Cefoperazone/sulbactam-induced hemolytic anemia.

Drug-induced hemolytic anemia (DIHA) is a rare complication of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound prepared from the third generation of cephalosporin and ß-lactamase inhibitor. There are limited data of DIHA induced from cefoperazone/sulbactam. A 93-year-old female patient, who had an operation on the biliary tract 3 months ago, was admitted to our hospital with an abdominal infection. After cefoperazone/sulbactam was given as anti-infection treatment, the patient developed hemolytic anemia on the third day. Cefoperazone/sulbactam was discontinued and replaced with meropenem. Subsequently the level of red blood cells, hemoglobin, and hematocrit returned to normal. Clinicians should pay attention to monitoring the possible adverse reactions during the use of cefoperazone/sulbactam and should be aware of the occurrence of DIHA, so as to give timely treatment.

[Effect of SLC7A11 gene downregulation on the gefitinib resistance of lung adenocarcinoma PC9/GR cells and its mechanism].

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 µmol/L and 64.01 µmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) µmol/mg vs. (82.18±7.77) µmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.

[A case report of chronic granulomatous disease with CYBB gene mutation in an adult].

We reported a 28-year-old male patient who had been admitted to a local hospital for several times in the past four years because of recurrent fever and cough. Each chest CT scan during hospitalization showed consolidation accompanied by exudation and mild pleural effusion. After treatment, the consolidation apparently absorbed, but similar symptoms recurred within half a year, and the new consolidation appeared. For this reason, he was diagnosed with tuberculosis or bacterial pneumonia several times in other hospitals, and was hospitalized two to three times a year. Finally, he was diagnosed with chronic granulomatous disease (CGD) with CYBB gene mutation through whole-exome sequencing.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Implementation of a classification strategy of Raman data collected in different clinical conditions: application to the diagnosis of chronic lymphocytic leukemia.

The literature is rich in proof of concept studies demonstrating the potential of Raman spectroscopy for disease diagnosis. However, few studies are conducted in a clinical context to demonstrate its applicability in current clinical practice and workflow. Indeed, this translational research remains far from the patient's bedside for several reasons. First, samples are often cultured cell lines. Second, they are prepared on non-standard substrates for clinical routine. Third, a unique supervised classification model is usually constructed using inadequate cross-validation strategy. Finally, the implemented models maximize classification accuracy without taking into account the clinician's needs. In this paper, we address these issues through a diagnosis problem in real clinical conditions, i.e., the diagnosis of chronic lymphocytic leukemia from fresh unstained blood smears spread on glass slides. From Raman data acquired in different experimental conditions, a repeated double cross-validation strategy was combined with different cross-validation approaches, a consensus label strategy and adaptive thresholds able to adapt to the clinician's needs. Combined with validation at the patient level, classification results were improved compared to traditional strategies.

[Clinical effect analysis of 146 cases of ipsilateral simultaneous pancreas and kidney transplantation].

Objective: To investigate the clinical effect of ipsilateral simultaneous pancreas and kidney transplantation (SPK). Methods: A total of 146 cases of SPK surgeries completed in the Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020 were selected to summarize the outcome, curative effect and complications of the operation. Results: The patients were followed up for 1 to 45 months. Good clinical results were obtained in 146 patients. Renal function indicators suggest that on the 7th day after operation, the serum creatinine returned to normal level [142.4 (108.6, 213.4)µmol/L]. The index of pancreatic function decreased to the normal level as expected. The level of blood amylase was 160.5(109.3, 249.8) U/L within 7 days after operation, and then decreased. The trend of urinary amylase was similar to that of blood amylase, which was 240(121.0, 370.0) U/L 7 days after operation, and glycosylated hemoglobin decreased to the normal level (5.8%±1.4%) 1 month after operation. The main medical complications were infection including pulmonary infection (26.03%, 38/146), urinary tract infection (26.03%,38/146), and abdominal infection (4.79%,7/146), acute rejection including renal graft rejection (5.8%,8/146), pancreas/duodenum rejection (18.49%,27/146), and renal graft combined pancreatic graft rejeciton (6.85%,10/146), as well as gastrointestinal bleeding (30.82%,45/146), of which 5 cases were severe bleeding (3.42%, 5/146). The main surgical complications were poor incision healing (10.27%, 15/146), serious surgical complications including arteriovenous thrombosis of the transplanted pancreas (2.05%, 3/146) and intestinal leakage (0.68%,1/146). The 1-year and 3-year patient, renal and pancreatic survival rates were both 92.5%, 91.5% and 89.5%, respectively, and despite the death, the 1-year, 3-year transplanted kidney survival rate was both 99.3%, and 95% for the the 1-year, 3-year pancreas survival rate. Conclusion: Strict preoperative evaluation of the function of large organs, reasonable surgical methods, perioperative anticoagulation, and prompt diagnosis of complications can achieve good clinical results for patients with SPK.

