Photodynamic therapy (PDT) has attracted wide attention due to its unique advantages such as minimal invasiveness, high efficiency and high selectivity, and its ability to induce anti-tumor immune response. However, the treatment process is heavily dependent on the oxygen content of the treatment site, and the widespread oxygen deficiency in malignant tumors severely limits its efficacy. In addition, PDT-mediated oxygen depletion exacerbates tumor hypoxia, which further reduces its therapeutic effect. In recent years, many researches have been devoted to overcoming this problem. This paper summarized various strategies based on tumor hypoxic PDT in recent years, discussing the advantages and disadvantages of these strategies, and analyzing the main challenges and future directions of PDT in the treatment of tumors, so as to provide references for the in-depth study of photodynamic therapy of tumors.

Objective To study the role of recombinant human epidermal growth factor (rhEGF) in the prognosis of multiple organ dysfunction syndrome (MODS) in mice. Methods One hundred and twenty clean male Kunming mice were randomly ( random number) divided into normal saline control group (n =15),MODS model control group (n =15) and MODS + rhEGF treatment group (n =90).The MODS models were made by using Caballero ME method with thioacetamide (TAA) 2000 mg/kg injected intraperitoneally to establish monophasic rapid onset pattern of MODS model in mice.MODS + rhEGF treatment group was further randomly divided into two subgroups,namely intraperitoneal injection group (n =45 ) and subcutaneous injection group (n =45 ).Each subgroup was divided again into three small subgroups (n =15) as per different doses of rhEGF used,namely 10 μg/kg,30 μg/kg and 50 μg/kg.Within 24 hours after modeling,the respiration,body weight,food eaten and general physical changes were observed.Mortality was calculated 24 hours after modeling.After the animals sacrificed,the tissues of viscus including liver,kidney,heart,brain,lung,spleen,pancreas,intestine and stomach were collected immediately.The histological changes of visceral tissues were studied by using hematoxylin -eosin staining under the light microscope.All the experimental data were presented in,and body weight changes were compared using t-test,and after different routes of administration with different doses of rhEGF used in MODS,the mice body weight changes were analysed by using the Dunnett method,and the mortalities of mice were compared by using Fisher exact test,and P ＜ 0.05 was considered statistically significant difference. Results There was no significant difference in mortality betweeu mice in rhEGF subcutaneous administration group and MODS model control group (P ＞ 0.05 ),but the total mortality of hrEGF MODS intraperitoneal administration group (6.7％ in dose of 50 μg/kg and 20％ in dose of 30 μg/kg) was significantly lower than that of MODS model control group (73.3％) ( P ＜ 0.05 ) and the mortality of mice treated with intraperitoneal 50μg/kg rhEGF (6.7％ ) was lower than that treated with 10μg/kg rhEGF (P=0.014).The mortality of mice in rhEGF MODS (50 μg/kg ) intraperitoneal administration group was significantly lower than that in subcutaneous administration group (40％) (P =0.031 ), The histopathological changes in rhEGF MODS treatment group were not as remarkable as seen in mice of control group.The histopathological changes were dose - dependent.The higher doses of rhEGF,the lesser hepatic congestion,liver cell apoptosis,hepatic cell cloudy swelling and cell vacuolization.Similarly,as RhEGF dosage increased,pulmonary interstitial congestion,inflammatory cells and apoptotic bodies reduced,and bronchial ciliated columnar epithelium less shed.Conclusions RhEGF plays a positive role in repairement of tissue damage in TAA - induced MODS murine model.The rhEGF given by intraperitoneal route of administration is more effective to reduce the 24 h mortality of MODS mice than that by subcutaneous route.

