Effect of pharmacogenomic testing on the clinical treatment of patients with depressive disorder: A randomized clinical trial.

BACKGROUND: Pharmacotherapy is one of the primary treatment modalities for depression. However, there is considerable variability in the individual response to antidepressant medications. Personalized medicine guided by pharmacogenomic testing may hold promise in addressing this issue. METHODS: In this study, 665 depressive patients were randomly enrolled into two groups: the pharmacogenomic testing group (n = 333) and the control group (n = 332). In the testing group, participants underwent pharmacogenomic testing, and clinicians customized the treatment plan with the result, while the control group relied solely on clinicians' experience. The primary outcomes were the proportion of remission and response, assessed with Hamilton Depression Rating Scale (HDRS). The secondary outcomes included changes in HDRS scores over time and frequency of adverse drug reactions by the participants. RESULTS: At week 8, the pharmacogenomic testing group showed significantly higher remission rates (24.0 % v.s. 15.1 %; RR = 1.117; P = 0.007) and response rates (39.3 % v.s. 25.7 %; RR = 1.225; P < 0.001) compared to the control group. By week 12, the pharmacogenomic testing group continued to demonstrate significant advantages in remission (31.0 % v.s. 20.0 %; RR = 1.159; P = 0.003) and response (48.7 % v.s. 37.3 %; RR = 1.224; P = 0.006). Additionally, adverse drug reactions were less frequent in the pharmacogenomic testing group. LIMITATIONS: This study is not blind to clinicians and it's a single-center study. CONCLUSIONS: Pharmacogenomic testing-guided drug therapy can provide greater assistance in the treatment of depression.

Bioinformatics analysis of high frequency mutations in myelodysplastic syndrome-related patients.

BACKGROUND: Myelodysplastic syndrome (MDS) is a group of hematological malignancies that may progress to acute myeloid leukemia (AML). Bioinformatics-based analysis of high-frequency mutation genes in MDS-related patients is still relatively rare, so we conducted our research to explore whether high-frequency mutation genes in MDS-related patients can play a reference role in clinical guidance and prognosis. METHODS: Next generation sequencing (NGS) technology was used to detect 32 mutations in 64 MDS-related patients. We classified the patients' genes and analyzed them by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) analysis, and then calculated the gene survival curve of high-frequency mutations. RESULTS: We discovered 32 mutant genes such as ASXL1, DNMT3A, KRAS, NRAS, TP53, SF3B1, and SRSF2. The overall survival (OS) of these genes decreased significantly after DNMT3A, ASXL1, RUNX1, and U2AF1 occurred mutation. These genes play a significant role in biological processes, not only in MDS but also in the occurrence and development of other diseases. Through retrospective analysis, genes associated with MDS-related diseases were identified, and their effects on the disease were predicted. CONCLUSIONS: Thirty-two mutant genes were determined in MDS and when mutations occur in DNMT3A, ASXL1, RUNX1, and U2AF1, their survival time decreases significantly. This results providing a theoretical basis for clinical and scientific research and broadening the scope of research on MDS.

Adsorption of Cr(VI) from aqueous solution by a litchi shell-based adsorbent.

Cr(VI) is a toxic metal pollutant existing in industrial effluents. In this study, Fe3O4 and layered double hydroxide (LDH) were inserted into the litchi shell (LS) successively by the co-precipitation method to synthesize the modified magnetic litchi shell adsorbent (MMLS) for removing Cr(VI). The advantageous structure characteristics of MMLS were confirmed by XRD, FT-IR, SEM and the hysteresis loop characterization. The batch experiments of optimizing the conditions (pH, adsorbent dosage, initial concentration, coexisting ions) for removing Cr(VI) were accomplished to in simulated wastewater at room temperature. And the optimal pH of 3 and initial concentration of 100 mg/L in simulated wastewater were similar to that in the actual chrome-plated rinse water with the stable MMLS. The effect of coexisting ions indicated anions and Cr(VI) competed with each other for the adsorption site, but the interactions were negligible in actual chrome-plated rinse water. Chemisorption as a rate-limiting step was confirmed with a good fit of pseudo-second-order kinetics. And the adsorption behavior of MMLS can not be explained by a single theory according to Sips model. The desorption and recycle experiments demonstrated MMLS was reusable in actual chrome-plated rinse water.

