Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

Mid-term clinical outcome of arthroscopic surgery on early knee osteoarthritis in middle-old aged patients / 中国骨伤

OBJECTIVE@#To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy.@*METHODS@#A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group.@*RESULTS@#Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676).@*CONCLUSION@#Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.

Consistency between quantitative fluorescent-polymerase chain reaction and karyotyping in prenatal diagnosis / 中华围产医学杂志

Objective:To analyze the consistency between karyotyping and quantitative fluorescent- polymerase chain reaction (QF-PCR) in prenatal diagnosis.Methods:This study retrospectively analyzed the clinical data of 10 967 patients undergoing karyotyping and QF-PCR for prenatal diagnosis in Guangzhou Women and Children's Hospital from January 2010 to December 2017. The failure rate, results, and diagnosis of common chromosomal disorders of the two methods were compared. The sensitivity and specificity of QF-PCR in detecting chromosomal mosaicism were evaluated using the receiver operative characteristic (ROC) curve.Results:(1) The failure rates of karyotyping and QF-PCR were 0.99% (109/10 967) and 0.10% (11/10 967), respectively. (2) The karyotypes of 9 960 out of the 10 858 successfully cultured samples were normal, and 99.89% (9 949/9 960) results were consistent between the two methods. The other 898 cases included 694 (77.28%) with common chromosomal abnormalities (trisomy 21, 18 and 13 and sex chromosomal abnormality) and 204 (22.72%) with other chromosomal abnormalities. The consistency between the two methods in detecting common chromosomal abnormalities was 95.68% (664/694). (3) The consistency in the detection of trisomy 21, 18 and 13 and sex chromosomal abnormality between karyotyping and QF-PCR were 99.74% (382/383), 100.00% (125/125), 100.00% (33/33) and 81.05% (124/153). However, the common chromosomal mosaicism was only noted for 44.44% (24/54). (4) Among cases with a mosaic ratio over 18.5%, the sensitivity and specificity of QF-PCR were 0.958 (95% CI: 0.789-0.999) and 0.600 (95% CI: 0.406-0.773) with the area under the ROC curve (AUC) of 0.811 (95% CI: 0.696-0.926, P<0.001). (5) Thirty cases with negative QF-PCR results but positive mosaic chromosomal aberrations were followed up. Ten (33.3%) pregnant women terminated their pregnancies, and two (6.7%) were lost to follow-up. The other 18 cases delivered healthy neonates that all survived after birth. Conclusions:In prenatal diagnosis, QF-PCR and karyotyping were highly consistent in the detection of trisomy 21, 13, and 18, but have significant discordance in the diagnosis of sex chromosomal abnormality.

Comparative measurement of intraocular pressure by Rebound and non-contact tonometry in patients wearing bandage contact lenses after pterygium excision / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the measurement of intraocular pressure(IOP)through a bandage contact lens with the “native” measurement by rebound tonometry and non-contact tonometry in patients after pterygium excision. <p>METHODS: Fifty consecutive patients(50 eyes)undergone pterygium excision(unilateral nasal, primary pterygium, horizontal length <4mm), and conjunctival autografting were included in this prospective study. IOP measurements were obtained by Rebound tonometry and non-contact tonometry in random order with(lens measurement)and without(native measurement)a bandage contact lens half a month after operation. We compared the mean values(validity parameter)and standard deviation(precision parameter)of the two individual measurements in each case using the paired t-test 14d after surgery. <p>RESULTS: With the rebound tonometry we detected statistically significant higher values in the contact lens measurements(18.20±3.19 <i>vs</i> 15.17±3.80mmHg in the native measurements; <i>P</i><0.001), a good correlation with <i>r</i>=0.884 and mean difference was 3.04±1.79mmHg; With the non-contact tonometry we detected statistically significant higher values in the contact lens measurements(15.74±3.23 <i>vs</i> 13.19±3.89mmHg in the native measurements; <i>P</i><0.001), a good correlation with <i>r</i>=0.876 and mean difference was 2.55±1.88mmHg. In the contact lens measurements and native measurements, we detected statistically significant higher values by Rebound tonometry than that by non-contact tonometry(<i>P</i><0.001), and mean difference was 2.46±1.45mmHg, 1.98±1.67mmHg. <p>CONCLUSION: The use of rebound tonometry and non-contact tonometry shows good consistency between lens measurement and native measurement. However, it should be noted that the average of the measurements over contact lens by rebound tonometry and non-contact tonometry were found to be higher than that in native measurement, and the average of the measurements with and without lens by rebound tonometer was found to be higher than what was measured by non-contact tonometry.

