Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium （KDBS-TE） by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group， model group， and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs， lncRNAs， and miRNAs were screened， and the disease-related specific competitive endogenous RNA （ceRNA） regulatory network was constructed. Furthermore， the gene ontology （GO） functional annotation and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group， the model group showed endometrial dysplasia， decreased endometrial thickness and endometrial/total uterine wall thickness ratio （P<0.01）， and differential expression of 18 circRNAs， 410 lncRNAs， and 7 miRNAs. Compared with the model group， the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness （P<0.05）. In addition， 21 circRNAs， 518 lncRNAs， and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs， 34 miRNAs， and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs， 10 miRNAs， and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway， autophagy-animal， axon guidance， etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs， lncRNAs， and miRNAs in the uterus and the ceRNA network.

Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Effect of sequential intervention of Traditional Chinese Medicine on pregnancy outcomes in patients with history of spontaneous abortion due to kidney deficiency / 国际中医中药杂志

Objective:To investigate the effect of the Traditional Chinese Medicine (TCM) intervention on the pregnancy outcomes of patients with a history of spontaneous abortion due to kidney deficiency syndrome.Methods:From February 2015 to July 2020, 41 patients with a history of spontaneous abortion due to kidney deficiency in our hospital were selected as the observation group, and 42 healthy pregnant women with no history of spontaneous abortion were selected as the control group. The observation group was treated with the TCM sequential intervention therapy with treatment principles of nourishing the kidney and promoting blood circulation before pregnancy and solidifying the kidney and tonifying after pregnancy, while the control group received no TCM intervention before and after pregnancy. Color Doppler ultrasonography was used to record the follicle diameter, endometrial thickness and shape during pregnancy, and B-ultrasound was used to monitor the NT value at 12 weeks. The serum D-dimer level was detected by ELISA, and the serum progesterone ,estradiol, human chorionic gonadotropin (HCG) levels were detected by radioimmunoassay. The conditions of term delivery, premature delivery and abortion were observed in both groups, and the successful delivery rate and term delivery rate were compared.Results:On the 30+, 40+, and 50+ days of pregnancy, there was no significant difference in serum progesterone, estradiol, and HCG levels between the two groups ( P>0.05). There was no significant difference in NT value between the two groups at 12 weeks of gestation ( P>0.05). The successful delivery rate of the observation group was 90.2% (37/41), the full-term delivery rate was 85.4% (35/41), the successful delivery rate of the control group was 100.0% (42/42), and the full-term delivery rate was 95.2% (40/42), there was no significant difference in the successful delivery rate and term delivery rate between the two groups ( P>0.05). Conclusion:The sequential intervention of TCM the principle of invigorating kidney and promoting blood circulation before pregnancy and strengthening kidney and calming fetus after pregnancy can improve the pregnancy outcome of spontaneous abortion patients with kidney deficiency syndrome.

Efficacy of Bushen Huoxue Decoction for Patients with Intra Uterine Adhesions After Trans Cervical Resection Adhesions Operation and Effect on Fibrotic Factors / 中国实验方剂学杂志

