Effect of Modified Huangqi Biejiatang Combined with Auricular Acupressure on Diabetic Peripheral Neuropathy of Qi-Yin Deficiency Syndrome and Serum MyD88/IκB Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of modified Huangqi Biejiatang combined with auricular acupressure on diabetic peripheral neuropathy （DPN） due to Qi and Yin deficiency and serum myeloid differentiation factor 88/inhibitor of nuclear factor-<italic>κ</italic>B （MyD88/I<italic>κ</italic>B） signaling pathway. Method:One hundred and forty cases were randomly divided into an observation group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70）. In addition to routine treatments like dietary intervention and the regulation of fasting blood glucose （FBG） and blood pressure， the modified Huangqi Biejiatang combined with auricular acupressure was further provided in the observation group， while mecobalamine was administered in the control group. After four-week intervention， the toronto clinical scoring system （TCSS） score， traditional Chinese medicine （TCM） syndrome score， the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve）， glucose metabolism indexes ［fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， and hemoglobin A1c （HbA1c）］， intestinal genera （<italic>Clostridium</italic>， <italic>Prauserella</italic>， <italic>Bacteroides</italic>， and <italic>Faecalibacterium</italic>）， as well as the serum MyD88， I<italic>κ</italic>B<italic>α</italic>， and phosphorylated I<italic>κ</italic>B<italic>α </italic>（p-I<italic>κ</italic>B<italic>α</italic>） levels in the MyD88/I<italic>κ</italic>B signaling pathway before and after treatment were observed in the two groups， for comparing their clinical efficacy and safety. Result:The total effective rate of the observation group was 85.3% （58/68）， which was higher than 48.5% （32/66） of the control group （<italic>χ</italic>²=6.143， <italic>P</italic><0.05）. The comparison with the control group revealed that the scores of TCSS and TCM syndrome， the levels of FPG， 2 h PG， HbA1c， MyD88， and p-I<italic>κ</italic>B<italic>α</italic>， as well as the abundances of <italic>Clostridium</italic> and <italic>Prauserella</italic> in the observation group were decreased （<italic>P</italic><0.05）， while the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve） were significantly accelerated （<italic>P</italic><0.05）. Besides， the abundances of <italic>Bacteroides</italic> and <italic>Faecalibacterium</italic> and I<italic>κ</italic>B<italic>α</italic> level were significantly elevated （<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 1.5% （1/68）， lower than 12.1% （8/66） in the control group （<italic>χ</italic>²=4.328， <italic>P</italic><0.05）. Conclusion:The modified Huangqi Biejiatang combined with auricular acupressure alleviates DPN due to Qi and Yin deficiency， which may be attributed to the regulation of serum MyD88/I<italic>κ</italic>B signaling pathway.