Comparative measurement of intraocular pressure by Rebound and non-contact tonometry in patients wearing bandage contact lenses after pterygium excision / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the measurement of intraocular pressure(IOP)through a bandage contact lens with the “native” measurement by rebound tonometry and non-contact tonometry in patients after pterygium excision. <p>METHODS: Fifty consecutive patients(50 eyes)undergone pterygium excision(unilateral nasal, primary pterygium, horizontal length <4mm), and conjunctival autografting were included in this prospective study. IOP measurements were obtained by Rebound tonometry and non-contact tonometry in random order with(lens measurement)and without(native measurement)a bandage contact lens half a month after operation. We compared the mean values(validity parameter)and standard deviation(precision parameter)of the two individual measurements in each case using the paired t-test 14d after surgery. <p>RESULTS: With the rebound tonometry we detected statistically significant higher values in the contact lens measurements(18.20±3.19 <i>vs</i> 15.17±3.80mmHg in the native measurements; <i>P</i><0.001), a good correlation with <i>r</i>=0.884 and mean difference was 3.04±1.79mmHg; With the non-contact tonometry we detected statistically significant higher values in the contact lens measurements(15.74±3.23 <i>vs</i> 13.19±3.89mmHg in the native measurements; <i>P</i><0.001), a good correlation with <i>r</i>=0.876 and mean difference was 2.55±1.88mmHg. In the contact lens measurements and native measurements, we detected statistically significant higher values by Rebound tonometry than that by non-contact tonometry(<i>P</i><0.001), and mean difference was 2.46±1.45mmHg, 1.98±1.67mmHg. <p>CONCLUSION: The use of rebound tonometry and non-contact tonometry shows good consistency between lens measurement and native measurement. However, it should be noted that the average of the measurements over contact lens by rebound tonometry and non-contact tonometry were found to be higher than that in native measurement, and the average of the measurements with and without lens by rebound tonometer was found to be higher than what was measured by non-contact tonometry.

Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. MATERIALS AND METHODS: PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. RESULTS: PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. CONCLUSION: These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

Effects of adenosine on brain metastasis of lung cancer and its possible mechanism / 临床与实验病理学杂志

Purpose To clarify the effect of adenosine on brain metastasis of lung cancer and the possible mechanism of adenosine promoting brain metastasis of lung cancer. Methods Western blot was used to dynamically detect the expression level of hypoxia inducible factor-1 (HIF-1) in lung cancer cells and tight junction protein ZO-1 in brain microvascular endothelial cells on blood-brain barrier. The content of adenosine in lung cancer cell culture was determined by ELISA. Fluorescence analysis was used to detect the changes of permeability of the blood-brain barrier model in vitro. Hemocytometer counts the number of A549 lung cancer cells in Transwell's lower chamber. Results The expression level of HIF-1 in lung cancer cells and the content of adenosine in lung cancer cell culture reached the highest level when lung cancer cells were deprived of oxygen for 12 hours. At the same time, the expression level of ZO-1 protein in the blood-brain barrier was the lowest, the blood-brain barrier permeability was the highest (7.11), and the number of lung cancer cells passing through the blood-brain barrier model was the highest (84.6). The permeability of the blood-brain barrier model increased after the action of adenosine, and its change trend was consistent with the effect of hypoxic lung cancer cell culture solution. Conclusion Hypoxia can induce the lung cancer cell to release adenosine, the increased adenosine can reduce the expression of tight junction protein ZO-1 in blood brain barrier, which leads to the increase of permeability of blood-brain barrier and eventually lead to brain metastasis of lung cancer.

Observation on the relationship between intension of snails secretion and the condition of wrecked schistosoma larvae in Oncomelania hupensis dually infected with Exorchis mupingensis and Schistosoma japonicum for different intervals / 中国人兽共患病学报

The Oncomelania hupensis snails were dually infected with Exorchis mupingensis and Schistosoma japonicum at different intervals for 21 d,37 d,55 d,70 d and 85 d.The results indicated that the development of all S.japonicum larvae were blocked in the snails of co-infection,and the complexity and number of secretions in and around all the wrecked S.japonicum larvae is proportional to the intervals of co-infection.In addition,we also described and compared the detailed change of snails' secretions in different conditions of infection,and determined that the snail's secretions may involve in the destruction and damage of S.japonicum larvae.The attack degrees on larval S.japonicum in O.hupensis snails dually infected by E.mupingensis and S.japonicum with longer intervals were stronger than that of shorter intervals,and snail haemo-lymphocytes numbers were more few in that of shorter intervals.But the secretions remarkably increased in more longer interval model experimental snail tissue.This finding may provide an alternative strategy for reducing and controlling the transmission of S.japonicum,and are very helpful for better understanding the host-parasite relationship.