[Current status and prospects of population exposure assessment of nanomaterials consumer products].

With the wide application of nanomaterials in consumer products in the market, it is necessary to understand the existence and release of nanomaterials in consumer products, as well as the current situation of exposure assessment of consumers. China has been a large industrial producer with a huge consumer market, but the supervision of consumer goods with nanomaterials is almost blank. This article summarized and classified the existing consumer products of nanomaterials in the international market, and discussed the release of key nanomaterials in consumer products and the exposure assessment methods of consumers, in order to provide a scientific basis for the establishment of a regulatory system for consumer products of nanomaterials in China in the future.

[Application of metabolomics in nanotoxicity].

As an emerging material with excellent property, nanoparticle has been widely used in multiple fields such as chemical industry, textile, biomedicine, etc., which has caused widespread concern about its potential toxicity in society. Due to the limitations of traditional toxicology technology, the high-throughput methods were urgently needed to assess the potential toxicity of particles at nanoparticle size systematically. Metabolomics has been recognized as an emerging omics technology developed by multidisciplinary combination of modern analytical techniques, biochemistry and bioinformatics, which has been widely used to screened early toxicity potential markers and metabolic pathway by analyzing changes in the types and quantities of metabolites in biological samples such as cells and tissues. This article reviewed the progress and challenges of metabolomics in nanotoxicology research.

[Clinical application of renal autotransplantation in complex urological diseases].

Objective: To summarize the experience of renal autotransplantation for severe iatrogenic proximal ureteral damage and renal artery aneurysms in eight patients and to explore the clinical application value of renal autotransplantation. Methods: Two patients of renal artery aneurysms and six patients of severe iatrogenic proximal ureteral damage between January 2010 and March 2018 in our center were retrospectively reviewed. Results: The procedures of eight cases were successful, with immediate return of renal function in the patients. The warm ischemia time was (3±1) minutes, the total operation time was (340±164) min, and the estimated blood loss was (180±60) ml, respectively. For renal artery anastomosis, six patients of severe iatrogenic proximal ureteral damage received end-to-end anastomosis between the internal iliac artery and renal artery, and two patients of renal artery aneurysms were treated with renal artery and internal iliac artery for reconstruction, then end-to-side anastomosis to recipien external iliac artery. A direct ureterovesical anastomosis was performed in seven patients, one patient was received pyeloureteroplasty. No serious complications of blood vessel and ureter were found during perioperative and long-term follow-up. All cases follow-up hitherto have normal renal function and blood pressure. Conclusions: Renal autotransplantation can be appropriate for patients with proximal ureteral loss and complex hilar renal artery aneurysms. In addition, it is able to protect renal functions to the most extent and provides a surgical alterative for complex renal diseases.

Temperature-dependent optical constants of highly transparent solids determined by the combined double optical pathlength transmission-ellipsometry method.

The optical constants of five highly transparent substrates (polycrystalline BaF2, CaF2, MgF2, ZnSe, and ZnS) were experimentally determined based on a combined technique using both the double optical pathlength transmission method and the ellipsometry method within temperature range 20°C-350°C in the ultraviolet-infrared region (0.2-20 µm). The results show that the refractive index spectra of polycrystalline BaF2, CaF2, and MgF2 are similar, but differ from that of polycrystalline ZnSe and ZnS. The thermo-optic coefficient of these highly transparent substrates increases with increasing temperature. The absorption indices show a significant temperature-dependent behavior, which increases with increasing temperature from 20°C to 350°C over the transparent region. For the sake of application, the fitted formulas of the refractive index of the five highly transparent substrates as a function of wavelength and temperature are presented.

Temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane.

