Tumor necrosis factor-α induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation.

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory factor that plays an important role in establishing a complicated connection between inflammation and cancer. TNF-α promotes tumor proliferation, migration, invasion, and angiogenesis according to numerous studies. Studies have shown the significant role of STAT3, a downstream transcription factor of another important inflammatory cytokine, IL-6 in the development and progression of different tumors especially colorectal cancer. In the present study, we investigated whether TNF-α has a role in proliferation and apoptosis of colorectal cancer cells through STAT3 activation. HCT116 cell line as human colorectal cancer cells was used in this study. Major assays were MTT assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that TNF-α significantly increased the phosphorylation of STAT3 and expression of all the STAT3 target genes related to cell proliferation, survival, and metastasis compared with control. Moreover, our data showed that the STAT3 phosphorylation and expression of its target genes significantly were reduced in the presence of TNF-α + STA-21 compared with TNF-α-treated group demonstrating that the increase in genes expression partially was due to the TNF-α-induced STAT3 activation. On the other hand, STAT3 phosphorylation and mRNA levels of its target genes were partially decreased in the presence of TNF-α + IL-6R supporting the indirect pathway of STAT3 activation by TNF-α through inducing IL-6 production in cancer cells. Given the growing evidence for STAT3 as a key mediator of inflammation-induced colon cancer, our findings support further investigation of STAT3 inhibitors as potential cancer therapies.

Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78.

Human colorectal cancer (CRC), a highly malignant and metastatic carcinoma, is resistant to many present anticancer therapies. The inhibition of tumor survival and growth through receptor suppression is a promising way to treat CRC. The study aimed to investigate the effect of a natural plant triterpenoid, berberine (BBR), on SW480 cells and whether its role is mediated by Glucose-regulated protein 78 (GRP78). MTT assay, wound healing assay, and Annexin V-FITC assay were used to measure the effect of BBR on the proliferation, migration, and apoptosis of SW480 cells, respectively. Immunofluorescence and western blotting were used to evaluate both the downregulation of BBR on GRP78 and the role of GRP78 in the effect of BBR on SW480 cells. Our results revealed that BBR inhibited the proliferation and migration, as well as induced the apoptosis of SW480 cells, in a dose-dependent manner. BBR induced the dose-dependent inhibition of cell proliferation in HT-29 cells. BBR inhibited the expression of GRP78 and its localization on the cell surface. Moreover, BBR inhibited the expression of Bax, Bcl-2, c-Myc, and Vimentin and up-regulated the cytokeratin expression in SW480 cells. In addition, we found that the effects of BBR on cell proliferation, migration, and apoptosis in SW480 cells were reversed by the overexpression of GRP78. Our findings demonstrated that BBR inhibited the proliferation and migration and induced the apoptosis of SW480 cells by downregulating the expression of GRP78, and targeting GRP78 might be a potential way to develop the effective anticancer therapy.

CircKIAA0907 Retards Cell Growth, Cell Cycle, and Autophagy of Gastric Cancer In Vitro and Inhibits Tumorigenesis In Vivo via the miR-452-5p/KAT6B Axis.

BACKGROUND The significant roles of circular ribonucleic acids (RNAs) in cancers have been discussed in many studies. This report aimed to investigate the biological functions of circKIAA0907 and its action mechanism in gastric cancer (GC). MATERIAL AND METHODS Relative RNA expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The examination of cell proliferation was performed via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay. Flow cytometry was used to analyze the apoptosis rate and cell cycle. Protein levels were quantified using western blot. Biotinylated RNA pull-down assay was used to find the microRNA target of circKIAA0907; target binding was validated through dual-luciferase reporter assay. The assay in vivo was executed via a xenograft tumor model to explore the role of circKIAA0907 in GC. RESULTS CircKIAA0907 was downregulated in GC and had higher stability than its linear isoform. Functionally, circKIAA0907 upregulation resulted in the repression of proliferation, cell cycle, and autophagy and promotion of apoptosis in GC cells. Mechanistically, circKIAA0907 bound to miR-452-5p as a specific sponge for it; lysine acetyltransferase 6B (KAT6B) was a target gene of miR-452-5p, so circKIAA0907 elevated KAT6B levels via sponging miR-452-5p. Reversion assays indicated that circKIAA0907 served as a tumor inhibitor by inhibiting miR-452-5p and increasing KAT6B; miR-452-5p inhibition impeded GC development by upregulating KAT6B. The miR-452-5p/KAT6B axis was also accountable for circKIAA0907-induced tumorigenesis suppression in vivo. CONCLUSIONS This work demonstrated that circKIAA0907 has diagnostic and therapeutic value in GC by acting as an oncogenic molecule via the miR-452-5p/KAT6B axis.

