Objective:To review the drug absorption evaluation methods for pulmonary delivery. Methods: The drug absorption cell models, in vitro pulmonary membrane model and in vivo animal model were systematically summarized, and the advantages and disadvantages of those models and applications were reviewed by referring to the databases in CNKI and Pubmed. Results:The appro-priate animal model and method for the study of pulmonary absorption should be chosen according to the experimental purpose and char-acteristics of drugs. Conclusion:The review provides the thoughts and theoretical basis for the research and development of pulmonary delivery.

Objective To investigate the effect of restraint stress on liver injury in mice induced by D-galactosamine and lipopolysaccharide (D+L).Methods Normal BALB/c (B/c) mice were randomly divided into normal control, stress control, D+L group, and D+L+stress group.The mice of normal control group were bred routinely.The stress group was giv-en stress regularly and quantitatively.Mice in the D+L group were injected intraperitoneally with mixed solution of D-galac-tosamine and lipopolysaccharide at final concentration of 30 mg/mL and 2μg/mL, respectively, once every two days.The D+L+stress group was given equal stress as stress group after injection of D-galactosamine and lipopolysaccharide mixed solution. Eight weeks later, blood samples were collected to test serum aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue samples from all animals were collected to evaluate the degree of liver fibrosis by HE and Masson staining.Results At the 8th week, the ALT and AST values in the D+L+stress group were significantly reduced( P＜0.01) and AST/ALT value was significantly increased(P＜0.01)compared with that in the D+L group.For HE and Masson staining, disordered structure of hepatic lobules, nodular hyperplasia, and necrosis of epithelial cells were present in animals of the D+L group.However, no obvious pathological changes were observewd in the D+L+stress group.For fibrosis scores, the fibrosis grade in the D+L+stress group was significantly decreased than that of the D+L group (P＜0.05).Conclusions Constraint stress presents pro-tective effect on D-galactosamine and lipopolysaccharide induced liver injury in mice.

Objective The aim of this study was to establish a mouse model of chronic hepatic injury induced by low dose carbon tetrachloride ( CCl4 ) .Methods Twenty SPF male B/C mice ( body weight 18-20 g) were randomly di-vided into three groups including the CCl 4-treated group , oil-treated group and non-treated control group ( n=5/group ) . Mice in the CCl4-treated group were intraperitoneally injected with 0.5% CCl4 prepared in oil.Mice in the oil group re-ceived intraperitoneal injection of oil .Mice in the non-treated control group were left untreated .After 6 weeks, the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, as well structure, cellular morphology and degree of fibrosis of the hepatic tissues were examined by histology with HE and Masson staining .Results After low dose CCL4 treatment, the serum ALT and AST were significantly increased (P =0.00).Histology with HE stai-ning showed extensive vacuolar degeneration of hepatic epithelial cells and large number of necrotic foci .Histology with Masson staining revealed fibrous hyperplasia mainly located around hepatic lobules .Quantitative analysis of the fibrosis showed that the degree of fibrosis and the integrated optical density of fibrosis were significantly increased after CCl 4 induc-tion( P=0.00) .Conclusion Low dose carbon tetrachloride can induce hepatic injury in B /C mouse models presenting pathological changes of hepatic injury and fibrosis .

Objective To research the method of Chronic hepatic injury modeling in mice induced by D -galactosamine and lipopolysaccharide combination . Methods Injected D-galactosamine ( 30 mg/mL ) and lipopolysaccharide ( 2μg/mL ) combination by intraperitoneal injection , two days at a time for 8 weeks .Monitored variation of diet and weight; detected serum level of alanine aminotransferase ( ALT ) and aspartate aminotransferase (AST), been put to death in mice and removed the liver tissue .strained hepatic tissue by the HE and Masoon dye to observe Liver tissue structure and cellular morphology and the degree of fibrosis .Results Lipopolysaccharide and D-galactosamine combination resulted in ALT rise , hepatocyte degeneration and necrosis ,collagen fiber hyperplasia obviously . Conclusion D-galactosamine and Lipopolysaccharide combination could induce mice chronic hepatic injury modeling .

