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Programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced non-small cell lung cancer(NSCLC), but patients with low PD-L1 expression have limited objective response and survival benefits. Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world. Therefore, researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different sub-groups in NSCLC. Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC. In addition to exploring different emerging combination options, how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy. This article reviews the mechanism of action, research progress, predictive biomarkers and future exploration directions of dual immunotherapy. .
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Humans , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunotherapy , Lung Neoplasms/drug therapy , PrognosisABSTRACT
Objective:To investigate the diagnosis and management of partial or complete hydatidiform mole with coexistent intrauterine pregnancy.Methods:Clinical data of 10 cases of hydatidiform mole with coexistent intrauterine pregnancy admitted to the Third Affiliated Hospital of Guangzhou Medical University, from September 2009 to May 2019 were retrospectively described.Results:(1) During the same period, 65 960 women were delivered at our hospital, and hydatidiform mole with coexistent intrauterine pregnancy was accounted for 1/6 596, among which complete hydatidiform mole and coexisting fetus (CHMCF) and partial hydatidiform mole and coexistent fetus (PHMCF) were found in four and six cases, respectively. The mean age of the ten patients were (30.9±4.1) years old, ranging from 26 to 35 years old, with 2.5 (1-4) times of pregnancies. Nine cases were identified at 22 +3 (12 +3-32 +3) gestational weeks and one at 9 + weeks. (2) Recurrent vaginal bleeding during pregnancy occurred in six cases, nausea and vomiting in three cases, and hyperthyroidism in mid- and late pregnancy in two cases. One patient developed preeclampsia and one case of severe mitral regurgitation with mild pulmonary hypertension. (3) In the 10 patients, the summit serum β -hCG level was 139 935 (16 990-546 033) U/L, and CHMCF and PHMCF patients were 212 500 (200 000-546 033) U/L and 60 768 (16 990-225 000) U/L, respectively. (4) The ultrasound results revealed a dark honeycomb area of the placenta in five cases, placental thickening in two cases, and vesicular placenta in one case. One case was found with bilateral giant luteinized ovarian cyst by ultrasound, multiple metastases in the left lower lobe of the lung by chest CT, multiple nodules in the pleural wall of the left lung by lung MRI, and CHMCF by pelvic MRI. In one case, ultrasound at 14 weeks of gestation showed interrupted fetal abdominal wall, visible mass, gastric bubble, liver, part of the intestinal echoes, and omphalocele. One case was found with embryo arrest. (5) The karyotype analysis of one case through amniocentesis was 46,XX with no anomalies, and chromosome microarray analysis was arr[hg19](1-22)×2. Prenatal diagnosis was refused in the remaining cases. (6) Among the ten patients, three were terminated by rivanol intra-amniotic injection, two received drug abortion, and uterine evacuation, and two with spontaneous abortion followed by curettage with a visible fetus and hydatidiform tissue. Total hysterectomy was performed in one patient due to partial invasion of the uterus by hydatidiform mole. One patient underwent a cesarean section on account of the left lower lung metastasis. One case developed preeclampsia at 33 +4 weeks of gestation and delivered two premature infants by cesarean section. Pathology examination found a complete and partial vesicular fetal mass in four and six cases, with P57 (－) and P57 (+), respectively. (7) During the follow-up, two women developed the persistent trophoblastic disease and received chemotherapy, while the remaining eight cases did not. Conclusions:When hydatidiform mole with coexistent intrauterine pregnancy is found, a timely differential diagnosis between CHMCF and PHMCF is needed. CHMCF is at a higher risk of abortion, intrauterine death, premature delivery, preeclampsia, and other maternal complications. Therefore, termination of CHMCF should be individualized. Most PHMCF patients have fetal malformation or fetal loss; thereby, timely termination is recommended.
