BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVE：To investigate drug use in an obstetrics and gynecology hospital and confirm the types of drugs that need to be monitored so as to provide reference for rational drug use in clinic. METHODS： Activity based classification （ABC） analysis， Vital-Essential-Nonessential Medicine （VEN） analysis and ABC-VEN matrix analysis were used to statistically analyze the types of drugs in the inpatients and outpatients of this hosptial during Jan. 2016-Dec. 2017， and consumption sum in the hospital so as to determine the types of monitoring focus drugs. RESULTS： The drugs were divided into class A， B， and C by using ABC analysis， and the constitute ratio of them were 6.08％， 7.71％ and 86.21％； the constitute ratio of consumption sum were 70.97％， 19.07％ and 9.96％， respectively. The drugs were divided into class V， E and N， and the constitute ratio of them were 36.51％， 43.61％ and 19.88％； constituent ratios of their consumption sum were 31.89％， 33.89％ and 34.22％， respectively. The drugs were divided into group Ⅰ （class AV， AE， AN， BV， CV）， group Ⅱ （class BE， CE， BN） and group Ⅲ （class CN） by using ABC-VEN matrix analysis； the constitute ratios of accumulative number of drug type were 40.56％， 44.43％ and 15.01％，while those of accumulative consumption sum were 77.29％， 20.52％ and 2.19％， respectively. Among class N， the constituent ratio of consumption sum of class AN as Chinese patent medicine， blood substitutes and perfusion solutions were higher， being 12.48％ and 7.92％； that of class BN as Chinese patent medicine was higher， being 3.21％； those of class CN as Chinese patent medicine， sex hormones and modulators of the genital system were higher， being 1.14％， 0.50％. CONCLUSIONS： In the Obstetrics and Gynecology Hospital， consumption sum of class A is the main part of the total consumption sum of drugs， and they should be seleted according to therapeutic efficacy. Active regulatory policies should be adopted for class V and E so that more drug types that possess cost- effectiveness advantages； for class N， management control and reasonable utilization should be monitored closely to reduce irrational drug use. Some Chinese patent medicines， blood substitutes and perfusion solutions among class AN should be monitored and controlled emphatically.

Objective: To understand the pollution characteristics and assess the pollution health risks of heavy metals in atmospheric PM_2.5 in Lanzhou. Methods: According to the regional characteristics of air pollution and industrial distribution characteristics in Lanzhou, atmospheric PM_2.5 was sampled monthly in Chengguan and Xigu Districts from January, 2015 to December, 2016. Detected the concentration of PM_2.5 and 12 kinds of elements (Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se and Tl) by weighing method and inductively coupled plasma mass spectrometry. Enrichment factor and geo-accumulation index were used to describe the pollution characteristics, while health risk assessment was conducted using the recommended United States Environmental Protection Agency (USA EPA) model. The health risks of non-carcinogens were evaluated by non-cancer hazard quotient (HQ), the non-carcinogenic risk was considered to be negligible when HQ<1, HQ>1 meant a health risk. With a single contaminant cancer Risk value to evaluate the health risks of carcinogens, when the Risk value between 10^-6 to10^-4 as an acceptable level. Results: The daily average concentrations of PM_2.5 was 83.0 μg/m³, 77.0 μg/m³ in Chengguan and Xigu Districts, respectively, during the sampling periods, and the concentration of PM_2.5 in winter/spring was higher than summer/fall in both districts. The concentration of Al in PM_2.5 was the highest and other elements in descending order: Pb, Mn, As, Sb/Cd, Tl in both districts. Enrichment factor results showed that Al and Mn were mainly affected by natural factors, the rest of five elements were all typical man-made pollution elements and according to geo-accumulation index pollution level of Cd was the strongest in the winter. The results of health risk assessment showed that Mn had the highest non-cancer risks (HQ>1) and affected the health of the children seriously. HQ reached up to 2.44 and 1.79 in Chengguan and Xigu Districts, respectively. Pb, As, Sb, Cd had slight health impact (HQ<1), could be negligible. The cancer risks range of As, Cr were 6.33×10^-6 to 6.46×10^-5 between the acceptable level of risk (10^-6 to 10^-4), which indicated that As and Cd had potential cancer-risks. Conclusions The pollution level of atmospheric PM_2.5 and the heavy metals in it was still grim;the non-cancer risks caused by multiple metals on children deserved attention. Although the cancer risks of As and Cd were between the acceptable level of risk, the potential cancer risk still shall not be ignored.