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients.

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

Suicide ideation and anhedonia among clinically stable adolescents with the recurrent depressive disorder during the COVID-19 pandemic: A network perspective.

BACKGROUND: Anhedonia is a suicide risk factor among adolescent patients with recurrent depressive disorder (depression hereafter). This study examined associations between suicidal ideation (SI) and residual depressive symptoms (RSD), including anhedonia, among clinically stable adolescents with depression. METHOD: A network analysis was performed to examine the association between RDS and SI among adolescents with depression. Node-specific predictive betweenness was computed to examine short paths between anhedonia and SI. Additionally, a Network Comparison Test (NCT) was conducted to examine gender differences in derived network model characteristics. RESULTS: The network analysis identified close associations of PHQ9 ("Suicide ideation") with PHQ1 ("Anhedonia") as well as some other RDS including PHQ6 ("Guilt"), PHQ2 ("Sad mood") and PHQ8 ("Motor disturbances"). Additionally, PHQ2 ("Sad mood") and PHQ4 ("Fatigue") were the main bridge nodes linking anhedonia and SI. Comparisons of network models did not find significant differences in network global strength or edge weights. LIMITATION: Causal relations between anhedonia and SI could not be determined due to the cross-sectional study design. CONCLUSIONS: SI was directly related to Anhedonia in addition to Guilt, Sad mood and Motor disturbances. Sad mood and Fatigue were the main bridge nodes linking Anhedonia and SI. To reduce the risk of SI among clinically stable adolescents with depression during the COVID-19 pandemic, specific RDS including Anhedonia, Guilt, Sad mood, Motor disturbances and Fatigue should be targeted in interventions.

Internet addiction and residual depressive symptoms among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic: a network analysis perspective.

To assess the inter-relationships between residual depressive symptoms (RDS) and Internet addiction (IA) using network analysis among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. RDS and IA were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Internet Addiction Test (IAT), respectively. Central symptoms and bridge symptoms in the network model were examined. A total of 1,454 adolescents met the study criteria and were included in the analyses. The prevalence of IA was 31.2% (95% CI: 28.8%-33.6%). In the network analysis, the nodes IAT15 ("Preoccupation with the Internet"), PHQ2 ("Sad mood"), and PHQ1 ("Anhedonia") were the most central symptoms in the IA-RDS network model. Bridge symptoms included IAT10 ("Sooth disturbing about your Internet use"), PHQ9 ("Suicide ideation"), and IAT3 ("Prefer the excitement online to the time with others"). Additionally, PHQ2 ("Sad mood") was the main node linking "Anhedonia" to other IA clusters. Internet addiction was common among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. Core and bridge symptoms identified in this study could be prioritized as targets for the prevention and treatment of IA in this population.

18α-glycyrrhetinic acid down-regulates expression of type I and III collagen via TGF-Β1/Smad signaling pathway in human and rat hepatic stellate cells.

OBJECTIVE: To investigate the effects of 18α-glycyrrhetinic acid (18α-GA) on the expression of type I and III collagen in human and rat hepatic stellate cells (HSC) and to explore the role of TGF-ß1/Smad signaling pathway involved. METHODS: Following 18α-GA treatment, the cell viability and cell growth were detected to determine the optimal concentration of 18α-GA. The expressions of TGF-ß1/Smad signaling-related genes including type I and III collagen in human and rat HSCs before and after 18α-GA treatment were measured by real time PCR. The expression of related proteins was verified by western blot assay. The phosphorylation level of Smad2 and Smad3 was detected by immunocytochemistry. The DNA binding activities of SP-1, AP-1 and NF-κB were measured by both EMSA and ArrayStar transcription factor activity assay. RESULTS: 18α-GA could decrease the mRNA and protein expression of Smad3, type I and III collagen, increase the Smad7 expression in human and rat HSCs (P<0.05), and reduce phosphorylation level of Smad3 at 24 h and 48 h after treatment. The DNA binding activities of transcription factors were suppressed by 18α-GA in human and rat HSCs at 24 h, and the activities reduced in a time dependent manner with the lowest activities at 48 h, especially for SP-1. CONCLUSION: 18α-GA could inhibit the mRNA and protein expression of type I and III collagen in human and rat HSCs, which may be attributed to down-regulation of Smad3, up-regulation of Smad7, and inhibition of DNA binding activities of SP-1, AP-1 and NF-κB.

