Knockdown of ribosome RNA processing protein 15 suppresses migration of hepatocellular carcinoma through inhibiting PATZ1-associated LAMC2/FAK pathway.

BACKGROUND: Ribosomal RNA processing protein 15 (RRP15) has been found to regulate the progression of hepatocellular carcinoma (HCC). Nevertheless, the extent to which it contributes to the spread of HCC cells remains uncertain. Thus, the objective of this research was to assess the biological function of RRP15 in the migration of HCC. METHODS: The expression of RRP15 in HCC tissue microarray (TMA), tumor tissues and cell lines were determined. In vitro, the effects of RRP15 knockdown on the migration, invasion and adhesion ability of HCC cells were assessed by wound healing assay, transwell and adhesion assay, respectively. The effect of RRP15 knockdown on HCC migration was also evaluated in vivo in a mouse model. RESULTS: Bioinformatics analysis showed that high expression of RRP15 was significantly associated with low survival rate of HCC. The expression level of RRP15 was strikingly upregulated in HCC tissues and cell lines compared with the corresponding controls, and TMA data also indicated that RRP15 was a pivotal prognostic factor for HCC. RRP15 knockdown in HCC cells reduced epithelial-to-mesenchymal transition (EMT) and inhibited migration in vitro and in vivo, independent of P53 expression. Mechanistically, blockade of RRP15 reduced the protein level of the transcription factor POZ/BTB and AT hook containing zinc finger 1 (PATZ1), resulting in decreased expression of the downstream genes encoding laminin 5 subunits, LAMC2 and LAMB3, eventually suppressing the integrin ß4 (ITGB4)/focal adhesion kinase (FAK)/nuclear factor κB kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. CONCLUSIONS: RRP15 promotes HCC migration by activating the LAMC2/ITGB4/FAK pathway, providing a new target for future HCC treatment.

Correction: Ionic migration induced loss analysis of perovskite solar cells: a poling study.

Correction for 'Ionic migration induced loss analysis of perovskite solar cells: a poling study' by Xue Zheng et al., Phys. Chem. Chem. Phys., 2022, 24, 7805-7814, https://doi.org/10.1039/D1CP05450C.

Prognostic factors of sarcomas occurring in bone and joint: A SEER based study.

To clarify the epidemiology, treatment, and prognosis of sarcomas occurring in the bones and joints. The surveillance, epidemiology, and end results (SEER) 18 registries, comprising sarcoma diagnoses made between 2008 and 2014, were queried for sarcomas arising in bones or joints. Kaplan-Meier analysis, multivariate logistic regression analysis, Cox proportional hazards model, and nomograms were used to identify prognostic factors. 2794 patients aged from 1 to 99 (55.8% male) with microscopically confirmed diagnosed as sarcomas (including osteosarcoma, chondrosarcoma, Ewing sarcoma, and soft tissue sarcomas) which primary site limited to bone and joint were identified. Eight independent factors, including age, race, sex, tumor site, histology, pathology grade, tumor size, and total number of malignant tumors (TNOMT), were associated with tumor metastasis. Nine independent prognostic factors, including age (>=60 year, hazard ratio [HR] = 4.145, 95% confidence interval [CI], P < .001), sex (female, HR = 0.814, 95%CI, P = .007), tumor site (spine, HR = 2.527, 95%CI, P < .001), histology, pathology grade (undifferentiated, HR = 5.816, 95%CI, P < .001), tumor size (>=20 cm, HR = 3.043, 95%CI, P < .001), tumor extent (distant, HR = 4.145, 95%CI, P < .001), surgery (no performed, HR = 2.436, 95%CI, P < .001), and TNOMT (1, HR = 0.679, 95%CI, P < .001, were identified and incorporated to construct a nomogram for 2- and 5-year overall survival (OS). The calibration curve for the probability of survival showed good agreement between prediction by the nomogram and actual observation. The C-index of the nomogram for survival prediction was 0.814. Patients who received chemotherapy had a significantly decreased risk of death only for Ewing sarcoma, poorly differentiated tumors, undifferentiated tumors, and distant tumor invasion (P < .05). However, radiotherapy did not show significant differences in OS. This study presents population-based estimates of prognosis for patients with bone sarcomas and demonstrates the impact of age, race, sex, tumor site, histology, pathology grade, tumor size, tumor extent, surgery, radiotherapy, chemotherapy, and the TNOMT on OS. Moreover, the nomogram resulted in a more accurate prognostic prediction. However, in our study, radiotherapy showed no survival benefit, perhaps because detailed data on treatment factors were unavailable and which may have influenced the results.

