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*

Purpose: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. Materials and Methods: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. Results: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. Conclusion AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

Objective To investigate the value of heparin-binding protein(HBP) in predicting urosepsis after endoscopic lithotripsy for upper urinary tract stones.Methods From January to November 2018,635 cases of upper urinary tract stones treated by endoscopic lithotripsy in our hospital was analyzed.According to the 2014 edition Chinese Guidelines of the diagnosis and treatment of urosepsis,all patients were divided into two groups,the definite urosepsis group (n =53,8.3％) and the no urosepsis group (n =582,91.7％).The serum of HBP level was detected by fluorescence immunoassay technology.The serum of procalcitonin (PCT) level was detected by cyclic enhanced immunofluorescent assay.C-reactive protein (CRP) level was detected by automatic chemiluminescence immunoassay analyzer.White blood cells (WBC) count was performed by hematology analyzer.Receiver operating characteristic(ROC) curves were constructed by SPSS 22 and MedCale,and areas under curves (AUC) were calculated and compared to illustrate the diagnostic power of HBP,PCT,CRP and WBC.The correlation between HBP and WBC was also significant (r =0.68,P ＜ 0.05).Results The level of HBP,PCT,CRP and WBC were significantly higher in the definite urosepsis group compared to the no urosepsis group.AUC of HBP,PCT,CRP and WBC were 0.930,0.878,0.727 and 0.617.When the cutoff of HBP,PCT,CRP and WBC were set as 51.5 ng/ml,0.41 ng/ml,64.2 mg/L and 11.7 × 109/L,the sensitivities were 89.2％,83.3％,83.5％ and 44.7％,and the specificity were 95.9％,75.6％,64.3％ and 77.1％,respectively.Conclusions The value of heparin-binding protein was superior to that of PCT,CRP and WBC in predicting urosepsis after endoscopic lithotripsy for upper urinary tract stones.Heparin-binding protein could be acted as a diagnostic marker for urosepsis.

Objective To reveal the virulence genes and the polymorphisms of chromosomal 16S rRNA gene of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province,2015. Methods Five virulence genes(ail,virF,yadA,ystA and ystB)of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province were detected by using polymerase chain reaction(PCR),and phylogenetic analysis of chromosomal 16S rRNA gene was performed by amplification and sequencing. Results In this study,73 Yersinia enterocolitic strains were collected in Jiangsu Province in 2015.Among them,56(76.7%)strains carried virulence genes,and ail-virF-yadA -ystA -ystB+were the dominate types in diarrhea patients and other hosts.All strains can be clustering into 4 groups according to the phylogenetic analysis of chromosomal 16S rRNA gene.Conclusions The non-pathogenic Yersinia enterocolitic(ystB+)is the dominant strain in Jiangsu province,and the pathogenic strains are also found in this region.The result of phylogenetic analysis of chromosomal 16S rRNA gene and the profiles of virulence genes are highly consistent.

Objective To evaluate the accuracy in placement of cervical anterior transpedicular screws (ATPS) under the guidance of our modified drilling template.Methods Eight wet cadaveric specimens of adult cervical spine,4 male and 4 female ones,were used for this experiment.Data of CT thin layer scanning of the cervical specimens in DICOM format were imported into software Mimics 17.0.After 3D models of the cervical vertebrae were reconstructed,the optimal trajectory was designed for ATPS placement in the transparent mode of the 3D models.Normal and our modified drilling templates for ATPS placement were designed and manufactured by 3D printing.The 2 kinds of drilling templates were used to assist ATPS placement onto one cervical vertebra,with laterality randomized.Altogether 64 pieces of ATPS were placed,with 32 ones for each drilling template.Postoperative CT scanning was conducted to evaluate the accuracy in ATPS placement.The 2 kinds of ATPS template were compared in terms of the deviations between actual and ideal trajectories in direction (caudal-angle and extroversive-angle) and position (X and Y axes) of the entry point.Results Our modified drilling template led to one screw penetrating the pedicle cortical bone while the normal drilling template led to 4 screws penetrating the pedicle cortical bone,yielding an accuracy rate of 96.9％ and of 87.5％ respectively.The extroversive-angle deviation (0.72°±0.69°),caudal-angle deviation (0.91°±0.70°),X axis shift (0.53 ±0.40 mm) and Y axis shift (0.54 ±0.42 mm) related to the modified template were all significantly smaller than those related to the normal template (1.16° ± 0.70°,1.49°±0.68°,0.88±0.40mm,1.22±0.42mm,respectively) (P ＜0.05).Conclusion Compared with a normal ATPS template,our modified drilling template for ATPS may be advantageous in better fitness,greater stability,increased accuracy in screw placement,and protection of adjacent discs.

