Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation. CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.

[Study on alleviating neuroinflammatory injury in ischemic stroke rats by electrical stimulation with scalp acupuncture based on IFN-γ mediated JAK/STAT1 signaling pathway].

OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.

[Scalp acupuncture regulates hypothalamic V1aR/CaMKâ ¡/AQP4 signaling pathway in rats with focal cerebral ischemia].

OBJECTIVE: To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(V1aR), phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ), and aquaporin 4(AQP4) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke. METHODS: A total of 96 male SD rats were randomly divided into normal， model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with V1aR inhibitor (30 µg/kg)，once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKⅡ and AQP4 proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of V1aR mRNA in hypothalamus was detected by real-time PCR. RESULTS: Compared with the normal group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly increased (P<0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly decreased (P<0.01) in the inhibitor and scalp acupuncture groups. CONCLUSION: Regulating the signaling pathway of V1aR/CaMKⅡ/AQP4 in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.

Thymic lipofibroadenoma of the anterior mediastinum: A rare case report.

BACKGROUND: Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site. CASE SUMMARY: A 21-year-old male was admitted with fever without obvious cause for 2 months. After admission, the patient's highest temperature was 38.3°C, accompanied by diarrhea. Physical examination showed coarse breath sounds in both lungs. Chest enhanced computed tomography (CT) showed a mass of mixed density shadow on the left side of the anterior mediastinum with a size of approximately 9.2 cm × 5 cm × 2.1 cm and a clear boundary mixed with a low fat density shadow. Mediastinal tumors were removed under general anesthesia by video-assisted thoracoscopic surgery. Macroscopically, a clear boundary was shown between the tumor and the remaining thymus. Microscopically, the tumor contained a large amount of mature adipose and fibrous tissue with scattered cord-like epithelial tissue and a small number of lymphocytes scattered in the stroma. The tumor lacked thymic bodies. The neoplastic epithelial cells were oval or polygonal and arranged in fissures, the nuclei were uniform in size and mild in shape, and mitosis was rare. Epithelial cells were positive for AE1/AE3 and CK19, lymphocytes were positive for CD3 and CD20, and fat and fibrous tissue were positive for S-100 and vimentin, respectively. The Ki67 labeling index was less than 5%. Based on histological features and immunophenotype, thymic lipofibroadenoma was diagnosed. The patient was followed up 1 year after the operation, and no recurrence or residual lesions were found on the X-ray re-examination. CONCLUSION: Lipofibroadenoma is a benign thymic tumor, and thymectomy is regarded as the best treatment. The biological behavior of thymic lipofibroadenoma is good, and the recurrence rate is low.

Case report: Cardiac metastatic leiomyoma in an Asian female.

Background: Uterine leiomyomas are the most common gynecological tumors in women of child-bearing age and premenopausal women, while benign metastasizing leiomyomas of the heart are rare. Case presentation: We report a rare case of metastasizing leiomyoma in the heart of a 54-year-old woman 10 years after a uterine leiomyoma was discovered during hysterectomy. Echocardiography, cardiac plain scan and enhanced MRI at presentation showed a soft tissue signal mass in the right ventricle. A large cardiac mass attached to the chordae of the tricuspid valve and later shown to be histopathologically consistent with uterine leiomyoma was successfully resected through a right atriotomy. Conclusions: Our case report highlights a rare type of tumor of the heart and suggests that metastasizing leiomyoma should be considered in the differential diagnosis of right-sided cardiac tumors. The complete surgical resection of the tumor was considered to be the best treatment.

Ferroptosis-A Novel Mechanism With Multifaceted Actions on Stroke.

As a neurological disease with high morbidity, disability, and mortality, the pathological mechanism underlying stroke involves complex processes such as neuroinflammation, oxidative stress, apoptosis, autophagy, and excitotoxicity; but the related research on these molecular mechanisms has not been effectively applied in clinical practice. As a form of iron-dependent regulated cell death, ferroptosis was first discovered in the pathological process of cancer, but recent studies have shown that ferroptosis is closely related to the onset and development of stroke. Therefore, a deeper understanding of the relationship between ferroptosis and stroke may lead to more effective treatment strategies. Herein, we reviewed the mechanism(s) underlying the onset of ferroptosis in stroke, the potential role of ferroptosis in stroke, and the crosstalk between ferroptosis and other pathological mechanisms. This will further deepen our understanding of ferroptosis and provide new approaches to the treatment of stroke.