Objective To evaluate the effect of a protein kinase CK2 inhibitor on intracellular levels of reactive oxygen species and DNA double?stand break in human non?small cell lung cancer H460 cells. Methods H460 cells were exposed to 0, 12?5, 25.0, and 50.0μmol/L quinalizarin, a specific inhibitor of protein kinase CK2, for 24 hours. The changes in protein and mRNA levels of CK2 subunits were measured. Flow cytometry was used to measure changes in the intracellular levels of reactive oxygen species in H460 cells after 4 or 24 hours of quinalizarin treatment. Immunofluorescence assays were performed to determine the effect of the CK2 inhibitor onγ?H2 AX expression and the average fluorescent number ofγ?H2 AX foci in H460 cells. Comparison was made by analysis of variance and t test. Results There were no significant differences in protein or mRNA levels of CK2 subunits in H460 cells after quinalizarin treatment ( CK2α,0μmol vs. 12?5 μmol/L, P=0?966;0 μmol/L vs. 25 μmol/L, P=0?355;0 μmol/L vs. 50 μmol/L, P=0?864, CK2α’ , 0 μmol/L vs. 12?5μmol/L,P=0?409;0μmol/L vs. 25μmol/L,P=0?833;0μmol/L vs. 50 μmol/L, P=0?0. 746, CK2β, 0 μmol/L vs. 12?5 μmol/L, P=0?532;0 μmol/L vs. 25 μmol/L, P=0?830;0 μmol/L vs. 50 μmol/L, P= 0?061 ) . The intracellular levels of reactive oxygen species were substantially elevated in H460 cells with the increase in quinalizarin concentration and treatment time. Different concentrations of quinalizarin resulted in dose?and time?dependent increases in the numbers of γ?H2 AX foci after 4 and 24 hours of treatment ( treated by Quianlizarin for 4 or 24 h, 0 μmol/L vs. 12?5μmol/L,12?5 μmol/L vs. 25 μmol/L, 25 μmol/L vs. 50 μmol/L, all P=0?000, concentration is 12?5μmol/L,25 μmol/L or 50 μmol/L, 4 h vs. 24 h, all all P=0?000 ) . Conclusions Quinalizarin can increase the intracellular levels of reactive oxygen species and DNA double?stand break in H460 cells by inhibition of protein kinase CK2 activity. This study provides a theoretical basis for using quinalizarin as a potential radiosensitizer for lung cancer.

[Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly suppressed, and the differences were statistically significant (P<0.01).In addition, the phosphorylation form of Akt and ERK (namely p-Akt and p-ERK) were significantly down-regulated by treating with quninalizarin and icotinib together in the H1650 cells while the expression of Akt and ERK changed little.Conclusions Quinalizarin, as a specific CK2 inhibitor, may overcome icotinib resistance by inhibiting proliferation mediated by Akt and ERK in human lung adenocarcinoma cell lines, and enhances the suppressive effect of icotinib on the proliferation of EGFR-TKIs-resistant human lung adenocarcinoma cells.

Nowadays, EGFR?TKIs are important treatment strategy in lung cancer, but the resistance to EGFR?TKIs remains an unsolved issue preventing the patients from further benefits. Recent studies have shown that casein kinase ( CK2) plays an important role in carcinogenesis and development of cancer. CK2 inhibitor has also demonstrated anti?tumor effects. Here we reviewed the mechanism of EGFR?TKIs and the potential reasons of resistance. Interestingly, there is a crosstalk between CK2 and EGFR downstream signaling pathways, therefore, it may be possible that CK2 inhibitor can overcome the EGFR?TKIs resistance.

[Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly suppressed, and the differences were statistically significant (P<0.01).In addition, the phosphorylation form of Akt and ERK (namely p-Akt and p-ERK) were significantly down-regulated by treating with quninalizarin and icotinib together in the H1650 cells while the expression of Akt and ERK changed little.Conclusions Quinalizarin, as a specific CK2 inhibitor, may overcome icotinib resistance by inhibiting proliferation mediated by Akt and ERK in human lung adenocarcinoma cell lines, and enhances the suppressive effect of icotinib on the proliferation of EGFR-TKIs-resistant human lung adenocarcinoma cells.

Nowadays, EGFR?TKIs are important treatment strategy in lung cancer, but the resistance to EGFR?TKIs remains an unsolved issue preventing the patients from further benefits. Recent studies have shown that casein kinase ( CK2) plays an important role in carcinogenesis and development of cancer. CK2 inhibitor has also demonstrated anti?tumor effects. Here we reviewed the mechanism of EGFR?TKIs and the potential reasons of resistance. Interestingly, there is a crosstalk between CK2 and EGFR downstream signaling pathways, therefore, it may be possible that CK2 inhibitor can overcome the EGFR?TKIs resistance.