Effect of Modified Fuyuanwan Combined with Auricular Acupressure Bean on Stage Ⅱ， Ⅲ Diabetic Nephropathy and Its Effect on Serum JAK/STAT Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the therapeutic effect of modified Fuyuanwan combined with auricular acupressure bean on stage Ⅱ， Ⅲ diabetic nephropathy and its effect on serum janus kinase （JAK）/ signal transducer and activator of tranions （STAT） signaling pathway. Method:A total of 180 cases were randomly divided into control group and observation group， 90 cases in each group. Losartan potassium， modified Fuyuanwan combined with auricular acupressure bean were given respectively for 12 weeks. Renal function indexes ［blood urea nitrogen （BUN）， serum creatinine （SCr）， urinary albumin excretion rate （UAER）， 24 h urinary protein quantitative （24 h Upor）］， relative abundance of intestinal flora （verruca microflora， scleriobacteriae， deferribacter， proteobacteria）， oxidative stress indicators ［advanced oxidation protein products （AOPPs）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， total superoxide dismutase （TSOD）］， renal blood flow index ［end-diastolic blood flow velocity （EDV）， peak systolic value （PSV）， pulse index （PI）， blood flow resistance index （RI）］， JAK/STAT signaling pathway ［JAK， phosphorylated JAK （p-JAK）， STAT， phosphorylated STAT （p-STAT） were observed before and after treatment. The safety indexes of two groups were evaluated after treatment. The efficacy was observed after treatment and followed up for 1 years and 2 years. Result:After treatment and follow-up for 1， 2 years， the total effective rates of patients in observation group were 97.8% （87/89）， 81.6% （71/87）， 59.8% （49/82）， respectively， observation group which were significantly higher than those in control group of 79.3%（69/87），57.8%（48/83），37.2%（29/78） （<italic>χ</italic>²=4.016， <italic>χ</italic>²=4.503， <italic>χ</italic>²=4.769， <italic>P</italic><0.05）. Compared with control group after treatment， UAER， BUN， SCr， 24 h Upor， firmicutes， actinobacillus， proteobacteria， AOPPs， ROS， PI， RI， p-JAK， p-STAT3 in observation group were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）， microflora verruca， GSH-PX， TSOD， JAK， STAT3 were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， EDV and PSV were significantly accelerated （<italic>P</italic><0.05，<italic>P</italic><0.01）. The incidence of adverse reactions was 1.1% （1/89） in observation group， lower than 13.8% （12/87） in control group （<italic>χ</italic>²=5.127， <italic>P</italic><0.05）. Conclusion:Modified Fuyuanwan combined with auricular acupressure bean can significantly improve the curative effect of stage Ⅱ， Ⅲ diabetic nephropathy， and its mechanism of action may be related to the serum JAK/STAT signaling pathway.

Clinical Efficacy of Modified Huqianwan Combined with Auricular Acupressure with Seeds on Central Precocious Puberty due to Yin Deficiency and Fire Hyperactivity / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huqianwan combined with auricular acupressure with seeds on girls with central precocious puberty （CPP） due to Yin deficiency and fire hyperactivity. Method:A total of 150 cases were randomly divided into three groups （A group，B group， and C group），with 50 cases in each group. The cases received modified Huqianwan，Zhibo Dihuangwan，and modified Huqianwan combined with auricular acupressure with seeds， respectively， for 12 weeks. The traditional Chinese medicine （TCM） symptoms，bone age difference/chronological age difference （ΔBA/ΔCA）， predicted adult height （PAH），ovarian volume，uterine volume，breast nodule index，serum sex hormones ［follicle-stimulating hormone （FSH），luteinizing hormone （LH），and estradiol （E₂）］，and serum kisspeptin-1 （KISS-1）/G protein-coupled receptor 54 （GPR54）/hypothalamic gonadotropin-releasing hormone （GnRH） signaling pathway of the three groups were observed before and after treatment. The clinical efficacy and safety of the three groups were evaluated. Result:The total effective rate was 97.9% in the C group， which was higher than 81.3% in the A group （<italic>χ</italic>²=4.516，<italic>P</italic><0.05） and 71.4% in the B group （<italic>χ</italic>²=5.162，<italic>P</italic><0.05）. Compared with the results in the A group after treatment，TCM syndrome，ΔBA/ΔCA，E₂，LH，KISS-1，GPR54，and GnRH decreased（<italic>P</italic><0.05），and ovarian volume，uterine volume，and breast nodule index were reduced （<italic>P</italic><0.05），but PAH increased in the C group （<italic>P</italic><0.05）. Compared with the B group after treatment，the C group showed decreased TCM syndrome，ΔBA/ΔCA， FSH，E₂，LH，KISS-1，GPR54，and GnRH （<italic>P</italic><0.05），reduced ovarian volume，uterine volume，and breast nodule index （<italic>P</italic><0.05），and increased PAH（<italic>P</italic><0.05）. During the study，there was one case of anorexia in the A group，and no obvious adverse reactions were found in the B group and the C group. Conclusion:Modified Huqianwan combined with auricular acupressure with seeds can significantly increase the PAH of girls with CPP due to Yin deficiency and fire hyperactivity and improve the serum sex hormones and the KISS-1/GPR54/GnRH signaling pathway.

Investigating Relationship Between Renal Damage and Endoplasmic Reticulum Stress in Diabetic Kidney Disease Rats with Blood Stasis Syndrome Based on Combination of Disease and Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of blood stasis syndrome on renal damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD) rats, and to explore the relationship between renal syndrome of blood stasis damage and ERS in DKD rats. Method:The 50 Male SD rats of SPF level were selected to establish DKD rat model by high fat and high sugar diet combined with intra-abdominal injection of streptozotocin(STZ). They were randomly divided into normal group, diabetes mellitus group and diabetes mellitus and blood stasis syndrome group（0.05 mg·kg-1）, among which diabetes mellitus and blood stasis syndrome group was prepared by dextran method. The general conditions, hemorheology indexes, 24 h urine protein, serum creatinine and renal pathology of the rats in each group were observed. Immunohistochemical analysis, Western blot and Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR)were used to detect mRNA and protein expressions of endoplasmic reticulum stress-related proteins glucose regulated protein 78(GRP78), activating transcription factor-6(ATF6) and renal fibrosis index fibronectin(FN), and alpha smooth muscle actin(α-SMA). Result:Compared with normal group, the rats in diabetes mellitus group showed polyphagia, polyuria and weight loss, increased hemorheology index of whole blood viscosity and plasma viscosity(P<0.05，P<0.01), increased 24 h urine protein, serum creatinine and urea nitrogen(P<0.01), and increased renal pathology, and increased mRNA and protein expression of GRP78, ATF6, FN and α-SMA(P<0.05，P<0.01). After dextran preparation of blood stasis model. Diabetes mellitus and blood stasis syndrome group increased mortality, signs of change is more obvious in the diabetic group, whole blood viscosity, plasma viscosity, 24 h urine protein ration, serum creatinine and urea nitrogen were significantly higher than those in diabetic rats(P<0.01), pathological changes aggravated in the diabetes group. At the same time， mRNA and protein expressions of GRP78, ATF6, FN, and α-SMA in renal tissue were significantly higher than those in diabetic mellitus group(P<0.05，P<0.01). Conclusion:Under the combined disease and syndrome model, the blood stasis syndrome may further aggravate the pathological damage of the kidney of DKD rats, and is related to the enhancement of ERS in the kidney of DKD rats.

Effect of Yiqi Huoxue Tongmai Method in Treating Atherosclerotic Lesions of Lower Extremity of Diabetes / 中国实验方剂学杂志

Objective:To observe the effect of Yiqi Huoxue Tongmai method in treating lower extremity atherosclerotic disease (LEAD) and on hemodynamic index and vascular endothelial function. Method:One hundred and five patients were randomly divided into control group (52 cases) and observation group (53 cases) by random number table. Patients in control group were treated for controlling blood sugar, blood fat, blood pressure and given aspirin enteric-coated tablets, 100 mg/day, cilostazol tablets, 100 mg/day, 2 times/day. In addition to the therapy of control group, patients in observation group were given modified Danggui Sini Tang and Buyang Huanwu Tang for oral and washout, 1 dose/day. The treatment course lasted for 12 weeks. Before and after treatment, ankle brachial index (ABI) was detected. And intimal thickness of shallow femoral shallower, arteriae tibialis posterior and arteriae dorsalis pedis, hardening degree, patch size and degree of stenosis were detected by color Doppler ultrasound diagnostic apparatus. Qi deficiency and blood stasis syndrome were scored. And levels of the whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), D-dimer (D-D), fibrinogen (FIB), erythrocyte electrophoresis, fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), serum 25-hydroxyvitamin D3 ([25(OH)D3]), endothelin (ET), nitric oxide (NO) and homocysteine (Hcy) were detected. Result:By the rank sum test, the clinical effect in observation group was better than that in control group (Z=2.371, PPPPPP3] and NO were higher than those in control group (PConclusion:Modified Danggui Sini Tang and Buyang Huanwu Tang can ameliorate hemodynamics and vascular endothelial function, improve ABI, relieve arteriosclerosis and narrow degrees, and alleviate clinical symptoms.