[Effect of scalp acupuncture stimulation on expression of pentraxin 3 in striatum in acute ische-mic cerebrovascular disease rats].

OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of pentraxin 3 (PTX3), Interleukin (IL)-1ß, zonula occludens-1(ZO-1) mRNA and Occludin mRNA in striatum in acute ischemic cerebrovascular disease (AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to control, model, IL-1Ra and IL-1Ra+scalp-acupuncture groups (n=12 rats in each group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the IL-1Ra group and IL-1Ra+scalp-acupuncture group received intraperitoneal injection of IL-1Ra (0.05 mg·kg-1·d-1), once daily for 6 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 6 days for rats in IL-1Ra+scalp-acupuncture group. Before and after intervention, the neurologic deficit score (NDS) was evalua-ted according to Longa's method. The expression of striatum PTX3 and IL-1ß was detected by immunohistochemistry, and ZO-1 mRNA and Occludin mRNA in the striatum tissue were detected by fluorescence quantitative real-time PCR. The Evans Blue (EB) tracer method was used to monitor the degree of blood-brain barrier (BBB) damage. RESULTS: Following modeling, the NDS, EB content and the expression of PTX3 and IL-1ß in the striatum tissue were significantly increased, and the ZO-1 mRNA and Occludin mRNA expression was considerably decreased in the model group compared with the control group (P<0.05). After the interventions and compared with the model group, the NDS, EB content in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra group were significantly down-regulated (P<0.05), while the striatum ZO-1 mRNA and Occludin mRNA expression in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra+scalp acupuncture group were obviously up-regulated (P<0.05), and the expression of IL-1ß was obviously down-regulated in the IL-1Ra+scalp acupuncture group (P<0.05) rather than in the IL-1Ra group (P>0.05). The effects of scalp acupuncture combined with IL-1Ra were obviously superior to that of IL-1Ra in down-regulating NDS, EB content and IL-1ß expression level, and in up-regulating PTX3, ZO-1 mRNA and Occludin mRNA expression levels (P<0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce the degree of BBB injury in AICD rats, which may be associated with its function in up-regulating the expression of PTX3 and in promoting the expression of ZO-1 mRNA and Occludin mRNA.

[ZHENG' Guo-Yan-Re needling technique for diabetic fundus hemorrhage].

OBJECTIVE: To observe the clinical effect of ZHENG ' Guo-Yan-Re needling technique for diabetic fundus hemorrhage. METHODS: With before-after study design, 34 patients with diabetic eyeground hemorrhage were treated with basic treatment (oral administration of antidiabetic medication or insulin injections to ensure blood glucose in the normal range); in addition, acupuncture was given at bilateral Fengchi (GB 20), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2), Sanyinjiao (SP 6) and Hegu (LI 4). The ZHENG ' Guo-Yan-Re needling technique was applied at Fengchi (GB 20); the heat reinforcing needling technique was applied at Taiyang (EX-HN 5); the slow needle insertion technique was applied at Jingming (BL 1); and the Xique-Dengmei needling technique was applied at Cuanzhu (BL 2); the neutral supplementation and draining method was applied at remaining acupoints. The acupuncture was given once a day, 6 times as one course, and totally 4 courses were given with an interval of 1 day between courses. The follow-up visit was 6 months after treatment. The TCM symptom scores, fundus examination results and vision improvement were observed before and after treatment, and the effect was observed. RESULTS: Compared before treatment, the visual acuity, TCM symptom scores, fundus microaneurysm and hemorrhage points in 34 patients (68 eyes) were significantly improved after treatment (P<0.05). The total effective rate was 88.2% (60/68) after treatment; at follow-up visit, the visual acuity, TCM symptom scores and fundus pathological changes were all improved (P<0.05) and stable at the post-treatment level (P>0.05). CONCLUSION: ZHENG ' Guo-Yan-Re needling technique could improve symptoms, promote the absorption of fundus hemorrhage, and improve vision in patients with diabetic fundus hemorrhage.