Objective:To discuss the efficacy of Bushen Huoxue decoction for recovery in patients with intra uterine adhesions （IUA） after trans cervical resection adhesions （TCRA） operation， and to investigate its effect on fibrosis factor. Method:The 110 patients were randomly divided into two groups by random number table （55 cases for control group and 55 cases for observation group）. The patients in both groups got TCRA， and after the operation， they got estradiol valerate tablets+progesterone capsules. The patients in control group additionally got Jinfengwan before meals， 10 g/time， 2 times/day. Patients in observation additionally got syndrome differentiation and treatment by Bushen Huoxuetang， 1 dose/day. The treatment course was 3 months in both groups， and 6 months' follow-up was recorded. Before and after treatment， menstrual volume， period and cycle were recorded. During the follow-up， pregnancy， ectopic pregnancy and abortion were also recorded. Endoscopy and vagina color Doppler ultrasound were conducted to detect endometrial thickness， uterine volume， resistance index （RI）， pulsation index （PI） and blood flow index （FI）. Scores of IUA and syndrome of kidney deficiency and blood stasis were graded. At the 6^th months after treatment， rate of intrauterine re-adhesion was recorded. Levels of transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁）， connective tissue growth factor （CTGF）， matrix metalloproteinase inhibitor-1 （TIMP-1）， platelet-derived growth factor （PDGF）， insulin-like growth factor-1 （IGF-1） and matrix metalloproteinase-9 （MMP-9） were detected， and safety was evaluated. Result:Total effective rate of clinical efficacy was 96.36% （53/55） in observation group， higher than 83.64% （46/55） in control group （<italic>χ</italic>²=4.959， <italic>P</italic><0.05）. Recovery rate of menstrual volume， period and cycle were 92.73% （51/55）， 90.91% （50/55）， and 94.55% （52/55） in observation group， higher than 72.73% （40/55）， 76.36% （42/55）， and 76.36% （42/55） in control group（<italic>χ</italic>²=7.698，<italic>χ</italic>²=4.245，<italic>χ</italic>²=7.313，<italic>P</italic><0.05， <italic>P</italic><0.01）. During the follow-up， rate of intrauterine re-adhesions was 23.64% （13/55） in observation group， lower than 43.64% （24/55） in control group （<italic>χ</italic>²=4.927，<italic>P</italic><0.05）. Pregnancy rate was 45.45% （25/55）， higher than 25.45% （14/55） in control group（<italic>χ</italic>²=4.807，<italic>P</italic><0.05）. Score of syndrome of kidney deficiency and blood stasis and IUA scores in observation group were lower than those in control group （<italic>P</italic><0.01）. Endometrial thickness， uterine volume， and FI were higher than those in control group （<italic>P</italic><0.01）. Levels of RI， PI， TGF-<italic>β</italic>₁， CTGF， PDGF， IGF-1 and TIMP-1 were lower than those in control group （<italic>P</italic><0.01）， while level of MMP-9 was higher than that in control group （<italic>P</italic><0.01）. No adverse reactions related to traditional Chinese medicine were found. Conclusion:Bushen Huoxue decoction can promote the recovery of menstruation， increase the thickness of endometrium， improve the blood circulation of uterus， regulate the expression of fibrogenic factors<italic> in vivo</italic>， prevent and treat intrauterine adhesions， reduce the rate of intrauterine re-adhesions， and improve the rate of pregnancy， with a good comprehensive effect and high safety for clinical use.

Clinical efficacy of Bushen Huoxue Culuan Formula in treatment of infertility caused by diminished ovarian reserve due to kidney deficiency and blood stasis / 中国中药杂志

To study the clinical efficacy and safety of Bushen Huoxue Culuan Formula in treating infertility caused by diminished ovarian reserve(DOR) with kidney deficiency and blood stasis. A total of 100 DOR patients treated at Xiyuan Hospital, Acupuncture Hospital and Clinic of China Academy of Chinese Medical Sciences from 2017 to 2020 in line with the inclusion criteria were selected and randomly divided into experimental group and control group at the ratio of 1∶1. The experimental group was treated with Bushen Huoxue Culuan Formular, while the control group was treated with Climen and Clomiphene for 3 menstrual cycles. The ovulation rate, pregnancy rate, pregnancy success rate, serum hormone levels, and traditional Chinese medicine(TCM) symptom scores were observed in the 2 groups. The total effective rate was 92.00% in the experimental group and 72.00% in the control group, with a statistical difference between the two groups(P<0.01); the experimental group was superior to the control group in reducing FSH level, increasing AMH level, improving TCM symptoms, increasing pregnancy rate and pregnancy success rate, with a significant difference(P<0.05). There was no abnormal safety indicator and adverse reaction. Bushen Huoxue Culuan Formular is effective in treating infertility caused by DOR due to kidney deficiency and blood stasis, with a safety and reliability.

Kidney-tonifying and blood-activating in treatment of infertility due to pelvic inflammatory disease:clinical experience of Professor MA Kun / 中国中药杂志

Pelvic inflammatory disease(PID) has become one of the leading causes of female infertility, with an increasing incidence in recent years. Modern medicine believes that risk factors of PID will affect the formation of eggs and embryo implantation, especially on the encounter of gametes, fertilization, and transport of fertilized eggs to the uterine cavity. Therapies for infertility due to PID include medication, sonographic hydrotubation, surgery, and assisted reproductive technology. Professor Ma Kun believes that the disease is located in the uterus with appendages with the main pathogenesis of kidney deficiency and blood stasis. Blood stasis is the pathological basis, and kidney deficiency is the fundamental pathogenesis, which exhibits deficiency-excess in complexity. Kidney deficiency will cause blood stasis over time, while blood stasis will aggravate kidney deficiency in turn, making PID-induced infertility refractory. In clinical practice, basic therapies follow the principles of kidney-tonifying and blood-activating, removing blood stasis, dredging collaterals, and coordinating thoroughfare and conception vessels. The oral administration of Chinese medicine combined with enema, external application, and external washing displays better efficacy in improving the pelvic microenvironment and increasing the pregnancy rate and pregnancy success rate in the treatment of PID-induced infertility.

