Imaging biomarkers on Angio-CT for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma.

Background: This study aimed to evaluate whether the lipiodol deposition pattern on intraprocedural Angio-CT could predict tumor treatment response in hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (c-TACE). Methods: This retrospective study enrolled intermediated and advanced HCC nodules treated with c-TACE and Angio-CT from June 2021 to June 2022. The therapeutic efficacy was evaluated according to the mRECIST standards. First, Angio-CT was used to determine lipiodol deposition at the end of c-TACE, redefined as complete, partial-complete, and incomplete groups. Second, the mean CT value of lipiodol deposition and its association with therapeutic efficacy were calculated in the complete model. Finally, the relationship between imaging biomarkers and efficacy was evaluated. Results: A total of 45 patients with 72 HCC nodules were enrolled with 28 nodules in the complete group, 31 nodules in the partial-complete group, and 13 nodules in the incomplete group. The complete response (CR) proportion was significantly higher in patients with good lipiodol deposition compared with patients with poor lipiodol deposition (P<0.0001). There was no significantly different CR rate between CT value ≥800 and <800 HU (P=0.119) in the complete group. Meanwhile, the non-CR rate in cases with hepatic vein development was significantly higher than that in cases with no hepatic vein development in the arterial phase (P<0.0001). Conclusions: Complete lipiodol deposition on Angio-CT during c-TACE was a predictive factor for therapeutic response to TACE. For HCC nodules with well-deposited lipiodol, hepatic vein development on Angio-CT in the arterial phase was strongly associated with poor efficacy of TACE.

[Bibliometric analysis on the literature characteristics of animal experiment research with acupuncture and moxibustion].

OBJECTIVE: To compare the diversities in the literature characteristics of animal experiments with acupuncture and moxibustion (acu-moxibustion) published in both Chinese and English, so as to summarize the similarities and differences in the reporting content for the animal experiment research with acu-moxibustion in the journals at home and abroad. METHODS: The articles of animal experiments with acu-moxibustion published from 2016 to 2018 were searched from CNKI, Wanfang, SinoMed, PubMed and Web of Science databases. The articles were screened according to the inclusion and exclusion criteria, and the database was established by importing the essential information, e.g. title, author, journal, impact factor, country, year of publication, citation frequency, funding, disease type, as well as the number of observation indicators and charts. The diversity was initially summarized among this type of articles between China and foreign countries. RESULTS: A total of 7 515 articles of animal experiments with acu-moxibustion were retrieved and 2 458 articles were eligible in compliance with the inclusion and exclusion criteria. Of them, there were 1 827 articles in Chinese and 631 in English. (1) Among those of Chinese-version, 169 articles (9.25%) were published in Acupuncture Research, listed the first of the article publications. Regarding the impact factor of published journal, Acupuncture Research was ranked the highest (3.187). For those published in English, 78 articles (12.36%) were published in Evidence-based Complementary and Alternative Medicine, listed the top of the article publications. Gastroenterology occupied the highest in terms of the impact factor (17.373) of published journal. (2) The first authors of Chinese-version articles were all from China, distributing in 461 institutions; of which, Beijing University of Chinese Medicine occupied the top for article publications (142 articles, 7.77%). For the English articles, 16 countries were involved regarding the first authors, and the most of them were from China (523 articles, 82.88%), followed by South Korea, Brazil, the United States and Japan. (3) The frequency of citations of Chinese articles was 7.50, which was significantly higher than that of English ones (4.61). (4) The funding supported Chinese and English articles were 1 680 (91.95%) and 569 (90.17%) respectively. (5) In the aspects of disease name and animal model, 135 and 220 diseases were included in Chinese and English articles respectively. The common top 10 diseases referred to 8 categories, i.e. stroke-related diseases, arthritis, Alzheimer's disease, depression, diabetes, spinal cord injury, hypertension and obesity. (6) In terms of the number of indicators, the maximum number was 6 for Chinese-version articles, averagely 2.46, while, it was 12 for English-version ones, 4.02 in average. (7) Among the articles of Chinese-version, the maximum number of charts was 17, and 1 028 articles had 2 to 4 charts, accounting the largest proportion (56.27%). Among those of English-version, the top number of charts was 27, and 347 articles had 4 to 6 charts, occupying the largest proportion (54.99%). CONCLUSION: The number of Chinese-version articles for acu-moxibustion experiment research is much higher than that of the English ones, the authorship is led by Chinese and most of the researches are supported by funds. There is less difference in the disease types between Chinese and English articles, but the frequency citation of Chinese articles is obviously higher than that of English ones; while, the numbers of observation indicators and charts in English articles are much more than those of Chinese ones. It is suggested that the great attention has been drawn on the acu-moxibustion experiment researches published in Chinese journals, and the reports of the researches are more complete in English journals.