Ring domains are essential for GATOR2-dependent mTORC1 activation.

The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation. However, the molecular function of the GATOR2 complex remains unknown. Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24 and confers its availability to UBE2D3 and subsequent ubiquitination of NPRL2, contributing to GATOR2-mediated GATOR1 inactivation. As such, WDR24 ablation or Ring deletion prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 in mice. Hence, our findings demonstrate that Ring domains are essential for GATOR2 to transmit amino acid availability to mTORC1 and further reveal the essentiality of nutrient sensing during embryonic development.

Effects of natural 24-epibrassinolide on inducing apoptosis and restricting metabolism in hepatocarcinoma cells.

BACKGROUND: 24-epibrassinolide (EBR) is a ubiquitous steroidal phytohormone with anticancer activity. Yet the cytotoxic effects and mechanism of EBR on hepatocarcinoma (HCC) cells remain elusive. METHODS: Cell counting kit-8 (CCK-8) assay was performed to evaluate cell viability. Real-time cell analysis (RTCA) technology and colony formation assays were used to evaluate cell proliferation. The apoptosis ratio was measured by flow cytometry. Seahorse XFe96 was applied to detect the effects of EBR on cellular bioenergetics. RNA-seq analysis was performed to investigate differences in gene expression profiles. Western blot and qRT-PCR were used to detect the changes in target molecules. RESULTS: EBR induced apoptosis and caused energy restriction in HCC, both of which were related to insulin-like growth factor-binding protein 1 (IGFBP1). EBR rapidly and massively induced IGBFP1, part of which was transcribed by activating transcription factor-4 (ATF4). The accumulation of secreted and cellular IGFBP1 had different important roles, in which secreted IGFBP1 affected cell energy metabolism by inhibiting the phosphorylation of Akt, while intracellular IGFBP1 acted as a pro-survival factor to resist apoptosis. Interestingly, the extracellular signal-regulated kinase (ERK) inhibitor SCH772984 and MAP/ERK kinase (MEK) inhibitor PD98059 not only attenuated the EBR-induced IGFBP1 expression but also the basal expression of IGFBP1. Thus, the treatment of cells with these inhibitors further enhances the cytotoxicity of EBR. CONCLUSION: Taken together, these findings suggested that EBR can be considered as a potential therapeutic compound for HCC due to its pro-apoptosis, restriction of energy metabolism, and other anti-cancer properties. Meanwhile, the high expression of IGFBP1 induced by EBR in HCC contributes to our understanding of the role of IGFBP1 in drug resistance.

Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5.

To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients.

Psychometric Properties of Four Common Clinical Tests for Assessing Hamstring Flexibility in Young Adults.