Objective To investigate the effect of fasudil on vascular endothelial function in patients with coronary slow flow( CSF) . Methods Eighty?two patients with CSF and normal coronary angiography were selected and randomly divided into conventional treatment group and fasudil group, 41 cases in each group. Patients in conventional treatment group were given conventional treatment( aspirin,nitrates and atorvasta?tin) ,while patients in the fasudil group were given fasudil on the basis of conventional treatment. The angina pectoris,TIMI,endothelial?dependent flow?mediated vasodilation( FMD) ,the levels of plasma nitric oxide( NO) , endothelin?1( ET?1) and Rho kinase( ROCKI) of the brachial artery were observed in the two groups before and after two weeks of treatment. Results The total effective rate of fasudil group was 87. 80%,higher than that of conventional treatment group of 65. 85%,the difference was significant(χ2=68. 176,P<0. 05) . TIMI,FMD im?proved in the fasudil group after treatment compared with before treatment, the difference was significant ( t =4. 37,4. 43;P<0. 05);plasma NO level increased compared with before treatment(t=5. 63,P<0. 01),while ROCKI,ET?1 level decreased(t=6. 19,5. 66;P<0. 01). Plasma NO,ET?1,ROCKI and FMD,TIMI of conven?tional treatment had no significantly changes before and after treatment(P<0. 05). The post?treatment of NO, FMD,TIMI levels in fasudil group were significantly increased compared with conventional group ( ( 36. 17 ±7. 64) μmol/L vs. (24. 99±8. 96) μmol/L,(9. 96±1. 76)% vs. (5. 86±1. 45)%,17. 53±5. 81 vs. 29. 71 ±7. 83;t=4. 06,4. 18,5. 41;P<0. 05),while ROCKI,ET?1 levels in fasudil group were significantly decreased compared with conventional group((19. 57±1. 33) μg/L vs. (34. 38±1. 51) μg/L,(14. 36±6. 05) ng/L vs. (20. 95±6. 57) ng/L;t=3. 87,4. 36,P<0. 01). Conclusion Fasudil can significantly improve the vascular en?dothelial function in patients with CSF.

ObjectiveTo investigate the expression of miR-21 in diffuse large B cell lymphoma (DLBCL)and normal lymph tissues and its potential relevance with clinicopathological characteristics.MethodsThe expression levels of miR-21 in 50 primary DLBCL and 12 normal lymph node tissue specimens were examined by TaqMan real-time polymerase chain reaction.The expression of bcl-2 and p53 was detected by immunohistochemistry staining. ResultsThe expression of miR-21 was significantly higher in tumor tissues than that in normal tissues, in GCB subtypes higher than in non-GCB subtypes. And it was negatively correlated with bcl-2(P=0.020),while positively correlated with p53(P=0.022). Up-regulated miR-21 expression was low in three years of survival rate. ConclusionMiR-21 may indicate a more aggressive phenotype and serve as a molecular prognostic marker in DLBCL. High-expression of miR-21 is a key feature that is correlated with cell proliferation in DLBCL.miR-21 may have some guiding significance in prognosis.bcl-2,p53 is possibly one of the targets of miR-21 in DLBCL.

Objective To investigate the effects of intervertebral bridging ossifications in patients of osteoporotic vertebral compression fracture (OVCF) on bone fracture healing.Methods A total of 170 patients of thoracolumbar vertebral endplate fracture who were admitted into our hospital were selected.Divided these patients into the observation group,namely 60 patients with nonunion of vertebral endplate after 3 months of conservative treatment,and the control group, including 110 patients with well healed vertebra after 3 months of conservative treatment.Compared the distribution of intervertebral bridging ossifications of the two groups 3 weeks after injury.Results The incidence of bridging ossification at levels of T9 to T10,T10to T11,T11to T12 in the observation group were significantly higher than that in the control group.And it showed a significantly higher incidence of bridging ossification at the second proximal intervertebral segment in the observation group than that of the control group.There was a significantly greater sagittal wedge angle in the observation group compared with the control group.Conclusion Conservative treatment may increase the risk of nonunion of osteoporotic vertebral compression fractures when there is a bridging ossification at the second proximal intervertebral level or the sagittal wedge angle was greater than 14.2°in a fresh osteoporotic vertebral compression fracture.It should be a careful choose whether to take conservative treatment or surgical intervention.

