In the present study, we carried out intratracheal administration of bone marrow-derived mononuclear cells (BM-MNCs) to dehydromonocrotaline (DMCT)-induced canine pulmonary artery hypertension (PH) of rat model to examine the security and feasibility, and the aim was to discuss the mechanism. All animals (n=30) were randomly divided into 3 groups (n=10 in each group), i. e. control group, PH group and BM-MNCs group. Six weeks after the transplantation, the hemodynamic data and right ventricle weight ratio were significantly improved for those in BM-MNCs group compared with those in PH group. The lung mRNA levels of vascular endothelial growth factor (VEGF) were higher, while preproendothelin-1 (ppET-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were lower compared with those in the PH group (P<0. 05). Immunofluorescence and histochemical results confirmed that 6 weeks after the administration, transplanted BM-MNCs were still alive and could differentiate into pulmonary vascular endothelial cells. These results showed that intratracheal administration of BM-MNCs could obviously reduce or even reverse the DMCT induction of PAH process. The mechanism could be explained as that the function was mainly through the paracrine effect to promote renewable and reduce inflammation.
Animals ; Bone Marrow Cells ; cytology ; Cell Transplantation ; methods ; Dogs ; Familial Primary Pulmonary Hypertension ; Female ; Hypertension, Pulmonary ; chemically induced ; therapy ; Leukocytes, Mononuclear ; transplantation ; Male ; Monocrotaline ; analogs & derivatives ; Rats

Objective To seek the curative effect of stereotactic radiation therapy (SRT) combined with gemcitabine for unresectable advanced pancreatic carcinoma.Methods 24 patients were treated by SRT of 6MV X-ray.Patients were fixed with the rack of stereotactic localization and heated plastics mould.The CT scanning results were put into the treatment planning system.According to the target area of tumor,sensitive organs and moving error drew GTV,CTV and PTV.The best plan was selected by the dose-volume histogram (DVH).5 to 7 beams of non-coplanar radiation ray were chosen.PTV was surrounded by ≥95 ％ isodose curves.Conventional fraction,5 fractions per week,1.8-2 Gy per fraction was used.All patients received a total dose of 50-60 Gy.Gemcitabine was performed 1000 mg/m2,once a week,iv gtt,in the 1st,2nd and 4th,5 th weeks.Results In chemo-radiotherapy,50.0 ％ (12/24) patients showed light nausea,41.7 ％ (10/24) patients showed leucopenia or thrombocytopenia of grade 1 or 2,after symptomatic treatment,all patients completed the planned treatment.In a period of one month to three months,after SRT combined with chemotherapy,appetite improvement was 83.3 ％ (20/24),jaundice disappeared in 6 of 6 patients (100.0 ％),abdominal pain was relieved in 21 of 24 patients (87.5 ％),3 patients were relieved completely among them.The complete remission (CR) rate was 16.7 ％ (4/24) and partial remission (PR) rate was 66.7 ％ (16/24),with CR+PR rate of 83.4 ％ (20/24).One-year survival rate was 70.8 ％ (17/24).As a consequence of cachexia,intestinal obstruction or bleeding,7 patients died within one year.Nobody survived more than 2 years.Conclusions SRT combined with gemcitabine for advanced pancreatic carcinoma may relieve symptoms.It is an effective approach to improve life quality and prolong survival time for advanced pancreatic carcinoma,especially lod and weak patients are more suitable to select SRT combined with gemcitabine.

ObjectiveTo evaluate the fourth-generation ultrasonic lithotripsy system for treating the urinary tract stones.Methods243 cases of urinary tract stones who received treatment of fourth-generation EMS ultrasonic lithotripsy system were analyzed retrospectively.ResultsImmediate phase I lithotrotrisy was performed successfully in 227 cases and the successful rate of phase I was 93.3％ (227/243).Delayed phase Ⅱ lithotripsy was performed for 16 patients.Complications happened in 2 cases,one case occurred hydropneumothorax during operation,required indwelling thoracic drainage tube processing,the other had severe bleeding which conservative treatment was ineffective,cured by the intervention of super-selective renal artery embolization.Conclusion Fourth generation of ultrasonic lithotripsy for treating stones on different anatomical locations of urinary system was safe,practical and efficient,worthy of clinical application.