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Objective To evaluate the role of thrombus elastograph (TEG) in evaluating the coagulation function of patients with acute ischemic stroke.Methods Totally 116 cases of patients with acute ischemic stroke and 116 cases of health physical examination people from our hospital were selected as case group and control group.The blood clotting index and thrombelastogram index of the groups were detected.Results In case group of acute phase,fibrinogen (FIB),two D-dimer (D-D),maximum blood clot strength (MA),0.5 h blood clot reduction rate of MA (LY30),alpha angle,integrated coagulation index (CI) and blood clot strength (G) were significantly higher than those of control group and the recovery period group.The difference was statistically significant(P＜0.01).In cases of acute phase,activated partial thromboplastin time (APTT),prothrombin time (PT),PT-INR,reaction time (R),clot formation time (K value) were significantly lower than those in the healthy control group and the recovery period cases,the difference was statistically significant (P＜0.01).MA,LY30,α Angle and CI were negatively correlated with PT,APTT,PT-INR,and were positively correlated with FIB,D-D(P＜0.05);R value,K value were positively correlated with PT,APTT,PT-INR,and were negatively correlated with FIB,D-D(P＜ 0.05).Conclusion TEG plays a significant role in monitoring and evaluating coagulation function in patients with acute ischemic stroke,and has important evaluation effect on the prognosis of disease.It is worthy of clinical application.
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Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions . Methods Retrospectively analyzed the contrast-enhanced ultrasound model and angiographic predictive model of 465 cases of the A prospective multicenter study of breast nodules contrast-enhanced ultrasound" that led the Sichuan Provincial People′s Hospital from January 2016 to April 2017 ,which included 69 cases of breast precancerous lesions and 396 other types benign lesions ,and the sensitivity ,specificity and accuracy of the diagnosis of breast precancerous lesions were calculated . Results The sensitivity of ultrasound predictive model for the diagnosis of precancerous lesions was 60 .9％ and AUC was 0 .681 . Precancerous lesions mainly showed non-concentricity , increased homogeneity , and increased lesions;other types of benign lesions mainly showed non-centripetal ,high uniformity enhancement and lesion size unchanged . Conclusions Contrast-enhanced ultrasound shows a potential value in the differential diagnosis of precancerous lesions and other types of benign lesions ,that can help clinicians to take early intervention measures for breast precancerous lesions ,but there are still many problems to be solved .
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Objective To obtain a more accurate assessment of prognostic significance of NLR in ovarian cancer. Methods A systematic literature search was conducted using the electronic databases PubMed ,Web of Science,and Embase up to May 2016. Hazard ratio(HR)and odds ratio(OR)with 95% confidence interval (95%CI)were calculated. Statistical analysis was performed using Stata 12.0. Results 12 studies,consisting of 3 ,854 patients ,were selected in this meta-analysis. High NLR level was significantly associated with poorer overall survival(OS)(HR:1.69)and shorter progression free survival(PFS)(HR 1.63). Additionally,increased NLR was significantly correlated with advanced FIGO stage(OR 2.32),higher level of CA-125(OR 3.33),more extensive ascites(OR 3.54)as well as less chemotheraputic response(OR 0.53). Conclusions Elevated pretreat-ment NLR can serve as a predicative factor of poor prognosis for ovarian cancer.
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Objective To explore the value of transrectal elastography and contrast-enhanced ultrasound in evaluation of the efficacy of neoadjuvant therapy for rectal cancer.Methods Forty patients with final diagnosis of advanced(T≥3) rectal cancer were respectively examined with transrectal ultrasound (TRUS),endorectal elastography and contrast-enhanced ultrasound(CEUS) before and after neoadjuvant therapy(NET).The tumor size,strain ratio and quantitative parameters of contrast-enhanced ultrasound including arrival time(AT),time-to-peak (TTP),peak intensity(PI) and area under the curve(AUC) were recorded and compared before and after NET.In addition,the TRUS stages and postoperative pathological diagnosis were compared after NET.Results ①There were significant decreases in tumor size and strain ratio after the therapy compared with pre-therapy in all these patients(t =-6.13,P ＜0.001;t =-24.92,P ＜ 0.001).②PI and AUC were lower after NET than those of pre-therapy and the differences were significant(t =-9.66,P =0.001;t =-13.58,P ＜0.001).However,the changes of AT and TTP were no statistical significances (t =-1.17,P =0.307;t =-1.26,P =0.275).③The accuracys of preoperative TRUS for T stage and N stage of tumor evaluated according to pathology were respectively 75.0 ％ (30/40,Kappa =0.593,P =0.000) and 72.5 ％ (29/40,Kappa =0.396,P =0.009).Conclusions Transrectal elastography and contrast-enhanced ultrasound can reflect the pathological changes and perfusion characteristics of lesions in a certain extent and have high value in clinical therapy.
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Objective To observe the blood flow changes of left ventricular cavity and quantify the energy loss (EL) and circulation of left ventricular during systole and diastole in patients with dilated cardiomyopathy(DCM) via vector flow mapping(VFM).Methods Thirty-six healthy volunteers and 32DCM patients were enrolled.According to the severity of mitral regurgitation(MR),DCM patients were divided into two groups.The quantitative parameters,including average energy loss(EL-base,EL mid,EL-apex) and circulation (vortex quantity,vortex area,circulation) were measured in the different periods of VFM imaging mode in apical four-chamber view,apical three-chamber view and apical two-chamber view respectively.The difference of parameters was evaluated between different groups during the different periods.The early transmitral valve blood flow velocity E,the late transmitral valve blood flow velocity A,the ratio of early transmitral valve blood flow velocity to the early diastolic mitral valve velocity E/e,the ratio of early transmitral valve blood flow velocity to the late transmitral valve blood flow velocity E/A and Tei index were derived via dual-Doppler imaging technology.Meanwhile,the correlation between VFM parameters with E,A,E/A,E/e or Tei index was also analyzed.Results ①The level of EL were decreased significantly among EL-mid and EL-apex during early diastole,EL-mid during mid-systole,EL-mid and EL-apex during late-systole (P ＜0.05),when compared with the control group.The vortex quantity,vortex area and circulation during early diastole and the vortex area and circulation during atrial contraction period were significantly different between two groups (all P ＜ 0.05).As for mid-diastole,only vortex area showed significant difference (P ＜0).01).(②) When compared with different grades of MR in DCM patients,the level of all segments EL during diastole and EL-base during systole increased with severity of MR(P ＜0.05).The circulation during diastole also increased with the severity of MR(P ＜0.05).③The vortex area and circulation had positive correlation with E/e during diastole in all subjects(all P ＜0.05).The vortex area during atrial contraction period and early diastole had positive correlation with E/A and Tei index in all subjects(r =0.630,0.345,0.468,0.316,0.663,0.264,respectively,allP ＜0.01).EL-mid during late-systole were negatively correlated with LV end diastolic volume,end systolic volume,but positively correlated with ejection fraction in all subjects(r =0.335,-0.312,0.340,respectively,all P ＜0.05).While,there was positive correlation between E/A with the basal segment of mid-diastole(r =0.376,P ＜0.01).Conclusions The visualization of hydromechanics inside the heart of DCM patients could be directly accomplished by VFM,which can provide a new method for diagnosis and evaluation of DCM.
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Objective To establish the gas chromatographic(GC) fingerprint of oleic acid of Whitmania pigra Whitman for its quality control. Methods Ten batches of Whitmania pigra from different sources and processed by different methods were analyzed with Agilent 6890N gas chromatography detector on DB-WAX(30 mm × 0.32 mm × 0.25μm)column at the vaporizing temperature of 270℃, column temperature of 130℃and flame ionization detector (FID) temperature of 280℃. We used a software of Similarity Evaluation System for Chromatographic Fingerprint of TCM(Version of 2004A) published by Chinese Pharmacopoeia Commission to calculate GC similarity. Results Oleic acid content of Whitmania pigra processed by different methods had significant differences (F2,7 = 7.350, P = 0.019). The oleic acid content of samples dried after washing with clean water significantly differed from that of the samples processed by alumen or the slices dried naturally(P = 0.021, P= 0.009). The similarity of the fingerprints was in the range of 0.458 - 0.998. The similarity of samples from Lipu of Guangxi Province was the lowest. Conclusion The fingerprints of most of the samples have very high similarity. The established GC fingerprints can be used to effectively identify the qualified or inferior Whitmania pigra products, which will provide some reference for the quality control of Whitmania pigra.