Objective To analyze the causes of revision surgery after percutaneous transforaminal endoscopic discectomy (PTED) for lumbar spinal stenosis,and to provide references for indications and operative methods.Methods From January 2015 to October 2017,206,491 and 60 patients of lumbar spinal stenosis were treated with PTED in Tianjin Hospital,Shanxi People's Hospital,Ningbo Sixth Hospital,respectively;among them,4,10 and 4 cases received revision surgery.Another 13 patients of lumbar spinal stenosis were treated with revision surgery due to poor results after PTED in other hospitals.Among 31 cases of reoperation,there were 16 males and 15 females,aged 27-82 years (average,66.2±12.7 years).The lesion segments included 1 case of L3,4,23 cases of L4,5,5 cases of L5S1,1 cases of L3-L5,and 1 cases of L4-S1.Patients were followed up after reoperation from 3 to 24 months (average,12.1 months).The causes of poor result and revision surgery were analyzed according to preoperative,intraoperative and postoperative data.Results All of 757 cases of lumbar spinal stenosis were treated with PTED in three hospitals,of which 18 cases (2.4％) were re-operated.The causes of reoperation included:bone slice displacement in 1 case;nerve injury in 4 cases;lumbar instability in 4 cases;disc protrusion in 10 cases (residual or recurrence);insufficient decompression in 21 cases;planed staging operation in 4 cases with bilateral or two-level stenosis.32 revision surgeries were performed for 31 patients,including PTED in 15 cases,microendoscopic discectomy (MED) in 1 case,mobile MED (MMED) in 5 cases,MMED assisted fusion in 2 cases,transforaminal lumbar interbody fusion (TLIF) in 4 cases,Minimally invasive TLIF (Mis-TLIF) in 2 cases,and open decompression and fusion in 3 cases.All patients experienced relieve of symptoms after revision surgery.At final follow-up,VAS leg pain deceased form 7.1±3.9 before revision surgeries to 1.9±1.2,VAS low back pain decreased form 6.3±3.2 to 1.8±1.3,ODI score decreased from 35％± 14％ to 7.6％±5％.According to the MacNab score,the result was excellent in 11 cases,good in 16 cases,and fair in 4 cases.Conclusion The treatment of lumbar stenosis with PTED has high technical requirements,the indications of PTED for lumbar stenosis should be strictly controlled according to technical conditions,and appropriate operative methods should be chosen according to the specific conditions of the lesions.Insufficient decompression,disc protrusion,lumbar instability and nerve injury are the common causes of reoperation.Suitable indications and proper operation should be selected.

Objective Retrospective study and report on cases of "symptomatic facet of residual bone mass" caused by percutaneous transforaminal endoscopic discectomy (PTED),to analysis of its causes and revision strategies.Methods Seven cases of "symptomatic facet of residual bone mass" after PTED were found in six medical centers from July 2015 to November 2017.Weintroduced the course of diagnosis and treatment,to analysis of the causes,clinical features and revision strategies of the rare complication.Results Seven patients came from different medical centers (2 cases in Ningbo No.6 Hospital and 1 case in each of the other medical centers).The average age of the subject is 67.29±9.64 years (range from 57-83 years).Among them there were 1 male and 6 female.PTED was performed for all cases with lumbar disc herniation or stenosis.The operative segments were 1 of L2,3,2 of L3,4,3 of L4,5,1 of L5S1.Symptoms occurred immediately after surgery in all cases except one after a week of operation and another one month later.Two cases were appeared symptom of contralateral irritation,and the rest were aggravated by the original symptoms.Two cerebrospinal fluid leakage caused by bone mass piercing the dural sac.The bone mass compressed the nerve root and caused 1 case of lower limb muscle weakness.Foraminoplasty was performed during PTED in all patients.After CT scan,5 cases of bone mass were found on the same side of operation,and 2 cases were in the contralateral side.The shortest time for revision was 2 days and the longest 3 months.After conservative treatment,the symptoms were relieved in only one case.Revision surgeries were performed for all the other 6 cases,2 with microendoscopic discectomy (MED),1 mobile microendoscopic discectomy (MMED),1 small incision operation,1 PTED and 1 with minimal invasive surgery of transforaminal lumbar intervertebral fusion (MIS-TLIF).The VAS scores of low back pain and leg pain was significantly relieved from 8.67±0.52 to 1.50±0.55.Conclusion FTED may lead to residual bone mass in lumbar foraminoplasty.The penetration of the bone mass block into the spinal canal can cause the compression symptoms of the corresponding segment.The patients showed the corresponding spinal canal stenosis and nerve root irritation symptoms.A revision operation is required to remove the oppressed bone mass to relieve the symptoms as soon as possible if the conservative treatment not effective.