Background Aspheric intraocular lens (IOL) is designed to reduce the spherical aberration of the eye after cataract surgery and to obtain better visual quality.However,the selection of a personalized aspheric IOL is a problem to be solved.Objective This study was to compare the wavefront aberration and quality of vision of patients between the implantation of negative spherical aberration IOL and non-aberration IOL,and to investigate the relationship between corneal Q values and postoperative spherical aberration.Methods One hundred and four eyes of 90 patients with age-related cataract were randomized into two groups.Fifty-two eyes of 46 patients who received a Tecnis Z9001 IOL implantation were assigned as the negative spherical aberration IOL group and 52 eyes of 44 patients who received Akreos AO IOL without aberration were assigned as the non-aberration IOL group.The preoperative corneal Q values were measured and the mean Q value(Q)was computed.Then the patients in the two groups were further divided into 2 subgroups,respectively,based on their Q values were over or below (Q）.The corneal Q values,root mean square(RMS) of ocular spherical aberration,coma and total higher-order aberrations(HOAs) for 5 mm diameter pupil,scotopic contrast sensitivity with or without glare at 6 mm pupil diameter were measured 3 months after surgery.Results The pre-and post-operative corneal Q values were insignificantly changed (t =1.447,P =0.151).The spherical aberration in the negative spherical aberration IOL group was(0.059-±0.047)μm,and that in the non-aberration IOL group was(0.110±0.066)μm,with a statistically significant difference between them (t =-4.567,P=0.000).Scotopic contrast sensitivities at intermediate and high frequencies were significantly better in the negative spherical aberration IOL group than in the non-aberration IOL group (t =2.495,t =2.359,P ＜ 0.05).There was no significant difference in coma and HOAs between the two groups after operation (P ＞ 0.05).Weak positive correlations were seen between the pre-and post-operative corneal Q values and spherical aberration in the two groups(r=0.277,0.292,0.285,0.325,all at P＜0.05).However,no significant differences were found in spherical aberration,contrast sensitivity and scotopic contrast sensitivity between the different subgroups (P ＞ 0.05).Conclusions Negative spherical aberration IOL has lower spherical aberration and better scotopic contrast sensitivity than non-aberration IOL.The results suggest that it may be not enough to choose the corneal Q value only as the single reference criterion for selection of aspheric IOL.

Tangcao pill is commonly applied in adjuvant and even alternative therapy for patients with AIDS. However, the herb contains complex ingredients, but with unknown effect against anti-HIV drug and unknown function. Because CYP450 emzyme is the main metabolic enzymes of the drug, it is of important significance to study the regulation of CYP450 enzymes before and after the combined administration of Tangcao pill and EFV. Proteomics, due to its high throughout and high sensitivity, has been widely applied in CYP450 enzyme study. In this paper, liver microsomes were separated through differential centrifugation. Their proteins were separated through SDS-PAGE. The three protein bands that CYP450 enzymes were located were cut and identified by liquid chromatography tandem mass spectrometry. Totally 16 CYP450 isoenzymes were identified. Furthermore, in order to make a quantitative analysis on the effect of tang herb on CYP450 emzyme, the multiple reaction monitoring (MRM) technology based on MS was adopted. The CYP2C11 was selected based on the results of the mass spectrum identification of proteins. The characteristic polypeptides were obtained through searching Expasy blast database. The m/z of the fragment ions was less than 800. In the paper, the m/z of ion pairs of CYP2C11 were 711.5/232.1, 711.5/319.2, 711.5/466.2 and 711.5/595.3, and the m/z of ESAT-6 (internal standard, IS) were 735.5/215.3, 735.5/389.3, 735.5/460.3 and 735.5/524.3. The relative peak (analyte/IS) area was adopted for the relative quantitative analysis. Compared with the EFV single administration group, the EFV and Tangcao pill combined administration group showed a 1.6-fold increase in CYP2C11. The results of the paper indicated that Tangcao pill may affect drug metabolism by regulating metabolic enzymes such as CYP2C11, but the specific mechanism still unknown.
Animals ; Cytochrome P-450 Enzyme System ; chemistry ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Electrophoresis, Polyacrylamide Gel ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Proteomics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of drug-containing serum of Chinese herbal compounds [Xiongshao Capsule (XS, for activating blood) and Huanglian Capsule (HL, for dispelling toxin)] on tumor necrosis factor-alpha (TNF-alpha)-induced adherence between human umbilical vein endothelial cells (HUVECs) and polymorphonuclear neutrophils (PMN), inflammatory reaction and expression of related proteins in mitogen-activated protein kinase (MAPK) pathway.

