1.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
2.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
3.Advantages and disadvantages of bidirectional cavopulmonary shunt with additional pulmonary blood flow : a theoretical analysis
Jihong HUANG ; Zhaokang SU ; Jinfen LIU ; Qi SUN ; Zhenying SHI ; Yanping ZHOU
Chinese Journal of Thoracic and Cardiovascular Surgery 2012;28(8):476-481
Objective The bidirectional cavopulmonary shunt (BCPS) is a major step in the staged palliation of functionally univentricular heart defects.Whether to preserve of additional pulmonary blood flow (APBF) has been a highly controversial issue.The purpose is to mathematical model and set out to determine the significa advantages and disadvantages of bidirectional cavopulmonary shunt with additional pulmonary blood flow:a theoretical analysis nce of APBF and the appropriate APBF ratio.Methods We used models of the univentricular circulation after the bidirectional cavopulmonary anastomosis with additional pulmonary blood and to computational analyze the impact of APBF on oxygen delivery,APBF flow on the CVP and SaO2.Results The influence of APBF depends on the ratio of superior vena cava flow to inferior vena cava flow ( QSVC/QIVC ).For QSVC/QIVC > 0.3,APBF may be associated with decreased oxygen delivery.For QSVC/QIVC < 0.3,appropriate APBF may be associated with increased oxygen delivery.A linear relationship exists between the increase of APBF and CVP,and the slope was depended on the value of pulmonary vascular resistance.Estimating APBF from CVP measurements may be a feasible method.A nonlinear relationship between the increase of APBF and oxygen saturation,and estimating APBF from SaO2 measurements may result in errors.BCPS and appropriate APBF may optimal the oxygen delivery with the increase of age and the decrease in QSVC/QIVC.For patients who accepted BCPS without APBF,there is a decreasing tendency of oxygen delivery with the increase of age and the decrease in QSVC/QIVC.For patients who suffered pulmonary arterivenous malformation,there is a more obvious decrease in oxygen delivery.ConclusionFor patients under age who has normal pulmonary vascularbed ( that is,QSVC/QVC > 0.3),elimination of additional pulmonary blood flow can improve the oxygen delivery under a given cardiac output.For patients who with hypoplastic pulmonary vascular or in older patients under age,APBF is necessary to improve oxygen delivery.For patients who have to accept BCPS as the final procedure,preserving of APBF is suggested.
4.Stimulating proliferation of aorta smooth muscle cells of rat by rat urotensin Ⅱ
Yonggang ZHANG ; Yongfen QI ; Chunfang XIA ; Yongzheng PANG ; Jun YANG ; Zhaokang ZHANG ; Chaoshu TANG
Chinese Pharmacological Bulletin 2001;17(2):155-157
AIM To investigate effect of urotensin Ⅱ (UⅡ)on proliferation of aort a smooth muscle cells (ASMC)of rat and study the signal transduction pathway o f it. METHODS In cultured ASMC of rat, UⅡ was used to stimulate proliferation of these cells and levels of [3H]-TdR incorporation were used to evaluate the speed of DNA synthesis, and different inhibitors were used to s tudy the action of different signal transduction pathway of mitogenic effect of UⅡ on VSMC. RESULTS 1×10-9~1×10-7 mol*L- 1 UⅡ caused marked concentration-dependent increasing of [3H]-TdR i ncor poration of ASMC. [3H]-TdR incorporation of 1×10-9,1×10-8 and 1×10-7 mol*L-1 UⅡ were 22%(P<0.05), 57%(P<0.01)and 65%(P<0.01)higher than control. Nicardipine, H7, W7 and PD98059 , which are inhibitors of calcium channel, PKC, CaM-PK and MAPK respectively, inhibited the effects of UⅡ obviously, with the inhibitory rate by 55%(P< 0.01), 27%(P<0.01),18%(P<0.05)and 16%(P<0.05)respectively . CONCLUSION UⅡ is a strong mitogen for VSMC and the mitogenic e ffect of UⅡ is probably mediated by Ca2+, PKC, CaM-PK and MAPK signal tr ansduction pathway.
5.Method for replantation of severed finger tip injury on nail root level
Ruchang CHEN ; Xiongferng QI ; Zhaokang WANG
Chinese Journal of Microsurgery 2000;0(03):-
Objective To evaluate the experience of replantation of severed finger tip and suggest a new method to replant the severed finger tip injury. Methods A total 25 cases of severed finger tip injuries on nail root level were retrospectively analysed.They were 18 males and 7 females,19~38 years old.The finger tips were completely cut down.The wound should be cleaned thoroughly under operative microscope and the cut ends of artery and nerve can be found on the wound.The important step was to dissect out all braches of the arch of the artery and ligate them but one small branch,so as to reduce the blood circulate into the finger tip.It was not necessary to joint the vein. Results Twenty-four fingers were survived,only one finger was necrosed.The course of 13 fingers were very prosperous.Twelve fingers had some cyanosis and 9 fingers turned red after a few punctures to release the venous blood and other 3 fingers should make a side incision torelease more venous blood.Then 2 fingers were survived and one finger was failured. Conclusion Only one artery should be anastomos for finger tip injury on nailroot level.No vein should be joint.But the branches of the artery arch should be ligated except one small branch.
6.Stimulating proliferation of aorta smooth muscle cells of rat by rat urotensin Ⅱ
Yonggang ZHANG ; Yongfen QI ; Chunfang XIA ; Yongzheng PANG ; Jun YANG ; Zhaokang ZHANG ; Chaoshu TANG
Chinese Pharmacological Bulletin 1987;0(02):-
AIM To investigate effect of urotensin Ⅱ (U Ⅱ )on proliferation of aorta smooth muscle cells (ASMC) of rat and study the signal transduction pathway of it. MEfHODS in cultured ASMC of rat, U Ⅱ was used to stimulate proliferation of these cells and levels of [3H]-TdR incorporation were used to evaluate the sped of DNA synthesis, and different inhibitors were ed to study the action of different signal transduction pathway of mitogenic effect of UⅡ on VSMC. RESULTS. 1 ? 10-9~l ? 10-7 mol. L-l U Ⅱ caused marked concentration-de pendent increasing of [3H]-TdR incorporation of ASMC [3H]-TdR incorporation of 1 ? 10-9, 1 ? 10-8 and 1 ? 10-7 mol. L-l U Ⅱ were 22%'(P

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