Advantages of integrated Chinese and western medicine in diagnosis and treatment of anovulatory infertility due to kidney deficiency and blood stasis / 中国中药杂志

Under the guidance of the theory of "kidney governing reproduction", this study demonstrated the mechanism of six types of ovulatory infertility caused by kidney deficiency and blood stasis, including anovulatory bleeding, polycystic ovary syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, luteal phase deficiency, and primary ovarian insufficiency. A series of studies have confirmed that integrated Chinese and western medicine can increase the responsiveness of the ovaries to gonadotropins and improve ovarian function by regulating the effects of estradiol(E_2), prolactin(PRL), and reducing follicle-stimulating hormone(FSH), luteinizing hormone(LH), progestin(P), and testosterone(T). It can also improve ovulation rate and pregnancy success rate by promoting follicle development, discharging, and synchronizing endometrial growth. This study illustrated the diagnosis and treatment of ovulatory infertility caused by kidney deficiency and blood stasis with integrated traditional Chinese and Western medicine in the "disease-syndrome-symptom" research mode, and highlighted the traditional Chinese medicine(TCM) idea of differentiating diseases based on syndromes and unique advantages of the combination of disease differentiation and syndrome differentiation, and interpreted TCM principle of "treating different diseases with the same method".

Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis / 中国针灸

OBJECTIVE@#To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis.@*METHODS@#A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups.@*RESULTS@#The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (@*CONCLUSION@#Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

Clinical Efficacy on Yishen Tongluofang for Treatment of Male Infertility with Deficiency and Stasis of Kidney / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Yishen Tongluofang in treating oligosperm type male infertility with kidney deficiency and blood stasis syndrome and explore its effect on serum sex hormones and seminal plasma microenviro. Method:One hundred and four patients were randomly divided into observation group and control group with 52 cases each. Patients in control group took compound Xuanju capsules orally， 3 capsules/time， 3 times/day. Patients in observation group took Yishen Tongluofang， 1 dose/day. Treatment courses continued three months and followed up for three months in both groups. The pregnancy situations of spouses within six months were recorded. Examination of semen parameters before and after treatment and score of kidney deficiency and blood stasis syndrome were conducted. The levels of seminal plasma zinc， fructose， elastase， acid phosphatase and <italic>α</italic>-glucosidase， serum follicle stimulating hormone （FSH）， luteinizing hormone （LH）， prolactin （PRT） and testosterone （T） were detected before and after treatment. Result:During the observation period of six months， the pregnancy rate of spouses in the observation group was 22.00%， higher than 10.00% in the control group， but the difference was not statistically significant （<italic>χ</italic>²=2.678，<italic>P</italic>>0.05）. The clinical efficacy in the observation group was better than that of the control group （<italic>Z</italic>=2.326，<italic>P</italic><0.01）. Sperm concentration， sperm motility， sperm motility， normal morphological sperm and linear movement speed of the observation group were all superior to those of the control group<italic> </italic>（<italic>P</italic><0.01）. The levels of zinc and fructose in seminal plasma of the observation group were higher than those of the control group （<italic>P</italic><0.01）， and the score of kidney deficiency and blood stasis syndrome was lower than that of the control group （<italic>P</italic><0.01）. Serum FSH， LH and PRT levels in the observation group were lower than those in the control group （<italic>P</italic><0.01）， and the T level was higher than that in the control group （<italic>P</italic><0.01）. The seminal plasma elastase of the observation group was lower than that of the control group， while the levels of acid phosphatase and <italic>α</italic>-glucosidase were higher than those of the control group （<italic>P</italic><0.01）. Conclusion:Yishen Tongluofang can significantly improve sperm parameters， regulate the level of sex hormones and seminal plasma environment in patients with oligosperm type male infertility， and improve the tendency of spouse pregnancy. Its clinical efficacy is better，so it is worthy of further research and application.