18α-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells.

BACKGROUND: To investigate the potential mechanisms underlying the protective effects of 18α Glycyrrhizin (GL) on rat hepatic stellate cells (HSCs) and hepatocytes in vivo and in vitro. MATERIAL/METHODS: Sprague-Dawley (SD) rats were randomly divided into 5 groups: normal control group, liver fibrosis group, high-dose 18α GL group (25 mg/ kg/d), intermediate-dose 18α GL group (12.5 mg/kg/d) and low-dose 18α GL group (6.25 mg/ kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of alpha-smooth muscle actin (αSMA) and NF-kappaB were determined by real-time PCR and immunohistochemistry. RESULTS: 18αGL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of αSMA between the fibrosis group and 18α-GL treatment groups, suggesting that 18α GL can suppress the proliferation and activation of HSCs. Few HSCs were apoptotic in the portal area and fibrous septum in the liver fibrosis group. However, the double-color staining of a-SMA and TUNEL showed that 18α-GL treatment groups increased HSC apoptosis. NF-kappaB was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-kappaB was noted in the 18αGL groups. In the in vitro experiments, 18α GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18α GL treatment and were largely apoptotic. CONCLUSIONS: 18α-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-kappaB into the nucleus, which plays an important role in the protective effect of 18α-GL on liver fibrosis.

Predicting Histological Healing and Recurrence in Ulcerative Colitis by Assessing Mucosal Vascular Pattern Under Narrow-Band Imaging Endoscopy.

This study investigated the predictive value of narrow-band imaging (NBI) endoscopic staging of different mucosal vascular patterns (MVPs) in patients with ulcerative colitis (UC) for histological healing or clinical recurrence of patients with UC. A total of 124 patients with UC in clinical remission attending the First Affiliated Hospital of Weifang Medical College were included in the study and underwent NBI colonoscopy. Inflammatory activity was assessed in the intestine using the Mayo endoscopic score (MES) and the MVP. Mucosal inflammation was histologically graded using the Nancy index (NI). The colons of 124 patients with UC were staged according to NBI endoscopic MVP staging criteria. The differences between NBI colonoscopy MVP typing and white light endoscopic MES in assessing histological healing (HH) were statistically significant (p < 0.001), and there was a moderate correlation between MES and the degree of HH (r = 0.471, p < 0.001). In addition, there was a significant correlation between the severity of mucosal activity determined by white light endoscopy (WLE) and MVP staging (r = 0.811, p < 0.001). The differences between NBI endoscopic MVP staging and white light endoscopic MES in assessing UC recurrence were statistically significant (p < 0.001). Spearman's correlation analysis showed a moderate correlation between NBI endoscopic MVP staging and clinical recurrence. NBI endoscopic MVP staging can predict HH and clinical recurrence status better than WLE.

Fabrication and Characterization of Antifungal Hydroxypropyl-ß-Cyclodextrin/Pyrimethanil Inclusion Compound Nanofibers Based on Electrospinning.

Pyrimethanil (PMT) is an anilinopyrimidine bactericide with poor water solubility, which limits its applications. To improve the physical and chemical properties of PMT, hydroxypropyl-ß-cyclodextrin/pyrimethanil inclusion compound nanofibers (HPßCD/PMT-IC-NFs) were fabricated via electrospinning. A variety of analytical techniques were used to confirm the formation of the inclusion compound. Scanning electron microscopy image displayed that HPßCD/PMT-IC-NF was homogeneous without particles. Thermogravimetric analysis indicated that the formation of the inclusion compound improved the thermostability of PMT. In addition, the phase solubility test illustrated that the inclusion compound formed by PMT and HPßCD had a stronger water solubility. The antifungal effect test exhibited that HPßCD/PMT-IC-NF had better antifungal properties. The release experiment confirmed that HPßCD/PMT-IC-NF had a sustained-release effect, and the release curve conformed to the first-order kinetic model equation. In short, the fabrication HPßCD/PMT-IC-NF inhibited improved solubility and thermostability of PMT, thus promoting the development of pesticide dosage form to water-based and low-pollution direction.

Safety evaluation of CuminUP60® - A novel curcumin complex.

Curcuma longa L. is one of the most recognized Curcuma species (Sharifi-Rad et al., 2020 [3]). Curcumin, the primary polyphenolic compound found in turmeric has been used for a variety of purposes for centuries. CuminUP60® is a curcumin complex composed of Curcuma longa L. rhizome extract and Poloxamer 407. The results of GLP compliant in vitro and in vivo safety studies conducted with CuminUP60® including a bacterial reverse mutation assay, an in vitro mammalian cell chromosome aberration study and an in vivo micronucleus study are reported here. In addition, a GLP compliant, a single dose toxicity study in Sprague-Dawley rats and a 4-week repeat dose study were also conducted. CuminUP60® was shown to not be mutagenic in a number of in vitro and one in vivo study, the results of which are reported here. A single oral dose of 5000 mg CuminUP60® was well tolerated by male and female Sprague-Dawley rats. The no observed adverse effect level (NOAEL) for CuminUP60® in male and female Sprague-Dawley rats in a 4-week repeat dose study was determined to be 1000 mg/kg bw/day.

Effect of music-based movement therapy on the freezing of gait in patients with Parkinson's disease: A randomized controlled trial.

Background: Progression of freezing of gait (FOG), a common pathological gait in Parkinson's disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients' motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD. Objective: To explore the effect of MMT on FOG in patients with PD. Materials and methods: This was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function. Results: After 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05). Conclusion: MMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Cyberbully victimization and its association with residual depressive symptoms among clinically stable adolescents with psychiatric disorders during the COVID-19 pandemic: A perspective from network analysis.

Objective: This study examined the prevalence of cyberbullying and its relationship with residual depressive symptoms in this patient population during the COVID-19 outbreak using network analysis. Methods: This was a multicenter, cross-sectional study. Adolescent patients attending maintenance treatment at outpatient departments of three major psychiatric hospitals were included. Experience of cyberbullying was measured with a standard question, while the severity of Internet addiction and depressive symptoms were measured using the Internet Addiction Test and the Patient Health Questionnaire-9, respectively. The network structure of depression and cyberbully were characterized and indices of "Expected Influence" was used to identify symptoms central to the network. To identify particular symptoms that were directly associated with cyberbully, the flow function was used. Results: Altogether 1,265 patients completed the assessments. The overall prevalence of cyberbullying was 92.3% (95% confidence interval (CI): 90.8-93.7%). Multiple logistic regression analysis revealed that male gender (p = 0.04, OR = 1.72, 95%CI: 1.04-2.85) was significantly associated with higher risk of cyberbullying, while a relapse of illness during the COVID-19 pandemic was significantly associated with a lower risk of cyberbullying (p = 0.03, OR = 0.50, 95%CI: 0.27-0.93). In the network of depression and cyberbully, "Sad mood," "Anhedonia" and "Energy" were the most central (influential) symptoms. Furthermore, "Suicidal ideation" had the strongest negative association with cyberbully followed by "Guilt". Conclusion: During the COVID-19 pandemic, the experience of cyberbullying was highly prevalent among clinically stable adolescent psychiatric patients, particularly male patients. This finding should raise awareness of this issue emphasizing the need for regular screening and interventions for adolescent patients. Central symptoms (e.g., "Sad mood," "Anhedonia" and "Energy") identified in this study should be targeted in interventions and preventive measures.

Improvement of freezing of gait in patients with Parkinson's disease by music exercise therapy: a study protocol for a randomized controlled trial.

BACKGROUND: Progression of freezing of gait, a common pathological gait in Parkinson's disease, is an important risk factor for diagnosing the disease and has been shown to predispose patients to easy falls, loss of independent living ability, and reduced quality of life. Treating Parkinson's disease with freezing of gait is very difficult, while the use of medicine and operation has been ineffective. Music exercise therapy, which entails listening to music as you exercise, has been proposed as a treatment technology that can change patients' behavior, emotions, and physiological activity. In recent years, music exercise therapy has been widely used in treatment of motor disorders and neurological diseases and achieved remarkable results. Results from our earlier pilot study revealed that music exercise therapy can improve the freezing of gait of Parkinson's patients and improve their quality of life. Therefore, we aim to validate clinical efficacy of this therapy on freezing of gait of Parkinson's patients using a larger sample size. METHODS/DESIGN: This three-arm randomized controlled trial will evaluate clinical efficacy of music exercise therapy in improving the freezing of gait in Parkinson's patients. We will recruit a total of 81 inpatients with Parkinson's disease, who meet the trial criteria. The patients will randomly receive music exercise with and without music as well as routine rehabilitation therapies, followed by analysis of changes in their gait and limb motor function after 4 weeks of intervention. We will first use a three-dimensional gait analysis system to evaluate changes in patients' gait, followed by assessment of their limb function, activity of daily living and fall risk. DISCUSSION: The findings of this trial are expected to affirm the clinical application of this therapy for future management of the disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026063 . Registered on September 20, 2019.