OBJECTIVE To explore the characteristics of cochlear hair cell injuries in guinea pigs exposed to blast underpressure(BUP). METHODS The guinea pigs were killed 14 days after exposure to experimental BUP. Their basilar membranes were stained by silver nitrate and the hair cell injuries were quantitatively assessed using the light microscope. RESULTS The outer hair cells(OHCs) of the guinea pigs clearly appeared to be injured following exposure to the experimental BUP at a peak underpressure varying between -22.4kPa and -63.3kPa. The most obvious injury was in the second turn and OHC loss was smallest in the first row and more severe in the second and third rows. OHC loss was seen in all of three experimental groups of animals following exposure to BUP. Furthermore, the higher the peak of underpressure, the more obvious the injury of OHCs. Quantitative morphological analysis of cochlear hair cells showed that the total OHC loss rates in all the experimental groups of guinea pigs exposed to BUP were significantly higher than that of control group animals(P

to observe the infarction volume.Nitrate reductase assay was used to detect the level of NO in brain tissue of the rats.The level of S100βin brain was detected by ELISA method.Results Compared with model group,the brain infarction volumes of the rats 24 and 72 h after cerebral ischemia reperfusion in curcumin group were significantly decreased (P<0.05).Compared with sham operation group,the NO and S100βlevels in the brain tissue 24 and 72 h after cerebral ischemia reperfusion of the rats in model group were significantly increased(P<0.05);compared with model group,the levels of NO in the brain tissue 24 and 72 h after cerebral ischemia reperfusion in curcumin group were remarkably decreased (P<0.05);compared with modee group,the level of S100βin the brain tissue 72 h after cerebral iscemia reperfusion in curcumin group was remarkably decreased (P < 0.05 ). Conclusion Curcumin can significantly reduce the degree of ischemia reperfusion injury in the rats and reduce the levels of NO and S100βin brain tissue,which suggests that the decrease of NO and S100βlevels in brain tissue may be associated with the neuroprotective effect of curcumin.

Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.

Tumor chemoprevention and treatment are two approaches aimed at improving the survival of patients with cancers. An ideal anti-tumor drug is that which not only kills tumor cells but also alleviates tumor-causing risk factors, such as precancerous lesions, and prevents tumor recurrence. Chinese herbal monomers are considered to be ideal treatment agents due to their multi-target effects. Astragaloside has been shown to possess tumor chemoprevention, direct anti-tumor, and chemotherapeutic drug sensitization effects. In this paper, we review the effects of astragaloside on tumor prevention and treatment and provide directions for further research.
Humans ; Chemoprevention ; Antineoplastic Agents ; Neoplasms/prevention & control* ; Saponins/pharmacology* ; Triterpenes/pharmacology*

OBJECTIVETo study the blocking effect of CXCR4 inhibitor AMD3100 on the adhesion of leukemia cells to osteoblast niche, and the reversal of multidrug resistance in leukemia cells.

METHODSMesenchymal stem cells (MSCs) from leukemia patients were planted on the bio-derived bone scaffolds and then induced into osteoblasts to establish the bio-osteoblast niche. The levels of SDF-1were tested with ELISA. The leukemia cell line MV4-11 cells with FLT3-ITD mutation were inoculated into the bio-osteoblast niche to build a three-dimensional co- culture system. The expression level of CXCR4, adhesion and apoptosis rates of leukemia cells were observed by flow cytometry after incubation with AMD3100 and Ara-C for 24 h and 48 h.

RESULTS(1)The supernatant levels of SDF-1 in cultured osteoblast were (304 ± 18), (410 ± 28) and (396 ± 16) pg/ml on 7 th, 14 th and 21 th day, respectively. It reached the highest on 14 th day. The expression level of CXCR4 in cultured MV4-11 cells was (72 ± 16)%. (2)Adhesion rate of MV4-11 cells to osteoblast niche was (40.1 ± 8.1)% after AMD3100 treatment for 24 h, while that of control group was (65.6 ± 12.1)% (P<0.05). (3)The apoptosis rate of MV4-11 cells incubated with AMD3100 for 24 h was (5.6 ± 0.8)%, while that of control group was (2.5 ± 0.5)%. The apoptosis rates of AMD3100-induced MV4-11 cells were (10.0 ± 2.4)%, (17.8 ± 2.3)% and (25.1 ± 2.4)% after treatment with Ara-C at 0.02, 0.20, 2.00 mg/ml respectively and they were (6.7 ± 1.0)%, (10.3 ± 1.5)%, (16.2 ± 3.1)% respectively in AMD3100-noninduced control group, the difference was significant (P<0.05).

CONCLUSIONAMD3100 can block the interaction between osteoblasts niches and leukemia cells, and play an important role in the reversal of multidrug resistance in leukemia cells.

Apoptosis ; Cell Adhesion ; Cell Line, Tumor ; Chemokine CXCL12 ; Coculture Techniques ; Cytarabine ; Drug Resistance ; Flow Cytometry ; Heterocyclic Compounds ; Humans ; Leukemia ; Mesenchymal Stromal Cells ; Osteoblasts ; Receptors, CXCR4 ; Signal Transduction