Modified Wenjingtang Affects Caspase-8， MMP-9， N-cadherin and E-cadherin in Local Microenvironment of EM Rats with Kidney Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis. Method:Healthy non-pregnant female Sprague-Dawley （SD） rats of SPF grade were randomly divided into the blank group and experimental group. After being modeled via soaking in ice water and subcutaneous injection of epinephrine hydrochloride， the ones in the experimental group were further divided into the sham operation group and EM model group， with the former only undergoing laparotomy and the latter further receiving autologous endometrial transplant for triggering EM. The successfully modeled rats with EM due to kidney deficiency and blood stasis were randomized into the positive drug （danazol， 63 mg·kg^-1） group and low- （5 g·kg^-1）， medium- （10 g·kg^-1）， and high-dose （20 g·kg^-1） modified Wenjingtang groups. The corresponding drugs were administered by gavage， once per day， for four weeks. Then the ectopic and eutopic endometrial tissues were stained with hematoxylin-eosin （HE） to observe the histopathological changes. The protein and mRNA expression levels of cysteinyl aspartate-specific proteinase-8 （Caspase-8）， matrix metalloproteinase-9 （MMP-9）， N-cadherin， and E-cadherin were detected by immunohistochemistry （IHC）， Western blotting， and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:The IHC and Western blot revealed that the protein expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly increased as compared with those in the sham operation group （<italic>P</italic><0.01）， while the levels of Caspase-8 and E-cadherin was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the danazol and low-， medium-， and high-dose modified Wenjingtang groups exhibited obviously down-regulated MMP-9 and N-cadherin protein expression in eutopic and ectopic endometrial tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）， but up-regulated Caspase-8 and E-cadherin （<italic>P</italic><0.05， <italic>P</italic><0.01）. Real-time PCR uncovered that the mRNA expression levels of MMP-9 and N-cadherin in eutopic and ectopic endometrial tissues of the model group were significantly elevated as compared with those in the sham operation group （<italic>P</italic><0.01）， whereas the levels of Caspase-8 and E-cadherin significantly declined （<italic>P</italic><0.01）. The comparison with the eutopic endometrial tissue in the model group showed that the mRNA expression levels of MMP-9 and N-cadherin in the danazol group and high- and medium-dose modified Wenjingtang groups were significantly down-regulated， while those of Caspase-8 and E-cadherin were significantly up-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Modified Wenjingtang alleviates the immunosuppression and blocks the angiogenesis in EM rats with kidney deficiency and blood stasis syndrome by regulating the expression of such cytokines as Caspase-8， MMP-9， N-cadherin， and E-cadherin， thus exerting the therapeutic effect against EM. The above-mentioned micro-indicators are potential markers reflecting the disease （EM）， syndrome （kidney deficiency and blood stasis）， and pathological mechanisms （immunosuppression and angiogenesis）.

Clinical Efficacy of Modified Bushen Huoxuetang Combined with LCP in Treatment of Nonunion of Limb Long Bone Shaft Fracture / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of modified Bushen Huoxuetang combined with autologous bone grafting and locking compression plate （LCP） in treating nonunion of long bone fractures， and the effect on microcirculation， osteogenic differentiation factor and bone metabolism index. Method:A total of 70 patients were randomly divided into control group and observation group by random number table， with 35 cases in each group. Patients in both groups received LCP. Patients in control group got Dieda Shenggu granule， 10 g/time， 1 time/day. Patients in observation group got Bushen Huoxuetang， 1 dose/day. The course of treatment lasted for 3 months， and 3-month follow-up data were recorded. On a weekly basis， the main symptoms， such as pain， tenderness， longitudinal percussion pain and swelling were checked， and the time of disappearing of main symptoms and signs were compared. On a weekly basis， a X-ray examination was performed for callus formation and fracture line， and the fracture healing time was recorded. Before and after treatment， Fugl-Meyer （FMA） was scored， and levels of fibrinogen （FIB）， whole blood viscosity （BV） （high shear， low shear）， plasma viscosity （PV）， platelet aggregation rate （PAR）， <italic>D</italic>-Dimer （<italic>D</italic>-D）， bone morphogenetic protein-2 （BMP-2）， BMP-7， insulin-like growth factor-1 （IGF-1）， vascular endothelial growth factor （VEGF）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， osteocalcin （BGP）， osteoprotegerin （OPG）， procollagen type Ⅰ N-terminal propeptideserum amino pro peptide （PINP）， serum type 1 collagen cross-linked C-terminal peptide （S-CTX） and serum tartrate resistant acid phosphatase （TRACP） of type I procollagen were detected， and the safety was evaluated. Result:Disappearance time of symptoms and signs and fracture healing time in observation group were all lower than those in control group （<italic>P</italic><0.01）. At the third month after treatment， and during the three-month follow-up， scores of callus and FMA （upper and lower limbs） in observation group were all higher than those in control group （<italic>P</italic><0.01）. Levels of <italic>D</italic>-D， FIB， PAR， BV and PV （high-cut and low-cut）， BMP-2， BMP-7， IGF-1， VEGF， TGF-<italic>β</italic>₁， S-CTX and TRACP were all lower than those in control group （<italic>P</italic><0.01）， whereas levels of BGP， OPG and PINP were higher than those in control group （<italic>P</italic><0.01）. The curative effect of fracture healing was better than that of control group （<italic>Z</italic>=1.977， <italic>P</italic><0.05）. And the limb function recovery was superior to that in control group （<italic>Z</italic>=1.970， <italic>P</italic><0.05）. Conclusion:Based on autogenous bone and LCP， modified Bushen Huoxuetang can promote the fracture healing， shorten the course of disease， and promote the recovery of limb function， with a good clinical efficacy. It can improve microcirculation， promote the expression of osteogenic differentiation factor， regulate bone metabolism， and play a role in promoting fracture healing， with a safety in clinical use.

