid plexus of the brain tissue， and improving impaired choroid plexus folate transport.

Research Progress on Active Ingredients of Chinese Medicine Based on AMPK Signaling Pathway to Improve Insulin Resistance in T2DM / 中国实验方剂学杂志

Insulin resistance （IR） is an important pathological and physiological mechanism of type 2 diabetes （T2DM）， and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose， resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase （AMPK） is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate （ATP） in the cell. In recent years， traditional Chinese medicine （TCM） has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols， flavonoids， polysaccharides， alkaloids， and saponins， as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response， thereby improving IR by regulating glucolipid metabolism， inhibiting inflammatory response， anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this， this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years， expecting to provide reference for further research， development and application of TCM in intervening IR and treating T2DM.

Role of p38 MAPK Pathway in Diabetic Peripheral Neuropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.

Effect of Zishenwan on Intestinal Barrier and Transcriptome of Skeletal Muscle of db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes （db/db） mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group， while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks， during which fasting blood glucose， body weight， and food intake were measured. Serum total cholesterol （TC） and triglyceride （TG） levels were determined， and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance （HOMA-IR）. After the treatment， skeletal muscle and ileum tissues were collected， followed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 （ZO-1） in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome， and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group， the model group showed increased fasting blood glucose， body weight， TC， TG， and HOMA-IR （P<0.01）. Compared with the model group， Zishenwan significantly reduced fasting blood glucose， body weight， TC， TG， and HOMA-IR in db/db mice （P<0.01）， while there was no statistically significant difference in food intake. Compared with the normal group， the model group exhibited lipid deposition in skeletal muscle， as well as structural changes in the ileum， with significant decreases in the protein expression levels of intestinal occludin and ZO-1 （P<0.01）. Compared with the model group， Zishenwan improved the pathological changes in skeletal muscle and ileum， and increased the protein expression of occludin and ZO-1 in the ileum （P<0.01）. Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice， and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.

Effect of Modified Huangqi Guizhi Wuwutang on Stress-related IRE1α/CHOP Pathway of Sciatic Nerve Endoplasmic Reticulum in Diabetes Rats / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang （MHGW） on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α （IRE1α） and CCAAT/enhancer-binding protein homologous protein （CHOP）. MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks， followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L-1 were included in study （n=48）. The rats were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg-1·d-1）， a high-dose MHGW group （2.5 g·kg-1·d-1）， and a low-dose MHGW group （1.25 g·kg-1·d-1）. Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks， the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue （LFB） staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species （ROS） levels. Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to evaluate the expression of p-IRE1α protein， IRE1α mRNA， CHOP protein， and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group， the model group showed elevated serum ROS levels （P<0.01）. In contrast， the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group （P<0.01）. The sciatic nerve of the model group showed pathological changes compared with that in the normal group， while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group （P<0.01）. However， the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group （P<0.05， P<0.01）. Furthermore， compared with the normal group， the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve （P<0.01）， while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group （P<0.01）. ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA， thereby preventing and treating peripheral neuropathy in diabetes.