[Effect of scalp acupuncture stimulation on cerebral infarct volume and expression of IL-10, IL-6 and IL-1ß in para-hippocampal gyrus in acute ischemic cerebrovascular disease rats].

OBJECTIVE: To observe the influence of scalp acupuncture on cerebral infarct size and expression of IL-10, IL-6, and IL-1ß in the para-hippocampal gyrus in acute ischemic cerebrovascular disease(AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to normal control (control), AICD model, medication, and scalp acupuncture groups (n＝12 per group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the medication group received intraperitoneal injection of Ammonium 1-Pyrrolidinedithiocarbamate (APDC, 100 mg•kg－1•d－1), once daily for 7 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 7 days. Before and after intervention, the neurologic deficit score (NDS) and the neurological score (NS) were evaluated according to Longa's and Schäbitz's methods, respectively. At the end of the intervention, the para-hippocampal gyrus and whole brain were collected respectively. The expression levels of IL-10, IL-6 and IL-1ß in the para-hippocampal gyrus tissue were detected by immunohistochemistry, and the cerebral infarct volume of the brain was detected by triphenyltetrazollium chloride (TTC) staining after sectioning. RESULTS: Following modeling, the NDS, NS and the expression of IL-10, IL-6 and IL-1ß in para-hippocampal gyrus were significantly increased in the model group compared with the control group (P<0.01). After the intervention, the NDS, NS and infarct volume, and the expression levels of IL-6 and IL-1ß in the para-hippocampal gyrus were significantly decreased in both medication and scalp acupuncture groups compared with the model group (P<0.05), and the expression of IL-10 was further obviously up-regulated in the scalp acupuncture group (P<0.05) rather than in the medication group (P>0.05). The effect of scalp acupuncture was obviously superior to that of medication in up-regulating IL-10 expression level (P<0.05). No significant differences were found between the medication and scalp acupuncture groups in the levels of NDS, NS, infarct volume, IL-6 and IL-1ß proteins (P>0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce infarct volume in AICD rats, which may be associated with its function in up-regulating the expression of IL-10 and in inhibiting the expression of IL-6 and IL-1ß to reduce inflammation reaction.

[Scalp-acupuncture improves neurological function by regulating expression of IL-10 mRNA, IL-6 mRNA and TNF-α of parahippocampal gyrus in cerebral ischemic rats].

OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the expression of Interleukin (IL)-10 mRNA, IL-6 mRNA and tumor necrosis factor (TNF) - α in the parahippocampal gyrus of cerebral ischemia (CI) rats, so as to explore its molecular mechanisms underlying improvement of CI. METHODS: A total of 64 male SD rats were randomized into normal control, model, medication and scalp-acupuncture groups (n＝16 rats in each group). The focal CI model was established by middle cerebral artery occlusion. Intraperitoneal injection of Ammonium Pyrrolidine Dithiocarbamate (100 mg•kg－1•d－1) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS6), followed by twirling the needles at 100 cycles/min for 1 min, once again every 10 min during 20 min' needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－4 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schabitz's (2004) methods, respectively. The expression levels of IL-10 mRNA and IL-6 mRNA were detected by fluorescence quantitative PCR, and the expression of TNF-α was detected by immunohistochemistry. RESULTS: After modeling, the neurologic deficit and neurological function scores and the expression levels of IL-10 mRNA, IL-6 mRNA and TNF-α protein in the parahippocampus were significantly increased in the model group than in the normal control group (P<0.01). Following the intervention, the neurologic deficit and neurological function scores as well as IL-6 mRNA and TNF-α protein expression were significantly down-regulated in both scalp-acupuncture and medication groups (P<0.05), and the expression of IL-10 mRNA was obviously increased (P<0.05) relevant to the model group. CONCLUSION: Scalp-acupuncture can improve neurologic function in CI rats, which is related to its effects in up-regulating the expression of IL-10, then down-regulating the expression of IL-6 and TNF-α (reducing inflammatory response) in the parahippocampal gyrus.

