Cognitive Enhancing Effect of High-Frequency Neuronavigated rTMS in Chronic Schizophrenia Patients With Predominant Negative Symptoms: A Double-Blind Controlled 32-Week Follow-up Study.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927.

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia.

Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

Twist1 confers multidrug resistance in colon cancer through upregulation of ATP-binding cassette transporters.

Multidrug resistance is a major problem in colon cancer treatment. However, its molecular mechanisms remain unclear. Recently, the epithelial-mesenchymal transition (EMT) in anticancer drug resistance has attracted increasing attention. This study investigated whether vincristine treatment induces EMT and promotes multidrug resistance in colon cancer. The result showed that vincristine treatment increases the expression of several ATP-binding cassette transporters in invasive human colon adenocarcinoma cell line (HCT-8). Vincristine-resistant HCT-8 cells (HCT-8/V) acquire a mesenchymal phenotype, and thus its migratory and invasive ability are increased both in vitro and in vivo. The master transcriptional factors of EMT, especially Twist1, were significantly increased in the HCT-8/V cell line. Moreover, the ectopic expression of Twist1 increased the chemoresistance of HCT-8 cells to vincristine and increased the expression levels and promoter activities of ABCB1 and ABCC1. Furthermore, Twist1 silencing reverses the EMT phenotype, enhances the chemosensitivity of HCT-8/ V cells to anticancer agents in vitro and in vivo, and downregulates the expression of ABCB1 and ABCC1. Twist1-mediated promotion of ABCB1 and ABCC1 expression levels plays an important role in the drug resistance of colon cancer cells.

[The expression of peripheral Th1 and Th17 cells in inflammatory bowel disease and its potential clinical value].

OBJECTIVE: To explore the probable role of Th1 and Th17 cells in the pathogenesis of inflammatory bowel disease (IBD). METHODS: The peripheral blood mononuclear cells (PBMCs) from peripheral blood specimens were collected in the study, including 40 healthy controls, 42 ulcerative colitis (UC) and 39 Crohn's disease (CD). The proportion of Th1 and Th17 cells in the PBMCs was detected with flow cytometry after stimulated by PMA and ionomycin. The result and the clinical data were analyzed. RESULT: The Th1 cell expression was increased in CD (38.32 ± 16.18)% and UC group (34.23 ± 11.60)%, compared with the controls (24.58 ± 10.02)% (P < 0.01). During the convalescence, the Th1 expression in the CD and UC groups in vivo was significantly reduced without difference between the two groups (P > 0.05) . In the IBD group , significant difference in the frequency of Th17 cells could be found between the CD group (2.51 ± 1.59)% and the UC group (4.15 ± 2.75)%, while the Th17 cells were increased in both groups, compared with the controls (1.44 ± 0.73)% (P < 0.05) . Obvious difference in the frequency of Th17 cells could be found between patients at different activity stages and remission stages. The proportion of Th17 cells were higher in the UC patients than that in the CD patients (P < 0.01) . The Th17/Th1 ratio of CD patients, UC patients were 0.08 ± 0.06, 0.14 ± 0.11, which were both higher that in the controls (0.07 ± 0.06). Significant difference could be found between the UC group and the CD group (P < 0.01). CONCLUSIONS: The higher proportion of Th1 and Th17 cells are detected in the peripheral blood of IBD patients, which is correlated closely to the activity of the disease. Th1 and Th17 cells may play an important role in the pathogenesis of IBD.

Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.

Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes. Moreover, the binding and releasing of the guests in the complexes could be controlled by potassium ions.

Complexation of triptycene-based macrotricyclic host toward (9-anthracylmethyl)benzylammonium salt: a Ba2+ selective fluorescence probe.

A new triptycene-based macrotricyclic host containing two dibenzo-30 crown-10 moieties (1) has been synthesized. It could form a 1:2 stable complex 1 x 3(2) with (9-anthracylmethyl)benzylammonium salt (3) in both solution and solid state, in which the 9-anthracyl groups were selectively positioned inside the cavity of the host. Moreover, the complexation and disassociation of complex 1 x 3(2) could be chemically controlled by the addition of base and acid. It was also found that Ba(2+) ion could considerably induce the fluorescence enhancement of complex 1 x 3(2), which might thus be utilized as a selective supramolecular fluorescence probe for Ba(2+) ion. Fluorescence and (1)H NMR spectroscopic titrations further showed that the complexation between complex 1 x 3(2) and barium ions underwent a two-step process.

Synthesis of a triptycene-derived bisparaphenylene-34-crown-10 and its complexation with both paraquat and cyclobis(paraquat-p-phenylene).

A novel triptycene-derived bisparaphenylene-34-crown-10 (1) has been synthesized, and shown to form 1:1 stable complexes with both the paraquat G1.2PF(6) and the cyclobis(paraquat-p-phenylene) G2.4PF(6) in different complexation modes in solution and solid state. Moreover, it was found that both the complexes 1.G1.2PF(6) and 1.G2.4PF(6) were formed by charge transfer interactions, and did not dissociate upon the first one-electron reduction process of the bipyridinium ring.