Objective: To examine the psychometric properties of four common hamstring muscle flexibility tests involving the straight leg raise (SLR), passive knee extension (PKE), sit and reach test (SRT) and toe touch test (TTT) in young adults. Methods: Forty-three young healthy adults (mean age 27.4 years) were recruited for 3 repeated sessions of hamstring flexibility assessments using the 4 tests mentioned above and the subsequent isokinetic examinations. The first two sessions (S1 and S2) were conducted by two different raters randomly on the first day (D1), and the third session (S3) was conducted by the same rater as S1 3 days later (D4). The next day (D5), the isokinetic performances of knee extensors and flexors of the dominant leg were assessed. To evaluate the interrater (S1 vs. S2) and test-retest (S1 vs. S3) reliability of hamstring flexibility tests, intraclass correlation coefficients (ICCs), standard errors of measurement, and the minimum detectable differences were calculated. Correlation analyses were performed to study the association of each hamstring flexibility test with the isokinetic muscle function of the knee flexors (H) and extensors (Q), including the peak torque (PT), total amount of work (TW) and average power (AP). Results: Excellent interrater and test-retest reliability of hamstring flexibility tests involving the SLR, PKE, SRT and TTT were confirmed with ICCs ranging from 0.923 to 0.986. Fair correlations were found between the 4 hamstring flexibility tests and the H/Q for the PT at angular speeds of 180°/s (Pearson's r at 0.330-0.449). In addition, the PKE was fairly correlated with the AP of the hamstring (Pearson's r = 0.320) and the H/Q for the TW (Pearson's r = 0.345) and AP (Pearson's r = 0.386) at angular speeds of 180°/s. Conclusions: This study confirmed that the SLR, PKE, SRT and TTT were reliable flexibility tests for hamstring muscles in young healthy adults, and the PKE might be a more valid outcome measure to predict hamstring injury.

A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.

The therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature based on hypoxia-related genes (HRGs). EWS patients from GSE17674 in the GEO database were analyzed as a training cohort, and differently expressed HRGs between tumor and normal samples were identified. The univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used in this study. A total of 57 EWS patients from the International Cancer Genome Consortium (ICGC) database were set as the validation cohort. A total of 506 differently expressed HRGs between tumor and normal tissues were identified, among which 52 were associated with the prognoses of EWS patients. Based on 52 HRGs, EWS patients were divided into two molecular subgroups with different survival statuses. In addition, a prognostic signature based on 4 HRGs (WSB1, RXYLT1, GLCE and RORA) was constructed, dividing EWS patients into low- and high-risk groups. The 2-, 3- and 5-years area under the receiver operator characteristic curve of this signature was 0.913, 0.97 and 0.985, respectively. It was found that the survival rates of patients in the high-risk group were significantly lower than those in the low-risk group (p < 0.001). The risk level based on the risk score could serve as an independent clinical factor for predicting the survival probabilities of EWS patients. Additionally, antigen-presenting cell (APC) related pathways and T cell co-inhibition were differently activated in two risk groups, which may result in different prognoses. CTLA4 may be an effective immune checkpoint inhibitor to treat EWS patients. All results were verified in the validation cohort. This study constructed 4-HRGs as a novel prognostic marker for predicting survival in EWS patients.

6-methoxydihydroavicine, the alkaloid extracted from Macleaya cordata (Willd.) R. Br. (Papaveraceae), triggers RIPK1/Caspase-dependent cell death in pancreatic cancer cells through the disruption of oxaloacetic acid metabolism and accumulation of reactive oxygen species.

BACKGROUND: Many extracts and purified alkaloids of M. cordata (Papaveraceae family) have been reported to display promising anti-tumor effects by inhibiting cancer cell growth and inducing apoptosis in many cancer types. However, no evidence currently exists for anti-pancreatic cancer activity of alkaloids extracted from M. cordata, including a novel alkaloid named 6­methoxy dihydrosphingosine (6-Methoxydihydroavicine, 6-ME) derived from M. cordata fruits. PURPOSE: The aim of this study was to investigate the anti-tumor effects of 6-ME on PC cells and the underlying mechanism. METHODS: CCK-8, RTCA, and colony-formation assays were used to analyze PC cell growth. Cell death ratios, changes in MMP and ROS levels were measured by flow cytometry within corresponding detection kits. A Seahorse XFe96 was employed to examine the effects of 6-ME on cellular bioenergetics. Western blot and q-RT-PCR were conducted to detect changes in target molecules. RESULTS: 6-ME effectively reduced the growth of PC cells and promoted PCD by activating RIPK1, caspases, and GSDME. Specifically, 6-ME treatment caused a disruption of OAA metabolism and increased ROS production, thereby affecting mitochondrial homeostasis and reducing aerobic glycolysis. These responses resulted in mitophagy and RIPK1-mediated cell death. CONCLUSION: 6-ME exhibited specific anti-tumor effects through interrupting OAA metabolic homeostasis to trigger ROS/RIPK1-dependent cell death and mitochondrial dysfunction, suggesting that 6-ME could be considered as a highly promising compound for PC intervention.

