BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To investigate the expression level and clinical significance of serum long noncoding RNA(lncRNA)H19,CHAST in patients with coronary heart disease(CHD).Methods A total of 135 patients with CHD who were admitted to the Department of Cardiovascular Medicine of Lianyungang Second People's Hospital from June 2021 to May 2022 were selected,including 76 cases of a-cute coronary syndrome and 59 cases of chronic coronary syndrome.We selected 62 patients in the control group who were hospitalized and excluded from CHD by coronary angiography.Real-time fluorescent quantitative PCR(RT-PCR)was used to detect the relative expres-sion level of lncRNA H19 and lncRNA CHAST in the circulating serum of the subjects.Meanwhile,the high sensitivity C-reactive pro-tein(hs-CRP)、tumor necrosis factor-α(TNF-α)、interleukin-6(IL-6)、low density lipoprotein(LDL)、high density lipoprotein(HDL)and other related indicators of each group were collected.The receiver operating characteristic(ROC)curve was used to analyze the clinical diagnostic value of circulating serum lncRNA H19 and lncRNA CHAST expression level in the diagnosis of CHD.Pearson cor-relation coefficient was used to analyze the correlation between serum lncRNA H19,lncRNA CHAST level,and other related indicators.Multivariate Logistic regression was used to analyze the risk factors of CHD.Results The serum expression levels of lncRNA H19 and ln-cRNA CHAST in the CHD group were higher than those in the control group(P＜0.05).The serum levels of hs-CRP、TNF-α、IL-6、and LDL in the experimental group were higher than those in the control group(P＜0.05),and the serum levels of HDL were lower than those in the control group(P＜0.05).The expression levels of lncRNA H19 and lncRNA CHAST were positively correlated with hs-CRP,IL-6 and LDL,and were negatively correlated with HDL.lncRNA H19 and lncRNA CHAST are risk factors for CHD,which may have a higher value in the diagnosis of CHD.Conclusion lncRNA H19 and lncRNA CHAST are risk factors for CHD and can be used as serum indicators for the diagnosis of CHD,and the combination of the two has a higher value in the diagnosis of CHD.In addition,the ex-pression levels of both were correlated with the levels of inflammatory factors and apolipoproteins.

Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.

Objective To investigate the relationship between Pre-S1 antigen and hepatic function of the patients with chronic hepatitis B.Methods Serum samples of 300 cases with chronic hepatitis B patients were collected,Pre-S1 antigen and alanine aminotransferase (ALT),aspartate aminotransferase (AST) were checked,and the correlation were analyzed.Results Among 300 cases,patients with positive Pre-S1 antigen were 58.33％(175/300).In patients with positive Pre-S1 antigen,the abnormal ALT(＞40 U/L) detection rate was 78.75％ (138/175),the abnormal AST(＞40 U/L) detection rate was 77.17％ (136/175),Pre-S1 antigen negative patients ALT abnormal detection rate was 51.20％ (64/125),AST anomaly detection rate was 42.40％ (53/125).There was significant difference between two groups(x2 =2.875,5.223;P＜0.05).Conclusion In patients with chronic hepatitis B,Pre-S1 antigens can be used as a marker of hepatitis B virus infection,copy and hepatic cell injury.

Objective To explore the reasons of abnormal decannulation in patients with malignant tumor undergoing chemotherapy during peripherally inserted central catheter ( PICC ) period. Methods A prospective study was conducted among 291 cancer patients who used PICC for chemotherapy in Hunan Provincial People′s Hospital from January 2012 to June 2014. The occurrence of complications during PICC period and the reasons of abnormal decannulation in patients were investigated and collected. The time of follow-up was one year. Results Among 291 patients, there were 72 cases ( 24. 74%) of PICC complications and 44 cases (15.12%) of abnormal decannulation, among which, there were 12 cases (4.12%) of upper extremity deep venous thrombosis ( UEDVT ) , 5 cases ( 1. 72%) of central line associated bloodstream infections (CLABSI), with an infection rate of 0.95 per 1 000 catheter days, 9 cases (3.09%) of exit-site infection, with an infection rate of 1.46 per 1 000 catheter days, 11 cases (3.78%) of catheter prolapse and 7 cases (2.41%) of occlusion. Single factor analysis showed that, the history of deep venous thrombosis ( DVT) and the types of chemotherapeutics could influence the incidence rate of abnormal decannulation of patients with PICC. Conclusions The incidence rate of abnormal decannulation in patients with malignant tumor undergoing chemotherapy during PICC is 15%. UEDVT is the main reason of abnormal decannulation of PICC, and the chemotherapeutics infusion is independent risk factor of abnormal decannulation.

OBJECTIVETo compare the various combined immunization schemes available for treatment of babies born to mothers with high-load hepatitis B virus (HBV) infection.