Liquid isopropanol, n-butanol, and n-decane are combustible organic compounds that are frequently used in theoretical and experimental researches on fuel combustion. In this work, the temperature-dependent optical constants of liquid isopropanol, n-butanol, and n-decane in the region 500-5500 cm-1 at ambient pressure are measured using the combined ellipsometry-transmission method. In the combined method, the optical constants are first measured by a modified ellipsometry method, and then the absorption indices for weak absorption regions are obtained by the transmission method using the refractive indices measured by the modified ellipsometry method. The refractive indices of liquid isopropanol, n-butanol, and n-decane are within the range from 1.3 to 1.45 in the studied wavelength and temperature region. The absorption indices of these liquids range from 10-5 to 10-1. In the temperature range studied, the refractive indices decrease with increasing temperature in an approximately linear manner, but the effects of the temperature on the absorption indices are much smaller. The characteristic wavenumbers of the main absorption peaks are consistent with the vibrational frequencies of major functional groups.

Wavelength and concentration-dependent optical constants of NaCl, KCl, MgCl2, CaCl2, and Na2SO4 multi-component mixed-salt solutions.

The optical constants of sodium chloride (NaCl), potassium chloride (KCl), magnesium chloride (MgCl2), calcium chloride (CaCl2) and sodium sulfate (Na2SO4) solutions at weight fractions ranging from 0 to 16.6667% are measured by the combined ellipsometry-transmission method in the spectral range 0.3-1.0 µm. In the combined method, a modified ellipsometry method is used to measure the refractive indices of liquids, and then the transmission method is conducted to obtain the extinction coefficients using the refractive indices obtained by the ellipsometry method. The experimental refractive indices of these binary solutions are utilized to obtain a mole-fraction weighted mixing rule, which relates the refractive index of multi-component mixed-salt solutions to the wavelength and concentration of each component. The effects of wavelength and concentration are taken into account by empirical expressions of the Lorentz-Lorenz formulized molar refraction. A mole-fraction weighted linear combined mixing rule is proposed to study the wavelength and concentration-dependent extinction coefficients of mixed-salt solutions. The optical constants of NaCl-KCl and NaCl-Na2SO4 ternary solutions, NaCl-KCl-CaCl2 quaternary solutions, and NaCl-KCl-MgCl2-CaCl2-Na2SO4 multi-component solutions are measured to verify the mixing rules. The results show that the optical constants calculated based on the mixing rules are in good agreement with experimental data, which demonstrate the feasibility of the proposed mixing rules. As the experimental analysis indicates, both the refractive indices and the extinction coefficients of the saline solutions increase with solute concentrations in the spectral range 0.3-1.0 µm.

Infrared optical constants of liquid palm oil and palm oil biodiesel determined by the combined ellipsometry-transmission method.

The optical constants of vegetable oils and biodiesels are the basic input parameters in the study of the thermal radiation transfer and monitoring the productivity of vegetable oils converting to biodiesels. In this work, a combined ellipsometry-transmission method is presented to obtain the optical constants of palm oil and palm oil biodiesel between 20°C and 150°C in the spectral range 600-4100 cm-1 and to study the temperature effect on the optical constants. In the combined method, a modified ellipsometry method is used to measure the optical constants of palm oil and palm oil biodiesel for the whole researched wave bands. For the weak absorption regions in which the ellipsometry method cannot give precise absorption indices, the transmission method is conducted to get the absorption indices using the refractive indices obtained by the proposed ellipsometry method. Deionized water and methanol are taken as examples to verify the combined ellipsometry-transmission method. It is shown that the combined method can overcome the deficiencies of the traditional ellipsometry and transmission method, which can be used for the measurements of both strong and weak absorption wave bands. The experimental analyses indicate that temperature exerts a noticeable influence on the infrared optical constants of palm oil and palm oil biodiesel. With the increase of temperature, the refractive indices at certain wavenumbers decrease nearly linearly, and the amplitudes of dominant absorption peaks show a decreasing trend. The absorption peaks located around 3550 cm-1 show blueshift trends as temperature increases. Comparing these two kinds of oils, palm oil presents larger values in refractive indices and dominant absorption peaks.

Investigation of ellipsometric parameters of 2D microrough surfaces by FDTD.

