Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway / 中国天然药物

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Effects of Ding Kundan on expression of TGF-β1,CTGF and AR in PCOS model rats / 中国免疫学杂志

Objective:To investigate the effect of Ding Kundan on the expression of TGF-β1,CTGF and AR in PCOS model rats,and to explore its treat mechanism on PCOS.Methods: The PCOS model rats induced by DHEA were intervened with high, medium and low dose of Ding Kundan(4.5,2.25,1.125 g/kg),ELISA,immunohistochemistry,RT-PCR and Western blot were used to detect serum hormone levels,mRNA and protein expression of TGF-β1,CTGF and AR in each group of rats.Results: Compared with model group Ding Kundan high,medium and low dose group of E2,LH and T were decreased,while FSH was increased.And the differences were statistically significant.Protein expression and mRNA of TGF-β1,CTGF and AR were decreased,and the differences were statistically significant.Conclusion: Ding Kundan shows significantly therapeutic efficacy on PCOS rats,and its possible mechanism is related to regulating expression levels of TGF-β1,CTGF and AR in ovarian tissue.

Effect of clomiphene citrate and Dingkun Dan on ovulation induction and clinical pregnancy of polycystic ovary syndrome / 中国中药杂志

The evaluation is based on clomiphene citrate (CC)+gonadotropin (Gn), clinical study on CC and Dingkun Dan's treatment on ovulation induction and clinical pregnancy effect of PCOS, and to provide ideas and methods for traditional Chinese medicine assisted reproductive treatment. This study selected 60 PCOS infertility patients treated with ovulation induction in reproductive medicine clinic, Jiangsu Province Hospital of traditional Chinese medicine during 2015-10-01-2017-04-23. They were randomly divided into two groups： Group A (CC+Gn+HCG) and Group B (CC+Gn+Dingkun Dan). These results were observed and compared including cycle ovulation rate, cycle cancellation rate, cycle pregnancy rate, cumulative pregnancy rate, endometrial thickness, duration of Gn, total amount of Gn, the occurring rate of luteinized unruptured follicle syndrome and ovarian hyperstimulation syndrome. Group A had lower cycle ovulation rate, cycle pregnancy rate, cumulative pregnancy rate and endometrial thickness, compared with Group B, the difference was statistically significant(P＜0.05). However, Group A had higher cycle cancellation rate, duration of Gn and total amount of Gn, compared with Group B, the difference was statistically significant(P＜0.05). In this study, no case of LUFS or OHSS was found in all patients. CC and Dingkun Dan had the effect of promoting ovulation on PCOS infertility patients, and CC+Gn+Dingkun Dan could elevate clinical pregnancy rate.

