OBJECTIVETo explore the correlation between hOCT1 polymorphism and imatinib mesylate (IM) effectiveness in chronic myelogenous leukemia(CML) patients, and to provide for the clinical individual personalized therapy.

METHODSFifty-three CML and 23 non-CML patients were enrolled in this study. Blood or bone marrow samples were collected. Amplification refractory mutation system (ARMS)-polymerase chain reaction was used to amplify the polymorphisms gene segment of hOCT1-P283L, R287G and M408V and their frequencies were statistically analysed. With clinical outcomes, the correlation between hOCT1 polymorphism and IM effectiveness in CML was analyzed.

RESULTS(1) For 74 Han Chinese, the allele frequencies of hOCT1-P283L, R287G and M408V were 39.86%, 29.05% and 45.27%, respectively. (2) The genotypes of hOCT1-P283L, R287G and M408V in 2 Tibetan Chinese were CC, CC, AG and CC, CG, AG, respectively. (3) In the CML patients with IM optimal response, the frequencies of 283T and 287G allele were predominant (P<0.05). No significant difference was found in the frequency distribution of hOCT1-M408V genotype and allele among the 3 different response groups (P>0.05).

CONCLUSION(1) Three single nucleotide polymorphisms (cSNP) P283L, R287G and M408V were found in the hOCT1 gene from 76 Chinese. (2) hOCT1 gene polymorphism is associated with the long-term molecular response of CML patients received IM therapy, indicating that the polymorphisms of hOCT1-283T, 287G may be good predictors for IM response. (3) There is no correlation between the polymorphisms of hOCT1-P283L, R287G, M408V and secondary IM resistance in CML patients.

Benzamides ; Female ; Gene Frequency ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Organic Cation Transporter 1 ; genetics ; Piperazines ; therapeutic use ; Polymorphism, Genetic ; Pyrimidines ; therapeutic use ; Treatment Outcome

Objective To explore the clinical features and prognostic factor of acute drug induced liver injury (DILI) associated with low molecular weight heparin (LMWH) in pulmonary thromboembolism patients.Methods International recognized Roussel Uclaf causality assessment method 2015 (RUCAM) was taken as standard.Basic clinical date,prescriptions and laboratory of pulmonary thromboembolism (PTE) patients in use of LMWH was collected and analyzed.Results Among 92 patients with acute DILI,according to RUCAM,there were 82.61％ with quite high probability and high probability (≥6).The hepatocellular injury type accounted for 18 patients (19.57％),mixed type accounted 45 patients (48.91％) and cholestatic type of DILI accounted for 29 patients (31.52％).Basic analysis showed the levels of alanine transaminase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP) and total bilirubine (TBIL) had statistically significant difference among 3 groups (P ＜ 0.05).Multivariate analysis indicated that severe infection (P ＜ 0.05) and high level of serum creatinine (Scr,P ＜ 0.05) were the independent adverse prognostic factors of mixed type and hepatocellular injury type of DILI,respectively.There was no statistically significant difference in the time to apparent onset of the reaction,the time upon the top level of abnormal liver function and outcomes among the 3 groups of DILI (P ＞ 0.05).Conclusion It is necessary to dynamically evaluate the liver function during hospitalization especially patients are with severe infection and/or high level of Scr.Specific treatment can be necessary in according with the type of DILI.

OBJECTIVE: To observe the open angle (OA), cervical curvature angle (CA), preoperative spinal cord compression rate(PSCR), postoperative spinal cord shift (PSCS) in patients with chronic compressive cervical myelopathy undergoing C3-7 single open laminoplasty, and to explore the possible mechanism and influencing factors of postoperative average spinal cord drift, so as to provide objective basis for predicting PSCS. METHODS: From May 2012 to July 2016, 32 patients with multi-segmental chronic compressive cervical myelopathy who underwent single-door laminoplasty in our department were analyzed retrospectively, including 14 cases of cervical spondylotic myelopathy, 8 cases of developmental cervical spinal stenosis with cervical myelopathy, and 10 cases of ossification of posterior longitudinal ligament. The OA of cervical spine was measured on CT, the CA was measured on X-ray, the PSCR and PSCS were measured on MRI. The patients were divided into two groups according to PSCS(group A>=2.5 mm, group B<2.5 mm). In the group A, there were 11 males and 6 females, with an average age of (56.58±9.80) years old, a mean course of the disease of (23.52±7.86) months; while in group B, there were 6 males and 9 females, with an average age of (58.46±12.53) years old, a mean course of disease of (21.13±7.75) months. The correlation analysis between PSCS and OA, CA and PSCR was performed, and multiple linear analysis of correlated parameters was carried out. RESULTS: The OA in group A was (40.47±9.45) °, in group B was (27.84±5.67) °. The OA in group A was higher than that in group B (<0.01), and OA was moderately correlated with PSCS (=0.794, =0.000). The CA was(11.56± 4.99) ° in group A and(6.64±3.28) ° in group B . The CA in group A was higher than that in group B (<0.01), and CA was moderately correlated with PSCS (=0.632, =0.000). The PSCR was (27.70±2.92) % in group A , was (24.59±2.80) % in group B . The PSCR in group A was higher than that in group B(<0.01), PSCR was moderately correlated with PSCS(=0.667, =0.000). The CA dependent variable was kicked out(>0.1), and the partial regression coefficients of OA and PSCR were 0.113 and 0.059 respectively. CONCLUSIONS PSCS is the result of OA, CA and PSCR, among which PSCR has the most important influence, OA is the second, CA is the least. PSCS can be predicted by 0.059×OA+0.113×PSCR-2.266 equation, which provides a theoretical basis for preoperative evaluation of spinal cord decompression after surgery.
Aged ; Cervical Vertebrae ; Female ; Humans ; Laminectomy ; Laminoplasty ; Male ; Middle Aged ; Retrospective Studies ; Spinal Cord Diseases ; Treatment Outcome