Effect of Modified Shoutaiwan on Recurrent Abortion Due to Prethrombotic Status and Effect on Coagulation Factors / 中国实验方剂学杂志

Objective::To observe the efficacy of modified Shoutaiwan on recurrent abortion due to prethrombotic status with kidney deficiency and blood stasis and investigate its effect on coagulation factors. Method::The 100 cases were randomly divided into control group and observation group, 50 cases in each group. Bushen Yangxue capsule + enoxaparin sodium were given in control group, while modified Shoutaiwan + enoxaparin sodium were given in observation group, with a treatment course of 60 d in both groups. The serum clotting factor activated protein S (PS), activated protein C (PC), platelet aggregation function (PAF), platelet aggregation rate (PagT), antithrombin (AT), lupus anticoagulant material positive positive predictive value (LA), anti cardiolipin antibody positive rate of positive predictive value (ACA), plasminogen activator inhibitor-1(PAI-1), tissue factor (TF), fibrinogen (Fig), fibrinogen (FIB), fibrinogen alpha granule membrane glycoprotein-140 (GMP-140), fibrinogen fragment (F1+ 2), tissue fibrinogen activation factor (t-PA), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were observed. Clinical efficacy, pregnancy rate, traditional Chinese medicine(TCM) syndromes and adverse reactions were compared between the two groups. Result::4 cases withdrew from the study. The total effective rate in observation group was 97.9% (48/49), higher than 85.1% (40/47) in control group (χ2=5.713, P<0.05). The pregnancy rate in observation group was 89.8% (44/49), higher than 70.2% (33/47) in control group (χ2=6.351, P<0.05). The score of traditional Chinese medicine syndromes in observation group was lower than that in control group. The indexes of PS, PC, AT, TF, Fig, FPA, APTT and TT in observation group were significantly higher than those in control group (P<0.05), while PAF, PagT, LA, ACA, PAI-1, PAP, TAT, FIB, GMP-140, F1+ 2, t-PA, D-D and PT were lower than those in control group (P<0.05). The incidence of adverse reactions in observation group was 10.2% (5/49), lower than 35.4% (17/48) in control group (P<0.05). Conclusion::Modified Shoutaiwan can effectively improve the clinical symptoms of recurrent abortion due to prethrombotic status and improve the coagulation factors in patients with kidney deficiency and blood stasis.

Efficacy of Modified Bushen Huoxuetang on Kidney Deficiency and Blood Stasis Type Early Unexplained Recurrent Abortion and Its Effect on Intestinal Flora / 中国实验方剂学杂志

Objective::To explore the clinical efficacy of modified Bushen Huoxuetang on kidney deficiency and blood stasis type early unexplained recurrent abortion and its effect on intestinal flora. Method::Totally 90 patients with kidney deficiency and blood stasis type early unexplained recurrent abortion were selected from March 2017 to October 2018.According to the random number table, they were divided into control group and observation group, with 45 cases in each group. The control group was given Bushen Huoxue capsule, while the observation group was given modified Bushen Huoxuetang. After treatment, the clinical efficacy, traditional Chinese medicine (TCM) syndrome scores and adverse reactions of two groups were compared, and the changes of serum inflammatory factors, coagulation function and intestinal flora were detected before and after treatment. Result::After treatment, the total effective rate of the observation group was 91.11%, which was higher than 77.78%of the control group (P<0.05). The scores of TCM syndromes in observation group were significantly lower than that in control group (P<0.05). The levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) in the observation group were significantly lower than those in control group (P<0.05). The thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) in observation group were significantly higher than those in control group, while fibrinogen (FIB) was significantly lower than that in control group (P<0.05). The numbers of enterococcus, yeast and Enterobacter in observation group were significantly lower than those of control group, while the numbers of bifidobacteria and Lactobacillus in observation group were significantly higher than those of control group (P<0.05). The incidence of adverse reactions in observation group was 11.11%, which was lower than 28.89%of the control group (P<0.05). Conclusion::Modified Bushen Huoxuetang has a good clinical efficacy in treating kidney deficiency and blood stasis type early unexplained recurrent abortion, and can reduce the TCM syndrome score. Its mechanism may be related to the reduction of inflammation, and improvement of coagulation function and intestinal flora, with a good safety.