Effect of Modified Huangqi Guizhi Wuwutang on Apoptosis-related Bax and Caspase-12 of Sciatic Nerve Cells in Diabetes Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Huangqi Guizhi Wuwutang （MHGW） on the protein and mRNA expression of B-cell lymphoma-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase-12 （Caspase-12） related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes. MethodAnimal experiments were conducted. A diabetes model was induced in sixty male sprague-dawley （SD） rats by feeding on a high-sugar and high-fat diet combined with streptozotocin （STZ） intraperitoneal injection. Rats with random blood glucose levels ≥ 16.7 mmol·L-1 for three consecutive days were considered to have successfully developed diabetes. Forty-eight rats that successfully developed diabetes were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg-1·d-1）， a high-dose MHGW group （2.5 g·kg-1·d-1）， and a low-dose MHGW group （1.25 g·kg-1·d-1）， with 12 rats in each group. Another 10 rats were assigned to the normal group. Body weight and random blood glucose levels of the rats were monitored. At the end of a 16-week intervention period， the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system. The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultCompared with the normal group， the model group showed a significant decrease in body weight （P<0.01） and a significant increase in random blood glucose levels （P<0.01）. After a 16-week intervention， compared with the model group， the high-dose MHGW group exhibited a significant increase in body weight （P<0.05）， while there were no statistically significant differences in body weight changes among the other treatment groups. Random blood glucose levels significantly decreased in all treatment groups （P<0.01）. After 16 weeks of intervention， compared with the normal group， the model group had significantly reduced motor and sensory nerve conduction velocities （P<0.01）. Compared with the model group， all treatment groups showed significant increases in motor and sensory nerve conduction velocities （P<0.05， P<0.01）. The expression of Bax and Caspase-12 proteins in the sciatic nerve cells was significantly elevated in the model group compared with that in the normal group （P<0.01）. In contrast， all treatment groups showed significant reductions in the expression of Bax and Caspase-12 proteins in the sciatic nerve cells as compared with that in the model group （P<0.01）. The expression of Bax and Caspase-12 mRNA in the sciatic nerve cells significantly increased in the model group compared with that in the normal group （P<0.01）. Compared with the model group， the α-lipoic acid group and the high-dose MHGW group showed significant reductions in the expression of Bax mRNA in the sciatic nerve cells （P<0.05， P<0.01）， while the low-dose MHGW group showed a decreasing trend in the expression of Bax mRNA. The expression of Caspase-12 mRNA in the sciatic nerve cells significantly decreased in all treatment groups （P<0.01）. ConclusionMHGW may improve and repair sciatic nerve damage in diabetes rats by inhibiting sciatic nerve cell apoptosis.

Anti-diabetic Effect of Zishenwan and Its Herbal Components： A Review / 中国实验方剂学杂志

Zishenwan， also known as Tongguanwan， is composed of three herbs：Anemarrhenae Rhizoma， Phellodendri Chinensis Cortex， and Cinnamomi Cortex， which thus is thought to be the representative formula to clear heat， purge fire， nourish Yin， and tonify Qi， and it is often used for treating anuresis and renal arthralgia. In recent years， this formula has become a commonly used combination of herbs and is used to treat diabetes （consumptive thirst disease） diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine （TCM） theory for Zishenwan. Moreover， based on modern pharmacological research， the previous studies on the components of Zishenwan， the improvement of diabetes-related diseases by Zishenwan， and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized， and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation， enhancing insulin sensitivity， and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them， including mangiferin， timosaponins， berberine， jatrorrhizine， cinnamaldehyde， and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues， suppressing inflammation， anti-oxidation， regulating lipid metabolism， enhancing insulin secretion， and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.

Mechanisms of Saponins in Chinese Medicinals Against Diabetic Nephropathy： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN）， the most feared microvascular complication of diabetes and one of the most common and serious complications of diabetes， is the major cause of end-stage renal disease worldwide， leading cause of morbidity and mortality in patients with diabetes， and the main non-communicable cause of death worldwide. There are many types of saponins， which are the main bioactive components of various Chinese medicinals. They have various pharmacological activities such as lowering blood glucose and blood lipids， improving insulin resistance， anti-inflammation， anti-oxidative stress， anti-tumor， and immune modulation. In recent years， it has been frequently verified that the saponins in Chinese medicinals have definite effect in regulating DN， showing multi-target， multi-pathway， multi-system， multi-effect characteristics. Thus， they have broad prospects in the prevention and treatment of this disease. There has been an explosion of research on the treatment of DN with saponins in Chinese medicinals in vivo and in vitro， but there is a lack of systematic and comprehensive summary. Therefore， this study summed up the studies of saponins in Chinese medicinals in the intervention of DN and summarized the mechanisms such as improving glucolipid metabolism， inhibiting oxidative stress， anti-inflammation， anti-apoptosis， regulating autophagy， anti-fibrosis， and protecting podocytes， with a view to providing ideas and references for the development of drugs related to DN.