OBJECTIVETo investigate the changes in the expression level of sRNA SpR19 and its potential target protein GroEL in clinical isolates of Streptococcus mutans with different cariogenicity exposed to different pH conditions and explore the possibility of using these molecules as biomarkers for assessing the cariogenicity of the bacteria.

METHODSThe total RNAs were extracted from the clinical isolates of Streptococcus mutans with high (strain 17) and low cariogenicity (strain 5) for high-throughput sequencing for profiling of the differentially expressed sRNAs. The candidate sRNA, SpR19, was selected for further study on the basis of bioinformatics analysis considering the role of its potential target in the cariogenic process. The differential expression levels of SpR19 in the strains exposed to both pH5.5 and pH7 culture conditions were verified by quantitative real-time PCR. The expression of the potential target of SpR19, GroEL, was also investigated at both the protein and mRNA level using Western blotting and quantitative real-time PCR.

RESULTSBioinformatic analysis suggested multiple potential target sites of SpR19 both in GroEL mRNA and in the upstream and downstream inter-genic regions. Under different pH conditions, the highly cariogenic strain 17 expressed consistently low levels of SpR19 as compared with the strain 5 with a low cariogenicity; GroEL showed a reverse expression pattern in the 2 strains. An inverse correlation was found between the expressions of SpR19 and GroEL.

CONCLUSIONThe highly cariogenic strain 17 expressed low levels of SpR19 and high levels of GroEL in both acidic and neutral culture conditions. SpR19 may negatively regulate the cariogenicity of Streptococcus mutants by targeting at GroEL.

OBJECTIVE: To explore the influencing factors and possible mechanism of axial symptoms(AS) after C₃-C₇ single open-door laminoplasty in patients with chronic compression cervical myelopathy. METHODS: The clinical data of 32 patients with multi-segment chronic compression cervical cord disease treated by C₃-C₇ single open-door laminectomy from May 2012 to July 2016 were retrospectively analyzed. Including cervical spondylotic myelopathy of 14 cases, developmental cervical stenosis complicated with cervical myelopathy of 8 cases, ossification of posterior longitudinal ligament(OPLL) of 10 cases. There were 17 males and 15 females, aged from 47 to 82 years old with an average of 57.46 year, the course of disease was 5 to 35 months with an average of 22.4 months. The opening angle(OA), cervical curvature angle(CA), preoperative spinal cord compression rate(PSCR) and postoperative spinal cord shift (PSCS) were recorded. After 2 weeks of surgery, determining whether occurred an AS condition according to the AS assessment criteria, the patients were divided into a axial symptom group and a non-axial symptom group, the general data and imaging parameters of the two groups were compared and the factors that may be postoperative AS were analyzed by binary Logistic regression analysis. RESULTS: At 2 weeks after operation, 13 patients occurred AS. There was no significant difference in gender, age and course of disease between axial symptom group and a non-axial symptom group (>0.05). In axial symptom group, OA was(36.76±9.35)°, CA was(11.53±4.36)°, PSCR was(27.83±1.72)%, PSCS was (3.17±0.81) mm, while in non-axial symptom group, above items were (33.03±10.52)°, (7.71±4.73)°, (25.16±3.59)%, (2.43±0.95) mm, respectively, there was significant difference in CA, PSCR, PSCS between two groups(<0.05), and there was no significant difference in OA between two groups(>0.05). The results of the binary Logistic regression analysis of 3 parameters(OA, PSCR, PSCS) and AS showed OA and PSCR were eliminated in dependent variables, and the partial regression coefficient of PSCR was 0.311, and =0.031. CONCLUSIONS CA, PSCR, and PSCS are related influencing factors of AS, and PSCS is a high risk factor for AS. C₄,₅ nerve traction caused by posterior spinal movement, postoperative dural self-expansion causes greater traction of the spinal cord, excessive deformation of the cervical spinal cord causes autonomic nerve damage or necrosis that dominates blood vessels may be the pathogenesis of AS, but this is only a theoretical inference, and further improved experiment is necessary to verify it in the future.
Aged ; Aged, 80 and over ; Cervical Vertebrae ; Female ; Humans ; Laminectomy ; Laminoplasty ; Male ; Middle Aged ; Retrospective Studies ; Spinal Cord Diseases ; Treatment Outcome

