Malignant mesothelioma is an aggressive malig na ncy that may be caused by environmental carcinogens(asbestos),viruses(SV40),and genetic predisposition.Diagnosis relies on radiographic studies as well as patho logy and mdecular bidogy tests.Most such patients are not suitable for surgical or radiotherapy treatment,and cytotoxic agents are the only options.Historically ,no single or combinations of agents consistently yielded response rates over 20 %.Recently,pemetrexed,a folate-based inhibitor of thymidylate synthase,has been evaluated in phase Ⅰ,ⅡandⅢ clinical trials with promising results.Moreover, low-dose folic acid and vitamin B 12 supplementation significantly reduced the toxicity observed with the use of pemetrexed.In light of these data,it is l ikely that pemetrexed/cisplatin will soon be recommended for malignant pleural m esothelioma as first-line standard chemotherapy.

Objective To investigate hemodynamie change in uremia complicating heart failure of elderly patients. Methods Totally 241 cases with uremia complicating heart failure received measurement of circulation dynamic detection(CD).The volume load,myocardial contractility and blood pressure were analyzed in the elderly group aged(71±6)years (n=116) and young and middleaged group aged(38± 10)years(n =125). Results The central venous pressure(CVP)[(26.7±11.3)cmH2O vs.(23.6 ± 10.7) cm H2O,t=2.410,P =0.010],effective circulation volume (ECV)[(4362± 1340)ml vs.(3085 ± 1001 ) ml,t =7.674,P =0.000],stroke volume(SV) [(185 ± 52) ml vs.(114±41)ml,t=7.803,P=0.000],cardiac output (CO)[( 13.9±4.3)L/min vs.(11.2±3.6)L/min,t=4.802,P=0.000],left ventricular end diastolic volume (LVD)[(388± 145)ml vs.(258±98)ml,t =7.673,P =0.000],left ventricular end systolic volume ( LSV ) [( 223 ± 95 ) ml vs.( 135 ± 59) ml,t =7.186,P=0.000] were significantly higher group than in young and middle-aged group.The ejection pressure (EP)[(178±29)mm Hg vs.(183±24)mm Hg,t=2.323,P=0.012],myocardium negative inotropic(MNC) [(0.609±0.149)vs.(0.683±0.188),t=3.113,P=0.002],ejection fraction (EF) [(0.433± 0.034) vs.(0.445 ± 0.031 ),t =2.451,P =0.010],diastolic blood pressure (DBP) [( 87 ±14)mm Hg vs.(1.08±22)mm Hg,t=8.141,P=0.000],systematic vascular resistance(SSR)[(952±207)gcm-4 s-2 vs.(1217± 308) gcm-4 s-2,t =7.143,P=0.000],ejection resistence(ER) [( 178± 29)vs.( 183 ± 24),t =2.323,P =0.012] were lower in elderly group than in young and middle-aged group.DBP(x2 =16.474,P=0.000,OR=0.752,95％CI:0.714-0.790),SBP(x2 =11.913,P=0.000,OR=1.148,95％CI:1.091-1.205),ER(x2 =17.892,P=0.000,OR=0.906,95％CI:0.861-0.951),CVP(x2 =14.672,P=0.000,OR=0.698,95％CI:0.663-0.733) and LDV(x2 =21.080,P=0.000,OR=0.942.95％ CI:0.895-0.989) were dangerous factors of uremia complicating heart failure.Conclnsions The increased volume load,decreased myocardial contractility and cardiac afterload may appear in the elderly patients with uremia complicating heart failure.

Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGF 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism. Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGF 165 group, Ad-hTIMP-1 group and Ad-hVEGF 165+Ad-hTIMP-1 group (hVEGF 165+hTIMP-1) ( n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference t-test. Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGF 165-hTIMP-1 group were significantly increased (both P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both P<0.05). LVEF and LVFS in the hVEGF 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGF 165 group (64.65±4.00) %, (30.95±2.57) % (both P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-Track group ( P<0.01 or P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGF 165-hTIMP-1 group were increased than those in the Ad-Track group ( P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-hVEGF 165 group (both P<0.05). There was no statistically difference in the mRNA expression of Bax, Caspase-3, Bad, and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). The protein expression of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.01), and the protein expression of Bcl-2 in the hVEGF 165-hTIMP-1 group was increased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.05). There were no statistically differences in the protein expression of Bax, Caspase-3 and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). Conclusions:Ad-hVEGF 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGF 165 and hTIMP-1 may have a synergistic effect on MI.

Objective To explore whether inhibiting autophagy can enhance the sensitivity of photothermal treatment under mild photothermal conditions. Methods CQ@PLGA@PDA NPs were prepared by an improved double emulsification method and a PDA-based surface modification method. After basic characterization, CCK-8 method was used to detect the cytotoxicity of nanoparticles; the near-infrared laser irradiation nanoparticle solution was used to detect the heating effect; CCK-8 method and live-dead cell staining were used to detect the killing effect of tumor cells; Western blot was used to detect the expression of autophagy-related proteins. Results The CQ@PLGA@PDA NPs were successfully prepared, with a particle size of 253.10±2.39 nm, a zeta potential of -22.57±0.80 mV, uniform particle size and good dispersion. The temperature of nanoparticle solution increased to 45℃ after the near-infrared laser irradiation for 10 min. CQ@PLGA@PDA NPs had no obvious toxicity to cells. The survival rates of breast cancer cell MDA-MB-231 and mouse embryonic fibroblast NIH-3T3 cell were above 95%. The inhibition of autophagy under mild photothermal conditions could improve the sensitivity of photothermal therapy. Conclusion The prepared CQ@PLGA@PDA NPs have good photothermal performance and high biological safety; by inhibiting autophagy, they can effectively kill tumor cells under mild photothermal conditions(< 50℃).

BACKGROUNDDendritic cell (DC)-based immunotherapy is a new approach and effective for some malignant tumors. The aim of this study is to observe the efficacy and toxicity of immunotherapy with carcinoembryonic antigen (CEA) peptide-pulsed DCs in patients with refractory advanced lung cancer.

METHODSLung cancer patients with high CEA expression were enrolled into this project. Autologous DCs were generated from patients' plastic-adherent peripheral blood mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells (CIK) were cultured from non-adherent peripheral blood mononuclear cells. DCs and CIK were transfused to patients. Responses and toxicities were observed.

RESULTSA total of 22 patients with lung cancer received DCs immunotherapy. DCs doses were 2.5×10⁶-9.6×10⁷ (5.03×10⁶). CIK doses were 3.4×10⁸-46×10⁸. CD3, CD8, NK and IFN-γ levels obviously increased after treatment (P < 0.05). The 1-year survival rate was 68.2% (15/22). Main toxicities were fever and rash.

CONCLUSIONSDCs-based immunotherapy is feasible and safe to patients with lung cancer.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.