Ionic migration induced loss analysis of perovskite solar cells: a poling study.

Understanding the interplay between ionic migration and defect trapping in photovoltaic perovskites is critical to develop targeted passivation techniques for performance enhancement. In this study, systematic poling experiments on Cs0.05(FA0.85MA0.15)0.95Pb(I0.85Br0.15)3 perovskite solar cells (PSCs) were conducted to resolve the principal effects of bias dependent pretreatment effects due to dynamic ionic migration. We find that under negative polarizations, iodine ion accumulation at perovskite/electron transport layer (ETL) interfaces causes enhanced global non-radiative recombination in PSCs and significant open-circuit voltage (Voc) losses. On the other hand, dramatic short-circuit current (Jsc) reduction occurs in positively polarized devices, which is ascribed to ineffective charge collection due to modified band-bending towards both charge transport materials. Spatiotemporally scanning probe microscopy on the surface of polarized perovskites provides an in situ estimation of iodine diffusion mobility and visualization of reorganizations under an external bias. Moreover, our findings suggest that the precondition effect of PSCs under operation due to defect ions is recoverable, therefore achieving a respectable lifetime of PSCs for commercialization is promising.

Theoretical studies on the g factors, optical absorption, and their concentration variations for Mo5+ in 40PbO-(10 - x)Y2 O3 -50P2 O5 :xMoO3 glass.

On the basis of the higher order perturbation formulas of g factors for a 4d1 group in tetragonally compressed octahedra, the g factors, optical absorption, local structure, and their concentration dependences of pentavalent molybdenum in 40PbO-(10 - x)Y2 O3 -50P2 O5 :xMoO3 (1 ≤ x ≤ 5 mol%) glass are uniformly investigated. The experimental optical absorption spectra and g factors for Mo5+ at various concentrations x are reasonably regenerated by using the reasonable exponential concentration functions of the cubic field parameter Dq , covalent factor N, and relative tetragonal compression ratio ρ. The tetragonal compression ratio ρ due to the Jahn-Teller effect was found in the range of 3.8% to 4.2%. The decreasing trend of Dq and N and the increasing trend of ρ with concentration can be interpreted as the fact that the variations of MoO3 and Y2 O3 concentrations lead to the modulations of local structure and electron cloud distribution around Mo5+ , associated with the adjustment of the glass network. The concentration dependence of optical basicity is also analyzed for the above glass systems.

A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis.

Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.

Dimethyl Fumarate Induces Metabolic Crisie to Suppress Pancreatic Carcinoma.

Dimethyl fumarate (DMF) is an approved drug used in the treatment of multiple sclerosis (MS) and psoriasis therapy. Multiple studies have demonstrated other pharmacological activities of DMF such as an anti-cancer agent. In particular, studies have shown that DMF can modulate the NRF2/HO1/NQO1 antioxidant signal pathway and inactivate NF-κB to suppress the growth of colon and breast cancer cells, and induce cell death. In this study, we aimed to evaluate the anti-tumor activities of DMF in pancreatic cancer (PC) focusing on cell death as the predominant mechanism of response. We showed that both mitochondrial respiration and aerobic glycolysis were severely depressed following treatment with DMF and the effects could be abrogated by treatment with L-cysteine and N-acetyl-L-cysteine (NAC). Importantly, we verified that DMF induced metabolic crisis and that cell death was not related to alterations in ROS. Our data implied that MTHFD1 could be a potential downstream target of DMF identified by molecular docking analysis. Finally, we confirmed that MTHFD1 is up-regulated in PC and overexpression of MTHFD1 was negatively related to outcomes of PC patients. Our data indicate that DMF induces metabolic crisie to suppress cell growth and could be a potential novel therapy in the treatment of PC.