Chinese Medicine Intervenes in Diabetic Kidney Disease Based on p38 MAPK Signaling Pathway：A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD）， a major microvascular complication of diabetes mellitus， serves as the most common cause of end-stage renal disease worldwide. The progression of DKD is closely related to oxidative stress， inflammatory response， apoptosis， and fibrosis in renal tissues activated by high glucose. Numerous studies have shown that the transduction of the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is involved in the pathological process of DKD in renal tissues， activating various pathological mechanisms， such as oxidation， inflammation， apoptosis， and fibrosis. Therefore， blocking the transduction of the p38 MAPK signaling pathway is beneficial to alleviating DKD. At present， the main treatment principles of western medicine are glucose lowering， lipid lowering， and blood pressure lowering， as well as medications with new drugs renal sodium-glucose co-transporter 2 （SGLT2）， mineralocorticoid receptor， and endothelin receptor， but the progression of DKD still cannot be stopped. The treatment of DKD by traditional Chinese medicine （TCM） has the advantages of simplicity， low cost， and convenience， and the symptoms and root causes can be both treated. In recent years， the basic research on Chinese medicine intervention in DKD has greatly advanced， and p38 MAPK is the key factor of Chinese medicine intervention in DKD. The present study searched and reviewed the literature on the Chinese medicine intervention in the p38 MAPK signaling pathway in DKD treatment in the past decade. The results showed that p38 MAPK interacted with transforming growth factor-β1 （TGF-β1）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nuclear factor-κB （NF-κB）， and other factors to activate fibrosis， inflammation， oxidative stress， and apoptosis. By acting on p38 MAPK and its upstream and downstream factors， Chinese medicine blocked the pathological processes of DKD and inhibited the pathological injury of DKD and the deterioration of renal function. This study is expected to provide new ideas and directions for the prevention and treatment of DKD with Chinese medicine.

Hypoglycemic Effect and Mechanism of Chinese Medicine Saponins： A Review / 中国实验方剂学杂志

Type 2 diabetes mellitus （T2DM） is a chronic metabolic disease characterized by insulin resistance， hyperinsulinemia， and disturbance of glucose and lipid metabolism， with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis， there is no effective treatment， which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources， elevated safety， and low adverse effects. As an essential active ingredient in Chinese medicine， Chinese medicine saponins have a variety of biological activities such as hypoglycemia， hypoglycaemia， anti-inflammation， antioxidation， anti-tumor， and immune modulation. In recent years， numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins， there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore， to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs， this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins， such as improving islet β-cell function， improving insulin resistance， inhibiting glycosidase activity， reducing the inflammatory response， anti-oxidative stress， and regulating intestinal flora， and analyzed the current research problems and development trends.

Effect of Loulianwan on Gut Microbiota in db/db Mice with Type 2 Diabetes Mellitus Based on 16S rRNA Sequencing Technology / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Loulianwan on the gut microbiota of db/db mice with type 2 diabetes mellitus （T2DM）. MethodMale db/m+ mice aged 4-5 weeks were assigned to the normal group， and male db/db model mice of the same age were randomly divided into model group， metformin group （0.25 g·kg-1·d-1）， and Loulianwan group （13 g·kg-1·d-1）， with six mice in each group. Drug intervention lasted five weeks. The body weight， water intake， and fasting blood glucose （FBG） of the mice were recorded every week. After five weeks， the FBG， liver triglyceride （TG）， liver total cholesterol （TC）， glycated serum protein （GSP）， and fasting serum insulin （FINS） were detected， and the insulin resistance index （HOMA-IR） was calculated. The feces in the mouse intestines were collected， and the 16S rRNA sequencing technology was used to detect the structural changes in the fecal gut microbiota of mice in each group. ResultCompared with the normal group， the model group showed increased body weight， water intake， FBG， liver TG， liver TC， GSP， FINS， and HOMA-IR （P<0.01）. Compared with the model group， the Loulianwan group showed reduced water intake， FBG， liver TG， liver TC， GSP， FINS， and HOMA-IR （P<0.01）. The gut microbiota in the Loulian Lills group changed from phylum to genus level. The relative abundance of beneficial bacteria increased and the relative abundance of harmful bacteria decreased. Among them， the abundance of Akkermansia muciniphila， Blautia， Ruminococcus， and Parabacteroides increased （P<0.01）. ConclusionLoulianwan can significantly improve glucose and lipid metabolism in db/db mice with T2DM， and its mechanism may be related to the increase in the abundance of Akkermansia muciniphila， Blautia， Ruminococcus， and Parabacteroides in the intestine.

