ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

Objective:To analyze the effect of Croton leaf on ERK1/2 pathway in hippocampal of rats with cerebral ischemia-reperfusion.Methods:A total of 216 SD male rats were divided into sham operation group, model group, nimodipine group, low-dose, medium-dose and high-dose groups of croton leaf according to random nubmer table method, with 36 rats in each group. The MACO model of rats was prepared by the method of wire embolization. The high, medium and low dose groups were intragastrated with the water decoction 0.06 g/ml, 0.12 g/ml and 0.18 g/ml of Croton leaf; nimodipine group was intragastrated with nimodipine suspension 1.08 g/L; sham operation group and model group were intragastrated with equal volume of normal saline. Garcia JH score was used to conduct neurological function score, and HE staining was used to observe the morphology of hippocampal neurons after 7 days of continuous administration. Apoptosis of hippocampal CA3/DG region was detected by TUNEL assay. Western Blot was used to detect the expression of ERK1/2 and p-ERK1/2 proteins.Results:Compared with the model group at simultaneous point, the neurological function scores of low-dose, medium-dose and high-dose groups of Croton leaf increased ( P<0.01), the number of apoptotic cells decreased ( P<0.01), the expression of p-ERK1/2 / ERK1/2 [1 d: (0.22±0.03, 0.34±0.02, 0.46±0.01 vs. 0.19±0.02); 3 d: (0.38±0.02, 0.50±0.02, 0.68±0.02 vs. 0.27±0.02); 7 d: (0.29±0.03, 0.43±0.02, 0.59±0.02 vs. 0.21±0.03)] in hippocampus of the low-dose, medium-dose and high-dose groups of Croton leaf significantly increased ( P<0.01). Conclusion:Croton leaf could regulate the expression of ERK1/2 pathway protein upward, effectively improve the neural function and resist the apoptosis of hippocampal CA3/DG area of rats with cerebral ischemia-reperfusion injury.

ObjectivesTo compare operative characteristics, postoperative residue, recurrence, and pregnancy outcome between laparoscopic myomectomy (LM) and transabdominal myomectomy (TAM),and investigate the favourable surgical approach in women with uterine myomas. MethodsFrom Jan 2008 to Dec 2008, 313 women undergoing LM and 148 women undergoing TAM were studied retrospectively in Peking Union Medical College Hospital. The patients' general information, including the largest diameter,mean numbers and weights of excised myomas, peri-operative characteristics (operating time, blood loss,and hemoglobin decrease), and residue, recurrence of myoma, and pregnancy outcome were compared and analyzed. Results The largest diameter, mean numbers and mean weight of myomas removed were larger in TAM group [( 7.6 ± 3.0) cm, (5.6 ± 5.5 ), ( 308 ± 364) g, respectively]than those in LM group [(6.8±2.0) cm, (2.4 ±2.1), (140 ± 109) g, respectively; P＜0.01]. While the extension of operating time [(89±32) versus (74 ±35) min], increased blood loss [(239 ±251 ) versus ( 149 ±252) ml]and hemoglobin decrease [(22 ± 14) versus ( 15 ± 12) g/L], and longer hospital stay [(6. 4 ± 1. 6)versus (4. 4 ± 1.3) d]were observed in TAM group when compared with those in LM group ( P ＜0. 01 ).However, the residue rate of LM and TAM was 2. 6％ versus 1.4％ respectively ( P = 0. 5130 ) ; the recurrence rate of LM and TAM was 11.1％ versus 12. 3％ (P ＞ 0. 05 ) ; the pregnancy rate of LM and TAM was 49. 2％ versus 9/13 separately, the difference was not statistically significant ( P = 0. 2330 ). The number of myomas removed was the significant risk factors associated with recurrence ( OR = 2. 805, 95％CI: 1. 192 -6. 601, P = 0. 0180). No uterine rapture occurred during pregnancy. ConclusionsBoth LM and TAM are effective surgical approaches for the patients with leiomyoma who desire to pregnancy, or to retain the integrity of their uteruses. Most of uterine myoma could be treated through laparoscopy. The residue rate of LM is higher than that of TAM. However, the short term recurrence rates of LM and TAM are similar. Multiple myomas is the risk factor associated with recurrence after myomectomy. The pregnancy rates are comparable between LM and TAM groups.