Effects of low frequency pulsed electromagnetic field on stomach blood circulation and ultra microstructure of stress ulcer in rats / 医疗卫生装备

Objective To determine non-thermal biological effect of low frequency pulsed electromagnetic field (LFPEF)on the stomach blood circulation and ultra microstructure of rat stress ulcer. Methods Thirty-six Sprague-Dawley rats were assigned to three equal groups:control,ulcer without interference group(UW)and ulcer exposure groups(UE).The rats stress ulcer models were constructed with the combination method of soak and bind in the low-pressure and hypoxia circumstance. Based on the singlechip,a LFPEF generator with adjustable frequency, amplitude and duty ratio was developed. Then the stomachs of the rats were exposed to the LFPEF generator 3 hours per day.On days 1,3,5 and 7,the blood circulation of the stomach was analyzed by the content of the serum NO and contrast ultrasonography.In addition,the ulcer tissue was taken out for section-staining. Finally, the pathological change of the stomach ultra microstructure was observed under a light microscope. Results On different days, the contents of the serum NO and microbubble concentration of UE group were significantly higher than those of the UW group(P<0.05). The pathological observation showed that the restoration of the gastric tissue in UE group was faster than that in the UW group(P<0.05).Conclusion LFPEF with certain proper parameter could improve the gastric tissue blood circulation and accelerate the stress ulcer restoration. [Chinese Medical Equipment Journal,2018,39(5):35-38]

Comparative research of setup error and registration for image-guided radiotherapy of lung cancer / 医疗卫生装备

Objective To explore the setup error and area registration error during lung cancer radiotherapy by using the on board imager (OBI) of the linear accelerator. Methods Totally 50 lung cancer patients underwent image-guided radiation therapy. Then OBI system was used for the scan validation by electronic portal imaging device (EPID) and cone beam CT (CBCT), and comparative analysis was executed on the setup errors of EPID and CBCT. Results The translation errors of EPID were (-1.62 ±1.58), (2.12 ±1.49) and (4.52 ±2.42)mm respectively at Lat, Vrt and Lng directions, while those of CBCT were (-1.27±1.25), (1.43±1.57) and (3.12±2.62) mm respectively. The registration errors at Lat, Vrt and Lng directions and rotation angle of lung tissue were (-1.27±1.25), (1.43±1.57), (3.12±2.62)mm and (0.5±1.6)° respectively, and those of target area were (-1.56±1.78), (1.68±2.39), (3.42±2.73)mm and (0.8±1.9)° respectively. CBCT and EPID had statistical differences (P<0.05) in setup error validation as well as setup errors at Vrt and Lng directions. There were no significant differences (P>0.05) when CBCT self-registration was involved in selecting different areas. Conclusion CBCT and EPID can both used for the setup validation of lung cancer, while the former behaved better than the latter.

Chorionic villus cell culture and karyotype analysis in 1983 cases of spontaneous miscarriage / 中华妇产科杂志

Objective To investigate the relationship between spontaneous miscarriage and embryonic chromosome abnormalities,and to evaluate the clinical application of karyotype analysis by chorionic villus cell culture. Methods The chorionic villus karyotype of 1983 cases of miscarriage from January 2010 to July 2016 in Guangzhou Women and Children′ s Mecical Center were analyzed retrospectively. The miscarried chorionic villi were obtained by curettage under sterilized condition. The chromosome specimens were prepared after chorionic villus cell culture. Karyotype analysis was performed by G-banding technique. Results In the 1983 samples, successful karyotype analysis was performed in 1770 cases, with the successful rate of 89.98%. Chromosomal abnormalities were found in 1038 cases (58.64%,1038/1770). Chromosomal structural abnormalities were found in 37 cases. The numeral abnormalities were more common than structural abnormalities, and most of the numeral abnormalities were aneupoidies. In turn, they were trisomy 16, 45,X, trisomy 22, trisomy 2, trisomy 21, trisomy 15. The most common structural abnormality was balanced translocation, including Robersonian translocation. Female embryoes accounted for 61.02%(1080/1770) miscarriages and for 57.4%(596/1770) of chromosomal abnormalities, while male embroyes acoounted for 61.02%(1080/1770),57.4%(596/1770)respectively. The proportion of female embryoes was higher than male embryoes. The median age of the patients was 30 years old(16-46 years old). As the maternal age increased, the proportion chromosomal abnormalities increased. The incidence of chromosomal abnormalities in the advanced age group (≥35 years) was 68.38%(240/351), which was significantly higher than that in the younger group (56.24% ,798/1419; χ2=17.10, P<0.01). Conclusions Embryonic chromosomal abnormalities are the most common cause of early spontaneous miscarriage. The abnormalities centralize in some karyotypes. There is certain relationship between maternal age and the incidence of miscarriage, as well as the embryonic gender. Chorionic villus cell culture and karyotype analysis are helpful in finding the cause of miscarriage and counsel the patients.

