Objective To study the expression and significance of P53 and nm23 in colorectal adenocarcinoma.Methods The expression of P53 and nm23 was examined by immunohistochemical technique in 83 cases of colorectal adenocarcinoma.Results In colorectal adenocarcinoma,the positive intensities of P53 and nm23 was associated with tumour depth,histological grade,lymph node metastasis diseases and distant metastasis disease(P0.05).Conclusion P53 and nm23 may play an important role in the development and metastasis of colorectal adenocarcinoma.It is an useful marker for predictinng the prognosis of colorectal adenocarcinoma.

Objective To investigate the short and long term therapeutic effects of prostaglandin E1 (PGEl) on diabetic nephropathy (DN). Methods Patients with DN in stage Ⅲ to Ⅴ according to Mogensen criteria were randomly assigned to four groups of PGE1, angiotensin-converting enzyme inhibitor (ACEI), PGE1 + ACEI and control drug. The levels of proteinuria and albuminuria were measured before and 15 days, 6 months and 18 months after treatment. Patients with DN in stage Ⅳ were subdivided into three groups according to proteinuria: early stage IV (protienuria was less than 1.5 g/d), middle stage Ⅳ (protienuria was between 1.5 g/d and 2.5 g/d) and late stage Ⅳ (protienuria was larger than 2.5 g/d). Results Fifteen days after treatment, the levels of proteinuria and albuminuria were significantly decreased compared with pre-treatment in PGE1 and PGE1 + ACEI groups (P<0. 01), and the therapeutic effect was better in PGE1 + ACE1 group than in ACEI group (P<0. 01). Six months after treatment, there were still significant differences in above parameters in patients with DN in stage Ⅲ and Ⅳ between PGE1 + ACEI and PGE1 groups. And for the patients in stage Ⅴ, statistic significance between pre-and post-treatment existed only in PGE1 + ACEI group (P<0. 05). but not in PGE1 and ACEI groups (both P>0. 05). Eighteen months atter treatment, the levels of proteinuria and albuminuria were significantly decreased in patients in stage HI and early stage IV in all treatment groups (P<0. 01). For patients in middle stage IV and late stage Ⅳ , the significant differences still occurred between pre-and post-treatment in PGE1 + ACEI group (P<0. 01 or P<0. 05), and were significantly better than in ACEI group (P<0. 01 or P<0. 05). However, the proteinuria of patients in late stage IV elevated in PGE1 group in post-treatment versus pre-treatment (P<0. 05). Conclusions The short term therapeutic effect of PGE1 is quick and good in patients with DN. The therapeutic effect is much better in patients in stage Ⅲ compared with stage Ⅴ. The combination of PGE1 and ACEI will get better best therapeutic effect than PGE1 or ACEI alone in long term.

Objective To investigate the effects of prostaglandin E1(PGEl)in improving proteinuria and albuminuria in the elderly people with diabetic nephropathy(DN). Methods Patients including stage Ⅲ,stage Ⅳ and stage Ⅴ were divided into four groups:conventional therapy group,PGE1 group,PGE1+ACEI group and ACEI group.Proteinuria and albuminuria were measured before and after treatment for 15 days,3 months,6 months. Results (1)In the DN patients in stage Ⅲ and stage Ⅳ (proteinuria＜2.5 g/d),the proteinuria and albuminuria descended markedly in PGE1+ACEI and PGEl group(P＜0.01).It was better than that in eonventionaI therapy and ACEI group.(2)In the DN patients in stage Ⅳ(proteinuria＞2.5 g/d),proteinuria and albuminuria were not changed significantly after 3 months and 6 months in PGE1+ACEI and PGE1 group,but they were increased in conventional group(P＜0.05).(3)In the DN patients in stage Ⅴ,the proteinuria and albuminuria were not changed much after 1 5 days,3 months and 6 months(P＜0.05).The proteinuria and albuminuria were increased by more than 10 percent(P＜0.01)in the conventional group after 3 and 6 months. Conclusions The therapeutic effects of PGE1 are obvious.Early treatment of nephropathy will get a better improvement in patients with diabetic nephropathy.

OBJECTIVETo compare the efficacy of internal fixation (including PFNA and PFN) versus hip replacement (including FHR or THA) in the treatment of trochanteric fractures in adults.

METHODSReports of studies using randomized controlled trials (RCT) to compare internal fixationg with hip replacement in the management of intertrochanteric fractures were retrieved (up to January 1, 2013) from the Cochrane Library, PUBMED Data, CNKI (China National Knowledge infrastructure), Elsevier, the Chinese Biomedical Database, Wanfang Data, and manually. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software RevMan 5.0 was used for data-analysis.