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Objective To investigate the clinical validity of the Chinese version of John Hopkins Adapted Cognitive Exam (ACE) for in-patients in neurological intensive care unit (NICU). Methods From May, 2014 to June, 2015, 94 inpatients in NICU and 52 healthy persons were assessed with the Chinese version of ACE and Mini-Mental State Examination (MMSE). Results The total score of ACE correlated with the total score of MMSE (r=0.805, P2.458, P<0.05). The area under the receiver operating curve was not different between ACE and MMSE (Z=0.707, P=0.480). Conclusion The Chinese version of ACE can be the tool for assessment of cognition for pa-tients in NICU.
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Objective To investigate the clinical efficacy of Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery for patients at the early stage of traumatic brain injury (TBI). Methods 72 patients with TBI hospitalized from January, 2013 to October, 2014 and 30 healthy controls matched gender, age and educational background were assessed with the Chinese version of LOTCA battery and Mini-Mental State Examination (MMSE) respectively. Results The score of MMSE and LOTCA were correlated (r=0.56, P<0.01). Compared with the controls, the scores of all the subtests of LOTCA decreased (P<0.01) in the patients, especially the orientation, visuomo-tor organization and thinking operation;with the more incidence of medium and serious dysfunction of all the subtests of LOTCA except perception (P<0.01), in which thinking operation was the most and attention was the least. The area under the receiver operating curve (ROC) was (0.84±0.04) in LOTCA, less than that of (0.91±0.03) in MMSE (P<0.05). Conclusion Cognition is widely impaired in patients after TBI, most involved thinking operation. LOTCA is less effective to identify cognitive dysfunction than MMSE, and can be used as an al-ternation or a supplement.
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Objective To compare the respective diagnostic efficiency for breast cancer with ultrasound diffusion optical imaging (DOI),ultrasonic elastography (UE),contrast-enhanced ultrasound (CEUS),X-ray mammography(XRM),magnetic resonance imaging (MRI),and combinations of these imaging modalities.Methods Seventy-five breast lesions were collected.These lesions were confirmed by surgery and histopathology.All of breast lesions were examined ultrasound,mammography and enhancedMRI examinations before surgical excision.The specificity,sensitivity,positive predictive value and negative predictive value of each modality were compared.Results The sensitivities and the diagnostic negative predictive values for MRI + US + XRM (97.44％,96.15％),CEUS (92.31％,90.63％) and MRI (94.87 ％,92.86％) were significantly higher than those for XRM (74.36 ％,71.43 ％),respectively.The sensitivity for DOI + CEUS + UE was the same as one for CEUS,they were not significantly higher than those for UE and DOI (P ＞0.05),while they were significantly higher than that for XRM (P ＜0.05).The kappa values for DOI,UE,CEUS,USG(UE + DOI + CEUS),XRM,MRI and MRI + US + XRM were 0.678,0.624,0.732,0.705,0.439,0.677 and 0.676,respectively.Conclusions Different imaging modalities have themselves advantages to diagnose malignant or benign lesions.CEUS,MRI and combinations of these imaging modalities have highly important clinical values in breast disease diagnosis.
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Objective To test the reliability and validity of the Chinese version of the John Hopkins Adapted Cognitive Exam ( ACE) in NICU patients. Methods The English ACE was translated and adapted into the Chinese version . Cognitive functions of 40 critically ill patients in NICU were assessed with the Chi?nese version of ACE and MMSE battery.The scores of ACE and MMSE were analyzed to test the content va?lidity,construct validity,concurrent validity,internal consistency,inter?rater reliability and test?retest reliabil?ity.Result The correlation coefficient between each factor and the total score ranged from 0.617 to 0.938, and the content validity was good.The ACE was significantly correlated with MMSE( r=0.822, P0.95) and test?retest reliabil?ity (ICC=0.652?0.979) of the Chinese version of ACE.Conclusions The Chinese version of ACE has been proved to be a reliable and valid screening tool for cognitive impairment in NICU patients.