METHODSThirty-two rats were randomly divided into four groups (8 in each group) using random digit table: the blank control group treated with distilled water, the test group I treated with Chinese herbal compound of XS (0.135 g/kg), the test group II treated with Chinese herbal compound of HL (0.135 g/kg), and the test group Ill treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All medication was given by gastrogavage once a day for a week. Rats' blood serum was harvested 1 h after the last administration to prepare drug-containing serum. HUVECs were exposed to TNF-alpha (100 ng/mL) to induce cell injury model and incubated with corresponding drug-containing serum (10%) for 24 h. Normal rats' serum was given to cells in the blank control group and the model group, while XC + HL containing serum was given to cells in the rest 3 groups. The adherence of HUVECs and PMN cells was detected by using rose bengal strain. Levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and interleukin-1beta (IL-1P) in the supernatant of cultured HU-VECs were determined by ELISA. Protein expressions of mitogen-activated protein kinases p38 (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK 12) were determined by Western blot.

RESULTSCompared with the blank control group, HUVECs were seriously injured; PMN adherence amount significantly increased; levels of E-selectin, ICAM-1, and IL-1beta increased; expression levels of p-p38MAPK and p-ERK 1/2 in the supernatant of HUVECs significantly increased in the model group (all P < 0.01). Compared with the model group, HUVECs-PMN adherence amount decreased (P < 0.05); levels of E-selectin, ICAM-1, and IL-1 beta in the supernatant of HUVECs decreased (P < 0.01, P < 0.05); expression levels of p-p38MAPK and p-ERK 1/2 of endothelial cells decreased in the test group I, II, and III (P < 0.01).

CONCLUSIONSDrug-containing serums of activating blood, activating blood and dispelling toxin could attenuate TNF-alpha induced injury of HUVECs, inhibit HUVECs-PMN adherence and the release of adhesion factors. Its mechanism might be involved with protein phosphorylation of p38MAPK and ERK 1/2 in the MAPK pathway.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; E-Selectin ; Endothelial Cells ; physiology ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-1beta ; Mitogen-Activated Protein Kinase 3 ; Neutrophils ; Rats ; Serum ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To evaluate the coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy(HCM) by MR first-pass perfusion and late gadolinium enhancement. Methods From January 2011 to May 2015, 47 cases with HCM (HCM group) from the second affiliated hospital of Nanchang University were retrospectively analyzed. Additionally, 21 healthy volunteers were recruited as the control group. HCM group and control group underwent cardiac MR examinations at rest, including short axial cine, first-pass myocardial perfusion and late gadolinium enhancement scanning. Time to peak(tpeak), maximal upslope of time-intensity curve(Slopemax), peak signal intensity(SIpeak), myocardial thickening, and late myocardial gadolinium enhancement(LGE) were assessed for each myocardial segment. HCM group were divided into LGE segments group and non-LGE segments group. LGE segments group were divided into mild, moderate and severe LGE segments group. The SIpeak, Slopemax and tpeak in multiple groups were compared by one-way ANOVA and Kruskal-Wallis test. Spearman correlation tests were used to determine the relationships between perfusion parameter and LGE. Results The average values of tpeak in non-LGE segments group (527 segments), LGE segments group (225 segments) and control group (336 segments) were (67.0 ± 27.4), (79.4 ± 27.4), (59.7 ± 21.6)s, respectively. The average values of Slopemax in the three groups were 17.2±7.0, 16.4±7.4, 20.4±6.3, respectively. The average values of SIpeak in the three groups were 442.7 ± 143.2, 465.1 ± 138.4, 521.9 ± 146.7, respectively. Compared to the control group, tpeak increased and Slopemax, SIpeak decreased in non-LGE segments group and LGE segments group (P<0.01), while tpeak increased more significantly in LGE segments group. The Slopemax and SIpeak showed no statistically significant differences between non-LGE segments group and LGE segments group (P>0.05). There were significant differences among LGE segments groups, as the tpeak and SIpeak increased with increasing degrees of myocardial LGE (P<0.01). The Slopemax showed no statistically significant difference among them (P>0.05). The degree of LGE were positively correlated with tpeak (r=0.237, P<0.01). Conclusions 3.0 T magnetic resonance myocardial perfusion imaging can show microvascular dysfunction accurately and reliably in non-LGE segments. It may be helpful in the early diagnosis of coronary microvascular dysfunction for HCM.

Aim To explore the protective effects of in-terleukin-17 ( IL-17 ) monoclonal antibody ( mAb ) on bleomycin-induced pulmonary fibrosis rats and the re-lated mechanisms. Methods Seventy-five male SD rats were randomly divided into normal control group, sham operation group, model group, non-specific IgG group and IL-17 mAb group. Each group included fif-teen rats. Rats in the latter three groups were intratra-cheally administered with bleomycin A5 to establish pulmonary fibrosis model, whereas the ones in sham operation group were treated with the same volume of physiological saline. On day 7, 14 and 21, rats in non-specific IgG group and IL-17 mAb group were in-jected with non-specific IgG and IL-17 mAb, respec-tively,through the caudal vein. However,the ones in the other groups were administered with the same volume of physiological saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson staining was performed. The contents of IL-17, IL-6 and tumor necrosis factor-α ( TNF-α) in pulmo-nary tissues were measured by enzyme linked immu-nosorbent assay ( ELISA ) . Western blot was used to analyze the pulmonary tissues protein expression of nu-clear factor-κB ( NF-κB) p65 in the nucleus as well as collagen type I ( Col Ⅰ) and collagen type III ( ColⅢ) in the whole cells. The levels of Col Ⅰ and ColⅢ in the pulmonary tissues were detected by fluores-cence real-time quantitative PCR. Serum was separa-ted, and the concentrations of procollagen type 1 carboxyterminal propeptide ( PICP ) and procollagen type III aminoterminal propeptide ( PIIINP ) in serum were then measured by ELISA. Results The severity of alveolitis and pulmonary fibrosis was lower in IL-17 mAb group than that in model group and non-specific IgG group ( P <0. 01 ) . In comparison with normal control group and sham operation group, pulmonary tissues IL-17, IL-6 and TNF-α contents, NF-κB p65 protein expression in the nucleus, Col Ⅰ and Col ⅢmRNA and protein levels, and serum PICP and PIIINP concentrations were significantly increased in model group and non-specific IgG group ( P<0. 01 ) . Follow-ing treatment with IL-17 mAb, the above indicators were significantly decreased as compared to model group and non-specific IgG group ( P<0. 01 ) . How-ever, there was no significant difference in these indi-cators between non-specific IgG group and model group ( P >0. 05 ) . Similar results were also seen between sham operation group and normal control group ( P >0. 05 ) . Conclusion IL-17 mAb protects rats from pulmonary fibrosis by inhibiting inflammatory response via downregulating NF-κB expression and decreasing collagen synthesis in the pulmonary tissues.

OBJECTIVE:To establish a method for the content determination of matrine,sophocarpine,emodin,rhein,chloro-genic acid,sarkosaponin a,aloe-emodin in Kuhuang injection.METHODS:UPLC-MS/MS was adopted. The determination was per-formed on Phenomenex Kenetix C18 column with mobile phase consisted of methanol-0.1% formic acid(gradient elution)at the flow rate of 0.5 mL/min. The column temperature was set at 20 ℃,and injector temperature was set at 10 ℃. The equilibrium time was 4 min and sample size was 5 μL. Ionization mode was electrospray ionization with spray voltage of 5500 V and -4500 V,at-omizing air pressure of 4.14×105 Pa,heater pressure of 4.48×105 Pa,curtain air of 1.72×105 Pa and ion source temperature of 600 ℃. The work mode was multiple reaction monitoring mode. RESULTS:The linear range were 1.25-80.0 ng/mL for matrine (r=0.9993),1.10-70.0 ng/mL for sophocarpine(r=0.9995),0.16-10.5 ng/mL for emodin(r=0.9993),2.61-168 ng/mL for rhe-in (r=0.9993),1.50-96.0 ng/mL for chlorogenic acid (r=0.9993),1.48-94.5 ng/mL for sarkosaponin a (r=0.9996) and 6.11-391 ng/mL for aloe-emodin(r=0.9991). The limits of quantification were 0.061,0.109,0.041,1.313,0.500,0.492,3.055 ng/mL,limits of detection were 0.025,0.054,0.016,0.656,0.150,0.148,1.528 ng/mL. RSDs of precision,stability and reproducibility tests were all no more than 3%. The recoveries of them were 95.45%-99.45%(RSD=1.43%,n=6),97.50%-101.00%(RSD=1.50%,n=6),95.67%-101.73%(RSD=2.85%,n=6),97.17%-100.57%(RSD=1.16%,n=6),95.19%-98.90%(RSD=1.71%, n=6),95.38%-103.85%(RSD=3.39%,n=6),95.50%-101.17%(RSD=1.20%,n=6),respectively. CONCLUSIONS:The method is simple,effective,accurate,reliable and suitable for simultaneous determination for 7 components in Kuhuang injection.