[Polymorphism of fifteen short tandem repeat loci in Tibetan of Changdu area].

OBJECTIVE: To investigate the genetic polymorphism of 15 autosomal short tandem repeat (STR) loci, i.e. D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX and D18S51, in Tibetan population of Changdu area, and to analyze the genetic relationship between this population and other Asian populations. METHODS: The 15 loci were amplified simultaneously using a multiplex PCR typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies and polymorphism parameters. RESULTS: There were 135 STR alleles in the 15 STRs of Changdu Tibetan, with allele frequencies ranging from 0.0065 to 0.5455. The average heterozygosity was 0.7340, the discrimination power was higher than 0.8 except for TPOX and TH01. The accumulative discrimination power was more than 0.9999998, and the accumulative non-parental exclusion probability was 0.99999997. CONCLUSION: The 15 STR loci of Changdu Tibetan possess characteristics of high genetic diversity. They can be employed in minority genetics investigation, and individual and paternity test in forensic medicine.

A pentiptycene-based bis(crown ether) host: synthesis and its complexation with cyclobis(paraquat-p-phenylene).

A novel pentiptycene-based bis(crown ether) host incorporating two dibenzo-24-crown-8 ether moieties has been synthesized, and its efficient complexation ability toward cyclobis(paraquat-p-phenylene) in solution and in the solid state has been explored.

[Genetic polymorphism of 15 short tandem repeats loci of Tibetan nationality and its affinity with other nationalities in Tibet].

OBJECTIVE: To determine the genetic diversity of short tandem repeats (STRs) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, upsilonWA, TPOX, D18S51, D5S818, and FGA), and to evaluate the genetic structure of Tibetan nationality and its affinity with other Tibetans (Changdu Tibetan, Luoba ethnic group, Deng population) and other Asian populations. METHODS: Fifteen STRs loci were amplified simultaneously using a multiplex PCR typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies and polymorphism parameters. The genetic distance (D(A)), coefficient of gene differentiation (Gst) values, and heterozygosity (Ht) were estimated using DISPAN. A phylogenetic tree from the allele frequency data at 8 STRs loci and 15 STRs loci obtained from the literature reported previously by using the D(A) and Neighbor-Joining (N-J) method was constructed using MEGA Version 4.0. Multidimensional scaling (MDS) analysis was performed using the SPSS 14.0 software package. RESULTS: We got 132 alleles in the population studied, with the frequency of 0.0050-0.5990. Ht, the power of discrimination (DP) and the polymorphism information content (PIC) were consistent with the forensic application. Cluster analysis and phylogenic trees revealed that Tibetan nationality had estrangement genetic affinity with other Chinese nationalities and Asian population. CONCLUSION: The genetic information demonstrates that the 15 chosen gene makers are highly informative loci and are suitable for population genetic research and forensic application.

Guest-dependent complexation of triptycene-based macrotricyclic host with paraquat derivatives and secondary ammonium salts: a chemically controlled complexation process.

The triptycene-based macrotricyclic host containing two dibenzo-[24]-crown-8 moieties has been found to form stable 1:1 or 1:2 complexes in different complexation modes with different functional paraquat derivatives and secondary ammonium salts in solution and in the solid state. Consequently, the alkyl-substituted paraquat derivatives thread the lateral crown cavities of the host to form 1:1 complexes. It was interestingly found that the paraquat derivatives containing two beta-hydroxyethyl or gamma-hydroxypropyl groups form 1:2 complexes, in which two guests thread the central cavity of the host. Other paraquat derivatives containing terminal hydroxy, methoxy, 9-anthracylmethyl, and amide groups were included in the cavity of the host to form 1:1 complexes. Moreover, the host also forms a 1:2 complex with two 9-anthracylmethylbenzylammonium salts, in which the 9-anthracyl groups were selectively positioned outside the lateral crown cavities. The competition complexation process between the host and two different guests (the propyl-substituted paraquat derivative and a dibenzylammonium salt) could be chemically controlled.

[Genetic polymorphisms of 14 Y-chromosomal short tandem repeat loci and haplotypes in Tibetan].

OBJECTIVE: To reveal the allelic frequencies and haplotype frequencies of fourteen Y-chromosome short tandem repeat (STR) loci in a Tibetan population. METHODS: The Y-chromosomal STR loci were analyzed from 126 healthy unrelated autochthonous male individuals of Chinese Tibetan using a multiplex PCR system. Allele and haplotype frequencies for these loci were determined by the AmpFISTR Y filer PCR Amplification kit. RESULTS: One hundred and twenty-one alleles were detected from the 14 STR loci. The allele diversity values (DP) for each locus ranged from 0.4104 (DYS391) to 0.9489 (DYS385a, b), the DP value of these loci were higher than 0.5 except for that of DYS391. A total of 105 haplotypes were identified in the Y-STR loci, among which 103 were unique, while two occurred more than once. The overall haplotype diversity for the Y-STR loci was 0.9998, and the discrimination capacity was 0.9898. CONCLUSION: The 14 STR loci above belong to loci of high discriminating ability, the haplotypes are highly polymorphic.