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Objective To investigate the preliminary experience of mechanical thrombectomy with a tri-axial system of the Solitaire AB stent through a Neuro delivery catheter to treat intracranial large artery occlusion. Methods A tri-axial system was used to deliver the Solitaire AB stent through a Neuro delivery catheter to provide intracranial aspiration in close proximity to the stent. This technique was used in 1 case of acute middle cerebral artery occlusion and 1 case of acute basilar artery occlusion. Results Successful revascularization was achieved in these 2 cases. Thrombolysis in cerebral infarction (TICI)score was 3. The clot length of acute middle cerebral artery occlusion was 3 cm and the modified Rankin Scale (mRS)score of this case was 3 at 90 days follow-up. Another patient with acute bilateral vertebral occlusion was revealed successful recanalization by angiography. Conclusion The results suggest that this technique of a tri-axial system used of the Solitaire stent through a Neuro delivery catheter can effectively retrieve clots from the occlusive artery and minimize the chance of antegrade blood flow dislodging the thrombus.
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Objective To evaluate the Montreal cognitive assessment (MoCA) for detecting the mild cognitive impairment (MCI) in brain trauma patients with normal mini-mental state examination (MMSE) scores.Methods Fifty brain trauma patients with normal MMSE scores hospitalized from January 2013 to June 2014 were subjected to the MoCA test.The patients were classified as cognitive impairment group scored less than 26 on the MoCA and cognitive normal group scored 26 or above on the MoCA.Differences in MMSE and MoCA scores of the two groups were compared.Receiver operative characteristic (ROC) curve was used to determine the optimal cut-off scores in screening for MCI.Results Overall MMSE and MoCA scores were (27.84 ± 0.89) points and (23.24 ± 2.90) points.There was a positive correlation between MoCA and MMSE total scores (r =0.355 2,P ＜ 0.05).MCI was found in 79％ of the brain trauma patients using the MoCA.MMSE total score and subscores were all similar between the two groups.MoCA total score and subscores of attention,language,abstraction and delayed recall were much higher in cognitive normal group than in cognitive impairment group (P ＜0.05),but there were no significant differences in visuospatial,naming and oritention domains.Area under the ROC curve for MoCA(0.871 ± 0.038) was larger compared with MMSE (0.796 ± 0.054) (Z =3.592,P ＜ 0.05).The optimal cut-off scores of MoCA and MMSE for the identification of MCI were 25.5 and 28.5 respectively.Conclusions MoCA and MMSE total scores are positively correlated.MoCA is a better detector for the identification of MCI in brain trauma patients than the MMSE.
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Objective To explore the impact of pre-implant hearing aid fitting on the early open-set word recognition in children who received a cochlear implant(CI) when they were infants .Methods A total of 289 chil‐dren who received a cochlear implant between 0 .9 and 3 .0 years of age were included in this study .According to pre-implant hearing aid fitting ,participants were divided into hearing aid group and non-hearing aid group .The open-set word identification abilities of the cochlear implant children were evaluated via Mandarin Lexical Neighborhood test(M -LNT) .Results Comparisons of the scores of M -LNT between two groups displayed no significant differ‐ence at the same identification age or duration of CI use .Conclusion The abilities of the early open-set word rec‐ognition between hearing aid group and non-hearing aid group didn’t make significant differences for the CI chil‐dren w ho received a cochlear implant betw een 0 .9 and 3 .0 years old .
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@#Objective To explore the risk factors of dysphagia in the patients with traumatic brain injuries (TBI). Methods 141 TBI patients were assessed with Gugging Swallowing Screen, and divided into the dysphagia (n=36) and normal (n=105) groups. The related factors were compared between 2 groups. Results The frequency increased in severe brain injury, brain stem injury, bilateral brain injury, tracheotomy, nasal-gastric tube insertion and cognitive defect in the dysphagia group compared with those in the normal group (P<0.05). Conclusion The severe brain injury, brain stem injury, bilateral brain injury, tracheotomy, nasal-gastric tube insertion and cognitive defect may be related with the dysphagia post TBI.