[Scalp-acupuncture Improves Neurological Function by Regulating Expression of NF-κB p 65 mRNA, IκB mRNA and IL-1 ß and TNF-α in Parahippocampal Gyrus of Cerebral Ischemia Rats].

OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the expression of parahippocampal factor-κB p 65 mRNA (NF-κB p 65 mRNA), IκB mRNA, interleukin-1 ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) in rats with cerebral ischemia (CI), so as to investigate its molecular mechanisms underlying improving CI by reducing inflammatory response. METHODS: A total of 64 SD rats were randomized into normal control, model, medication and scalp-acupuncture groups, with 16 rats in each group. The focal CI model was established by middle cerebral artery occlusion (MCAO). Intraperitoneal injection of Pyrrolidine Dithiocarbamate (100 mg•kg－1•d－1) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), followed by twirling the needles at 200 cycles/min for 1 min, once again every 10 min during 30 min's needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－5 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schäbitz's (2004) methods, respectively. The expression levels of NF-κB p 65 mRNA and IκB mRNA in the parahippocampus gyrus tissue were detected by fluorescence quantitative reverse transcription-PCR, and IL-1 ß and TNF-α proteins in the parahippocampus gyrus tissue were detected by immunohistochemistry. RESULTS: After modeling, the neurologic deficit and neurological function scores and the expression levels of NF-κB p 65 mRNA, IL-1 ß and TNF-α in the parahip-pocampus were significantly increased in the model group than in the normal group (P<0.01), while the expression of IκB mRNA was considerably down-regulated (P<0.01). Following treatment intervention, the neurologic deficit and neurological function scores as well as NF-κB p 65 mRNA, and IL-1 ß and TNF-α protein expression were significantly decreased in both scalp-acupuncture and medication groups compared with the model group (P<0.05, P<0.01), and the decreased expression of IκB mRNA was obviously increased (P<0.05)．. CONCLUSION: Scalp-acupuncture can improve neurologic function in cerebral ischemic rats, which is related with its effects in up-regulating the expression of IκB to inhibit the dissociation of NF-κB, then decreasing the expression of IL-1 ß and TNF-α (reducing inflammatory response) in the parahippocampal gyrus tissue.

[Mechanism of Heat-reinforcing Needling for Rheumatoid Arthritis Rabbits with Cold Syndrome Based on Metabonomics].

OBJECTIVE: To explore the specific mechanism of heat-reinforcing needling (HRN) for rheumatoid arthritis (RA) rabbits with cold syndrome based on metabolomics. METHODS: A total of 40 healthy rabbits were randomly divided into a normal group, a model group, a reinforcing-reducing needling(RRN) group, a twirling-reinforcing needling (TRN) group and a HRN group (n=8 rabbits/group). The RA model with cold syndrome was established with ovalbumin and freezing. Except the normal and model groups, RRN, TRN and HRN were given at "Zusanli" (ST 36) in the corresponding acupuncture groups for 30 min, once a day for 7 days. After the interventions, the pain threshold and the local skin temperature of each group were observed. The endogenous metabolites in the serum were analyzed by the gas chromatography mass spectrometry (GC-MS) technology combined with the pattern-recognition method. RESULTS: The pain threshold and the local skin temperature in the model group were lower than those in the normal group (P<0.05). The pain thresholds and the local skin temperatures in the three acupuncture groups were higher than those in the model group after interventions (P<0.05), and those in the HRN group were obviously higher than those in the RRN and TRN groups (P<0.05). The serum metabolites of leucine, valine, isoleucine, and arachidonic acid in the model group were increased compared with those in the normal group (P<0.05), and the metabolites of α-ketoglutaric acid, citric acid, succinic acid, glucose, inositol, palmitic acid, stearic acid, lactose, d-ribose, and D-mannose were decreased (P<0.05). The above-mentioned metabolites in the three acupuncture groups were significantly reversed relevant to the model group (P<0.05), and the effect of HRN group was significantly superior to those of the RRN and TRN groups in regulating α-ketoglutaric acid, citric acid, succinic acid, glucose, inositol, d-ribose, and D-mannose (P<0.05). CONCLUSIONS: HRN for RA with cold syndrome is effective, which may be related to the specific regulation for the krebs cycle and glycometabolism.