A benzene-bridged divanadium complex-early transition metal catalyst for alkene alkylarylation with PhI(O2CR)2via decarboxylation.

The synthesis, structure and catalytic activity of a benzene-bridged divanadium complex were comprehensively studied. The reduction of (Nacnac)VCl2 (1) (Nacnac = (2,6-iPr2C6H3NCMe)2HC) supported by ß-diketiminate with potassium graphite (KC8) by employing benzene as the solvent allows access to the benzene-bridged inverted-sandwich divanadium complex (µ-η6:η6-C6H6)[V(Nacnac)]2 (2a), which can catalyze alkene alkylarylation with hypervalent iodine(iii) reagents (HIRs) via decarboxylation to generate regioselectively diverse indolinones. Furthermore, the mild nature of this reaction was amenable to a wide range of functionalities on alkenes and HIRs. Mechanistic studies revealed a relay sequence of decarboxylative radical alkylation/radical arylation/oxidative re-aromatization.

Elevated Platelet Parameter in First-Episode Schizophrenia Patients: A Cross-Sectional Study.

Serotonin (5-HT) and inflammation are 2 major hypotheses in schizophrenia (SZ) pathogenesis, both of which involve platelets. However, the association between platelet and SZ has not been well studied. The aim of this study was to evaluate changes of platelet count (PLT), mean platelet volume (MPV), platelet-large cell ratio (P-LCR), platelet distribution width (PDW), and plateletcrit (PCT) in patients with first-episode schizophrenia (FES). Meanwhile, 3 inflammation markers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), were evaluated. Complete blood count of 106 FES patients, 82 first-episode depression (FED) patients, and 120 healthy controls (HCs) were compared. In addition, PLR, NLR, and MLR were calculated and compared among 3 groups. Our data suggested that PLT, MPV, P-LCR, PDW, PCT, NLR, PLR, and MLR in FES patients were significantly increased than those in the HCs (P < 0.01 or P < 0.05, respectively). PLT, PCT, PLR, and MLR in FED patients were significantly higher than those in the HCs (P < 0.01). However, no significant difference in MPV, P-LCR, and NLR was identified between FED patients and HCs (P > 0.05). Moreover, MPV, P-LCR, PDW, NLR, and MLR in FES patients were significantly higher than those in FED patients (P < 0.01 or P < 0.05, respectively). The elevation of PLT, MPV, P-LCR, PDW, PCT, NLR, PLR, and MLR in FES patients supported 5-HT and inflammation hypotheses in SZ pathogenesis. Further, our data suggested that increasing levels of MPV, P-LCR, PDW, NLR, and MLR might help to distinguish FES from FED. Clinical Trials.gov ID: 2018JJ2580.

Chinese Herbal Formula Xuefu Zhuyu for Tension-Type Headache with Qi-Stagnation and Blood-Stasis Pattern (CheruXTH): Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Tension-type headache (TTH) is the most common headache disorder. Current treatments for TTH have been reported to be associated with insufficient long-term benefits and unwanted adverse events (AEs). The Chinese herbal formula Xuefu Zhuyu (XFZY) has been utilized in TTH treatment, but the evidence supporting its efficacy remains unclear. This study will evaluate the efficacy and safety of XFZY for TTH. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial will be undertaken in China. A total of 174 eligible participants will be randomly assigned to either an XFZY group or a placebo group (20 ml each dose, three times daily for 4 weeks) at a ratio of 1 : 1. The primary outcome is the change in mean headache intensity measured by a 10 cm visual analogue scale (VAS). Secondary outcomes include the area-under-the headache curve (AUC), headache frequency, rescue medication use, qi-stagnation and blood-stasis pattern measurement, quality of life measured by the EuroQol-5-Dimensions-5-Level (EQ-5D-5L), global evaluation of medication, and health economic indexes. Discussion. The results of the study are expected to provide evidence of high methodological and reporting quality on the efficacy and safety of XFZY for TTH. This trail is registered with ChiCTR1900026716 (registered on 19 October, 2019).