Analysis on interrelation between electroacupuncture-induced cumulative analgesic effect and hypothalamic cholinergic activities in chronic neuropathic pain rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of repeated electroacupuncture (EA) of Zusanli (ST36)- Yanglingquan (GB34) on hypothalamic acetylcholinesterase (AchE) and vesicular acetylcholine (ACh) transporter (VAChT) activities and choline acetyltransferase (ChAT) mRNA and muscarinic M1 receptor (M1R) mRNA expression in chronic constrictive injury (CCI) and/or ovariectomy (OVX) rats so as to reveal its underlying mechanism in cumulative analgesia.</p><p><b>METHODS</b>A total of 103 female Wistar rats were randomly divided into normal control (n =15), CCI (n =15), CCI+EA2d (n =15), CCI+EA2W (n =15), OVX+CCI =13), OVX+CCI+EA2d (n =15), and OVX+CCI+EA2W groups (n =15). CCI model was established by ligature of the unilateral sciatic nerve with surgical suture. Memory impairment model was established by removal of the bilateral ovaries. Morris water test was conducted to evaluate the OVX rats' memory learning ability, and the thermal pain threshold (PT) of the bilateral paws was detected the next morning after EA. EA (2/15 Hz, 1 mA) was applied to bilateral ST36-GB34 for 30 min, once daily for 2 days or 2 weeks, respectively. Hypothalamic AChE activity was detected by histochemistry, VAChT immunoactivity was determined by immunohistochemistry, and ChAT mRNA and M1R mRNA expressions were assayed by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>In comparison with the normal control group, the AChE activity in hypothalamic arcuate nucleus (ARC) and supraoptic nucleus (SON) regions of CCI group, AChE activity in paraventricular nucleus (PVN), ARC, and SON regions of OVX+CCI group, and hypothalamic muscarinic M1R mRNA expression levels in both CCI and OVX+CCI groups were down-regulated significantly (P <0.05). Compared with the CCI group, the AChE activities in hypothalamic ARC and SON regions of CCI+EA2d and CCI+EA2W groups and PVN region of CCI+EA2W group and hypothalamic ChAT mRNA and M1R mRNA expression levels in CCI+EA2W group were up-regulated considerably (P <0.05). In comparison with the OVX+CCI group, the AChE activities in PVN, ARC, and SON regions and the expressions of hypothalamic ChAT mRNA and VAChT in ARC region of OVX+CCI+EA2W group were up-regulated remarkably (P <0.05). The effects in rats of CCI+EA2W group were evidently superior to those of OVX+CCI+EA2d group in up-regulating AChE activities in PVN, ARC, and SON regions, VAChT immunoactivity in ARC region, and expression levels of hypothalamic ChAT mRNA and M1R mRNA (P <0.05). Similar situations were found in OVX+CCI rats after EA2W. It suggested a cumulative effect after repeated EA of ST36-GB34. Comparison between CCI+EA2W and OVX+CCI+EA2W groups showed that the effects in rats of the former group were evidently better than those of the latter group in up-regulating AChE activity in ARC and SON regions and the expressions of hypothalamic ChAT mRNA and M1 mRNA (P <0.05), suggesting a reduction of EA2W effects after OVX.</p><p><b>CONCLUSION</b>Repeated EA can significantly up-regulate AChE and VAChT activities and ChAT mRNA and M1R mRNA expressions in the hypothalamus of CCI and OVX+CCI rats, which may contribute to the cumulative analgesic effects of repeated EA and be closely related to the animals' neuromemory ability.</p>

Addition of ulinastatin to preservation solution promotes protection against ischemia-reperfusion injury in rabbit lung / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose (LPDG), an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion (I/R) injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.</p><p><b>METHODS</b>Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50,000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis (PaO₂, PaCO₂), mean pulmonary artery pressure (MPAP) and serum TNF-α level were measured intermittently. The pulmonary water index (D/W), tissue myeloperoxidase (MPO) activity, tissue malondialdehyde (MDA) content and morphologic changes were analyzed.</p><p><b>RESULTS</b>The study group showed significantly higher PaO₂ and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.</p><p><b>CONCLUSIONS</b>This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions, inhibiting the release of inflammatory factors and neutrophils immigration.</p>