Study on efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with regorafenib and PD-1 antibody versus continued TACE combined with regorafenib in patients with hepatocellular carcinoma after failed second-line treatment with regorafenib.

Background: At present, there is no standard for the posterior treatment of hepatocellular carcinoma (HCC). This study isTo evaluate and compare the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with regorafenib and anti-PD-1 antibody with continued TACE combined with regorafenib in patients with HCC after the failure of second-line treatment with regorafenib. Methods: We enrolled patients with advanced HCC who were treated with sorafenib and sequential regorafenib. All patients were treated with TACE and found to have tumor progression in 2021. After tumor progression, patients were treated with TACE combined with regorafenib and PD-1 antibody or with continued TACE combined with regorafenib according to the wishes of the patient. Efficacy was evaluated after 1 month of treatment. The objective response rate (ORR), disease-control rate (DCR), and safety were evaluated according to adverse reactions of patients. Results: Nine patients were treated with TACE combined with regorafenib and PD-1 antibody, and the 9 patients continued to receive TACE combined with regorafenib. There was no significant difference in baseline data between the 2 groups. In the PD-1 group five patients achieved a partial response (PR), three achieved stable disease (SD), and one patient had progressive disease (PD) after 1 month of treatment. The ORR was 55.6% and the DCR was 88.9%. In the continued TACE-regorafenib group, four patients achieved PR, one achieved SD, and four patients achieved PD after 1 month of treatment, while the ORR was 44.4% and the DCR was 55.6%. There was a significant difference in the DCR between the two groups (P=0.012), while adverse events were similar in both. Conclusions: TACE combined with regorafenib and PD-1 antibody had a higher DCR and was more effective than continued TACE combined with regorafenib in patients with HCC who failed second-line treatment with regorafenib. However, PD-1 antibody therapy might increase the risk of death by causing an uncontrollable immune response. Given the risk of an immune response, patients may choose to continue TACE combined with regorafenib, given the similar ORR of the two treatments.

Study on safety and efficacy of regorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma after first-line targeted therapy.

Background: Targeted drug therapy and transcatheter arterial chemoembolization (TACE) is the most effective control method for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib as the second-line treatment of patients with advanced HCC, combined with TACE treatment still achieved good results in clinic. However, there is no relevant research at present. However, there is no relevant research at present. This study was to investigate the efficacy and safety of regorafenib combined with TACE in the treatment of patients with advanced HCC after the failure of first-line targeted treatment. Methods: Fifty-nine patients with advanced HCC received second-line regorafenib treatment between October 2019 and September 2021 were enrolled in the study. Patients were treated with routine TACE. Oral administration of regorafenib was started 1 week after the operation for 3 weeks and then stopped for 1 week. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (m-PFS), and safety were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (m-RECIST). In our study, most of the analyses are descriptive. Results: One patient achieved complete response (CR), and 24 patients achieved partial response (PR). stable disease (SD) was observed in 14 patients, while progression disease (PD) was observed in 20 patients. The ORR was 42.3% (25/59), and the DCR was 66.1% (39/59). The longest follow-up was 23 months, and the shortest was 1 month. Disease progression was found in 45 patients during follow-up. Among these patients, the longest interval before the detection of disease progression was 16 months, and the shortest was 1 month. Among patients who had disease progression, the median PFS was 8 months. Adverse events (AEs) were observed in 59 patients. These included hand-foot reaction (n=50, 84.7%), weight decrease (n=18, 30.5%), hypertension (n=8, 13.6%), proteinuria (n=1, 1.7%), weakness (n=12, 20.3%), diarrhea (n=1, 1.7%), and hoarseness (n=9, 15.3%). No treatment-related death occurred. Conclusions: Regorafenib combined with TACE achieved a good ORR and DCR among patients with advanced HCC receiving second-line targeted therapy, with only 9 patients experiencing grade 3 or 4 adverse reactions. Therefore, regorafenib combined with TACE is effective and safe in the treatment of advanced HCC.