Objective To investigate the optimal trajectory of posterior occipital condyle screw fixation via radiological and anatomical study.Methods Twelve adult craniocervical junction complete specimens were selected.The length,width and height of occipital condyle and the inclination angle of the longest axis were measured by CT scanning and reconstruction.Subsequently,occipital condyle screws were inserted with reference to CT measurements.After screw fixation,accuracy and safety of the placement of occipital condyle screw were verified by gross observation and CT scanning.Results Preoperative measurements of height and width of the occipital condyles indicated the placement of 4.0 mm bicortical screws was secure.Left vertebral artery horizontal sections of 2 specimens were slightly pressed without damage.CT scanning identified no damage to the inner or outer wall of the occipital condyle and the hypoglossal canal.Trajectory parameters between the right and left sides were slightly different,but no significant difference was observed (P ＞ 0.05).Average screw channel length and inclination angle were (20.8 ±2.6)mm and (37.1 ± 4.7)°respectively.Angle between screw and skull base tangent was observed as (8.5 ± 1.7) °.Distance between screw axis and hypoglossal canal was observed as (3.1 ± 1.1) mm.And the distance averaged (4.6 ± 1.4) mm between occipital condyle screw entry point and skull base and (6.1 ± 1.5) mm between entry point and inside edge of the occipital condyle.Conclusion Occipital condyle can be used as a new alternative fixed point in occipitocervical fusion.

Objective:To explore the expression of aquaporin1 (AQP1) in human glioma tissues and its relationship with the clini-copathological parameters and prognosis of this tumor. This study also observed the function of AQP1 in the proliferation and invasion of LN229 glioblastoma cells. Methods:The expression of AQP1 in 135 cases of glioma was detected by immunohistochemical meth-od, and the correlation between AQP1 and pathological features of glioma was analyzed. The relationship of AQP1 with survival was al-so investigated using 103 specimens with complete clinical data. AQP1 was successfully transfected into LN229 cells with lentiviral vector, and the expression of AQP1 protein was tested by Western blot. Cell proliferation was detected by using methyl thiazolyl tetrazo-lium assay, whereas cell invasion was determined by Transwell assay. Results:The expression of AQP1 was positively correlated with pathological grading. High AQP1 expression was associated with poor prognosis (P<0.05). Moreover, the overexpression of AQP1 can significantly increase the proliferation and invasion of LN229 cells (P<0.05). Conclusion:AQP1 is closely associated with the progres-sion of glioma. Upregulation of the AQP1 expression promoted the proliferation and metastasis of glioma cells. These findings indicat-ed that AQP1 can function as a therapeutic target for glioma in future research.

BACKGROUNDPaclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients, but clinical studies showed that some breast cancer patients were insensitive to PAC, which led to chemotherapy failure. It was reported that Notch1 signaling participated in drug resistance of breast cancer. Here, we show whether Notch1 expression is related to PAC sensitivity of breast cancer.

METHODSWe employed Notch1 siRNA and Notch1 inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT), to down regulate Notch1 expression in human breast cancer cells MDA-MB-231, and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction, respectively. After 24 hours exposure to different concentration of PAC (0, 1, 5, 10, 15, 20, and 25 µg/ml), the viability of the control group and experimental group cells was tested by MTT. We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients, respectively by immunohistochemistry (IHC). The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).

RESULTSDown regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P < 0.05). Also, the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P < 0.01).

CONCLUSIONNotch1 expression has an effect on PAC sensitivity in breast cancer patients, and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dipeptides ; pharmacology ; Humans ; Immunohistochemistry ; Paclitaxel ; pharmacology ; Receptor, Notch1 ; antagonists & inhibitors ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction