The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

Objective To observe the therapeutic efficacy of Jisheng Shenqi Pills combined with endocrine therapy in alleviating lower urinary tract obstruction symptoms of patients with advanced prostatecancer(PCa).Methods A total of 68 patients with advanced PCa complicated by lower uri-nary tract obstruction symptoms were randomly divided into observation group and control group,with 34 cases in each group.The control group received endocrine therapy alone,while the observation group received Jisheng Shenqi Pills on the basis of the control group.Both groups underwent a course of 3-month treatment.The total therapeutic effectiveness rate,traditional Chinese medicine(TCM)syndrome scores,maximum urinary flow rate(Qmax),residual urinary volume(RUV),International Prostate Symptom Score(IPSS),prostate-specific antigen(PSA)levels,and Quality of Life(QOL)Scale scores were compared between the two groups.Results The total therapeutic effectiveness rate in the observation group was 94.12％,which was significantly higher than 82.35％in the control group(P＜0.05).After treatment,TCM syndrome scores decreased in both groups,with the obser-vation group had significantly lower scores than the control group(P＜0.05).Both groups exhibited an increase in Qmax and a decrease in RUV after treatment,with the observation group had significant-ly higher Qmax and lower RUV compared to the control group(P＜0.05).PSA level decreased signif-icantly in both groups after treatment(P＜0.05),but no significant difference was observed between the two groups(P＞0.05).IPSS score was decreased while QOL score was increased in both groups after treatment,with the observation group had significantly lower IPSS score and higher QOL score compared to the control group(P＜0.05).Conclusion Jisheng Shenqi Pills combined with endo-crine therapy effectively alleviates urinary obstruction symptoms,improves TCM syndromes,and en-hances quality of life in patients with advanced PCa.

Skeletal muscle plays a crucial role in maintaining metabolism,energy homeostasis,movement,as well as endocrine function.The gestation period is a critical stage for myogenesis and development of the skeletal muscle.Adverse environmental exposures during pregnancy may impose various effects on the skeletal muscle health of the offspring.Maternal obesity during pregnancy can mediate lipid deposition in the skeletal muscle of the offspring by affecting fetal skeletal muscle metabolism and inflammation-related pathways.Poor dietary habits during pregnancy,such as high sugar and high fat intake,can affect autophagy of skeletal muscle mitochondria and reduce the quality of the offspring skeletal muscle.Nutritional deficiencies during pregnancy can affect the development of the offspring skeletal muscle through epigenetic modifications.Gestational diabetes may affect the function of the offspring skeletal muscle by upregulating the levels of miR-15a and miR-15b in the offspring.Exposure to environmental endocrine disruptors during pregnancy may impair skeletal muscle function by interfering with insulin receptor-related signaling pathways.This article reviews the research progress on effects and possible mechanisms of adverse maternal exposures during pregnancy on the offspring skeletal muscle function based on clinical and animal studies,aiming to provide scientific evidence for the prevention and treatment strategies of birth defects in the skeletal muscle.

OBJECTIVE To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency. METHODS The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied for Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT＞4MIC≥40% and Cmin≤27.5 mg/L were calculated respectively to optimize the dosing regimen. RESULTS For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h”“ 1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“ 1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h“”1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”， Cmin＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur. CONCLUSIONS For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time.

Skeletal muscle plays a crucial role in maintaining metabolic function, energy homeostasis, movement function, as well as endocrine function. The gestation period is a critical stage for the myogenesis and development of skeletal muscle. Adverse environmental exposures during pregnancy would impose various effects on the skeletal muscle health of offspring. Maternal obesity during pregnancy can mediate lipid deposition in skeletal muscle of offspring by affecting fetal skeletal muscle metabolism and inflammation-related pathways. Poor dietary habits during pregnancy, such as high sugar and high fat intake, can affect the autophagy function of skeletal muscle mitochondria and reduce the quality of offspring skeletal muscle. Nutritional deficiencies during pregnancy can affect the development of offspring skeletal muscle through epigenetic modifications. Gestational diabetes may affect the function of offspring skeletal muscle by upregulating the levels of miR-15a and miR-15b in offspring. Exposure to environmental endocrine disruptors during pregnancy may impair skeletal muscle function by interfering with insulin receptor-related signaling pathways in offspring. This article reviews the research progress on effects and possible mechanisms of adverse maternal exposures during pregnancy on offspring skeletal muscle function in clinical and animal studies, aiming to provide scientific evidence for the prevention and treatment strategy of birth defects in skeletal muscle.

