Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation.

PURPOSE: This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. RESULTS: After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. CONCLUSION: POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Antidepressant-like effects of Z-ligustilide on chronic unpredictable mild stress-induced depression in rats.

Depression is a significant public health issue and its neuropathogenesis is associated with the dysfunction of progesterone and allopregnanolone biosynthesis. Z-ligustilide (LIG), one of the main components of the herb Angelica sinensis (Oliv.) Diels (AS), is reported to have antidepressant activities. The present study aimed to evaluate the antidepressant-like effects of LIG via behavioral tests and to measure the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. The results demonstrated that LIG (20 and 40 mg/kg) exerted antidepressant-like effects, confirmed by increased mobility, locomotion, rearing frequency and preference to sucrose. Furthermore, the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus were markedly increased following treatment with LIG (20 and 40 mg/kg), indicating that both neurosteroids could serve a significant role in the antidepressant-like effects of LIG.

Protective effects of quercetin and crocin in the kidneys and liver of obese Sprague-Dawley rats with Type 2 diabetes: Effects of quercetin and crocin on T2DM rats.

Quercetin and crocin are the main active constituents of Eucommia and Gardenia species, respectively. This study was conducted to explore the effects of quercetin and crocin on fat reduction and renal fibrosis and the relationship of these compounds with autophagy. First, a model of high-fat diet- and streptozotocin-induced type 2 diabetes was established and then subjected model animals to 8 weeks of metformin, quercetin and crocin gavage. Then, a high glucose-induced rat mesangial cells (RMCs) model was established, and these cells were cocultured with quercetin and crocin. The results showed that quercetin and crocin can decrease fasting blood glucose levels, reduce fat accumulation in the liver, alleviate renal fibrosis, and reduce blood lipid levels. Quercetin and crocin increased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the liver and decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the kidneys. Moreover, quercetin and crocin inhibited the excessive proliferation of RMCs induced by high-glucose (HG) conditions, decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels, and decreased TGF-ß1 expression. Importantly, cotreatment with quercetin and crocin had a more significant effect than treatment with either compound alone. These results suggest that combined administration of quercetin and crocin can more significantly reduce blood glucose/lipid levels and improve renal fibrosis than administration of either compound alone and that AMPK-dependent autophagy might be involved in this process. Eucommia ulmoides Oliv. and Gardenia could be developed as drugs for Type 2 diabetes treatment.

ZEB1 modulates endometrial receptivity through epithelial-mesenchymal transition in endometrial epithelial cells in vitro.

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been identified. The present study sought to verify if ZEB1 plays a role in endometrial receptivity through regulation of EMT during embryo implantation. Endometrial epithelium from sixty patients in phase of the menstrual cycle (including proliferative and secretory phases) were collected for assessment of mRNA/protein expression. In human endometrial adenocarcinoma cell line RL95-2, ZEB1 expression was suppressed by using shRNA, and the cell function and mRNA/protein expression were evaluated. RL95-2 cells and human choriocarcinoma cell line JAR were co-cultured to establish embryo implantation model in vitro. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in human endometrium during mid-secretory phase of the menstrual cycle. Knockdown of ZEB1 expression in RL95-2 cells attenuated cell growth, migration, DNA replication, and altered expression of E-cadherin and vimentin at both mRNA and protein levels. Interestingly, knockdown of ZEB1 expression in RL95-2 cells potently suppressed JAR spheroid attachment in vitro (P < 0.01). Additionally, the. Conclusively, knockdown of ZEB1 suppressed embryo implantation in vitro, paralleled with alteration of EMT markers. ZEB1 is likely to modulate endometrial receptivity through promotion of EMT, that could be crucial for embryo implantation process.

Evaluation of manual and electronic healthcare-associated infections surveillance: a multi-center study with 21 tertiary general hospitals in China.