[Effect of Scalp-acupuncture Stimulation on Neurological Function and Expression of ASIC 1 a and ASIC 2 b of Hippocampal CA 1 Region in Cerebral Ischemia Rats].

OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of acid-sensing ion channels (ASICs) 1 a and 2 b of hippocampal CA 1 region in cerebral ischemia (CI) rats, so as to investigate its mechanism underlying improvement of ischemic stroke. METHODS: Thirty-two male SD rats were randomly allocated to normal control, model, scalp-acupuncture and Amiloride group (n=8 in each group). The model of focal CI was established by middle cerebral artery occlusion (MCAO). Scalp acupuncture stimulation was applied to bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), once daily for 7 days. Rats of the Amiloride group were fed with Amiloride solution, twice a day for 7 days, and those of the normal control and model groups were grabbled and fixed in the same way with the acupuncture and Amiloride groups. The neurological deficit score was given according to Longa's method. The expression of hippocampal ASIC 1 a and ASIC 2 b was detected by immunohistochemistry, and the Ca2+ concentration in the hippocampal tissue assayed using flowing cytometry. RESULTS: After the intervention, the neurological deficit score of both the scalp-acupuncture and Amiloride groups were significantly decreased in comparison with pre-treatment (P<0.01), and the effect of scalp-acupuncture was markedly superior to that of Amiloride in reducing neurological deficit score (P<0.05). The expression of ASIC 1 a and ASIC 2 b in the hippocampal CA 1 region and hip-pocampal Ca2+ concentration were significantly up-regulated in the model group compared with the normal control group (P<0.01), and obviously down-regulated in both scalp-acupuncture and Amiloride groups (P<0.01, P<0.05),without significant differences between the two treatment groups in the ASIC 1 a and ASIC 2 b expression and Ca2+ concentration (P>0.05). CONCLUSIONS: Scalp-acupuncture stimulation can improve neurological function in CI rats, which may be related to its effects in suppressing the increased expression of hippocampal ASIC 1 a and ASIC 2 b proteins and in reducing calcium overload in hip-pocampal neurocytes.

SOX9 was involved in TKIs resistance in renal cell carcinoma via Raf/MEK/ERK signaling pathway.

Renal cell carcinoma (RCC) is common genitourinary malignancy in human, 30-40% of patients with RCC would be diagnosed with metastatic RCC (mRCC). Even in the era of targeted therapy, patients with mRCC would inevitably progress due to drug resistance. Herein, exploration of the mechanisms of resistance is noteworthy to study. In the present study, we firstly reported the expression profile of SOX9 in renal carcinoma cells and tissues, and found that its expression was significantly associated with Fuhrman grading. Dual luciferase analysis confirmed that Raf/MEK/ERK pathway could directly be regulated by SOX9, and sequential experiments demonstrated that, renal carcinoma cells could sensitize to Sorafenib/Sunitinib through Raf/MEK/ERK signaling pathway inhibition regulated by SOX9 down-regulation. In a small cases with mRCC treated with Sorafenib/Sunitinib (n=38), comparative analysis showed that patients with SOX9 (-) had much better therapeutic response to TKIs than those with SOX9 (+) (PD: 9.1% vs. 56.2%, P=0.002, DCR: 90.9% vs. 43.8%, P=0.002). Based on these findings, we concluded that, SOX9 was firstly described to be highly expressed in renal cell carcinoma, and its expression was involved in TKIs drug resistance through activation of Raf/MEK/ERK pathway. In vitro, patients with SOX9 (-) was related to better response to TKIs treatment than those with SOX9 (+). SOX9 could be expected to be a promising biomarker predicting TKIs response and even expected to be another novel target in the treatment of mRCC.