[κ-opioid receptor is involved in electroacupuncture analgesia via inhibition of spinal microglial Toll-like receptor 4 in neuropathic pain rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of lumbar spinal κ-opioid receptor (KOR) and Toll-like receptor 4(TLR4) in microglia in neuropathic pain rats, so as to explore the role of cross-talk between KOR and TLK4 in EA-induced alleviation of chronic neuropathic pain. METHODS: Wistar male rats were randomized into control, model, EA and EA plus KOR inhibitor (EA+inhibitor) groups (n=18 in each group). The neuropathic pain model was established in rats by ligature of the right sciatic nerve. EA was applied at bilateral "Zusanli"(ST36) and "Yanglingquan"(GB34) for 30 min, once daily for 5 days. JDTic dihydrochloride (a KOR inhibitor) was administrated by intraperitoneal injection before EA intervention. The difference value of paw withdrawal thermal latency (PWLD) of the bilateral hind-limbs was used as the thermal pain reaction level. At the end of experiments, the rat's lumbar spinal cord (L2-L4) was taken for detecting the expression of CD68 mRNA (a marker of the activated microglia) and Iba-1 (a marker for the activated and resting microglia) immunoactivity, and dynorphin content, and KOR mRNA and TLR4 protein (in immunomagnetic microbead method separated microglia) by using fluorescence quantitative PCR, immunofluorescence, radioimmunoassay and Western blot, separately. RESULTS: Compared with the control group, a strong thermal hyperalgesia was induced, the expression levels of Iba-1 and CD68 mRNA in the spinal cord, TLR4 protein of the spinal microglia were significantly increased(P<0.01) in the model group. The microglia were characterized by somatic hypertrophy and thickened branches in the model group. After EA intervention, the PWLD, the expression of Iba-1, CD68 mRNA and TLR4 protein of the microglia were significantly decreased(P<0.05), while the content of spinal dynorphin and the expression of KOR mRNA of the microglia increased in the EA group relative to the model group(P<0.05). The hypertrophic microglia shrinked slightly in the EA group. After injection of KOR inhibitor, the PWLD and expression levels of Iba-1, CD68 mRNA and TLR4 protein were significantly increased(P<0.05), and the expression of KOR mRNA was significantly decreased(P<0.05) in the EA+inhibitor group in comparison with the EA group. CONCLUSION: The analgesia effect of EA may partly mediated by spinal microglial KOR and the activation of KOR of microglia may be a target for inhibition of microglial TLR4-induced pro-inflammatory signaling.

A convergent synthetic platform for dual anticancer drugs functionalized by reduced graphene nanocomposite delivery for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is widespread cancer with a high degree of morbidity and mortality in individuals worldwide and a serious concern for its resistance to present chemotherapy drugs. In this investigation, the combination of cisplatin (CPT) and metformin (MET) to kill the HepG2 and caco-2 cells was developed into a new pH-responding magnetic nanocomposite based on reduced graphene oxide. Polyhydroxyethyl methacrylic (PHEA) was then linked employing grafting from approach to the reduced graphene oxide by ATRP polymerization (Fe3O4@rGO-G-PSEA). FT-IR, SEM, XRD, DLS, and TGA analyses evaluated physicochemical characteristics of the nanocomposite. In addition, the cellular uptake property of the nanocomposites was examined by the HepG2 cells. The outcomes of cell viability results indicate that the nanoparticles loaded with MET&CPT showed the lowest concentration rate of HepG2 and Caco-2 cells compared to the drug-loaded single nanocomposite groups and free drugs. The histological analysis has demonstrated relatively safe and does not produce different stress such as swelling and inflammation of the mice organs. Our results show the enhancement in cytotoxicity in HepG2 and Cocoa-2 cells by MET and CPT graphene oxide-based nanocomposite by promoting apoptotic response. Moreover, Fe3O4@rGO-G-PSEA showed potent in vivo antitumor efficacy but showed no adverse toxicity to normal tissues. Together, this study can provide insight into how surface embellishment may tune these nanocomposites' tumor specificity and provide the basis for developing anticancer efficacy.

[Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may parti-cipate in electroacupuncture analgesia in rats with chronic neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of Toll like receptor 4(TLR4)and heat shock protein 90(HSP90) in the spinal cord of rats with chronic constriction injury (CCI) of sciatic nerve, so as to explore the mechanism of spinal cord TLR4 and HSP90 in alleviating chronic neuropathic pain by EA. METHODS: Male Wistar rats were randomized into control, model, EA, HSP90 inhibitor (inhibitor) and EA+ inhibitor groups (n=10 in each group). The neuropathic pain model was established by ligature of the right sciatic nerve to induce CCI. EA (1 mA，2 Hz/15 Hz)was applied at bilateral "Zusanli"(ST36) and "Yanglingquan"(GB34) for 30 min, once daily for 5 days. Rats of the inhibitor and EA+inhibitor groups were given a subcutaneous injection of HSP90 inhibitor geldanamycin (50 µg/kg) at the neck before daily EA. The paw withdrawal latency (PWL) of the bilateral hind-limbs was detected by using an algesia-detector. The contents of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in the lumbar spinal cord (L2-L4) tissue were detected by enzyme-linked immunosorbent assay. The relative expression levels of HSP90 and TLR4 proteins in the lumbar spinal cord (L2-L4) were detected using Western blot and immunofluorescence double labeling, respectively. RESULTS: Following CCI, a strong thermal hyperalgesia, an apparent up-regulation of expression of HSP90 and TLR4 proteins and TLR4 in microglia, and increasing levels of IL-1ß and TNF-α in the spinal cord were induced in the model group relevant to the control group (P<0.01，P<0.05). Five sessions of EA intervention or inhibitor injection significantly attenuated hyperalgesia, reversed the increase of IL-1ß and TNF-α, and down-regulated the expression of TLR4 in microglia (P<0.05). Compared with the model group, the expression of HSP90 was further increased (P<0.05), and those of TLR4 in microglia and neurons were significantly decreased and increased, respectively in the EA group (P<0.05). Compared with the EA group, the levels of PWLD,TLR4 and HSP90 expression, and the proportions of neuronal nuclei antigen（NeuN） and TLR4, and ionized calcium binding adapter molecule （Iba1） and TLR4 co-expressed cells were significantly decreased in the inhibitor group and EA+inhibitor group (P<0.05). The proportion of NeuN and TLR4 co-expression cells in the EA+inhibitor group was significantly higher than that of the inhibitor group (P<0.05). CONCLUSION: EA stimulation of ST36 and GB34 can alleviate thermal hyperalgesia in CCI rats, which is closely associated with its effect in regulating the expression of TLR4 in the spinal cord neurons and microglia. HSP90 in the spinal cord may be a co-stimulatory molecule for EA induced relief of neuropathic pain by regulating TLR4.

Modified Microcoil for Preoperative Localization of Solitary Pulmonary Nodules: A Prospective, Single-Arm, Multicenter Clinical Study.

PURPOSE: To evaluate the efficacy and safety of placement of a modified microcoil for precise preoperative localization of solitary pulmonary nodules (SPNs) before video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: This prospective, single-arm, multicenter study included patients who underwent computed tomography (CT)-guided modified microcoil insertion prior to SPN resection by VATS between January 2018 and June 2018. The patient demographics, nodule characteristics, and histopathologic findings were recorded. The primary endpoints included efficacy and safety. RESULTS: A total of 96 patients (41 men and 55 women; mean age, 59.3 years ± 8.9) with 96 SPNs were eligible for enrolment in the study. The mean maximal transverse diameter of the nodules was 10.3 mm ± 5.2 (range, 8-20 mm). The mean time between CT-guided microcoil insertion and the start of the surgical procedure was 14.6 hours (range, 12-24 hours). The duration of the preoperative CT-guided microcoil localization procedure was 29 minutes ± 9 (range, 10-35 minutes), and the intraoperative fluoroscopy time was 0.7 minutes ± 0.7 (range, 0.5-3 minutes). The clinical success rate was 96.9% (93/96), and all nodules were successfully resected using VATS. One patient experienced asymptomatic pneumothorax, but there were no cases of pulmonary hemorrhage. CONCLUSIONS: SPN localization with the modified microcoil is feasible and safe. The modified microcoil can facilitate the thoracoscopic resection of SPNs.