Up-regulation of CKAP2L expression promotes lung adenocarcinoma invasion and is associated with poor prognosis.

AIM: The purpose of this study is to consider the function of cytoskeleton-associated protein 2-like (CKAP2L) in lung adenocarcinoma (LAD) development and its prognostic value. METHODS: The mRNA expression of CKAP2L and its correlation with clinical factors in LAD patients were analyzed from the data taken from The Cancer Genome Atlas and The First Affiliated Hospital of Kunming Medical University. We constructed H460 and A549 cell lines with silenced CKAP2L using RNA interference. Cell counting kit-8 assay and colony formation assays were carried out to determine the function of CKAP2L in H460 and A549 cell proliferation. Transwell and wound healing assays were applied to determine the effect of CKAP2L on H460 and A549 cell invasion and migration. The influences of CKAP2L on mitogen-activated protein kinase signaling pathway-related proteins were tested by Western blotting. RESULTS: CKAP2L expression is enhanced in LAD tissues and is predictive of poor prognosis in LAD patients. High expression of CKAP2L is associated with stage (P<0.001), lymph node status (P=0.002), and metastasis (P=0.025). Depletion of CKAP2L dramatically suppressed the proliferation, migration, and invasion of H460 and A549 cells. Moreover, the ratio of p-MEK/ MEK and p-ERK/ERK reduced obviously in A549 cells after depleting CKAP2L. CONCLUSION: Our findings implied that CKAP2L might be a promoter of LAD and could serve as a predictor for LAD patients.

TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway.

Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells. TRIM22 knockdown significantly induced cell cycle arrest by regulating the level of CDK4, Cyclin D1, P70S6K, and P53 in K562 cell. Moreover, loss of TRIM22 also promoted apoptosis through modulation of Bcl-2, Bax and active Caspase 3 in K562 cell. Furthermore, we demonstrated that TRIM22 knockdown inhibited the activation of PI3K/Akt/mTOR pathway by decreasing the level of the phosphorylated form p-Akt and p-mTOR in K562 cell. In conclusion, loss of TRIM22 suppresses the progression and invasion of CML through regulation of PI3K/Akt/mTOR pathway, suggesting that TRIM22 might be as a potential target for the treatment strategy of CML.

Fabrication of Dish-Shaped Micro Parts by Laser Indirect Shocking Compound Process.

Compound process technology has been investigated for many years on a macro scale, but only a few studies can be found on a micro scale due to the difficulties in tool manufacturing, parts transporting and punch-die alignment. In this paper, a novel technology of combining the laser shock wave and soft punch was introduced to fabricate the dish-shaped micro-parts on copper to solve these difficulties. This compound process includes deep drawing, punching and blanking and these processes can be completed almost at the same time because the duration time of laser is quite short, so the precision of the micro-parts can be ensured. A reasonable laser energy of 1550 mJ made the morphology, depth of deformation, dimensional accuracy and surface roughness achieve their best results when the thickness of the soft punches was 200 µm. In addition, thicker soft punches may hinder the compound process due to the action of unloading waves based on the elastic wave theory. So, the greatest thickness of the soft punches was 200 µm.

An Experimental Study on Micro Clinching of Metal Foils with Cutting by Laser Shock Forming.

This paper describes a novel technique for joining similar and dissimilar metal foils, namely micro clinching with cutting by laser shock forming. A series of experiments were conducted to study the deformation behavior of single layer material, during which many important process parameters were determined. The process window of the 1060 pure aluminum foils and annealed copper foils produced by micro clinching with cutting was analyzed. Moreover, similar material combination (annealed copper foils) and dissimilar material combination (1060 pure aluminum foils and 304 stainless steel foils) were successfully achieved. The effect of laser energy on the interlock and minimum thickness of upper foils was investigated. In addition, the mechanical strength of different material combinations joined by micro clinching with cutting was measured in single lap shearing tests. According to the achieved results, this novel technique is more suitable for material combinations where the upper foil is thicker than lower foil. With the increase of laser energy, the interlock increased while the minimum thickness of upper foil decreased gradually. The shear strength of 1060 pure aluminum foils and 304 stainless steel foils combination was three times as large as that of 1060 pure aluminum foils and annealed copper foils combination.