To explore the clinical efficacy and possible mechanism of Tai Ji Quan for post-stroke depression (PSD), literature related to Tai Ji Quan and PSD were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full- text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and PubMed, screened and then summarized. The results showed that Tai Ji Quan could effectively improve the depression and quality of life of stroke patients, and there were differences in the clinical efficacy among different training programs. Tai Ji Quan has the characteristics of "regulating mind", "regulating breath", and "regulating body". It may achieve the effect of "combined physique-spirit treatment" by improving social psychology, increasing the level of neurotrophin, regulating neuroendocrine, reducing inflammatory factors, and regulating neural circuits.

AIM: To build a meropenem population pharmacokinetic model for Chinese elderly through model-based meta-analysis. METHODS: Informations including dosing regimen, sampling times, concentrations, sample size, age, gender, body weight (BW) and creatinine clearance were extracted after the literature were retrieved. The model was built by NONMEM. Stepwise covariate modeling strategy was used for covariates analysis. RESULTS: A two-compartment model was applied to describe meropenem pharmacokinetics. After stepwise covariate modeling, covariates that remained significant in the final model were creatinine clearance (CLcr) on CL and the BW on V

Objective:To investigate the treatment effect of marrow mesenchymal stem cells (MSC)/endothelial progenitor cells (EPC) extracellular matrix-based tissue engineering bone (ECM-TEB) in repair of femoral defects in rats.Methods:Bone marrow-derived MSC and EPC were isolated and cultured for functional identification, and planted on the nanocrystalline collagen-based artificial bone particles. After culturing for 14 days, the cells were lyophilized to obtain MSC/EPC ECM-TEB and MSC ECM-TEB. A scanning electron microscope was used to observe the morphology of MSC and EPC on the surface of the scaffold. The protein extracts of MSC ECM-TEBs (control group) and the protein extracts of MSC/EPC ECM-TEBs (experimental group) were added to the EPC culture system for migration test, scratch repair assay, and tube formation detection; and to the MSC culture system for alizarin red staining and alkaline phosphatase? (ALP) staining detection. The cell recruitment, angiogenesis and osteogenic differentiation were observed. A total of 12 SD rats were selected to establish a femoral defect model. According to the random number table, the rats were divided into: (1) sham group: debridement treatment was performed only at the defect; (2) MSC ECM -TEB group: MSC ECM-TEB was implanted at the defect; (3) MSC/EPC ECM-TEB group: MSC/EPC ECM-TEB was implanted at the defect, with 4 rats per group. Two months later, micro-computed tomography (Micro-CT) and Masson's tricolor staining were performed to observe the treatment effect of the bone defect. When the cells were stored at low temperature for three months after lyophilization, the different protein profile between MSC ECM-TEB and MSC/EPC ECM-TEB in vascularization was detected by isotope relative labeling and absolute quantification technology (iTRAQ). The gene ontology/Kyoto Encyclopedia of Gene and Genome Technology (GO/ KEGG) function enrichment was used to analyze the key differences.Results:MSC and EPC grew well and formed a smooth cell layered structure on the surface of the scaffold. The number of cell migration, ratio of scratch repair, and length of the tube in experimental group were respective 121.6±8.3, (61.5±5.9)%, (11.3±0.6)mm, significantly increased compared with control group [85.0±6.7, (39.3±3.6)%, (5.9±0.4)mm] (all P<0.01). Alizarin red staining and ALP staining results showed that the proportion of calcium nodule mineralized area in experimental group increased significantly compared with control group [(38.8±3.3)%∶(49.9±3.0)%, (38.8±2.4)%∶(45.3±3.3)%] (all P<0.05). Base on the Micro-CT and Masson staining, bone defect healing was good in MSC/EPC ECM-TEB group, only a small amount of new bone was formed in MSC ECM-TEB group, and there was almost no new bone regenerated in sham group. Significant differences were found in bone volume/total volume, trabecular number and trabecular thickness among groups (all P<0.05), which were in line with Micro-CT and Masson staining results. The protein profile analysis showed that 83 angiogenesis-related factors in MSC/EPC ECM-TEB group were significantly up-regulated compared with MSC ECM-TEB group (fold change>2, P<0.05). GO/KEGG function enrichment analysis showed that MSC/EPC ECM-TEB group had projecting ascendancy in "vascular development" and in "vascular smooth muscle contraction pathway" compared with MSC ECM-TEB group (both P<0.01). Conclusion:MSC/EPC ECM-TEB has advantages in cell recruitment, angiogenesis, and new bone formation compared with MSC ECM-TEB, and is a better construction strategy for repair of traumatic bone defect.

BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.
Absorption ; China ; Cyclosporine* ; Drug Monitoring ; Heart ; Humans ; Immunoassay* ; Korea ; Liver ; Malaysia ; Methods ; Tacrolimus* ; Transplants