BACKGROUND: Healthcare-associated infections (HAIs) are still a major health threats worldwide. Traditional surveillance methods involving manual surveillance by infection control practitioners (ICPs) for data collection processes are laborious, inefficient, and generate data of variable quality. In this study, we sought to evaluate the impact of surveillance and interaction platform system (SIPS) for HAIs surveillance compared to manual survey in tertiary general hospitals. METHODS: A large multi-center study including 21 tertiary general hospitals and 63 wards were performed to evaluate the impact of electronic SIPS for HAIs. RESULTS: We collected 4,098 consecutive patients and found that the hospitals installed with SIPS significantly increased work efficiency of ICPs achieving satisfactory diagnostic performance of HAIs with 0.73 for sensitivity, 0.81 for specificity and 0.81 area under the curve (AUC). However, there were significant heterogeneity own to regions, time of SIPS installation, departments and sample size. CONCLUSIONS: SIPS significantly improved ICPs efficiency and HAIs monitoring effectiveness, but there were shortcomings such as untimely maintenance and high cost.

Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes.

PURPOSE: Tuberous sclerosis complex (TSC) is characterized by the development of hamartomas in multiple organ systems. This study attempted to screen mutations and to investigate the mutation distribution and related phenotypes including epilepsy of Chinese TSC patients. METHODS: We performed the genotypic analysis of TSC1 and TSC2 genes in 77 unrelated Chinese TSC patients using direct Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). RESULTS: Mutations were identified in a total of 63 (81.8%) cases, including 18 TSC1 mutations (8 nonsense mutations, 6 frameshift, 1 in-frame shift, 1 missense and 2 splice-site) and 45 TSC2 mutations (13 missense, 3 nonsense, 6 splicing, 6 in-frame shift,12 frameshift mutations and 5 large deletions). Large deletions were presented exclusively in TSC2 gene, accounting for 7.9% of all mutations in this study. Fourteen novel mutations were identified in this study. CONCLUSIONS: Epilepsy occurs in approximately 75.3% (58/77) of patients. Hypomelanotic macules occurred significantly more often in patients with TSC2 mutations and cases with TSC1/TSC2 mutations had a significantly higher frequency of cortical nodule than patients with no mutations identified. Overall, our data expands the spectrum of mutations associated with the TSC loci and will be of value to the genetic counseling in patients with the disease.

Effect of silencing HOXA5 gene expression using RNA interference on cell cycle and apoptosis in Jurkat cells.

Acute lymphocytic leukemia (ALL) is a common malignant tumor with a high morbidity rate among children, accounting for approximately 80% of leukemia cases. Although there have been improvements in the treatment of patients frequent relapse lead to a poor prognosis. The aim of the present study was to determine whether HOXA5 may be used as a target for gene therapy in leukemia in order to provide a new treatment. Mononuclear cells were extracted from the bone marrow according to the clinical research aims. After testing for ALL in the acute stage, the relative mRNA and protein expression of HOXA5 was detected in the ALL remission groups (n=25 cases per group) and the control group [n=20 cases, immune thrombocytopenia (ITP)]. Gene silencing by RNA interference (RNAi) was used to investigate the effect of silencing HOXA5 after small interfering RNA (siRNA) transfection to Jurkat cells. The HOXA5-specific siRNA was transfected to Jurkat cells using lipofectamine. The experiment was divided into the experimental group (liposomal transfection of HOXA5 targeting siRNA), the negative control group (liposomal transfection of cells with negative control siRNA) and the control group (plus an equal amount of cells and culture media only). Western blotting and quantitative fluorescent polymerase chain reaction (QF­PCR) were used to detect the relative HOXA5 mRNA expression and protein distribution in each cell group. Cell distribution in the cell cycle and the rate of cells undergoing apoptosis were determined using flow cytometry. The expression of HOXA5 at the mRNA and protein levels in the acute phase of ALL was significantly higher than that in ALL in the remission and control groups. In cells transfected with HOXA5-specific siRNA, the expression of HOXA5 at the mRNA and protein levels decreased significantly (P<0.05). The distribution of cells in the cell cycle was also altered. Specifically, more cells were present in the G0/G1 phase compared to the S phase (P<0.05). In addition, the apoptotic rate was significantly higher in cells transfected with HOXA5­specific siRNA (P<0.05). In conclusion, high expression levels of HOXA5 mRNA and protein in children with ALL indicate that HOXA5 is closely associated with childhood ALL. In addition, HOXA5-specific siRNA effectively silences HOXA5 gene expression and induces apoptosis and cell-cycle arrest in Jurkat cells, thus inhibiting cell proliferation.