Objective To study the high-field MRI findings of gastrointestinal stromal tumors(GIST), investigate the diagnostic value of the tumor.Methods The image findings and clinical date of 45 cases with GIST proved by pathology were analyzed retrospectively.Results In 45 cases of GIST,tumors were located in the sacroanterior 2 cases, in the perineum 5 cases, in the small bowel 5 cases, in the rectum 10 cases and in the stomach 23 cases.Of 45 cases, there were 11 cases of recurrence,and 34 cases of new-onset.High-field MRI showed the tumors with inhomogeneous signal intensity, the small lesions with even homogeneous signals, the larger with non-uniform signalwhich may be cystic degeneration, necrosis, hemorrhage.After enhanced scan,the solid part of the tumor were abnormal enhancement,necrosis andcystic degeneration no enhancement.Clear or not clear of tumor boundaries andadjacent tissue pressure were prone to metastasis or intraperitoneal planting.Pathology results showed: the tumors cut surface was gray, gray-red, visible envelope.The microscopic morphology was varied, ranging from the number of spindle cells.Immunohistochemical findings were as following: CD34(+) in 43 cases;CD117(+) in 40 cases;Desmin(+) in 18 cases;Vimentin(+) in 15 cases.Conclusion High-field MRI can accurately position gastrointestinal stromal tumor, and has great value for its diagnosis and differential diagnosis.

Objective:To investigate the perinatal risk factors and correlation between bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).Methods:A retrospective analysis was performed on 173 preterm infants born at less than 32 weeks' gestation with BPD who were admitted to the neonatal intensive care unit (NICU) of the Women and Children's Hospital of Qingdao University from June 2017 to July 2022. According to the diagnostic criteria for ROP, these preterm infants were divided into the ROP group ( n=64) and the non-ROP group ( n=109). Chi-square test, two independent samples t-test, and Mann-Whitney U test were used to compare the general data, treatment, and the incidence of complications between the two groups. Multivariate logistic stepwise regression analysis was used to analyze the independent risk factors of ROP in preterm infants with BPD and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of independent risk factors on ROP. The correlation between the severity of BPD and the incidence of ROP was analyzed. Results:The gestational age at birth [(28.0±1.1) vs. (28.8±1.2) weeks, t=4.01], the birth weight [(1 075.9±141.4) vs. (1 143.2±168.6) g, t=2.68], the partial pressure of carbon dioxide [42.5 mmHg (1 mmHg=0.133 kPa) (34.0-51.0 mmHg) vs. 47.0 mmHg (39.0-54.0 mmHg), Z=－2.31], and the total fluid intake on the first day of birth [80.0 ml (72.3-88.7 ml) vs. 83.6 ml (76.6-92.8 ml), Z=－2.28] in the ROP group were all lower than those in the non-ROP group (all P<0.05). While the prothrombin time [15.7 s (14.1-17.7 s) vs. 14.6 s (13.1-16.7 s), Z=－2.17], activated partial thromboplastin time [64.7 s (52.9-77.9 s) vs. 55.8 s (48.4-68.9 s), Z=－2.12], the proportion of patients treated with pulmonary surfactant [71.9% (46/64) vs. 49.5% (54/109), χ 2=8.25], the total duration of oxygen supplementation [50.5 d (40.0-64.0 d) vs. 45.0 d (37.0-52.0 d), Z=－2.77], the duration of invasive ventilation [5.0 d (1.0-11.0 d) vs. 1.0 d (0.0-5.0 d), Z=－4.03], the duration of noninvasive ventilation or high-flow oxygen therapy [(31.7±12.7) vs. (26.4±13.1) d, t=－2.59], and the incidence of neonatal respiratory distress syndrome [76.6% (49/64) vs. 57.8% (63/109), χ 2=6.22] were increased in the ROP group (all P<0.05). There was no significant difference in the proportion of BPD treated with corticosteroids between the ROP and non-ROP groups [60.3% (38/63) vs. 74.3% (81/109), χ 2=3.67, P=0.055]. Multivariate logistic stepwise regression analysis showed that smaller gestational age ( OR=1.599, 95% CI: 1.126-2.272, P=0.009), less fluid intake on the first day ( OR=1.033, 95% CI: 1.004-1.062, P=0.024), and longer duration of invasive ventilation ( OR=1.076, 95% CI:1.017-1.138, P=0.011) were independent risk factors for ROP in BPD infants, while glucocorticoid treatment was an independent protective factor ( OR=0.378, 95% CI:0.173-0.827, P=0.015). Most patients with mild or moderate BPD did not develop ROP [64.6% (73/113) and 66.7% (34/51)], while those with severe BPD were more likely to be complicated by ROP (7/9) ( χ 2=6.84, P=0.033). Conclusions:BPD infants with smaller gestational age, longer duration of invasive ventilation, and less fluid intake on the first day of birth are more likely to develop ROP, while glucocorticoid therapy can reduce the incidence of ROP in this population. Severe BPD may increase the risk of ROP in infants.