Simultaneous modulated accelerated radiotherapy in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy.

OBJECTIVE: To compare the dosimetry, toxicity, and efficacy of simultaneous modulated accelerated radiotherapy (SMART) with 3-dimensional conformal radiotherapy (3DCRT) in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy. METHODS: Total 32 patients who underwent SMART were retrospectively evaluated. Daily fractions of 2.2 to 2.4 Gy and 1.8 to 2 Gy were prescribed and delivered to gross tumor volume and clinical target volume to a total dose of 63.8 and 52.2 Gy, respectively. A 3DCRT plan was designed for the SMART group and planned to deliver the same prescribed dose. The doses of organs at risk (OARs) were compared. Thirty-six patients who received 3DCRT were used to compare the target dose, toxicities, and efficacy with 32 cases who received SMART. RESULTS: The mean doses delivered to gross tumor volume and clinical target volume were significantly higher in the SMART group than in the 3DCRT group (63.8 vs 55.2 Gy [P < 0.01] and 52.5 vs 48.6 Gy [P < 0.01], respectively). For SMART plan, the doses of OARs were significantly lower than that of 3DCRT plans (small intestine: 25.1 vs 30.9 Gy [P < 0.01], bladder: 35.3 vs 46.3 [P < 0.01], and rectum: 31.7 vs 43.7 [P = 0.002], respectively). The patients experienced less acute and late toxicities in the SMART group (acute toxicities: enteroproctitis, P = 0.019; cystitis, P = 0.013; leukopenia, P = 0.025; late toxicities: enteroproctitis, P = 0.007; and cystitis, P = 0.026, respectively). No significant difference was found for 1-year survival (78.7% vs 67.7%, P = 0.222), but SMART group had a higher 2-year survival rate (2-year: 63.1% vs 39.1%, P = 0.029). CONCLUSIONS: Simultaneous modulated accelerated radiotherapy plans yielded higher dose to the targets and better sparing of OARs than did 3DCRT in cervical cancer with retroperitoneal lymph node metastasis after radical hysterectomy and pelvic lymphadenectomy. Simultaneous modulated accelerated radiotherapy provided better clinical outcomes than did 3DCRT. Long-term follow-up and studies involving more patients are needed to confirm our results.

Distribution pattern of circumflex iliac node distal to the external iliac node metastasis in stage IA to IIA cervical carcinoma.

OBJECTIVES: This study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients. METHODS: Six hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed. RESULTS: The PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6-386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis. CONCLUSIONS: Circumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.

[The expression and function of anti-apoptotic Bfl-1 in prostate cancer].

OBJECTIVE: To determine the expression of Bcl2 related protein A1(Bfl-1) mRNA in prostate cancer cell lines and tissues, and to explore the functions of Bfl-1 in prostate adenocarcinoma. METHODS: RT-PCR, real-time quantitative PCR (Q-PCR)and in situ hybridization (ISH) were used to detect the expression of Bfl-1 mRNA in prostate cancer cell lines, tissues and benign prostate hyperplasia (BPH) tissue samples. The relationship between Bfl-1 expression and clinicopathological parameters was analyzed. Antisense oligonucleotides (ASONs) were used to interfere the expression of Bfl-1 and its effects on prostate cancer cells. MTT was used to detect the survival, morphologic changes of prostate cancer cells was observed by inverted microscope. RESULTS: Bfl-1 mRNA, detected by RT-PCR, Q-PCR and ISH, was overexpressed in the androgen-independent prostate cancer cell lines PC-3 and DU145, but not detectable in the androgen-dependent prostate cancer cell line LNCaP and BPH tissue samples (P < 0.05). Significantly higher Bfl-1 mRNA levels were observed in higher stage and metastatic prostate cancer cases than those without metastasis or of low stage. ASONs targeting Bfl-1 significantly inhibited androgen-independent prostate cancer cell growth (P < 0.05), cell was rounding off or fragmentation. CONCLUSION: Bfl-1 is involved in maintaining the hormone-independent prostate cancer cell growth. Bfl-1 may become a new therapeutic target in advanced prostate cancer.