Computational fluid dynamics study of the effect of transverse sinus stenosis on the blood flow pattern in the ipsilateral superior curve of the sigmoid sinus.

OBJECTIVE: To investigate the effect of different types of transverse sinus stenosis on blood flow patterns in the ipsilateral superior curve of the sigmoid sinus. METHODS: According to the morphology of transverse and sigmoid sinus sections in pulsatile tinnitus patients, ten idealized models with different degrees and positions of transverse sinus stenosis were constructed. Computational fluid dynamics simulations were performed to compare the hemodynamic characteristics among these models. Follow-up images of previous cases were included, which preliminarily confirmed the hypothesis that bone plate erosion of the sigmoid sinus sulcus is related to blood flow impingement. RESULTS: Blood flow impingement on the superior curve of the sigmoid sinus wall intensified with increasing degree of stenosis and decreased with increasing distance between the stenosis and the sigmoid sinus. The impact zone was generally confined to the anterior and lateral walls of the superior curve of the sigmoid sinus. When the stenosis was located far from the middle of the transverse sinus, the blood flow impingement on the sigmoid sinus wall was very weak. CONCLUSIONS: When stenosis is located far from the sigmoid sinus, the causes of tinnitus should be comprehensively considered instead of assuming that stenosis is the main cause. Bone plate erosion of the sigmoid sinus sulcus was promoted by blood flow impingement. KEY POINTS: • Ten idealized models with different degrees and positions of stenosis were constructed. • The causes of pulsatile tinnitus should be comprehensively considered. • Sigmoid sinus plate dehiscence was promoted by blood flow impingement.

[How to improve the quality of histological pictures in the manuscripts of Acupuncture Research].

Histological pictures are important parts of medical research articles, and a good histological picture not only visualizes the content of the article, but also makes it easier for readers to understand. With the rapid development of microscopic technology and image processing technology, journals have higher requirements for the quality of histological pictures and more strict requirements for the editing and annotation of pictures. Based on an analysis of the current status of histological pictures in the articles of Acupuncture Research, this article proposes our suggestions and Methods for rational use of histological pictures, so as to provide a reference for improving the quality of histological pictures in the articles published in Acupuncture Research.

Proton pump inhibitors and odds of cholangiocarcinoma: A retrospective case-control study.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have been reported to be associated with cholangitis and might possibly be carcinogenic. However, few studies have been conducted to investigate the association of PPIs with cholangiocarcinoma (CCA). Thus, a hospital-based case-control study was carried out in China to explore the association between PPIs and CCA. METHODS: In this study, 1468 CCA cases (826 intrahepatic cholangiocarcinoma (ICC) and 642 extrahepatic cholangiocarcinoma (ECC)) were included, which were observed at Beijing Friendship Hospital, from February 2002 to October 2018. We retrospectively extracted PPI use and other possible risk factors from clinical records, followed by an investigation of the relationship with CCA via calculation of odds ratios (ORs), adjusted odds ratios (AORs), and 95% confidence intervals (CIs) using logistic regression analysis. RESULTS: PPIs were used by 135 (9.2%) CCA cases and 173 (5.9%) controls. We found that PPI use was associated with a 1.61-fold elevated CCA odds (P < .001) (AOR = 1.61, 95% CI = 1.28-2.05; P < .001). After stratification by CCA subtypes, the AORs of PPIs were consistent for both CCA subtypes, with ORs of 1.36 (AOR = 1.36, 95% CI = 1.02-1.83; P = .003) and 1.95 (AOR = 1.95, 95% CI = 1.46-2.62; P < .001) for ICC and ECC respectively. Our results also showed that PPI use was slightly linked to the odds of CCA in a dose-dependent manner. CONCLUSION: PPI use was correlated with a significant 61% increased odds of CCA, particularly in the ECC. However, the retrospective design and observational nature cannot establish causation. Larger scale, multi-centre prospective studies are required for further validation.

Iodine-125 seed implantation combined with arterial chemoembolization therapy for pain palliation in metastatic bone cancer: a retrospective study.