METHODSA total of 118 mothers with HBV infection status of hepatitis B surface antigen-positive (HBsAg+), hepatitis B e antigen-positive (HBeAg+) and HBV DNA load of more than 1.0 * 61og10 IU/mL were included in the study. All of the participants' babies received the main-passive immunization therapy according to the wishes of their families. For analysis,the infants were grouped according to the various dosages of the vaccine program (group A: hepatitis B immunoglobulin (HBIG) 200 IU and HBVac 20 mug intramuscular;group B:HBIG 200 IU and HBVac 10 mug intramuscular; group C HBIG 100 IU and HBVac 20 mug intramuscular injection) and times, and followed-up to 7 months of age.All results were statistically analyzed using SPSS software.

RESULTSAll of the infants produced anti-HBs after vaccination.After the HBIG injection schedule was completed in January, the mean concentrations of anti-HBs in groups A, B, and C were 263.56 ± 50.98,231.06 ± 74.07, and 99.23 ± 29.82 mIU/mL respectively;the concentrations were significantly different between groups A and C, and between groups B and C (P < 0.001). In July, the titers of anti-HBs in groups A, B, and C were 788.10 ± 281.96,428.39 ± 347.48, and 708.44 ± 315.69 mIU/mL respectively; the concentrations were significantly different between groups A and B, and between groups B and C (P < 0.05).

CONCLUSIONAdminisWation of the hepatitis B vaccine combined with HBIG at birth can achieve immune protection for babies born to highly viremic mothers. In January, the HBIG dosage of 200 IU was more reliable than 100 IU. The hepatitis B 20 tg dose vaccine was safe and effective.

Hepatitis B ; Hepatitis B Antibodies ; Hepatitis B Vaccines ; Hepatitis B e Antigens ; Hepatitis B virus ; Humans ; Immunization ; Immunoglobulins ; Infant ; Mothers ; Serologic Tests ; Vaccines, Combined ; Viral Load

Objective To analyze the relevance between the consumption of various antimicrobials and antimicrobial re-sistance of Acinetobacter baumanni in a grade three hospital during 2007 -2010 .Methods A retrospective analysis was per-formed to count and sort the defined daily doses (DDDs) and the consumption of various antimicrobials in the hospital between 2007 and 2010 .Meanwhile the resistance rates of Acinetobacter baumanni to different antimicrobials were collected in the same period .Data was analyzed by SAS 8 .2 statistical software package using Spearman correlation method .Results The resistance rate of Acinetobacter baumanni to imipenem was significantly positively correlated with the consumption of carbapenems (r=0 .954 6 ,P<0 .01) ,it is positively correlated with the dosage of imipenem (r=0 .849 2 ,P<0 .05) ,it is also significantly posi-tively correlated with the consumption of meropenem (r=0 .999 2 ,P<0 .05) ,and the consumption of amoxicillin/clavulanate potassium ,respectively(r=0 .800 5 ,P<0 .05) .There was no correlation between the resistance rate of Acinetobacter bauman-ni and the dosage of aminoglycosides ,fluoroquinolones ,even β-lactamase inhibitors(P>0 .05) .Conclusion The use of car-bapenems should be correlated with their indications strictly ,only applying to severe infection of Acinetobacter baumanni .The aminoglycosides of amikacin and β-lactamase inhibitors of cefoperazone/sulbactam are the better options to treat A cinetobacter baumanni infection .

Objective To investigate the correlation between the expression of P-SAPK/JNK and neuronal apoptosis in the striatum during permanent middle cerebral artery occlusion (pMCAO) in rats.Methods Fifty-four male Sprague-Dawley rats were randomly divided into sham operation group and pMCAO 1-,3-,6-,12-,and 24-hour groups (n =9 in each group).Apoptotic neurons in the striatum during cerebral ischemia were detected by TUNEL assay,the nuclear translocation of P-SAPK/JNK in the striatum by immunohistochemical staining expressions of P-SAPK/JNK protein by Western blot.Results The numbers TUNEL- and P-SAPK/JNK-positive cells in the striatum at 1 hour after pMCAO increased significantly (P =0.000 1),and reached the peak at 6 hours.The numbers of TUNEL-positive cells decreased at 12 hours,however,it still higher than the sham operation group (P =0.000 2).Western blot analysis showed that the expression of P-SAPK/JNK after pMCAO increased significantly,and the time-course change was in accord with the result of immunohistochemical staining Neuronal apoptosis in the striatum was significantly positively correlated with the expression of P-SAPK/ JNK (r =0.984,P =0.000 4).Conclusions Cerebral ischemia may induce neuronal apoptosis in the striatum through the activation of P-SAPK/JNK.