Clinical Observation of Jiawei Bushen Huoxuetang Combined with Fumigation of Traditional Chinese Medicine After Operation of Vertebral Compression Fracture / 中国实验方剂学杂志

Objective: To observe the effect of Jiawei Bushen Huoxuetang on osteoporotic vertebral compression fractures (OVCF), bone density and bone metabolism. Method: One hundred and sixteen patients with OVCF operation were randomly divided into control group (58 cases) and observation group (58 cases) by random number table. Patients in control group got Alendronate sodium tablets, 70 mg/time, 1 time/week. Menatetrenone soft capsules, 15 mg/time, 3 times/days after meals. Calcium carbonate D3 chewable tablets (Ⅱ), 1 tablet/time, 2 times/days. Based on the treatment in control group, patients in observation group received additional Jiawei Bushen Huoxue decoction, 1 dose/day. The course of treatment was 24 weeks in both groups. The treatment of traditional Chinese medicine(TCM) fumigation was used in combination with the TCM for 2 weeks. At the 4th, 8th, 12th and 24th weeks after treatment, pain degree of waist and back were evaluated by pain visual analogue scale (VAS), and waist dysfunction was evaluated by Oswestry disability index (ODI). Before and after treatment, anterior vertebral height (AVBH), Cobb, femoral neck, lumbar spine bone mineral density and Chinese osteoporosis quality of life scale were evaluated. Before and after treatment, levels of carboxy terminal propeptide of type I collagen (CICP), C-terminal cross-linking peptide of type I collagen (CTX-I), tartrate resistant acid phosphatase (TRACP), bone alkaline phosphatase (BALP) and bone glaprotein(BGP) were detected. Result:By rank sum test, the clinical efficacy in observation was better than that in control group (Z=2.026, Pth, 8th, 12th and 24th weeks after treatment, scores of lumbago and back pain VAS and ODI were lower than those in control group (PPPPPConclusion:Jiawei Bushen Huoxuetang can enhance bone mineral density, regulate bone metabolism, reduce back pain, promote healing of fracture, and ameliorate osteoporosis, with obvious clinical efficacy.

Establishment of premature ovarian insufficiency kidney deficiency and blood stasis pattern mouse model with Tripterygium wilfordii polyglycoside for Bushen Culuan Decoction therapy / 中国中药杂志

To establish a mouse model of premature ovarian insufficiency( POI) with kidney deficiency and blood stasis pattern by Tripterygium wilfordii polyglycoside( TWP) gavage,and to evaluate the ovarian function and fertility of the model,in order to find Bushen Culuan Decoction therapeutic mechanism. 60 SPF level Blab/c female mice with normal estrous cycle were randomly divided into 6 groups of 10 each: blank group 1( BG1),blank group 2( BG2),blank fertility group( BFG),model group( MG),model recovery group( MRG) and model fertility group( MFG). The mice in three model groups were treated by gastric gavage with TWP suspension 40 mg·kg-1 twice a day for 14 days,while the mice in three blank groups were treated by gastric gavage with same volume normal saline for 14 days. The mice in BG1 and MG were sacrificed and dissected on day 15. The mice in BG2,BFG,MRG and MFG were returned normal feeding from day 15 and were sacrificed and dissected on day 29. The mice in BFG and MFG were cohabited with male mice with a ratio of 2 ∶1( female ∶male) from day 15. The general situation and estrous cycles of all mice were observed every day. Serum sex hormone levels,ovarian index,uterine index,ovarian morphology,follicle count,ovarian VEGF and ES index were observed within the mice in BG1,BG2,MG and MRG. Pregnancy rate,litter size,survival number of newborn mice and male-female proportion were reported within the mice in BFG and MFG. In model establishing stage,the body weight of mice significantly decreased( P <0. 05) in MG and MFG. Compared with BG1,the mice in model group had irregular estrous cycle,decreased ovarian and uterine indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression and decreased ES expression( P <0. 05). Compared with blank group 2,the mice in model recovery group had irregular estrous cycle,increased FSH level,decreased ovarian indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression( P<0. 05). Compared with blank fertility group,the mice in model fertility group had smaller litter size and newborn mice survival count( P<0. 05). Gastric gavage with TWP 40 mg·kg-1 twice a day for 14 days is a feasible way to establish a POI kidney deficiency and blood stasis pattern mouse model. The mice ovarian functions didn't recovery on day 14 after stopping TWP intervening,which could suggest the effectiveness of subsequent therapeutic intervention.