Determination of salsolinol N-methyltransferase activity in 6-OHDA-lesioned rats / 中国比较医学杂志

Objective The aim of this study was to establish a rat model of Parkinson''s disease ( PD) by using 6-hydroxydopamine (6-OHDA) and detect the salsolinol N-methyltransferase ( SNMT) activity in peripheral lymphocytes of PD rats for the development of a biomarker for early diagnosis of PD. Methods Rat model of PD was established by unilateral double-pointed injection of 6-OHDA into the striatum and was verified by behavior observation. An analytical method was developed based on multiple reaction monitoring with HPLC-ESI-QQQ to determine the SNMT activity in peripheral lymphocytes. Results Seven of 18 rats injected with 6-OHDA showed steadily apomorphine-induced rotation ( >7 r/min) . The success rate was 38. 9%. A sensitive and stable quantitative method with internal standard added was created, based on multiple reaction monitoring mode to analyze SNMT activity. The limit of detection ( LOD) and limit of quantitation ( LQD) of N-methyl-salsolinol, which is the product of Salsolinol catalyzed by SNMT, were 49 pmol/L and 98 pmol/L, respectively. The precisions of intra-day and inter-day assays both were below 6. 0%. SNMT activity of peripheral lymphocytes in the 6-OHDA-lesioned rats was significantly increased [43. 37 ±9. 49 pmol/(h·mg)NMSal] in comparison with that in the normal group [2. 16 ±5. 82 pmol/(h·mg)NMSal] and the sham-operated group [0. 58 ±2. 32 pmol/(h· mg)NMSal](P< 0. 01, n=5). There was no significant difference between the normal group and sham-operated group (P< 0. 05, n =5). Conclusions Our results indicate that SNMT activity may reflect the changes in the course of Parkison''s disease and may become a potential clinical biomarker in diagnosis of this disease.

Construction of retrovirol vector containing novel gene mgt-16 and its expression in mouse mesenchymal stem cells / 第二军医大学学报

Objective To construct the retroviral vector carrying novel gene mgt-16 and to investigate its expression in mouse mesenchymal stem cells C3H/10T1/2(10T1/2). Methods DNA sequences containing mouse novil gene mgt-16 was used as a template for PCR amplification of full length mgt-16 cDNA. Then the DNA fragment was cloned into pEGFP-N1 vector to produce pEGFP-N1-16 vector after T-A cloning with pMD18T plasmid and sequencing. The pEGFP-N1-16 vector was confirmed by PCR, restriction enzyme digestion and sequencing analysis. The retroviral vector, pLEGFP-N1-16, was constructed using retroviral vector, pLEGFP-N1, and pEGFP-N1-16 vector including mgt-16 gene. The pLEGFP-N1-16 vector was verified by restriction enzyme digestion, sequenced, and then transfected into packaging cell line Phoenix to prepare EGFP fused mgt-16 retrovirus particles, whichwere collected and used to infect 10T1/2 cells. G418 (400 (μg/mL) continuous selection was conducted to obtain 10T1/2 cell clones stably overexpressing EGFP fused mg-16. Fluorescence microscope was employed to determine the expression and subcellular localization of MGT-16 in Phoenix and 10T1/2 cells. Results A band of about 300 bp size was observed by agarose gel electrophoresis after PCR amplification for mgt-16 gene, and the result of sequencing showed that the sequence of insert fragment in T-A clones was identical to mg-16 gene reported in Genbank. PCR, restriction enzyme digestion and sequencing revealed that the pEGFP-Nl-16 plasmid was successfully constructed. Restriction enzyme digestion and sequencing revealed that the pLEGFP-Nl-16 plasmid was also successfully constructed. Phoenix and 10T1/2 cells overexpressing MGT-16 showed green fluorescence distribution in thecytoplasmic, especially around the perinucleararea. Conclusion We have successfully constructed a recombinant retroviral vector carrying novll gene, mg-16, and expressed it in mouse mesenchymal stem cells, which provides a basis for studying the role of novel gene mg-16 in mesenchymal stem cells.