Objective:To explore the effect of the hospital discharge readiness plan based on deep integration of medical nursing and rehabilitation in children with cerebral palsy.Methods:From January 2020 to September 2021, 60 children with cerebral palsy and their 60 parents admitted to the Children's Rehabilitation Department of Anhui Children's Hospital were selected as the research object. The children and parents were divided into the observation group and the control group by random number table, with 30 children and 30 parents in each group. The control group was given routine nursing, and the observation group was given the hospital discharge readiness plan based on the deep integration of medical nursing and rehabilitation. On the first day of admission and the day before discharge, the effects were evaluated using the Chinese version of the Chinese version of the Readiness for Hospital Discharge Scale (RHDS) -Parent Form, the Chinese version of the Quality of Discharge Teaching Scale (QDTS) -Parent Form, the Activities of Daily Living (ADL) Rehabilitation Nursing Rating Scale for Children with Cerebral Palsy.Results:After the intervention, the scores of the observation group were higher than those of the control group in terms of readiness for hospital discharge, quality of discharge teaching, and the differences were statistically significant ( P<0.05) . Conclusions:The hospital discharge readiness plan based on deep integration of medical nursing and rehabilitation in children with cerebral palsy can effectively improve their discharge readiness, the quality of discharge teaching and the ADL of children with cerebral palsy.

Epididymitis is a commonly diagnosed disease associated with male infertility. However, little is known about the molecules that are involved in its development. This study was to identify critical genes associated with lipopolysaccharide-induced epididymitis and analyze the molecular mechanism of epididymitis through RNA sequencing. Experimental epididymitis models were generated by administering male Sprague-Dawley rats' lipopolysaccharide. A total of 1378 differentially expressed genes, including 531 upregulated and 847 downregulated genes, were identified in the epididymitis model rats compared with those in sham-operated rats by RNA sequencing. Functional enrichment analyses suggested that the upregulated genes were markedly enriched in inflammation-related biological processes, as well as in the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interactions, complement and coagulation cascades, and in the chemokine signaling pathway. Four downregulated genes (collagen type XXVIII alpha 1 chain [Col28α1], cyclin-dependent kinase-like 1 [Cdkl1], phosphoserine phosphatase [Psph], and fatty acid desaturase 2 [Fads2]) and ten upregulated genes (CCAAT/enhancer-binding protein beta [Cebpβ], C-X-C motif chemokine receptor 2 [Cxcr2], interleukin 11 [Il11], C-C motif chemokine ligand 20 [Ccl20], nuclear factor-kappa-B inhibitor alpha [Nfkbiα], claudin 4 [Cldn4], matrix metallopeptidase 9 [Mmp9], heat shock 70 kDa protein 8 [Hspa8], intercellular cell adhesion molecule-1 [Icam1], and Jun) were successfully confirmed by real-time polymerase chain reaction. Western blot demonstrated that CDKL1 was decreased, while MMP9 and NFKBIA were increased in the experimental model group compared with those in the sham-operated group. Our study sheds new light on the understanding of the early response of the epididymis during bacterial epididymitis.
Animals ; Base Sequence/genetics* ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Epididymis/metabolism* ; Epididymitis/metabolism* ; Gene Expression Profiling ; Genes/genetics* ; Lipopolysaccharides/pharmacology* ; Male ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; blood ; China ; epidemiology ; Female ; Humans ; Hypothyroidism ; epidemiology ; Iodine ; administration & dosage ; urine ; Male ; Middle Aged ; Prevalence ; Thyroid Gland ; immunology ; Thyrotropin ; blood

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

Objective: To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. Methods: A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. Results: The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
1-Alkyl-2-acetylglycerophosphocholine Esterase/blood* ; Asians ; Cardiovascular Diseases/diagnosis* ; China/epidemiology* ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Mortality ; Myocardial Infarction/blood* ; Predictive Value of Tests ; Risk Factors ; Stroke/blood*