Bone metastases are the most common sites for malignant tumors. Patients who failed to respond to initial first-line treatment with bisphosphonates usually suffer from extreme pain. The aim of this study was to observe the efficacy of arterial chemoembolization combined with Iodine-125 seed implantation in the treatment of bone metastatic cancer pain. All 14 patients with metastatic bone tumor wo failed first-line treatment underwent arterial chemoembolization the day before the implantation of the particles. A computer stereoscopic TPS was used to design the treatment plans, the number and dose of particles required for implantation. Pain relief was evaluated using several parameters such as Visual Analog Scale (VAS) and Verbal Rating Scales (VRS). Pain intensity was measured pre-operation and 1-week, 1-month, 3-month after the treatment. Meanwhile, we also assessed tumor size using computer tomography (CT). Pain palliation was observed in 35.7% (5/14), 57.1% (8/14), and 78.6% (11/14) of all patients at 1-week, 1-month and 3-month post treatment. Likewise, our analysis showed that the combination therapy resulted in a significant decrease of VAS score (6.71 ± 0.49 before treatment vs 3.36 ± 0.40 at 3 month post treatment) and overall responding rate of 92.0% using VRS pain assessment. Consistently, tumor size was reduced from 42.16 ± 10.32 before treatment to 29.11 ± 8.73 at 3 months post treatment. No serious complications were detected. Our study demonstrate that the combination of arterial chemoembolization and 125I particles resulted in evident pain relief and reduction of tumor burden, suggesting that the combination treatment could be a feasible and promising therapy for bone tumor management.

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study.

As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.

[High Mobility Group Box 1/ CD 24 Receptor/ß-EP Signaling in "Zusanli" (ST 36) Region Contributes to Electroacupuncture Analgesia in Rats with Neuropathic Pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of high mobility group box 1 (HMGB 1) and its receptor CD 24 proteins and ß-endorphin (ß-EP) content in "Zusanli" (ST 36) region in rats with chronic constriction injury (CCI), so as to explore its mechanisms underlying pain relief. METHODS: Thirty male Wistar rats were rando-mized into control, CCI model and EA groups (n＝ 10 rats in each). The neuropathic pain model was established by ligature of the left sciatic nerve to induce CCI in the model and EA groups, and sham operation was performed in rats of the control group. Paw with drawal latency (PWL, thermal pain threshold) of the bilateral hind-limbs was detected by using an algesia-detector. Eight days after CCI operation, EA was applied to bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 30 min, once daily for 5 days. The acetylated-HMGB 1 expression was determined by immunoprecipitation, and the expression of HMGB 1 and toll like receptor 4 (TLR 4) proteins and CD 24 mRNA were detected using Western blot and fluorescent quantitative real time-PCR, respectively, and the content of ß-EP in the acupoint region was assayed by enzyme linked immunosorbent assay (ELISA). Anti-CD 24 neutralizing antibody (200 µL, 100 µg/mL) was injected into ST 36 region once daily for 3 days for verifying the involvement of HMGB 1/CD 24 signaling in EA analgesia. RESULTS: Compared with the control group, the bilateral PWL difference values in the other two groups were significantly increased (P<0.05), meaning an occurrence of hyperalgesia after CCI. In comparison with the CCI model group, the hyperalgesia in the EA group was obviously decreased (P<0.05). After CCI, the expression levels of HMGB 1 and TLR 4 proteins were considerably increased compared with those in the control group (P<0.05). After 5-times' EA, the acetylated-HMGB 1, the expression of CD 24 mRNA, and the content of ß-EP were notably up-regulated (P<0.05), and there were no obvious changes in the expression levels of HMGB 1 and TLR 4 proteins (P>0.05). After local injection of anti-CD 24 antibody, EA-induced increases of ß-EP content and reduction of thermal pain threshold were significantly suppressed (P<0.05). CONCLUSION: EA of ST 36 and GB 34 can alleviate neuropathic pain in CCI rats, which is associated with its effects in up-regulating ß-EP content, and HMGB 1 protein and CD 24 mRNA expression levels in ST 36 region. The activated HMGB 1/CD 24/ß-EP signaling contributes to EA-ST 36 induced analgesia.

Computational Fluid Dynamics Simulation of Hemodynamic Alterations in Sigmoid Sinus Diverticulum and Ipsilateral Upstream Sinus Stenosis After Stent Implantation in Patients with Pulsatile Tinnitus.