Therapeutic effects and possible mechanisms of sirolimus on nephritic mice with chronic rejection / 国际药学研究杂志

Objective To explore the therapeutic effects of sirolimus on nephritic mice with chronic rejection, and the possible mechanisms. Methods B6D2F1 mice transplanted with cell mixture of spleen, thymus, and lymph nodes from DBA/2 spleen, thymus, and lymph nodes cell mixture were used to construct murine model with chronic rejection, and the transplanted mice were randomly divided into two groups. Mice in the sirolimus-treated group were given sirolimus orally in a dose of 1 mg(kg*d) for 12 consecutive weeks, while mice in the control group were administered with equal amounts of olive oil. Nephritis in mice was confirmed by urine protein determination and histopathological analysis. Enzyme immunoassay was used to detect the serum levels of anti-DNA antibodies including anti-ds DNA IgG, anti-ds DNA IgG1, anti-ds DNA IgG2a, anti-ss DNA IgG, anti-ss DNA IgG1, and anti-ss DNA IgG 2a. Real-time PCR analysis was conducted to evaluate the gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (α), interferon-γ (IFN-γ), interleukin-1 β (IL-lβ), monocyte chemoattractant protein 1 (MCP-1), regulated upon activation n T cell expressed and secreted (RANTES), B lymphocyte chemoattractant (BLC), transforming growth factor βi (TGF-βi), and gen I. The proportion and activation of T and B lymphocytes in peripheral blood or spleen were determined by flow cytometric ana Results At the end of observation period, the incidence of nephritis in mice treated with sirolimus was significantly lower than t mice treated with olive oil (P < 0. 05). Histopathological evaluation of kidney specimen showed evident vascular intimal hyper and mononuclear cell infiltration in control group. In contrast, no obvious kidney lesions was observed in sirolimus-treated mice. thermore, the levels of anti-DNA antibodies and the transcriptional expression of lupus IL-6, TNF-α, IFN-γ, IL-lβ, MCP-1, ] TES, BLC, TGF-βi, and collgen I were significantly down-regulated in sirolimus-treated group as compared with control group. cytometric analysis indicated that both of the proportion of activated/memory T cells in peripheral blood and the expression level o face activation markers on T and B lymphocytes in spleen were significantly decreased in mice exposed to sirolimus as comparec those exposed to olive oil (P <0. 05). On the other hand, the proportion of CD4 + FOXP3 + regulatory T cells in spleen was si cantly upregulated in sirolimus-treated group as compared with control group. Conclusion Sirolimus may inhibit the proliferatio activation of effector cells and downregulate the expression of chemokines and inflammatory factors through up-regulation of (FOXP3 3T cells, thus effectively ameliorating the progression of nephritis in mice.

A novel immunosuppressant fingolimod: Research advances / 国际药学研究杂志

Fingolimod (FTY720), a novel immunosuppressive agent, is synthesized by modification of myriocin (ISP-1) from a raditional Chinese herbal medicine Isaclaria sinclrii. Unlike he traditional immunosuppressive agents, fingolimod exerts immunosuppressive and mmunoregulatory functions mainly hrough nteraction with shhingosine-1-phosphate receptors (SIPR) on he cell surface without affecting activation and proliferation of lymphocytes. This article briefly reviews the effects of fingolimod on he distribution and cytokine production of lymphocytes as well as natural immune cells (dendritic cell, macrophage, natural killer cell and natural killer T cell), suggesting he mmunosuppression and mmune regulation functions of fingolimod n nflammation. Then he atest research progress about the herapeutic application of fingolimod n autoimmune diseases, graft-versus-host diseases and umors, the adverse effects of fingolimod and possible solutions are summarized.