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Objective To explore the risk factors of dysphagia in the patients with traumatic brain injuries (TBI). Methods 141 TBI pa-tients were assessed with Gugging Swallowing Screen, and divided into the dysphagia (n=36) and normal (n=105) groups. The related fac-tors were compared between 2 groups. Results The frequency increased in severe brain injury, brain stem injury, bilateral brain injury, tra-cheotomy, nasal-gastric tube insertion and cognitive defect in the dysphagia group compared with those in the normal group (P<0.05). Con-clusion The severe brain injury, brain stem injury, bilateral brain injury, tracheotomy, nasal-gastric tube insertion and cognitive defect may be related with the dysphagia post TBI.
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Objective To compare the validity of Montreal cognitive assessment (MoCA) versus mini-mental state examination (MMSE) in screening cognition impairment in elderly patients with cranio-cerebral trauma.Methods Cognitive function in 40 elderly patients with cranio-cerebral trauma and 40 healthy elderly individuals were assessed by MoCA and MMSE.Receiver operating characteristic (ROC) curve analysis were performed to determine the optimal sensitivity and specificity of MoCA and MMSE.Results The total score and all the sub-test scores of MoCA were much lower in cranio-cerebral trauma patients than in the control group (all P＜0.05).The total score and orientation,calculation,recall,language sub scores of MMSE were significantly decreased in the elderly patients with cranio-cerebral trauma as compared with those in the controls (P＜0.05),while there were no significant differences in the immediate memory and language scores between the two groups (both P＞0.05).The area under the receiver operating characteristic curve showed that MoCA (0.92±0.03) ＞ MMSE (0.74±0.06) (Z=2.460,P＜0.01).When screening the cognition impairment in elderly patients with cranio cerebral trauma,the best cut-off scores of MoCA and MMSE were 24.5 and 27.5 respectively.Conclusions Cognition impairment is decreased in elderly patients with cranio cerebral trauma.The MoCA is superior to the MMSE as a screening instrument in detecting cognition impairment in elderly patients with cranio-cerebral trauma.
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Objective To observe the effect of cognitive rehabilitation training based on games on cognition of the traumatic brain injury (TBI) patients.Methods 60 cases of patients according with the inclusion and exclusion criteria were divided into the control group and the training group with 30 cases in each group.The Montreal cognitive assessment (MoCA) test scores of all patients were lower than 26 points.The training group accepted the cognitive rehabilitation training based on games such as exactly the same game,drum game and picture memory game,while the control group did not accept the training.After one month,all patients accepted the MoCA test again.Then we analyzed the differences of the cognition between the two groups.Results After 30 days of training,all items of the cognitive function increased except the sub-item of abstraction.While in the control group,only the scores of attention,delayed recall,orientation and the total score showed alleviation.And all the scores of the training group were higher than those of the control group except the sub-item of abstraction.Conclusions Cognitive rehabilitation training based on games can effectively improve the cognitive function of TBI patients.
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ObjectiveTo test the reproducibility of wave intensity (WI)analysis derived measurements of pulse wave velocity (PWV),and to compare it with the traditional method-applanation tonometry.MethodsOne hundred and ten outpatient volunteers were enrolled in the study.The R-W1 of right brachial artery and right posterior tibial artery were measured through WI in diagnostic ultrasound equipment (Aloka α10),and were used to calculate the right brachial artery PWV which were also measured by tonometry (VP-1000) simutaneously;thus 30 of these volunteers were randomly selected to repeat the above examinations in the same session.Differences between the two methods were investigated by means of a paired t-test,and their linear correlations were also analyzed.Bland-Altman method was used to analyze the agreement between the two methods and their intraobserver intrasession variabilities.ResultsMean baPWVs determined by WI and tonometry were (13.03 ± 1.93) m/s and ( 12.05 ± 2.02) m/s,respectively (P ＜0.001),and the mean of their difference was (0.98 ± 1.1)m/s giving 95 ％ limits of agreement of ( - 1.18 m/s,3.14 m/s).Values of PWV obtained by the two systems were highly correlated( r =0.85,P＜ 0.001 ),with their intraobserver intrasession variabilities being 8.2％ and 7.0％,respectively.ConclusionsWI provides a new noninvasive and convenient method to measure PWV with good agreement and similar reproducibility to the standard tonometry system.