Clinical experience of Bushen Huoxue therapy in treatment of infertility due to endometriosis / 中国中药杂志

Endometriosis is a common and difficult gynecological disease. The incidence of endometriosis has been increasing year by year. Because endometriosis mostly occurs in childbearing age,it can cause persistent damage to the fertility of patients,and is an important cause of infertility. Although endometriosis is a benign disease,it has malignant behavior,and is easy for relapse and metastasis and difficult to treat in clinic. Early diagnosis,comprehensive evaluation,formulation of programs and timely treatment play an important role in protecting patients' fertility. The pathogenesis of endometriosis is still unclear in modern medicine. Drugs,surgery and assisted reproductive technology are the main therapies. The author has achieved a good efficacy in the long-term treatment of infertility due to endometriosis. She believes that the disease is caused by kidney deficiency and blood stasis. They are cause and effect to each other,which form a vicious circle. In view of the basic pathogenesis of kidney deficiency and blood stasis,we should make good use of the method of Bushen Huoxue,and emphasize the treatment by stages: promoting blood circulation and removing blood stasis,and treating diarrhea with purgative in the menstrual stage; nourishing kidney and blood,and regulating thoroughfare and conception vessels in the postmenstrual stage; warming kidney and supporting Yang,and dredging collaterals and hastening excretion in the interval stage;and tonifying kidney and spleen,and managing Qi and activating blood in the premenstruum stage. Leech is commonly adopted in clinic prescriptions to remove accumulation of persistent blood stasis and regulate mood,and combined with enema of traditional Chinese medicine,hot compress and other external therapies to enhance the curative effect.

Infertility caused by salpingitis treated based on theory of kidney deficiency and blood stasis / 中国中药杂志

Infertility caused by salpingitis is one of the main causes of secondary infertility in women. In recent years,the incidence has been increasing year by year. Modern medicine believes that this disease is a complication due to incomplete or delayed treatment of acute and chronic salpingitis,with no satisfactory drug therapy at present. Clinical therapies mainly include surgical treatment,interventional treatment and assisted reproductive technology. After summarizing the experience of predecessors and the clinical practice of treating infertility for many years,the author considers that the disease location is the cell veins,and the nature is mostly mixed of deficiency and excess. Kidney deficiency and blood stasis are the main pathogenesis of infertility caused by salpingitis. Blood stasis is the pathological basis,while kidney deficiency is the fundamental pathogenesis. Long-term kidney deficiency will lead to blood stasis,and blood stasis will aggravate kidney deficiency. Both of them are cause and effect to each other. Infertility caused by salpingitis is difficult to cure. Based on the theory of kidney deficiency and blood stasis,the basic principles of clinical treatment are tonifying kidney and activating blood circulation,removing blood stasis and dredging collaterals. Oral administration with traditional Chinese medicine combined with external therapies,such as enema,external application,acupuncture and moxibustion,have been achieved a good efficacy in repairing fallopian tube function and improving pregnancy rate. Therefore,the treatment of infertility caused by salpingitis based on " kidney deficiency and blood stasis" is worthy of further discussion in both clinical and experimental aspects.

Clinical observation of modified Shenqi Decoction in the treatment for patients with early-to-middle stage nontraumatic osteonecrosis of femoral head / 中成药

AIM To investigate the clinical therapeutic effects of modified Shenqi Decoction in treating earlyto-middle stage nontraumatic osteonecrosis of femoral head (NONFH) due to kindey deficiency and blood stasis syndrome,and its impacts on serum TNF-α,CRP,NO,SOD as well.METHODS Totally,104 cases of eligible patients were randomly divided into traditional Chinese medicine (TCM) group,chemical medicine group and TCM combined with chemical medicine group,38 cases in each group,for a three-month course of treatment.The TCM group was dosed with modified Shenqi Decoction,the chemical medicine group with sodium alendronate,and the TCM combined with chemical medicine group with both modified Shenqi Decoction and sodium alendronate.The Harris SF-36,SF-36,FPS-R and TCM symptoms assessment were applied to estimating the efficacy of three groups before and after the treatment.So were the check of the serum TNF-α,CRP,NO,SOD levels,and rates of efficiency after treatments and six-month follow-ups,and incidence of adverse reactions during the treatment among all the three groups.RESULTS The efficiency rates were found to be in the following sequence:the chemical medicine group (76.5％) ＜ the TCM group (83.8％) ＜ the TCM combined with chemical medicine group (97.2％) (P ＜ 0.05).The TCM combined with chemical medicine group had its post-treatment scores of Harris SF-36,FPS-R,FPS-R,TCM symptom and the serum TNF-α,CRP,NO,SOD levels significantly improved as compared with other two groups (P ＜ 0.05).And the revealed incidence of adverse reactions was ranked as the TCM group (2.7％) ＜ the TCM combined with chemical group (30.6％) ＜ the chemical medicine group (70.6％) (P ＜ 0.05).CONCLUSION Modified Shenqi Decoction is superior to sodium alendronate in the treatment of NONFH due to kidney deficiency and blood stasis syndrome for its better performance in both the efficacy and the incidence of adverse reactions,and its synergistic effect with use of sodium alendronate may associate with its capability in offsetting the adverse reactions of sodium alendronate.