Changes of Serum Melatonin, Interleukin-6, Homocysteine, and Complement C3 and C4 Levels in Patients With Depression.

OBJECTIVES: Cytokine activation and low complement levels are common in depression patients. This study is aimed at investigating the clinical significance of changes in serum concentrations of melatonin (MT), interleukin-6 (IL-6), homocysteine (hcy), and complement C3 and C4 in depression patients and relationships of them with depression activity. METHODS: A total of 95 depression patients, including first-episode group (n = 43) and recurrent group (n = 52), and 45 age- and gender-matched healthy controls (HC) were recruited. Serum levels of MT, IL-6, hcy, C3, and C4 in all samples were measured by using enzyme-linked immunosorbent assay (ELISA), chemiluminescence method, enzyme circulation method, and immuno-scatter turbidimetric assay, respectively. RESULTS: The serum MT, IL-6, and hcy levels in the first-episode group (113.08 ± 5.06 pg/ml, 2.06 ± 0.12 ng/L, and 13.87 ± 0.45 µmol/L), and recurrent group (117.63 ± 4.63 pg/ml, 2.20 ± 0.12 ng/L, and 13.61 ± 0.46 µmol/L) were significantly higher than those in the control group (89.50 ± 5.10 pg/ml, 1.57 ± 0.06 ng/L, and 11.34 ± 0.40 µmol/L). The serum levels of C3 in the first-episode group (0.95 ± 0.02 ng/L) were significantly lower than those in the recurrent group (1.05 ± 0.03 ng/L) and control group (1.12 ± 0.03 ng/L). There was no significant difference in serum C4 level between each group. CONCLUSION: These results suggest that higher serum MT, IL-6, and hcy levels were correlated with pathogenesis of depression.

[Therapeutic effect of nape cluster acupuncture combined with swallowing function training on post-stroke dysphagia].

OBJECTIVE: To observe the effect on swallowing function in patients with post-stroke dysphagia treated with nape cluster acupuncture and the immediate effect of acupuncture at Fengchi (GB 20). METHODS: A total of 60 patients with post-stroke dysphagia were randomized into an observation group and a control group, 30 cases in each one.On the basis of conventional western medication treatment, swallowing function training was applied in the control group, once a day.On the base of the treatment as the control group, nape cluster acupuncture was applied at Fengchi (GB 20), Tianzhu (BL 10), Wangu (GB 12), Lianquan (CV 23), Panglianquan (Extra), Jinjin (EX-HN 12) and Yuye (EX-HN 13) in the observation group, once a day. Additionally, pricking blood was applied at Jinjin (EX-HN 12) and Yuye (EX-HN 13), 2 times a week. The treatment was given 30 min each time, a week as one course and 4 courses were required. Before and after treatment, the standardized swallowing assessment (SSA) score and video fluoroscopic swallowing study (VFSS) score were compared in the two groups. The ultrasonic diagnostic device of swallowing and surface electromyography were used to observe the immediate effect on swallowing related muscles of acupuncture at Fengchi (GB 20). RESULTS: Compared before treatment, the SSA scores were reduced after treatment in the two groups (P<0.05), and the change of the observation group was larger than the control group (P<0.05). Compared before treatment, the VFSS scores were increased after treatment in the two groups (P<0.05), and the change of the observation group was larger than the control group (P<0.05). Acupuncture at Fengchi (GB 20) immediately increased the amplitude of submental muscles and infrahyoid muscles in the observation group (P<0.05), the geniohyoid muscle movement time was reduced and geniohyoid muscle displacement was increased (P<0.05). CONCLUSION: On the base of the routine treatment, nape cluster acupuncture could improve swallowing function in patients with post-stroke dysphagia. Acupuncture at Fengchi (GB 20) could immediately affect swallowing related muscles, improve muscle amplitude and reduce swallowing time.

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial.

OBJECTIVE: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). METHODS: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. RESULTS: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). CONCLUSIONS: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).