Effects of repeated electroacupuncture on beta-endorphin and adrencorticotropic hormone levels in the hypothalamus and pituitary in rats with chronic pain and ovariectomy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of electroacupuncture (EA)-induced cumulative analgesic effects on chronic pain in rats with or without ovariectomy (OVX).</p><p><b>METHODS</b>A total of 110 female Wistar rats were randomized into normal control (n=10), chronic constrictive injury (CCI, n=10), CCI+EA (n=30), OVX+CCI (n=30), and OVX+CCI+EA (n=30) groups. Each of the latter 3 groups was further divided into 2 days (2 d), 2 weeks (2 W) and 3 weeks (3 W) subgroups, respectively (n=10 in each subgroup). The CCI pain model was established by ligature of the right sciatic nerve, and the memory impairment model duplicated by OVX. The paw withdrawal latency (PWL, pain threshold) of the bilateral footplates was detected by radiant heat irradiation, and the bilateral difference in PWL (PWLD) was used to evaluate changes in the pain reaction. Morris water maze test was conducted for evaluating the rats' learning-memory ability. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 2 d, 2 W and 3 W, respectively. Pituitary and hypothalamic beta-endorphin (EP) and adrenocorticotrophic hormone (ACTH) contents were detected by immunoradioassay.</p><p><b>RESULTS</b>Compared with the CCI group, PWLD of the CCI+EA-3 W group decreased significantly (P<0.05). Compared with the OVX+CCI group, PWLD of the OVX+CCI+EA-3 W group was lowered considerably (P<0.05), but the value was markedly higher than its basal value and those of the normal control and CCI+EA groups (P<0.05). In comparison with the sham-OVX group, the escape latency, swimming distance (SD) in the target quadrant and total SD were increased remarkably in the OVX group (P<0.05), while the number of target platform crossings was decreased significantly (P<0.05), suggesting an impairment of the OVX rats' learning-memory ability. In simple CCI rats, both beta-EP and ACTH contents of the pituitary increased markedly (P<0.05), and those of the hypothalamus decreased obviously compared to the normal control group (P<0.05). After EA, pituitary and hypothalamic ACTH levels were significantly lowered at 2 d and hypothalamic ACTH and beta-EP contents increased obviously at 3 W in comparison with the CCI group (P<0.05). In OVX+CCI rats, following EA, pituitary beta-EP contents at 2 d, 2 W and 3 W, and hypothalamic beta-EP and ACTH contents at 2 W and hypothalamic ACTH levels at 3 W increased significantly (P<0.05), but hypothalamic beta-EP level at 3W decreased markedly (P<0.05). The effects of repeated EA in lowering pituitary ACTH and raising hypothalamic beta-EP and ACTH levels disappeared after OVX+CCI.</p><p><b>CONCLUSIONS</b>Repeated EA has a cumulative analgesic effect, which is closely associated with its effects in regulating pituitary and hypothalamic beta-EP and ACTH levels. OVX may weaken the analgesic effect of EA by affecting hypothalamic-pituitary axis activity.</p>

Effects of electroacupuncture at different acupoints on electrohystorogram in pregnant rats / 中国针灸

<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) of different acupoints on abnormal electrohysterogram (EHG) in pregnant rats, so as to analyze their regularities in regulating dysfunction of the viscera.</p><p><b>METHODS</b>A total of 48 Wistar pregnant rats (18-20 days) anesthetized with mixture solution of 1.5% chloralose and 25% urethane (i. p) were randomized into control (n=10), "Sanyinjiao" (SP 6, n=9), "Hegu" (LI 4, n=8), "Neiguan" (PC 6, n=0), and "SP 6 + LI 4" (n=11) groups. EHG was recorded by using a bipolar stainless steel electrode inserted in the sub-perimetrium layer of the left mid part of the uterus. The reference electrode was placed beneath the skin of the incision. Oxytocin and gesterol were given to the local uterus nearby the recording electrode to induce abnormal excitement and suppression of EHG respectively. EA (1-2 mA, 2/15 Hz) was applied to the above-mentioned acupoints separately for 20 min in the EA groups and the influences of EA on the amplitude and frequency of burst (fast) waves and slow waves of EHG were analyzed.</p><p><b>RESULTS</b>Compared with the control group, EA of SP 6 + LI 4 and SP 6 groups had apparent inhibitory effects on oxytocin-induced increases of the frequency and amplitude of both fast and slow waves (P<0.05); and EA of LI 4 also had a markedly inhibitory effect on the amplitude of fast waves (P<0.05). No marked effects on both frequency and amplitude of fast waves and slow waves of EHG were found in the PC 6 group (P>0.05). In comparison with the control group, EA of SP 6+LI 4 and SP 6 could relieve or significantly relieve progesterone-induced suppression of the frequency and amplitude of both fast and slow waves (P<0.05); and the effects of SP 6 + LI 4 appeared earlier and lasted longer than those of SP 6; while EA of LI 4 and PC 6 had no obvious effect on progesterone-induced changes of the frequency and amplitude of both fast and slow waves (P>0.05).</p><p><b>CONCLUSION</b>EA different acupoints have their own relative specificity in regulating abnormal EHG.</p>

Clinical features and treatment of invasive fungal infection in 47 patients with hematological malignancies / 中南大学学报(医学版)

OBJECTIVE@#To analyze the clinical features of invasive fungal infection in patients with hematological malignancies and to compare the the therapeutic effect of fluconazole and intraconazole.@*METHODS@#The clinical manifestations, mycological features, and the therapeutic results of 47 patients were retrospectively analyzed. Fluconazole was given to 17 paitents, intraconazole was given to 21 patients, and intraconazole to the other 9 patients after they had no effect with fluconazole.@*RESULTS@#All patients had fever. The lung and the mouth cavity were the main locations of infection (53.2% and 21.3%, respectively). Fungi were found in 23 (48.9%) patients, in which the majority were Candida albicans and Aspergillus (56.5% and 26.1%, respectively). Intraconazole was more effective than fluconazole (63.3% vs. 34.6%, P<0.05) with no serious side effect.@*CONCLUSION@#The most common clinical features of IFI are fever, lung infection, and oral infection in patients with hematological malignancies. Candida albicans and Aspergillus infection are common. Intraconazole is safe and effective for invasive fungal infection.

Effects of NKG2D and its ligands RAE-1 and H60 on graft-versus-tumor response / 中国实验血液学杂志

The study was purposed to explore the effects of NKG2D receptor and its ligands RAE-1 and H60 on graft-versus-tumor (GVT) response induced by MHC haploidentical bone marrow/spleen cell transplantation. Female (BALB/c x C57BL/6) F1 mice (CB6F1, H-2K(b/d)) inoculated with H22 cells to develop a solid tumor model were the recipients, and bone marrow mixed with spleen cells of the healthy male C57BL/6 (H-2K(b)) mice were the donor cells. GVT response was observed after transplantation that from donor cells T and NK cells were purged with anti-CD3 and anti-NK monoclonal antibody, and the NKG2D receptor was blocked with anti-NKG2D monoclonal antibody, the expression levels of RAE-1 and H60 mRNA in tumor tissue were measured by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) at different time points after transplantation. The results showed that the GVT response of transplantation was reduced after in vitro depletion of T and NK cells or blocking NKG2D receptor in donor cells of the graft, the expression levels of RAE-1 and H60 mRNA in tumor tissue increased after transplantation of haploidential bone marrow mixed with spleen cells. It is concluded that NKG2D and its ligands RAE-1 and H60 may play important roles in GVT response.

Acupuncture-serum decreases Ca2+ content in cultured rat myocardial cells / 中国针灸

<p><b>OBJECTIVE</b>To explore whether humoral factors play a role in the mechanisms of acupuncture.</p><p><b>METHODS</b>Primary culture of myocardial cells of neonatal rats were carried out. Five days later, they were labeled by fluorescent molecular probe Fluo-3AM. Changes of Ca2+ contents in the cultured myocardial cells after addition of the normal rat serum or acupuncture-serum of the rat who received acupuncture at "Neiguan" (PC 6) and Jianshi (PC 5), were dynamically observed by a confocal laser scanning microscopy.</p><p><b>RESULTS</b>After addition of normal serum of the rat, the intracellular Ca2+ level increased to a certain degree, and then gradually tended to stability, which was significantly decreased by addition of the acupuncture-serum (P < 0.01).</p><p><b>CONCLUSION</b>The serum of the rat who received acupuncture at acupoints can decrease the Ca2+ level in cultured myocardial cells, which provides a direct evidence for serum factors involving in acupuncture mechanism.</p>

Blood supply features and interventional therapy of pedunculated hepatocellular carcinoma / 介入放射学杂志

Objective To evaluate the blood supply features and effectiveness of arterial chemoembolization for pedunculated hepatocellular carcinoma.Methods Angiography and chemoembolization via supplying blood arteries of tumor were performed in five patients with pedunculated hepatocellular carcinoma.Interventional procedure was carried out with tumor vascular infusion of 350 mg hot elemene emulsion and tumor embolization by cisplantin-lipidol emulsion(cisplantin 60-80 mg+lipidol 8-15 ml)and glutin.Results Ten interventional procedures(TACE)were undertaken in 5 patients.Angiography showed that tumor blood supply mainly coming from collateral circulation adjacent to the tumors,but partially from hepatic artery.Tumor sizes decreased from 30% to 50% in 5 cases,and AFP declined in 4 cases after the treatment. Conclusion Pedunculated hepatocellular carcinoma possessing different blood supply features from intrahepatocellular carcinomas.But transarterial ehemoembolization is still an effective method of choice for this treatment.