Prevalence of Internet Addiction Disorder and Its Correlates Among Clinically Stable Adolescents With Psychiatric Disorders in China During the COVID-19 Outbreak.

Background: Since the Coronavirus disease 2019 (COVID-19) pandemic emerged, Internet usage has increased among adolescents. Due to this trend, the prevalence of Internet addiction disorder (IAD) may have increased within this group. This study examined the prevalence of IAD and its correlates among clinically stable adolescents with psychiatric disorders in China during the COVID-19 outbreak. Method: A multi-center, cross-sectional study was carried out between April 29 and June 9, 2020 in three major tertiary mental health centers in China. IAD and depressive symptoms were assessed using the Internet Addiction Test (IAT) and the 9-item Patient Health Questionnaire (PHQ-9), respectively. Results: A total of 1,454 adolescent psychiatric patients were included in final analyses. The prevalence of IAD was 31.2% (95% CI: 28.8-33.6%) during the COVID-19 pandemic. A multiple logistic regression analysis revealed that poor relationships with parents (P < 0.001, OR = 2.34, 95%CI: 1.49-3.68) and elevated total PHQ-9 scores (P < 0.001, OR = 1.19, 95%CI: 1.16-1.21) were significantly associated with higher risk for IAD while longer daily physical exercise durations (P = 0.04, OR = 0.67, 95%CI: 0.46-0.98) and rural residence (P = 0.003, OR = 0.62, 95%CI: 0.46-0.85) were significant correlates of lower risk for IAD. Conclusions: IAD was common among adolescent patients with clinically stable psychiatric disorders during the COVID-19 pandemic; regular physical exercise, healthy relationships with parents and fewer symptoms of depression were associated with lower risk within this population.

Shell-cross-linked micelles from PNIPAM-b-(PLL)2 Y-shaped miktoarm star copolymer as drug carriers.

Well-defined AB2 Y-shaped miktoarm star copolymers of PNIPAM-b-(PZLL)2 and PNIPAM-b-(PLL)2 were synthesized through the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and click chemistry, where PNIPAM, PZLL, and PLL are poly(N-isopropylacrylamide), poly(epsilon-benzyloxy-carbonyl-L-lysine), and poly(L-lysine), respectively. Propargyl amine was employed as ROP initiator for the preparation of alkynyl-terminated PZLL. Diazide-terminated PNIPAM was obtained with an azide-containing ATRP initiator. The subsequent click reaction led to the formation of PNIPAM-b-(PZLL)2. After the removal of the benzyloxycarbonyl group, water-soluble PNIPAM-b-(PLL)2 was obtained. The core-shell micelles of PNIPAM-b-(PLL)2 were formed above lower critical solution temperature of PNIPAM block. At this temperature, the shell cross-linking was performed through the reaction between glutaraldehyde and the primary amine groups of the PLL shell, affording the micelles with the endurance to temperature and pH changes. These shell-cross-linked micelles were used as drug nanocarriers and the release profile was dually controlled by the solution temperature and the cross-linking degree.

Highly bioavailable curcumin preparation with a co-grinding and solvent-free process.

Curcumin (Cur.) is a natural product isolated from the rhizome of Curcuma longa, with a variety of biological and pharmacological activities in food and pharmaceutical products. However, curcumin's poor solubility in water greatly limits its bioavailability and clinical applications. In this study, co-grinding curcumin with food additives produced a mixture, which was evaluated for the solubility in water, dissolution, material morphology, in vivo bioavailability, cell uptake and entry mechanism. We tested 9 food additives in total and found that poloxamers performed the best. The 2 co-grinding mixtures Cur./Kolliphor® P407 and Cur./Kolliphor® P188 with high drug loading at 65.5% significantly improved the curcumin aqueous solubility, subsequently increased its intestinal epithelial cell uptake and oral bioavailability. The relative bioavailabilities for the 2 co-grinding mixtures were 309% and 163%, respectively, compared with curcumin API. Co-grinding process has a broad application prospect and is suitable for industrial production.