Effect of antiarrhythmic peptide on ventricular arrhythmia induced by lysophosphatidic acid / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.</p><p><b>METHODS</b>Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.</p><p><b>RESULTS</b>Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.</p><p><b>CONCLUSIONS</b>LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.</p>

Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known. This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 (ERK 1/2) in airway mucus hypersecretion induced by cigarette smoke in rats.</p><p><b>METHODS</b>A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks.Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126, a specific MEK1 kinase inhibitor, at doses of 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg for 14 days. Expression of MUC5AC mRNA and protein, ERK 1/2 and phosphorylated-ERK 1/2 (p-ERK 1/2) were detected by RT-PCR, immunohistochemistry and Western blotting.</p><p><b>RESULTS</b>Cigarette smoke significantly increased airway goblet cells metaplasia, induced the overexpression of MUC5AC mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK 1/2 and ERK 1/2. U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke (P < 0.05). Moreover, there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein (P < 0.05).</p><p><b>CONCLUSIONS</b>Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein. ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo.</p>

The effects of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the effect of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits.</p><p><b>METHODS</b>Thirty-six male New Zealand white rabbits, aged 5 months and weighing 2.8 to 3.0 kg, were randomly divided into 3 groups: group A, group B and group C, with 12 rabbits in each group. First, a section about 6 cm long of vein was cut from the right external jugular vein of each rabbit and severed to have 3 equal-length segments. Next, each distal segment prepared for anastomosis. The proximal segment invaginating middle segment in group A and only middle segment in group B were used for the external stent. Later, the left common carotid artery was separated from surrounding tissue, from it a section about 0.5 cm long was cut away. Finally, the vein graft was inverted and end-to-end anastomosed to the two ends of the artery with a 9-0 suture. After bloodstream re-established, the diameter of each vein graft was measured. At 2 and 4 weeks postoperative, the graft veins were cut off and histologically examined by the means of HE staining and Masson staining. The smooth muscle cells (SMC) proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen.</p><p><b>RESULTS</b>After bloodstream re-established, the diameters of vein graft of group A and group B and group C were (1.6 +/- 0.3) mm, (2.2 +/- 0.4) mm and (2.6 +/- 0.6) mm respectively (P < 0.05). At 4 weeks postoperative, the data of the ratio of intima to media thickness and the index of the proliferating cells of the intima were as follow: group A (1.01 +/- 0.07 and 6.84 +/- 1.98), group B (1.32 +/- 0.08 and 11.01 +/- 2.61), group C (1.55 +/- 0.03 and 14.96 +/- 4.14). Both the data of group A were obviously less than that in group B, and that of group B was less than group C (P < 0.05).</p><p><b>CONCLUSION</b>The autologous venous two-layer external stents inhibit intimal hyperplasia of the vein grafts.</p>

Effects of combined amiodarone and antiarrhythmic peptide use on the cardiac gap junctions and incidence of induced ventricular arrhythmias in healed myocardial infarction rabbit models / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.</p><p><b>METHODS</b>Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.</p><p><b>RESULTS</b>The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.</p><p><b>CONCLUSIONS</b>The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.</p>

Biomechanical study on the calcaneal fracture fixed by the self-designed calcaneal anatomical plate and pre-cut gudgeon / 中国骨伤

<p><b>OBJECTIVE</b>To study the biomechanical properties of self-designed calcaneal anatomical plate and pre-cut gudgeon system and its efficacy for calcaneal fracture fixation.</p><p><b>METHODS</b>Sixteen fresh foot specimens were randomly divided into experimental group and the control group. Axial compressive load were applied to all specimens in order to create a calcaneal fracture model, and the maximum load and the maximum arch displacement of experimental group were recorded. In experimental group, self-designed intenal fixation system were utilized, while the AO plate internal fixation system were utilized in the control group. Axial compressive test were applied again to both groups, and the maximum load, the foot arch displacement and calcanus broadens were measured and recorded.</p><p><b>RESULTS</b>Comparison between before and after fixing the calcaneus fracture by self-designed internal fixation system in experimental group, the difference of the maximum load was significant (P<0.01), but there was no significant difference (P>0.05) of the maximum arch displacement. All parameters were significantly different (P<0.01) between the experimental group and the control group.</p><p><b>CONCLUSION</b>The fractured calcaneus will be able to regain normal foot biomechanical function after treated by self-designed internal fixation system, and able to support foot arch to bear great load. The self-designed internal fixation and pre-cut gudgeon system is considered to outperform the conventional AO internal fixation system with its better effectiveness and outcome in treating calcaneus fractures.</p>