OBJECTIVE:To investigate the present situation of domestic and foreign metabolomics study,and to preliminarily discuss research hotspots and development rules. METHODS:By using bibliometric methods and GoPubMed literature analysis tool,usingMetabolomicsas subject,all literatures were retrieved from PubMed database up to Jul. 31,2016. Those literatures were ranked and analyzed in respects of publication amount,countries and cities,journal sources,research topics,core authors and authors collaborative networks. UsingMetabolomicsMetabonomicsas subjects,all literatures were retrieved from Web of Science database up to Aug. 1,2016. The literatures with high citation frequency were analyzed during 2007-2016 by using the sort-ing function of citation frequency. RESULTS:A total of 15449 domestic and foreign metabolomics literatures were retrieved. The researchers of 2189 literatures came from China,and the amount of published literatures showed a rising trend. 15449 literatures were distributed in 129 countries and regions;10 countries,such as the United States,China,Britain and Germany,were the core countries,and the total number of literatures issued was 12847(83.16%). The United States held the largest share of world publi-cations(4288 literatures,27.76%),and the following was China in order(2189 literatures,14.17%). The city with the largest amount of publications was London(467 literatures),followed by Shanghai,Beijing. A total of 2168 periodicals were involved, and there were 7.1 published literatures averagely. All of the top 20 periodicals were from the United States and European countries (4377 literatures,28.33%). The first 3 subjects with the highest frequency of occurrence were metabolomics,metabolome and me-tabolism;related researches mainly focused on metabolic processes,metabolic networks and pathways,biological markers,pro-teome and genome;main research methods included spectrum analysis and magnetic resonance spectroscopy. Main 6 groups of au-thors were involved,mainly Nicholoson JK,Holmes E,Lindon J and other researchers. None of Chinese researchers had been found among the core authors and author groups. The literatures with high citation frequency mainly focused on the association of metabolism with disease,metabolomics database,metabolomics research methods and biological markers related to disease predic-tion. CONCLUSIONS:Metabolomics has aroused worldwide interest among researchers,and metabolic pathways and biological markers are the focuses in this field. Our researchers have published a large amount of literatures on metabolomics,but there are not high quality periodical carrier or enough cooperation between researchers. It is suggested to enhance the cooperation between various research institutions or grasp the frontier and hotspots of the research in this field so as to push forward the development di-versification and depth of metabolomics research in China.

Objective To investigate the association of interferon (IFN) γ gene polymorphisms and risk and prognosis of HPV cervical infection.Methods PCR-ASP was used for detectiug IFN-γ rs2430561 polymorphism in 179 HPV positive patients and 328 HPV negative normal controls.Results The frequency of A allele of 63.7％ (228/358) was significantly higher than the frequency of T allele of 36.3％ (130/358) in HPV positive group (P =0.045).The frequencies were 41.3％ (74/179) in AA genotype and 14.0％ (25/179) in TT genotype,women carrying AA genotype increased the risk of HPV infection compare with those with TT genotype (OR =1.784,95％ CI:1.031-3.088,P =0.039).During follow-up,the rate of HPV positive again in AA genotype was 83.8％ (62/74),while TT genotype was 20.0％ (5/25).In the analysis of Kaplan-Meier,the cumulative HPV negative rates of AA,TA and TT genotype exhibited significantly different (P =0.008).The cumulative HPV negative rate of AA genotype was the lowest (1.1％-5.9％).Conclusions IFN-γ rs2430561 polymorphisms confer the susceptibility to HPV infection.Women with AA genotype exhibited higher risk of infection and inclined to be continuous status and recurrence after HPV infection.