ZEB1 promotes epithelial-mesenchymal transition in cervical cancer metastasis.

OBJECTIVE: To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in cervical cancer tissue (squamous cell carcinoma, SCC). DESIGN: Exploratory study. SETTING: University hospital. PATIENT(S): Sixty patients with SCC, including stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10), and IIB (n = 10) were studied. INTERVENTION(S): Caski cells were transfected with recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1-knockdown Caski cells. MAIN OUTCOME MEASURE(S): ZEB1 expression was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry in cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression corresponded with changes in the proliferation and migratory ability of Caski cells. RESULT(S): Quantitative real-time polymerase chain reaction and immunohistochemistry results revealed that ZEB1 expression and the ratio of Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with advanced International Federation of Gynecology and Obstetrics stage, tumor size >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1 shRNA in Caski cells significantly decreased the messenger RNA and protein expression of ZEB1, parallel with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker Vimentin. Furthermore, the proliferation and migratory ability of Caski cells were significantly lower in the transfected group than in the nontransfected control group. CONCLUSION(S): Down-regulation of ZEB1 expression may protect the invasive front of the tumors from converting to a mesenchymal phenotype by reducing the proliferation and motility of cervical cancer cells, suggesting that ZEB1 might be a potential therapeutic target for SCC.

Effect of conjugated linoleic acid supplementation on weight loss and body fat composition in a Chinese population.

OBJECTIVE: Conjugated linoleic acid (CLA) has several benefits, including body fat reduction, as proved in animals. However, the results of CLA-induced body composition alterations in humans are inconsistent, and no related data are available for Chinese populations. This study aimed to determine whether CLA affects body weight (BW) loss and body composition of overweight and obese Chinese subjects. METHODS: In this randomized, double-blind, placebo-controlled trial, subjects with a body mass index (BMI) of 24 to 35 kg/m(2) randomly received 1.7 g of cis-9,trans-11 and trans-10,cis-12 CLA (n = 30) or placebo (salad oil; n = 33) in 200 mL of sterilized milk twice daily for 12 wk. Changes in body composition were determined by bioimpedance measurements. RESULTS: Sixty-three subjects completed the study (CLA, n = 30). After 12 wk, compared with the baseline, the BW, BMI, total fat mass, fat percentage, subcutaneous fat mass, and waist-to-hip ratio decreased in the CLA group (P < 0.05). The CLA group was stratified by BMI and gender. The BW, BMI, subcutaneous fat mass, and waist-to-hip ratio decreased in 27 subjects with a BMI ≥ 27, and these indices, except subcutaneous fat mass, were lower in female subjects. The levels of total cholesterol, triacylglycerol, low-density lipoprotein, and plasma fasting glucose increased, whereas those of high-density lipoprotein decreased after 3 mo of CLA treatment. The changes were not significantly different from the baseline values. CONCLUSION: The supplementation of CLA for 12 wk in overweight and grade I obese Chinese subjects yielded lower obesity indices, with no obvious adverse effects.

[Phenotype and genotype analysis of hemoglobin E].

OBJECTIVE: To analyze the genotype and phenotype correlation in the hemoglobin E (HbE) carriers, and to investigate the effect of HbE on hematological parameters. METHODS: The capillary electrophoresis was used to screen total 14 141 samples and blood cell analysis was further processed to the HbE carrying samples. Gap-PCR and reverse dot blot hybridization method were used for the detection of Chinese common mutation of α and ß thalassemia. RESULTS: There is a statistical difference in hematological phenotype index (HGB, MCV, MCH, HbE, HbA(2)) between samples of HbE heterozygous (53 samples), HbE homozygous (2 samples), HbE composite α thalassemia (α-thal, 7 samples) and HbE composite ß thalassemia (ß-thal, 8 samples). Among the four groups, HbE heterozygous \[HGB (122.7 ± 19.99) g/L, MCV (78.65 ± 5.03) fl\] and HbE composite α-thal \[HGB (113.6 ± 22.68) g/L, MCV (73.50 ± 7.73) fl\] had slight effect on hematological parameters, but HbE composite ß-thal \[HGB (76.4 ± 12.30) g/L\], MCV (59.23 ± 5.28) fl\] had the heaviest effect on hematological parameters. CONCLUSION: Co-existence of HbE heterozygous and other type thalassemias showed variation in their hematological phenotype, so patients should be informed of genetics in prenatal diagnosis.