RESULTSSeven articles were included in the meta-analysis. The results showed that,compared internal fixation with hip replacement,there were statistical significance in the duration of surgery time [WMD = -2.66, 95% CI (-5.25,-0.06), P = 0.05], intra-operative blood loss [WMD = -24.20, 95% CI (-30.38, -18.02), P < 0.000 01], hospital stays time [WMD = -4.72, 95% CI (-5.18, -4.25), P < 0.000 01], bearing load time [WMD = -29.54, 95% CI (-30.77, -28.31), P < 0.000 01], total complications rate [WMD = 0.15, 95% CI (0.11, 0.22), P < 0.000 01], the good rate of Harris scores [WMD = 1.09, 95% CI (0.54,1.32), P < 0.05]. However, there were no statistical significance in the rate of deep venous thrombosis [WMD = 1.09, 95% CI (0.47, 2.55), P > 0.05]. CON- CLUSION: Hip replacement (containing FHR or THA) for the treatment of intertrochanteric fractures is superior to internal fixa- tion in regards to the duration of surgery time, the mean duration of hosipital stays, mean post-operative down time, intra-opera- tive blood loss, the rate of post-operative good Harris scores. But there is not enough evidence to show any difference between hip replacement (containing THA or FHR) and internal fixation in regards to the rate of deep venous thrombosis. However, internal fixation for the treatment of intertrochanteric fractures is superior to hip replacement (containing FHR or THA) in regards to total complications rate.

Background Researches have showed that the extraocular muscle injection of insulin-like growth factor(IGF) results in the thickness of extraocular muscle and enhancement of contractility,and lack of IGF probably is associated with pathogenesis of strabismus.If extraocular muscle injection of insulin-like growth factor binding protein 4(IGFBP-4),an inhibitor of IGF,can further ensure the effect of IGF is still under-investigation.Objective The aim of this study was to evaluate the effects of IGFBP-4 on the developing extraocular muscle.Methods IGFBP-4 of 2 μl(1 g/L)was injected into superior rectus muscles via supraorbital margin in the left eyes of 24 postnatal l-day-old chickens once every other day for five times,and the equivalent amount of normal saline solution was used in the same way in the fellow eyes as controls.The animals were sacrificed by overdose of anesthesia 2 days after the final injection and 12 animals were randomly selected for the maximal contractility test of superior rectus muscle.The other 12 pieces of superior rectus muscle of the chickens were obtained for the hematoxylin & eosin staining to evaluate the morphology of superior rectus muscle and calculate the myofiber diameter using imaging system.Results The maximal contractility was (1.602 ± 0.080) mN and(1.815±0.O10)mN in the IGFBP-4 injection group and normal saline solution group respectivily,showing a significant difference between the two groups(t =13.65,P＜0.01).The maximal contraction force in cross-sectional area was (95.500 ± 7.420) mN/cm2 in the IGFBP-4 injection group and it was significantly lower than that of the normal saline solution group(101.510±5.220)mN/cm2(t =28.81,P＜0.01).Histological examination showed that thin myofibers were obvious more in the IGFBP-4 injection group than those with saline injection.The mean diameter was (8.7 ± 0.5) μm in the IGFBP-4 injected group,and that of the normal saline group was(9.1 ±0.4) μm,there was no significant difference between them (t =0.75,P =0.46).However,significant differences were found in the number of different diameters of myofibers between the two groups(all at P＜0.05).Conclusions IGF is one of the key nutrition factors in the development of extraocular musele.The extraocular muscle injection of IGFBP-4 may cause the dysfunction and morphologic abnormality of extraocular muscle.

Objective To explore the effects of surface modification of PLGA-[ASP-PEG] scaffold with typeⅠcollagen on the adhesion,proliferation and osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs).Methods After PLGA-[ASP-PEG] materials were modified with typeⅠcollagen chemically,the collagen was coated onto the materials physically.The BMSCs obtained from rabbits were cultured on the modified PLGA-[ ASP-PEG] and on the unmodified PLGA-[ ASP-PEG] as control.The adhesion and proliferation behavior of the cells was analyzed and the expressions of osteogenie marker alkaline phosphatase,osteocalcin,osteopontin,typeⅠcollagen and core binding factor al were also detected.Results X-ray photoelectron spectrometry(XPS) confirmed that TypeⅠcollagen was grafted onto the surface of PLGA-[ASP-PEG] successfully and the collagen content on the materials modified chemically and physically was significantly increased.The abilities of adhesion and proliferation and the expressions of osteogenie makers of the BMSCs were significantly greater than those in the control group(P＜0.05).Conclusion Since Type collagen I can improve the biocompatibility of PLGA- [ASP-PEG] scaffold materials,it can be used as a new way to optimize scaffolds in tissue engineering.