1-(2-Furylmethyl-ene)-2-(2-nitro-phen-yl)hydrazine.

The title Schiff base compound, C(11)H(9)N(3)O(3), was obtained from a condensation reaction of furan-2-carbaldehyde and 2-nitro-phenyl-hydrazine. The mol-ecule is roughly planar, the largest deviation from the mean plane defined by all non-H atoms being 0.097 (4). An in ntra-molecular N-H⋯O hydrogen bond might influence the planar conformation of the mol-ecule. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules, forming a chain.

Effects of neoadjuvant chemotherapy combined with enteral nutrition on perioperative immunity, inflammation and intestinal flora in gastric cancer patients.

PURPOSE: To investigate the effects of neoadjuvant chemotherapy combined with enteral nutrition on perioperative immunity, inflammation and intestinal flora in gastric cancer patients. METHODS: A total of 96 gastric cancer patients scheduled to undergo operation were selected and randomly divided into the observation group (n=48) and the control group (n=48). The patients in the control group were treated with neoadjuvant chemotherapy before operation, while those in the observation group received enteral nutrition before operation based on the treatment in the control group. The changes in immune indexes, inflammatory indexes and intestinal flora were compared between the two groups. RESULTS: After treatment, the levels of serum interleukin-2 (IL-2), IL-6, IL-10 and C-reactive protein (CRP) elevated gradually, while the level of serum tumor necrosis factor-alpha (TNF-α) lowered gradually in both groups (p<0.05). The indexes of nutritional status in the control group declined gradually after operation, and the levels of nutritional indexes, T cell subsets and immunoglobulins in the observation group were significantly higher than those in the control group (p<0.05). In the observation group, after operation, the levels of Bifidobacterium and Lactobacillus rose gradually, but those of Escherichia coli and Enterococcus exhibited progressive decline (p<0.05). CONCLUSIONS: Neoadjuvant chemotherapy combined with enteral nutrition can markedly relieve the perioperative inflammatory responses, improve the body immunity and maintain the structure of intestinal flora in gastric cancer patients, so it has certain clinical application value.

[Therapeutic effects on rheumatoid arthritis treated with shu-deep needling and bloodletting techniques].

OBJECTIVE: To observe the difference in the therapeutic effects on rheumatoid arthritis (RA) between the combined shu-deep needling and bloodletting technique and the regular needling technique. METHODS: A total of 70 patients were randomized into an observation group (35 cases) and a control group (35 cases, 4 cases dropped-out). Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jinsuo (GV 8), Ganshu (BL 18), Shenshu (BL 23), Zhibian (BL 54), Weizhong (BL 40), Taixi (KI 3) and Tianzong (SI 11), etc. were selected in the two groups. Additionally, in the observation group the shu-deep needling technique was adopted at Tianzong (SI 11) and Zhibian (BL 54), the bloodletting technique at the local swollen area and the even-needling technique at the rest acupoints. In the control group, the even-needling technique was applied to all of the acupoints. Acupuncture treatment was given once every two days, 3 times a week and for 12 weeks totally. The numbers of tender points at the knee joint, the numbers of swollen sites at the knee joint, the visual analogue scale (VAS) score and the American health assessment questionnaire (HAQ) score were observed in the two groups before and after treatment, as well as the changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The American College of Rheumatology (ACR) criteria was adopted to evaluate the therapeutic effects of the two groups. RESULTS: After treatment, the numbers of tender points, the numbers of swollen sites, VAS score and HAQ score were all improved as compared with those before treatment in the two groups (all P<0.01), and the results in the observation group were better than those in the control group (all P<0.05). After treatment, ESR and CRP levels were all reduced as compared with those before treatment in the two groups (all P<0.01), but there was no significant differences between the two groups (both P>0.05). The standard-reaching rates of ACR 20 and ACR 50 in the observation group were 94.3% (33/35) and 31.4% (11/35) respectively, which were better than 67.7% (21/31) and 6.5% (2/31) in the control group (P<0.01, P<0.05). CONCLUSION: The acupuncture with the shu-deep and bloodletting techniques and the acupuncture with regular needling technique are all effective on RA. The therapeutic effects of the acupuncture treatment with the shu-deep and bloodletting techniques are better than that with regular needling technique.