Objective To observe the illness change trend of drinking water type endemic arsenic poisoning in Qinghai Province, comprehensively evaluate the effect of prevention and control measures, in order to provide a scientific basis for timely adjustment of the prevention and control measures. Methods From 2010 to 2013, according to the Drinking Water Type Endemic Arsenic Poisoning Monitoring Programs, 3 villages in 2 counties within Qinghai Province were randomly selected as monitoring sites. The arsenic content in drinking water of residents was measured, water improvement projects in all monitoring villages were investigated; at the same time an investigation of arsenic disease in resident population was conducted, and urinary arsenic content was monitored. Arsenic in drinking water and urine was determined by hydride generation atomic fluorescence spectrometry, and arsenic poisoning was diagnosed using Endemic Arsenic Poisoning Diagnostic Criteria (WS/T 211-2001). Results Of the three water improvement projects, two were water arsenic exceeded the standard, and one was intermittently operated. From 2010 to 2013, the arsenic poisoning detec tion rate in Baoning Village was 27.30% (193/707), 31.90%(245/768), 29.35%(221/753) and 28.22%(219/776); in Kecai Village was 32.62%(107/328), 34.83%(124/356), 31.26%(131/419) and 29.35%(118/402);and in Manimotai Village was 56.58%(43/76), 52.81%(47/89), 45.10%(46/102) and 34.69% (34/98), there was no significant difference statistically of the arsenic poisoning detection rates in the three monitored villages in the 4 years (χ2 =3.09, 0.04, 0.92, all P>0.05). From 2010 to 2013, women arsenic poisoning detection rate was 36.45%(203/557), 40.59%(246/606), 36.12%(225/623) and 34.77%(218/627), respectively;men was 25.27%(140/554), 28.01%(170/607), 26.57%(173/651) and 23.57%(153/649), respectively;women arsenic poisoning detection rates were higher than those of men (χ2 = 16.25, 21.32, 13.49, 19.38, all P < 0.05). Arsenic poisoning detection rate of people younger than 60 years old had a tendency to increase with age. In 2012 and 2013, 105 and 93 urine samples were tested, respectively; urinary arsenic geometric mean was 0.113 and 0.149 mg/L. Conclusions Water improvement projects and water quality are not optimistic, and prevalence of arsenic poisoning is still at a higher level. A sound long-term monitoring program should be established as soon as possible, the management and maintenance of water improvement projects should be strengthened, and the monitoring and prevention work should not be neglected.