Ellipsometry is a powerful method for measuring the optical constants of materials and is very sensitive to surface roughness. In previous ellipsometric measurement of optical constants of solid materials with rough surfaces, researchers frequently used effective medium approximation (EMA) with roughness already known to fit the complex refractive index of the material. However, the ignored correlation length, the other important parameter of rough surfaces, will definitely result in fitting errors. Hence it is necessary to consider the influence of surface roughness and correlation length on the ellipsometric parameters Δ (phase difference) and Ψ (azimuth) characterizing practical systems. In this paper, the influence of roughness of two-dimensional randomly microrough surfaces (relative roughness σ/λ ranges from 0.001 to 0.025) of silicon on ellipsometric parameters was simulated by the finite-difference time-domain method which was validated with experimental results. The effects of incident angle, relative roughness, and correlation length were numerically investigated for two-dimensional Gaussian distributed randomly microrough surfaces, respectively. The simulated results showed that compared with the smooth surface, only tiny changes of the ellipsometric parameter Δ could be observed for microrough silicon surface in the vicinity of the Brewster angle, but obviously changes of Ψ occur especially in the vicinity of the Brewster angle. More differences between the ellipsometric parameters of the rough surface and smooth surface can been seen especially in the vicinity of the Brewster angle as the relative roughness σ/λ increases or correlation length τ decreases. The results reveal that when we measure the optical constants of solid materials by ellipsometry, the smaller roughness, larger correlation length and larger incident wavelength will lead to the higher precision of measurements.

Improved transmission method for measuring the optical extinction coefficient of micro/nano particle suspensions.

Extinction coefficients are fundamental for analyzing radiative transport in micro/nano particle suspensions. In the traditional transmission method for measuring the extinction coefficient of particles in a cuvette, a reference system is used to compensate for the influence of the cuvette and base fluid. However, the multiple reflections and refractions between the air-glass and liquid-glass interfaces cannot be sufficiently eliminated by using the reference system, and the induced measurement error increases significantly with increasing difference in refractive index between the two neighboring media at these interfaces. In this paper, an improved transmission method is proposed to measure the extinction coefficient of micro/nano particles. The extinction coefficient of the particles is determined based on an optical model, taking into account the multiple reflection and refraction at the glass-liquid interfaces. An experimental validation was conducted for suspensions with various mean particle sizes. By considering the higher-order transmission terms, the improved transmission method generally achieved high-accuracy improvement over the traditional transmission method for extinction coefficient measurement, especially for the case with a small optical thickness of particle suspensions. This work provides an alternative and more accurate way for measuring the extinction characteristics of micro/nano particle suspensions.

Influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on intramammary infection in dairy cows.

The aim of this study was to evaluate the influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on bacterial intramammary infection (IMI) in dairy cows. A total of 2,106 mastitis pathogens in 12 species were isolated from 125 dairy farms distributed in 30 different cities in China, and the information about these factors was recorded at the same time. Mastitis pathogens were isolated from 63.43% of the milk samples, whereas Streptococcus agalactiae accounted for 38.61% of all pathogens, followed by Str. dysgalactiae (28.16%), Staphylococcus aureus (19.10%), Escherichia coli (6.90%), and other pathogens (7.23%). According to our investigation, IMI was more common in spring with the isolation rate of pathogens at 81.04%, and lowest in winter (52.34%). Cows were more likely to be infected by environmental pathogens (E. coli or Str. uberis) in summer, in rear quarters and in cows with higher daily milk yield or lower somatic cell count. In addition, Str. dysgalactiae exhibited a higher prevalence with increased parity. Different clinical symptoms of quarters with bacterial IMI were seen in this study, and mastitis pathogens were isolated from healthy quarters.

Short communication: N-Acetylcysteine-mediated modulation of antibiotic susceptibility of bovine mastitis pathogens.

The aim of this study was to investigate the effects of N-acetylcysteine (NAC) on antibiotic susceptibility of bovine mastitis pathogens including Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, and Streptococcus agalactiae. Minimum inhibitory concentrations (MIC) were tested by the agar-based E-test method. The presence of 10mM NAC reduced the MIC of penicillin and ampicillin but enhanced the MIC of erythromycin and ciprofloxacin for all of the strains. In addition, NAC-mediated modulation of MIC of kanamycin, tetracycline, and vancomycin was diverse, depending on the target bacterial pathogen and antibiotic being used. The results suggest that NAC is an important modulator of antibiotic activity against the major bovine mastitis pathogens.

The distribution of different virulence grass carp reovirus strains in some neglected tissues.

Grass carp reovirus (GCRV) is the causative agent of hemorrhagic disease in infected grass carp. During an outbreak, a mortality rate of up to 85% can be experienced, thus leading to substantial economic losses. The current understanding of disease pathogenesis is limited, with the distribution and dynamics of replication amongst different GCRV strains in vivo largely unknown. We determined distribution of different GCRV strains in infected grass carp, especially in some neglected tissues, such as the gill, brain, blood and so on. The results showed elevated viral RNA copy numbers in the blood, with some tissues such as the kidney, heart, brain, and bladder exhibiting even higher viral loads following infection with the virulent GCRV-CL strain. Even more interesting is that the brain exhibited the highest viral load, with a copy number of 800,000 following GCRV-CL infection. Overall, this study provides further insight into GCRV viral load distributions following infection and potentially identified some new viral tropism sites to provide a foundation for further studies aimed at characterizing GCRV viral pathogenesis.