Traditional Chinese Medicine Treats Diabetic Nephropathy by Inhibiting Pyroptosis and Inflammasome： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is a serious complication of diabetes， a major risk factor for chronic renal failure and end-stage renal disease， a major cause of deaths of diabetic patients， and a major cause of noncommunicable disease-associated deaths in the world. Pyroptosis and inflammasome activation are closely associated with the occurrence and development of DN. They can mediate a variety of pathological changes such as the loss and fusion of podocytes， up-regulated expression of inflammatory cytokines， macrophage infiltration， glomerular mesangial matrix expansion， and increased urinary albumin-to-creatinine ratio， eventually leading to nephron loss and kidney injury. The available studies have reported that the active ingredients in Chinese medicinal herbs or classical prescriptions play a role in the treatment of DN by lowering blood glucose and lipid levels， mitigating insulin resistance， reducing inflammation， alleviating oxidative stress， and regulating immunity. Moreover， the active ingredients can inhibit the activation of inflammasomes and the pyroptosis of renal cells， repair the inflammation-induced damage， improve renal function， and slow the progression of DN， demonstrating definite therapeutic effect. Chinese medicines can treat DN in a multi-target， multi-pathway， and multi-system manner， possessing broad prospects in the prevention and treatment of DN. Despite the extensive studies about the traditional Chinese medicine （TCM） intervention of DN in vivo and in vitro， a comprehensive summary of experimental studies on the TCM intervention of DN model remains to be carried out. This paper reviews the research progress in pyroptosis， inflammasomes， roles of pyroptosis and inflammasomes in DN， and TCM intervention of DN， aiming to provide ideas and reference for the research and development of drugs for this disease.

Quantitative index study on multi-modal image registration quality of pancreatic cancer / 肿瘤

Objective:To identify the anatomical landmarks with stable and consistent performance in both rigid and deformation registrations,and to investigate the feasibility that take them as the quantitative indexes for quantitative evaluation of multimodality image registration for pancreatic cancer in clinical practice. Methods:Twenty-five patients with pancreatic cancer were selected.Both the rigid and deformation registrations were performed between simulated CT and MRI T1-weighted images.Seven anatomical landmarks,which were left adrenal gland,portal vein,celiac trunk artery,superior mesenteric artery,lumbar vertebral body,inferior vena cava and abdominal aorta,were selected.The anatomical landmarks were marked on the simulated CT and the registered MRI,respectively.The distances between the geometric centers of each anatomical landmarks in two kinds of images were statistically analyzed.The Wilcoxon rank sum test was implemented to compare the differences between rigid and deformation registrations.In addition,the correlations between anatomical landmarks were analyzed as well. Results:The mean distances of centers for the seven anatomical markers under rigid registration ranged from 0.405 cm to 1.097 cm,while they ranged from 0.433 cm to 0.740 cm under deformation registration.There was no significant difference in the registration of anatomical markers between rigid and deformation registration,except the left adrenal gland.The registration differences of celiac trunk artery and abdominal aorta were of most stable in 25 patients.Correlation study showed that all anatomical markers except abdominal aorta and inferior vena cava were independent and significant. Conclusion:It is feasible to quantitatively evaluate the registration quality of multimodality image registration for pancreatic cancer by using anatomical landmarks.It is recommended to use celiac trunk artery and abdominal aorta as the anatomical markers in clinical procedure.They are both stable in rigid and deformation registration,and the correlation between them is low,with means they can be used as independent evaluation criteria.

Establishment and application of the physiologically-based pharmacokinetic model of amikacin in elderly patients with renal insufficiency / 中国药房

OBJECTIVE To establish a physiologically-based pharmacokinetic （PBPK） model of amikacin in elderly patients with renal insufficiency. METHODS PK-SIM® software was adopted for model building， optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit， relative residual， and mean folding error （MFE） were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency， and the efficacy and safety of commonly used clinical dosing regimens were evaluated， and the recommended regimens were proposed. RESULTS The established PBPK model of amikacin had good prediction performance in both adult and elderly populations， with the absolute mean of relative residual value of 25%； the MFE of peak concentration （cmax） and area under the plasma concentration curve （AUC0－∞） in all simulation occasions ranged ＞0.5-＜2. The simulation results showed that， compared with healthy adults， no significant clinical difference in cmax was observed in the elderly with renal insufficiency at the same dosing regimen， but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity. CONCLUSIONS The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency， and shows good predictive performance.