Objective To analyze the relationships between the drinking water fluoride and bone mineral density (BMD), and serum osteocalcin (BGP) and to explore the BMD and serum BGP as significant early screening biomarkers for fluorosis especially for early bone damage in endemic fluorosis areas. Methods Wamiao (severe endemic fluorosis area, as fluoride exposed group) and Xinhuai (non endemic fluorosis area, as control group) Village were selected in 2006. One hundred and fouty-six objects were chosen from 2 villages (103 in Wamiao, 43 in Xinhuai). The sex, age, body height, body weight, drinking water fluoride in each object's household well, BMD, and serum BGP were investigated, and the dose-response relationships were analyzed between the drinking water fluoride and BMD, and serum BGP. CurveExpert 1.3 Software was used to fit the dose-response relationships between the rate of abnormal BMD, the rate of abnormal serum BGP, and the drinking water fluoride. Results The levels of drinking water fluoride in males' and females' families in fluoride exposed group were [(2.38±0.68), (2.62±0.91 )mg/L] significant higher than that in control group [(0.35±0.08), (0.36±0.07)mg/L], the difference being statistically significant(t values were 14.27 and 11.08,and P<0.01, respectively). BMD in males in fluoride exposed group [(0.78±0.07)g/cm2] was significant lower than that in control group[(0.83±0.08)g/cm2], the difference being statistically significant (t=2.37,P<0.05). Serum BGP in males and females in fluoride exposed group [(4.17±0.67), (4.11±0.57) μg/L] were significant higher than that in control group [(1.48±0.40), (1.44±0.39)μg/L], the difference being statistically significant (t values were 17.64 and 19.40, and P<0.01, respectively]. BMD in the group with drinking water fluoride≥2.92 mg/L[(0.66±0.15 )g/cm2] was significant lower than that in the group with drinking water fluoride<0.42 mg/L [(0.76±0.12)g/cm2], the difference being statistically significant (P<0.01). The levels of serum BGP in the groups with the drinking water 0.42-,2.05-, ≥.92 mg/L[(3.83±1.07), (4.22±0.72), (3.99±0.63) μg/L] were significant higher than that in the group with the drinking water<0.42 mg/L [(1.44±0.37) μg/L], the difference being statistically significant (P<0.01). The equation for the dose-response relationship between the drinking water fluoride and the rate of abnormal BMD was y=(0.284-0.058x)-1.260, r=0.999 94; and y=100.05/(1+78.62e-4.5x), r=0.999 99 for the drinking water fluoride and the rate of abnormal serum BGP. Conclusions There were significant dose-response relationships between drinking water fluoride and BMD and serum BGP. It indicated that BMD and BGP might be considered as early screening biomarkers for endemic fluorosis, especially for the bone damage.

This study investigated the protective effect of chrysin on hepatic fibrosis by regulating AMP-activated kinase (AMPK)-NOD-like receptor protein 3 (NLRP3) mediated pyroptosis pathway. The hepatic fibrosis model of mice was established by thioacetamide (TAA) in vivo. Except the control and chrysin alone groups, the mice were injected intraperitoneally with TAA at 100 mg·kg^-1, three times per week for the first week. From the 2^nd to 5^th week, mice were injected intraperitoneally with TAA at 200 mg·kg^-1, three times per week for the next 4 weeks. Chrysin groups were intragastrically administrated once per day to 5^th week. The histopathological changes were detected by HE and Masson staining. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed by the kits. All animal experiments were approved by the Medical Ethics Committee of Affiliated Zhongshan Hospital of Dalian University (DWLL2019060). LX-2 cells were stimulated by (transforming growth factor-β, TGF-β) in vitro. The protein expressions of AMPKα, p-AMPKα, NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD) were detected by Western blot, and the mRNA levels of collagen-Ι, α-smooth muscle actin (α-SMA), interleukin-1β (IL-1β), IL-18, caspase-1, GSDMD were analysis by reverse transcription-polymerase chain reaction (RT-PCR). Chrysin attenuated the increases in serum AST and ALT levels in the TAA group, while significantly improved the changes of liver morphology, reduced liver tissue inflammatory cell infiltration and inhibited collagens deposition. Compared with TAA group, chrysin effectively activated AMPKα phosphorylation and inhibited hepatic NLRP3 inflammasome activation. Additionally, the protein expressions and mRNA levels of IL-1β, IL-18, caspase-1 and GSDMD in chrysin groups were decreased. Chrysin inhibited the expressions of collagen-Ι and α-SMA, enhanced the phosphorylation of AMPKα, and decreased the expressions of NLRP3 and GSDMD. Therefore, chrysin may inhibit inflammatory injury and pyroptosis possibly by activating AMPK and inhibiting NLRP3 inflammasome to alleviate hepatic fibrosis.

ObjectiveTo investigate bone marrow mesenchymal stem cells(BMSC) express brain derived neurotrophic factor(BDNF) and nerve growth factor(NGF) and their protective effect for neural stem cells (NSCs).MethodsBMSC were obtained from rat tibiae and femurs and centrifuged with Ficoll. The passage 3 cells were chosen to make immunocytochemical stain for CD44, CD71 and CD45. The expression of BDNF and NGF was detected in BMSC with RT-PCR, as well as in the media with ELISA. The media that cultured BMSC were collected as BMSC condition media. NSCs were obtained from cerebral cortex of new-born rat and cultured in vitro. After different ratio of BMSC condition midia were added, NSCs were induced to apoptosis with heat-shock, then NSCs were dyed with Annexin V-FITC/PI apoptosis kit and apoptosis rates were tested with flow cytometry. ResultsBMSC were CD44(+), CD45(-), CD71(+) and expressed BDNF and NGF mRNA. BDNF and NGF could be tested in the media of cultured BMSC and increase with cultured time. BMSC condition media could reduce the ratio of heat-induced apoptosis of NSCs, and more BMSC condition media showed better effect. ConclusionBMSC can express neurotrophic factores and protect neural stem cells from heat-induced apoptosis.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.