OBJECTIVE: To investigate the relationships between upstream venous sinus stenosis and pulsatile tinnitus (PT), and to assess the correlation with diverticulum growth and the effectiveness of stent implantation. METHODS: Patient-specific geometric models were constructed using computed tomography venography images from a patient with PT, with sigmoid sinus diverticulum, and with upstream transverse sinus stenosis, in whom stenting of the upstream sinus stenosis alone achieved complete remission of PT. Computational fluid dynamics simulation based on this patient-specific geometry was performed using commercially available finite element software (ANSYS-14) to qualitatively and quantitatively compare the flow velocity, flow rate, velocity vector, pressure, vorticity, and wall shear stress on the affected side transverse and sigmoid sinuses, before and after stent implantation. RESULTS: Stenting improved the flow direction and magnitude. After stenting, the flow pattern became smoother and more regular. High-speed blood flow at the level of the diverticulum neck was confined to a smaller area, and its direction changed from approximately perpendicular to the diverticular dome to the distal side of the diverticular neck. The diverticulum showed obvious flow reduction, with decreases of 80.7%, 68.7%, 96.1%, and 91.3% in peak velocity, inflow rate, pressure gradient, and peak vorticity, respectively. The abnormally low wall shear stress at the dome of diverticulum was eliminated. CONCLUSIONS: Our findings strongly support a major role of diverticulum stenosis before in PT development and suggest that such stenosis is a causative factor of diverticulum growth. They also confirm the effectiveness of stent implantation for the treatment of PT.

Transcriptome Profile of Near-Isogenic Soybean Lines for ß-Conglycinin α-Subunit Deficiency during Seed Maturation.

Crossing, backcrossing, and molecular marker-assisted background selection produced a soybean (Glycine max) near-isogenic line (cgy-2-NIL) containing the cgy-2 allele, which is responsible for the absence of the allergenic α-subunit of ß-conglycinin. To identify α-null-related transcriptional changes, the gene expressions of cgy-2-NIL and its recurrent parent DN47 were compared using Illumina high-throughput RNA-sequencing of samples at 25, 35, 50, and 55 days after flowering (DAF). Seeds at 18 DAF served as the control. Comparison of the transcript profiles identified 3,543 differentially expressed genes (DEGs) between the two genotypes, with 2,193 genes downregulated and 1,350 genes upregulated. The largest numbers of DEGs were identified at 55 DAF. The DEGs identified at 25 DAF represented a unique pattern of GO category distributions. KEGG pathway analyses identified 541 altered metabolic pathways in cgy-2-NIL. At 18DAF, 12 DEGs were involved in arginine and proline metabolism. The cgy-2 allele in the homozygous form modified the expression of several Cupin allergen genes. The cgy-2 allele is an alteration of a functional allele that is closely related to soybean protein amino acid quality, and is useful for hypoallergenic soybean breeding programs that aim to improve seed protein quality.

[Effect of Electroacupuncture Intervention on Expression of Pain Sensory and Affective Proce- ssing-related µ-opioid Receptor, etc. in the Amygdala in Chronic Neuropathy Pain Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of pain sensory and affective processing-related µ-opioid receptor (MOR), glutamatergic AMPA receptor subunit GIuA 1, extracellular signal-regulated kinase (ERK 1/2), cAMP response element binding protein(CREB) in the amygdala in chronic constrictive injury (CC) + negative affection(NA) rats, so as to reveal its mechanism underlying pain relief. METHODS: A total of 32 male Wistar rats were randomized into normal control, model, EA, and anesthesia+ EA (AEA) groups (n = 8 in each group). The neuropathic pain NA model was established by ligation of the left sciatic nerve and repeated electrical stimulation of the paw-bottom in the pain-paired compartment. EA was applied to bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 30 min, once daily for 7 days. Thermal pain threshold (paw withdrawl latency, PWL) of the bilateral paws was measured by using a Tail-Flick Unit. The expression levels of MOR and p-CREB in the central amygdala (CeA) and those of MOR, GluA 1, p-ERK 1/2 and p-CREB in the right amygdala area were determined using immunofluorescence and Western blot, respectively. RESULTS: in comparison with the normal group, PWL difference (PWLD) values of the model group were significantly increased (P < 0.001), and the time spent in the CPA-paired. compartment was considerably decreased (P < 0.001). After EA, the PWLD levels of both EA and AEA groups were apparently decreased (P < 0.05), showing a pain relief; and the time spent in the CPA-paired compartment was apparently increased in the EA group (P < 0.05) , rather than in the AEA group (P > 0.05). Additionally , compared to the normal group, the expression level of MOR protein in the amygdala was remarkably increased (P < 0.05) and those of GIuA 1, p-ERK 2 and p-CREB proteins were apparently decreased (P < 0.05). After EA intervention for 7 days, the expression levels of these four proteins in the EA group, and those of MOR, p-ERK 2 and p-CREB in the AEA group were significantly up-regulated (P < 0.001, P < 0.01, P < 0.05). The expression level of GIuA 1 was significantly higher in the EA group than in the AEA group (P < 0.05). CONCLUSION: Repeated EA stimulation of ST 36-GB 34 has a definite effect in relieving both sensation and affection dimensions of pain in NA rats, which may be related to its effect in up-regulating the expression of GIuA 1 in the amygdala, but the effects of MOR, p-ERK 2 and p-CREB need being researched further.

