Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

A rapid analytical method for the determination of dezocine and pethidine in hair samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.After cleaned hair was extracted by grinding with methanol and ultrasonic, the final solution was analyzed by UPLC-MS/MS.The targets were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 0.1% formic acid-water and methanol as mobile phase at a flow rate of 0.4 mL/min.The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of dezocine and pethidine.Dezocine and pethidine showed good linearity in the range of 0.01-8 ng/mg, with the limit of detection of 0.005 ng/mg and the LOQs of 0.01 ng/mg.The accuracy, precision, matrix effect, extraction recovery, and stability all met the requirements.The established method is simple, rapid, and accurate for the qualitative and quantitative determination of dezocine and pethidine in hair, which can be applied in the case analysis of dezocine and/or pethidine abuse.

A rapid determination of methamphetamine, amphetamine, 6-monoacetylmorphine, and morphine in hair samples by UPLC-MS/MS was established and optimized.The concentration of target compounds in the hair of drug abusers and drug laboratory technicians was investigated and the cut-off value was evaluated.After cleaned hair was extracted by grinding with methanol-water (7∶3) at 3 000 r/min for 100 s, the final solution after adjusting the volume to methanol-water (1∶1) was analyzed by UPLC-MS/MS.The analytes were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and acetonitrile as mobile phase at a flow rate of 0.4 mL/min. The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of the four target compounds. All analytes showed good linearity (R2 ≥ 0.999 6) in the range of 0.01-5 ng/mg (except amphetamine in 0.01-4 ng/mg), limit of the quantitation was 0.01 ng/mg, and the limit of detection was 0.001-0.008 ng/mg.The accuracy, precision, matrix effect, and recovery all met the requirements of biological sample methodology.According to the comprehensive consideration of the receiver operating characteristic (ROC) curve, Youden index, law enforcement cost and intensity, the reference cut-off values were methamphetamine ≥ 0.1 ng/mg; amphetamine ≥ 0.025 ng/mg; 6-monoacetylmorphine ≥ 0.05 ng/mg; morphine ≥ 0.05 ng/mg.The method established in our research can quickly and accurately detect the contents of methamphetamine, amphetamine, 6-monoacetylmorphine, and morphine in hair.This study provides some reference for the public security system to make more rational cut-off values in the norm of drug-related personnel hair samples detection in the future.

Objective To investigate the vitamin B 12 status of vegetarians in Shanghai.Methods A total of 282 adult vegetarians and 282 omnivores matching by gender and age were recruited in Shanghai.Their dietary intakes were collected.The serum concentrations of vitamin B12,folate and homocysteine were tested.The red blood cell,hematocrit value,mean corpuscular volume and mean erythrocyte width were also examined.Results The daily average intake of dietary vitamin B12 was (0.46± 1.01) μg/d in vegetarians and only (0.1±0.46) μg/d in vegans,which was lower than that of omnivores [(3.91±6.92) μg/d,F=50.57,P＜0.01].137 omnivores and 274 vegetarians had less dietary vitamin B12 level than recommended nutrient intake (RNI) and the difference was statistically significant (x2 =114.77,P＜ 0.01).54.26％ of vegetarians,68.92％ vegans,49.04％ ovo-lacto vegetarians and 15.60％ omnivores had hyperhomocysteinemia and the differences between vegetarians and omnivores were statistically significant (all P＜0.01).After adjusting the confounding factors the hematocrit value was higher in vegetarians,vegans and ovo-lacto vegetarians than in omnivores (27.42％± 18.32％,28.73％± 18.19％,26.95％± 18.38％ vs.8.96％± 16.59％,P＜0.01).Vegans had lower red blood cell counts and higher hematocrit value and mean corpuscular volume than omnivores.Conclusion Vitamin B12 deficiency combined with an elevated level of homocysteine and red blood cell volume growth are common but serious issue in vegetarians,especially in vegans.

Objective Investigated the treatment effect of ISCOM leukemia vaccine combination with 1-methyl tryptophan on tumor burden mice .Methods Saponin was added lipase protein (1 mg/mL) 7 ℃ for 12 h ,adding 80 μL lipid mixed solution and 5 mL saponin solution (1 mg/mL ) to prepare ISCOM leukemia vaccine .C57BL /6 mice were randomly divided into model group , ISCOM leukemia vaccine group ,1-methyl tryptophan group and combination group ,Mice were injected FBL-3 cell to built leukemia tumor-burdened mice model .After treatment for 4 weeks ,tumors weight ,NK and Mφ and CTL cell killing activity ,serum levels of IL-10 ,IL-12 were detected .Results Tumor weight in combination group was less than 1-methyl tryptophan and ISCOM leukemia group [(0 .64 ± 0 .26)g vs .(2 .49 ± 0 .91)g ,P< 0 .01 ,(0 .64 ± 0 .26)g vs .(1 .28 ± 0 .73)g ,P< 0 .05] ;NK cell killing activity in com-bination group was higher than 1-methyl tryptophan group[(38 .41 ± 8 .27)% vs .(67 .22 ± 12 .74)% ,all P< 0 .01)] ;M φ activity in combination group was significantly higher than 1-methyl tryptophan group[(55 .69 ± 13 .69)% vs .(69 .47 ± 14 .79)% ,P< 0 .01] ;CTL activity in combination group was significantly higher than 1-methyl tryptophan group and ISCOM leukemia group[(43 .77 ± 8 .89)% vs .(69 .68 ± 11 .44)% ,P< 0 .01 ,(58 .87 ± 9 .45)% vs .(69 .68 ± 11 .44)% ,P < 0 .05] ;IL-10 in combination group were significantly lower than 1 - methyl tryptophan group and ISCOM leukemia group [(76 .2 ± 6 .82)pg /L vs .(98 .3 ± 13 .4)pg/L ,P<0 .01 ,(76 .2 ± 6 .82)pg/L vs .(202 .3 ± 44 .5)pg/L ,P < 0 .01] ;IL-12 in combination group were significantly higher than 1-methyl tryptophan group and ISCOM leukemia group[(381 .2 ± 47 .3)pg/L vs .(332 .1 ± 30 .2)pg/L ,P < 0 .05 ,(381 .2 ± 47 .3)pg /L vs . (291 .2 ± 17 .3)pg/L ,P< 0 .01] .Conclusion Combination with 1-methyl tryptophan and ISCOM leukemia vaccine has a well anti-tumor effect ,its mechanism may be through mediated and the expression of IL-12 and IL-10 .

Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.

OBJECTIVE: To explore the exact mechanisms of programmed cell death (PCD) induced by Type II anti-CD20 mAb in CD20+ non-Hodgkin lymphoma (NHL) cells, and to provide theoretical basis for anti-tumor ability of new CD20 mAb.
 METHODS: After incubation with Rituximab (a Type I anti-CD20 mAb) and Tositumomab (a Type II anti-CD20 mAb), Raji cells were stained by annexin V & propidium iodide (PI). The ratio of programmed death cells were measured by two channel flow cytometry (FCM). Before the treatment of anti-CD20 mAbs, Raji cells was incubated with a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD-FMK) and a dihydroceramide synthase inhibitor fumonisin B1 (FB1) for 30 minutes to assess their inhibitory effect on PCD. High performance liquid chromatography (HPLC) was utilized to compare the ratio of programmed death cells between the pretreatment group (treated by Rituximab and Tositumomab) and the non-pretreatment group. The anti-CD20 mAbs-treated Raji cells were collected, and the ceramide levels in the Raji cells in the different pretreatment groups were also examined by HPLC, and the inhibitory effect of FB1 on the changes of ceramide levels in the Raji cells was measured. The Raji cells were incubated with different concentration C2-ceramide, C2-Ceramide-induced PCD was also evaluated by annexin V & PI staining after 16 hours. 
 RESULTS: Tositumomab (10 µg/mL) but not Rituximab (10 µg/mL) can induce significant PCD (28.6±4.2)% in Raji cells, with significant difference (t=26.48, P<0.01), which cannot be blocked by Z-VAD-FMK with a concentration range from 10 to 30 µmol/L (F=3.01, P>0.05). The cellular ceramide levels in Raji cells were significantly elevated after the treatment of Tositumomab (t=28.48, P<0.01). C2-ceramide can significantly induce PCD in Raji cells in a dose-dependent manner with a concentration range from 5 to 40 µmol/L (F=2.71, P>0.05). The dihydroceramide synthase inhibitor FB1 can significantly inhibit the elevated cellular ceramide levels (F=20.18, P<0.01) and cell programmed death induced by Tositumomab (F=17.02, P<0.01).
 CONCLUSION Type II but not Type I anti-CD20 mAbs can induce caspase independent PCD in CD20+ NHL cells through the elevation of cellular ceramide levels. The PCD is not associated with classic caspase pathway.
Amino Acid Chloromethyl Ketones ; Apoptosis ; drug effects ; Cell Line, Tumor ; drug effects ; Humans ; Lymphoma, Non-Hodgkin ; Rituximab ; pharmacology ; Sphingosine ; analogs & derivatives ; pharmacology

Objective To compare the clinic value of uterine artery embolism (UAE) and total hysterectomy (TH) for intractable postpartum hemorrhage. Methods 15 cases of intractable postpartum hemorrhage were performed UAE and other 17 cases of intractable postpartum hemorrhage were performed HE in our hospital during 10 years. Two groups' preoperative preparation time, operation time and the hospitalization time were compared. Results The preoperative preparation time (26.2±1.6) min of UAE was significantly longer than TH group (13.5±1.4) min (P<0.01; the former group's average operation time was (47.8±16.2) min, and the latter group's was (100.6±18.7) min (P<0.01); the hospitalization time of UAE (6.1±0.1) days was significantly shorter than TH group (8.8±0.5) days)(P<0.01). Conclusion With short operation time, low morbidity rate and possibility of preserving reproductive function, UAE is proved to be very effective in the treatment of intractable postpartum hemorrhage, but in some cases, UAE can't replace TH yet.

To explore the intracellular signal pathways for beta-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used to examine phosphorylated ERK1/2 protein and regulated effects by different singal kinase inhibitants. It was found that beta-VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators, it was observed that the effect of beta-VLDL induced VLDL receptor transcription, which was monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but extremely abolished by pretreating cells with PD98059, an inhibitor of ERK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC-ERK1/2 cascade is the essential signaling pathway by which beta-VLDL activated VLDL-R mRNA expression. Inhibition of the ERK1/2 signaling cascade resulted in suppression of the cellular lipid accumulation induced by beta-VLDL in macrophages.
Cells, Cultured ; Lipoproteins, VLDL ; metabolism ; Macrophages ; cytology ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; physiology ; Mitogen-Activated Protein Kinase 3 ; metabolism ; physiology ; Protein Kinase C ; antagonists & inhibitors ; metabolism ; Receptors, LDL ; biosynthesis ; genetics ; Signal Transduction ; Transcription Factors ; metabolism ; Transcription, Genetic ; Up-Regulation