Objective To investigate the efficacy and safety of different doses of dezocine at different administration time on analgesia after laparoscopic cholecystectomy.Methods 80 patients elected from ASA Ⅰ-Ⅱ grade laparoscopic cholecystectomy were randomly divided into four groups,20 cases in each group.Group Ⅰ was anesthetized by intravenously injected dezocine 0.10mg/kg before the surgery,group Ⅱ was anesthetized by dezocine 0.15mg/kg before the surgery,group Ⅲ was anesthetized by intravenously injected dezocine 0.10mg/kg after stopping anesthetic surgery,and group Ⅳ was anesthetized by intravenously injected dezocine 0.15mg/kg after stopping anesthetic surgery.The postoperative pain scores were observed 1,6,12,24 hours after operation in the four groups by using visual analog scale (VAS),comfort score (BCS),and anesthesia recovery score (modified Aldrete score).Results TheVAS of the four groups 1 hour after surgery:group Ⅰ and group Ⅲ was significantly different(t =2.308,P =0.036),group Ⅰ and group Ⅳ was significantly different (t =2.106,P =0.042),group Ⅱ and group Ⅲ was significantly different (t =2.711,P =0.014),group Ⅱ and group Ⅳ was significantly different (t =2.317,P =0.037).The BCS 1 hour after surgery:group Ⅰ and group Ⅲ was significantly different(t =2.108,P =0.042),group Ⅰ and group Ⅳ was significantly different(t =2.069,P =0.048),group Ⅱ and group Ⅲ was significantly different (t =2.353,P =0.033),group Ⅱ and group Ⅳ was significantly different (t =2.361,P =0.036).The VAS 6 hours after surgery:group Ⅰ and group Ⅲ was significantly different (t =2.084,P =0.045),group Ⅱ and group Ⅲ was significantly different(t =2.309,P =0.038),group Ⅱ and group Ⅳ was significantly different(t =2.303,P =0.040).The BCS 6 hours after surgery:group Ⅰ and group Ⅲ was significantly different (t =2.294,P =0.041),group Ⅱ and group Ⅲ was significantly different(t =2.322,P =0.035),group Ⅱ and group Ⅳ was significantly different (t =2.070,P =0.048).The BCS 12 hours after surgery:group Ⅱ and group Ⅲ was significantly different(t =2.518,P =0.047).VAS and BCS scores at other time points had no significant difference (P ＞ 0.05).Conclusion The analgesic after laparoscopic gallbladder surgery using dezocine 0.10mg/kg-0.15mg/kg,especially 0.15mg/kg administered anesthesia before surgery,can effectively relieve postoperative pain and improve postoperative comfort,reduce postoperative analgesic(pain pump) and has less adverse reactions,which is worthy of promotion.

OBJECTIVETo investigate the therapeutic effect of Dachaihutang on the development of atherosclerosis (AS) in rabbits and its possible mechanism by detecting the expression level of carnitine patmitoyl transferase-1 (CPT-1) in vascular smooth muscle layer of atherosclerotic rabbits, and search the new way and evidence for AS cures.

METHODThirty six male New Zealand white rabbits were divided randomly into control group, model control group, simvastatin group and Chinese traditional medicine dachaihutang group. After 9 weeks and 20 weeks of treatment, serum total cholesterol (TC) and triglyceride (TG) and low-density lipoprotein (LDL) levels were examined. At the end of 25 th weeks, histological changes in ascending aorta were studied by HE staining and histomorphometric analysis. The gene expression of CPT-1 in vascular smooth muscle layer of thoracic aorta was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTCompared with model control group, in dachaihutang group serum TC and TG and LDL levels attenuated. Pathomorphology indicated that intima and media (I + M) became thinned, and the ratios of the thickness of intima to media(I/M) and the area of intima to media (SI/SM) were decreased (P < 0.05). Aortic intimal proliferation in Dachaihutang group was associated with a marked increase in CPT-1 expression in vascular smooth muscle layer of thoracic aorta. Compared to simvastatin group, except TG value, other values were higher in Dachaihutang group, however, there were no significant differences between the two groups.

CONCLUSIONThese findings suggest that early treatment with Dachaihutang not only induces a significant regression of arterial lesions of high cholesterol diet rabbits, but also has a crucial inhibited genesis and development of atherosclerosis effect by up-regulating CPT-1 expression in vascular smooth muscle layer.

Animals ; Aorta ; cytology ; drug effects ; enzymology ; Atherosclerosis ; drug therapy ; enzymology ; genetics ; Carnitine O-Palmitoyltransferase ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Humans ; Male ; Myocytes, Smooth Muscle ; drug effects ; enzymology ; Rabbits ; Random Allocation