Analysis and Thoughts about the Negative Results of International Clinical Trials on Acupuncture.

An increasing number of randomized controlled trials (RCTs) of acupuncture have proved the clinical benefits of acupuncture; however, there are some results that have shown negative results or placebo effects. The paper carried out an in-depth analysis on 33 RCTs in the 2011 SCI database, the quality of the reports was judged according to Jadad scores, and the "Necessary Information Included in Reporting Interventions in Clinical Trials of Acupuncture (STRICTA 2010)" was taken as the standard to analyze the rationality of the therapeutic principle. The difference between the methodology (Jadad) scores of the two types of research reports did not constitute statistical significance (P > 0.05). The studies with negative results or placebo effects showed the following deficiencies with respect to intervention details: (1) incompletely rational acupoint selection; (2) inconsistent ability of acupuncturists; (3) negligible needling response to needling; (4) acupuncture treatment frequency too low in most studies; and (5) irrational setting of placebo control. Thus, the primary basis for the negative results or placebo effects of international clinical trials on acupuncture is not in the quality of the methodology, but in noncompliance with the essential requirements proposed by acupuncture theory in terms of clinical manipulation details.

Effects of Deep Electroacupuncture Stimulation at "Huantiao" (GB 30) on Expression of Apoptosis-Related Factors in Rats with Acute Sciatic Nerve Injury.

SD rats were randomly divided into normal control, model, deep EA, and shallow EA groups. The model was established by mechanical clamping of the sciatic nerve stem. For deep and shallow EA, the needles were inserted into "Huantiao" (GB 30) by about 16 mm and 7 mm, respectively, once daily for 14 days. The results showed that, compared with the normal control group, the nerve-muscle excitability of rat's hip muscle decreased and the nerve conduction velocity of sciatic nerve slowed down in the model group; meanwhile, the number of apoptotic cells and the expression level of Bax protein in the injured nerve increased significantly, and the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax decreased considerably. Compared with the model group, the indices mentioned above were reversed in the two treatment groups, and the changes in the deep EA group were more significant than those in the shallow EA group. These results indicate that EA stimulation at GB 30 can improve the function of injured sciatic nerve, which is closely associated with its effects in upregulating the expression of apoptosis inhibitive factor Bcl-2 and downregulating apoptosis promotive factor Bax. Deep EA is relatively better.

[On the necessity of intellectual property rights involving standardization of acupuncture and moxibustion therapies].

In the process of working out and implementing standardization of acupuncture-moxibustion (acu-moxi) therapy, the issue of intellectual property rights has been frequently involved. Whether is the standardization inevitably involved in intellectual property rights? A reasonable answer to this question is definitely of important realistic guiding value and significance for acu-moxi standardization work. For this reason, authors of the present paper sum up historical development of correlation between acu-moxi standardization and intellectual property rights, and fully analyze the related causes under the conditions of knowledge economy from 1) increasing protection of acu-moxi intellectual property rights, 2) intrinsic requirements for raising the standardization level of acu-moxi, 3) profits drive of the intellectual property rights owners, and 4) increasing impetuous international economic trade competition.