[Effects of n-hexane exposure on human serum myelin basic proteins].

OBJECTIVE: To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. METHODS: In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. RESULTS: The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). CONCLUSION: The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure.

Single-incision transumbilical laparoscopic adjustable gastric banding: a novel minimally invasive surgical technique.

Single-incision laparoscopic surgery is a new approach considered as an alternative to natural orifice transluminal endoscopic surgery. Here, we describe a novel technique for laparoscopic adjustable gastric banding (LAGB) using a single-incision transumbilical (SITU) approach and an intraoperative method for liver retraction. Three patients (18 to 23 y) with a mean body mass index of 38.1 kg/m2 underwent LAGB with the "pars flaccida" technique through an SITU approach. Retraction of the left liver lobe was achieved with a specially designed "liver suspension tape" attached with sutures to the left upper quadrant abdominal wall and midline. The mean operative time was 62 minutes, with no intraoperative complications. These patients responded well postoperatively and were discharged after 2 days. SITU-LAGB is a safe, technically feasible, and reproducible procedure resulting in a more beneficial cosmetic appearance as the incision wound is hidden in the umbilicus, thus avoiding visible abdominal scars.

[Radiolysis of aqueous solution of thiocyanate by gamma-rays].

Radiolysis of aqueous solution of thiocyanate by 60Co gamma-rays was studied. In condition of pH = 1 and pH = 3,25 mg/L SCN- was decomposed under the dose of 6 kGy, with decomposition rate of 98.11% (pH = 1) and 95.97% (pH = 3) respectively. 25 mg/L SCN- (pH = 7) was decomposed under the dose of 9 kGy and the decomposition rate is 99.33%. In the alkaline condition, pH = 10 and pH = 12, the dose of 18 kGy was need, and the decomposition rate is 99.64% and 99.93% respectively. High SCN- concentration means that more radiation dose is need. From the comparison of before radiolysis and after radiolysis's TOC (total organic carbon) and TN (total nitrogen) of SCN- solution, little TOC and TN was removed. The determination of SO4(2-) and NO3- concentration indicated that sulfur element was removed and converted to SO4(2-), and nitrogen element rarely converted to NO3-, but converted to other forms of nitrogen.

[Radiolysis of aqueous thiocyanate and its complicated system].

We studied the 60Co gamma-ray radiolysis of thiocyanate aqueous solutions in the presence of free radical scavengers, determination of cyanide of radiated thiocyanate solutions, degradation of cyanide and thiocyanate complicated system and cyanide, thiocyanate and copper (I) cyanide complicated system. The presence of NaHCO3 and n-butanol made the degradation efficiency of thiocyanate decreased, in the radiation procession of thiocyanate, cyanide was produced; and the possible reaction equation is SCN(-) + 8*OH-->SO4(2-) + CN(-) +4H2O, in the cyanide and thiocyanate system, the thiocyanate degradation rate can obtained 30%, free cyanide degradation was little effected by coexistence of thiocyanate; and due to strong complex ability of copper (I), the main form of copper (I) cyanide is Cu(CN)3(2-), the total cyanide of the system can't be degraded completely and degradation rate is about 80%.

[Helping a family primary caregiver adjust to caregiving stress].

The authors present a case study of a nursing experience with a primary caregiver who cared for his wife for more than 10 years (1/18/92 to 1/29/02). Data were collected by observation, interviews, physical examination, and an assessment instrument consisting of the Barthrel Index, Karnofsky Scale, Caregiver Burden, Risk of Impaired Nutritional Status, Quality of Caregiving Index, Norton Skin Index, and Major nursing problems for both the care receiver and caregiver were: a) everyday quality of life was severely impacted by an overload of caregiving stress, b) insufficient social support, and c) deficiencies in family functioning. The authors describe the details of the primary intervention effort, primarily helping the patient and caregiver locate and contact formal and informal social support resources.