Effect of histone methylase EZH2 on proliferation and apoptosis of hypertrophic myocardial cells of AC16 / 国际生物医学工程杂志

Objective:To explore the molecular mechanism of the effect of the histone methylase zeste gene enhancer homolog 2 (EZH2) on the proliferation and apoptosis of human hypertrophic cardiomyocytes AC16.Methods:The AC16 hypertrophic cardiomyocyte model was constructed by adding angiotensin Ⅱ to the AC16 cell culture medium. The cells were divided into four groups, including the blank control group, the angiotensin Ⅱ group, the empty vector + angiotensin Ⅱ group, and the EZH2 overexpression + angiotensin Ⅱ group. The expression levels of EZH2 and brain natriuretic peptide ( BNP) genes were measured using fluorescent quantitative PCR. The EZH2, trimethylation of lysine at position 27 of histone H3 (H3K27me3), and BNP proteins expression were detected by Western Blot. The MTS method was used to detect the proliferation of AC16 cell. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of AC16 cell. Results:Compared with the blank control group, the expression levels of EZH2 and H3K27me3 in the angiotensin Ⅱ group were decreased, the expression level of BNP was increased, cell proliferation was decreased, and apoptosis was increased (all P < 0.001). Compared with the empty vector + angiotensin Ⅱ group, the expression levels of EZH2 and H3K27me3 in the EZH2 overexpression + angiotensin Ⅱ group were increased, the expression level of BNP was decreased, the cell proliferation level was increased, and the apoptosis level was decreased (all P < 0.001). There was no significant difference between the angiotensin Ⅱ group and the empty vector + angiotensin Ⅱ group (all P > 0.05). Conclusions:Histone methylase EZH2 has an effect on the proliferation and apoptosis of AC16 cell, providing a reference for the treatment of myocardial hypertrophy and revealing the exact pathogenesis of myocardial hypertrophy.

Clinical study on the comprehensive treatment of diet and Chinese medicine on type 2 diabetes mellitus based on pattern differentiation / 国际中医中药杂志

Objective:To explore the effectiveness and safety of comprehensive treatment of type 2 diabetes mellitus (T2DM) based on syndrome differentiation and diet.Methods:Prospective clinical study. A total of 147 patients with T2DM from September 2021 to August 2022 who met the inclusion criteria were included in the self-controlled trial. On the basis of diet and exercise intervention, the subjects were treated and observed with comprehensive treatment based on syndrome differentiation for 120 days. The main outcome indicators including TCM symptom score, fasting blood glucose (FPG), 2 hPG, HbA1c , Fasting insulin (FINS), C-peptide(C-PR), and the secondary outcome indicators including blood lipid (TC, TG, HDL-C, LDL-C), blood pressure, and safety indicators were performed before and after treatment.Results:After treatment, the FPG of subjects decreased from (8.75±2.26) mmol/L to (7.05±1.23) mmol/L, 2 hPG decreased from (10.75±3.01) mmol/L to (7.07±0.78) mmol/L, HbA1c decreased from (6.82±1.47)% to (5.49±0.63)%, and FINS decreased from (15.4±9.33) μIU/ml to (8.82±7.28) μIU/ml, C-PR decreases from (1.95±0.91) nmol/L to (1.72±1.53) nmol/L, SBP decreased from (137.51±17.94) mmHg to (125.79±7.57) mmHg, DBP decreased from (82.85±9.65) mmHg to (77.54±6.21) mmHg,TG decreased from (1.57±1.04) mmol/L to (1.25±1.24) mmol/L, HDL-C increased from　(1.48±0.41) mmol/L to (1.66±0.46)mmol/L. The above differences were statistically significant ( P<0.05). Conclusion:The comprehensive treatment of T2DM based on syndrome differentiation and diet can significantly reduce the blood glucose indicators including FPG, 2 hPG, HbA1c, FINS and C-PR, and benefit blood pressure and blood lipids with no adverse reactions.