[Expression of Slit3/Robo signal pathway in mouse aortic smooth muscle cell and its impact on proliferation and migration].

OBJECTIVE: To observe the expression of neural axon guidance molecules Slit3 and Robo receptors in mouse aortic smooth muscle cell(MASMC) and investigate the effect of exogenous Slit3 protein on migration and proliferation of MASMC. METHODS: The primary cultured MASMC were identified by immunofluorescent assay. The expression of Slit3/Robo signal pathway was detected by RT-PCR and immunocytochemical staining. MASMC were divided into 6 groups: the negative control group (DMEM medium containing bovine serum albumin 86 µg/L), Slit3 0 µg/L group (DMEM medium without Slit3), Slit3 24 µg/L group (DMEM medium containing Slit3 24 µg/L), Slit3 40 µg/L group (DMEM medium containing Slit3 40 µg/L), Slit3 80 µg/L group (DMEM medium containing Slit3 80 µg/L) and the positive control group (DMEM medium containing platelet derived growth factor 10 µg/L). The effects of exogenous Slit3 on MASMC proliferation and migration were detected by CCK-8 and scratched cells and transwell chambers respectively. RESULTS: (1) The mRNA and protein expressions of Slit2, Slit3, Robo1 and Robo4 were detected in MASMC. mRNA level of Slit2 was lower than Slit3 (P<0.05) and there were no significant difference between mRNA level of Robo1 and Robo4. (2) The mitogenic responses of MASMC were significantly enhanced in Slit3 24 µg/L group, Slit3 40 µg/L group and Slit3 80 µg/L group compared with negative control group (1.13±0.04, 1.19±0.02, 1.18±0.08 and 0.64±0.10 respectively, all P<0.05). The mitogenic activity of MASMC was the strongest in Slit3 40 µg/L group (compared with positive control group 1.27±0.05, P>0.05). (3)The autonomous migration activity of MASMC were significantly increased in Slit3 24 µg/L group, Slit3 40 µg/L group, Slit3 80 µg/L group compared with negative control group (cell scratch width were (0.40±0.03)cm, (0.32±0.03)cm, (0.30±0.02)cm and (0.49±0.01)cm respectively, all P<0.05). The autonomous migration activity of MASMC was the strongest in Slit3 80 µg/L group (compared with positive control group (0.22±0.01)cm, P>0.05). The transmembrane migration activity of MASMC were significantly increased in Slit3 24 µg/L group, Slit3 40 µg/L group, Slit3 80 µg/L group compared with negative control group (the number of cell migration were 46.67±2.23, 65.33±3.43, 81.67±4.22 and 39.33±2.03 respectively, all P<0.05). The transmembrane migration activity of MASMC was the strongest in Slit3 80 µg/L group (compared with positive control group 84.00±2.02, P>0.05). CONCLUSION: Slit2, Slit3, Robo1 and Robo4 were expressed in MASMC, and exogenous Slit3 could promote proliferation and migration of MASMC in vitro.

Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients.

We examined the influence of the cytochrome P450 3A5 (CYP3A5) genes in both donors and recipients on the concentration-dosage ratio (C/D) of tacrolimus in Chinese liver transplant patients. Fifty-one adult liver transplant patients who received tacrolimus were included in this study. The CYP3A5 polymorphism in donors and recipients was determined at the time of transplantation, and tacrolimus-based immunosuppressive therapy was started based on each patient's genetic constitution. The relationship between the C/D of tacrolimus for 3 months after surgery and the CYP3A5 genotype was analyzed. A stepwise regression model was used to analyze the relationship between C/D of tacrolimus and genotype, time course, age, and liver weight in liver transplant patients. Three months after liver transplantation, C/D was both affected by the CYP3A5 genotype of both the donors and the recipients. The C/D of tacrolimus in patients with the CYP3A5*1 allele or carrying CYP3A5*1 allele in the liver was lower than that in CYP3A5*3/*3 patients with the CYP3A5*3/*3 genotype in the liver (P < 0.01). The CYP3A5*1 genotype in donors as well as in patients both contributes to interindividual variation in the C/D of tacrolimus in adult liver transplantation.