Clinical Research on Bushen Huoxue Decoction in Treating Carotid Atherosclerotic Plaque / 中国中医药信息杂志

Objective To investigate the efficacy and safety of Bushen Huoxue Decoction in the treatment of carotid atherosclerotic plaque. Methods Totally 50 patients of carotid atherosclerotic plaque were collected to conduct health education. At the same time, they were given Bushen Huoxue Decoction, one dosage a day, twice a day, decoction, for 12 weeks. The correlation indexes of carotid artery before and after treatment were observed, and TCM syndrome integrals were evaluated before and after 4, 8 and 12 weeks treatment. FBG, TC, LDL-C, CRP HCY, IL-6, IGF-1, and OPG were detected before and after treatment. Hematuria routine, liver and renal function were monitored. Results After treatment, the Crouse score and the plaque grade score of carotid atherosclerotic plaque showed a tendency to decrease, without statistical significance (P=0.060, P=0.336). Carotid maximal plaque area and modified total score of carotid atherosclerotic plaque were significantly reduced compared with that before treatment (P<0.05). TCM syndrome integrals were significantly reduced compared with that before treatment (P<0.05), and the scores decreased significantly with the prolongation of treatment time. TCM syndrome integrals after 4, 8, and 12 weeks were significantly reduced compared with that before treatment (F=160.352, P<0.001). Total effective rate of treatment in the efficacy of TCM syndrome was 85.11％ (40/47). Serum levels of FBG and TC decreased significantly after the treatment compared with that before the treatment, with statistical significance (P<0.05). Serum levels of LDL-C, HCY, CRP, IL-6, IGF-1, and OPG all showed a tendency to decrease, without statistical significance (P>0.05). No abnormality in hematuria routine, liver and renal function examinations were found during the research. Conclusion Bushen Huoxue Decoction has obvious clinical efficacy for carotid atherosclerotic plaque, which can improve clinical symptoms of patients, it also could stabilize and reduce plaque with high safety.

Study on the mechanism of Bushen Culuan Chongji treating "kidney deficiency and blood stasis" in ovulatory dysfunctional infertility / 中国中药杂志

Kidney deficiency and blood stasis is the main cause of ovulatory dysfunctional infertility. Kidney deficiency is the main pathological mechanism. Blood stasis is the main pathological manifestation, and it is an important factor throughout. Bushen Culuan Chongji is under the guidance of traditional Chinese medicine(TCM) theory, previous years of clinical experience, combined with the etiology and pathogenesis of anovulatory infertility and modern pharmacological research results, selected, not only maintains the TCM syndrome differentiation and different diseases features, but also reflects the superiority of the combination of disease. In the study of Bushen Culuan Chongji in the treatment of anovulatory infertility, there was no acute toxicity and no LD50 was detected. No adverse effects and side effects were found in the reproductive, genetic, toxicity, teratogenic, and perinatal tests in their high and low dose groups. In pharmacodynamics experiments, it can promote the development and maturation of follicles and the formation of corpus luteum in rats. Taking the kidney deficiency and blood stasis syndrome as the breakthrough point, systematically study the efficacy, safety and mechanism of six ovulatory dysfunctional infertility diseases, including abnormal uterine bleeding-ovulatory disorders, polycystic ovary syndrome, high prolactin, luteinized unruptured follicle syndrome, luteal phase defect and diminished ovarian reserve/premature ovarian failure. It verified the contribution degree of reinforcing kidney and resolving stasis TCM, reflected the characteristics of combination between disease differentiation and syndrome differentiation, interpreted the treatment principles of treating different diseases with the same method, and provided scientific basis for clinical treatment.