Programmed cell death-1 inhibitor combined with immunochemotherapy in treatment of refractory primary mediastinal large B-cell lymphoma: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy of programmed cell death-1 (PD-1) inhibitor combined with immunochemotherapy in the treatment of refractory primary mediastinal large B-cell lymphoma (PMBCL).Methods:The clinical data of 2 refractory PMBCL patients who were achieving remission after applying PD-1 inhibitor combined with immunochemotherapy in Qilu Hospital of Shandong University (Qingdao) in July 2019 and January 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The two patients were initially treated with CDOPE and R-CDOPE regimens, respectively, but the disease did not reach remission state. Later, they were adjusted to PD-1 inhibitor combined with immunochemotherapy to achieve remission. Radiotherapy and autologous hematopoietic stem cell transplantation were used as consolidation treatment, and maintenance therapy with PD-1 inhibitors was effective and had a good safety profile.Conclusions:For refractory PMBCL patients, PD-1 inhibitor combined with immunochemotherapy may have good efficacy.

Advances of Lefamulin: a new pleuromutilin antibiotic / 药学学报

Lefamulin (BC-3781) is a semi-synthetic pleuromutilin antibiotic, approved for the treatment of community-acquired bacterial pneumonia (CABP) by Food and Drug Administration (USA) in August 2019, with the commodity name of Xenleta. It is the first pleuromutilin antibiotics used for systemic treatment of bacterial infections in human. Lefamulin binds to the peptidyl transferase center of the 50S ribosomal subunit to prevent peptide transfer, thus inhibits protein synthesis. Lefamulin displays expanded activity against gram-positive organisms, and also shows high activity against atypical microorganism like Mycoplasma pneumoniae. This review discusses the mechanism, bacterial spectrum of activity, preclinical and clinical data of Lefamulin.

Advances in researches on neoadjuvant therapy for resectable colorectal liver metastasis / 中华胃肠外科杂志

Surgery is recognized as the core treatment for colorectal liver metastasis (CRLM), while its recurrence rate remains relatively high, even for resectable CRLM. This hints that the efficacy of treatment involves not only technological factors of surgery, but also biological behavior of tumor. For resectable CRLM, neoadjuvant therapy is beneficial to eliminate the micro-metastasis, reduce postoperative recurrence rate, screen tumor biological behavior and improve prognosis. However, questions about which kind of CRLM patients fits for neoadjuvant therapy and what regimen should be used are still debatable. This paper reviews stratified management of resectable CRLM, choice of neoadjuvant regimen, especially the application value of targeted therapy, based on the latest guidelines and studies.

Quantitative evaluation of extracellular volume fraction after acute ST segment elevation myocardial infarction by iodine density based on spectral detector CT / 中华放射学杂志

Objective:To explore the feasibility of quantitative evaluation of extracellular volume (ECV) fraction in acute ST-segment elevation myocardial infarction (STEMI) by dual-layer spectral detector CT.Methods:The clinical and imaging data of 20 patients with STEMI who underwent cardiac contrast-enhanced CT and MRI from January to October 2019 in Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed.The dual spectral detector was used in the enhanced CT scan of the coronary artery with retrospectively gate and the late iodine enhancement with prospective gate. Conventional image and holographic spectral image were obtained by iterative and spectral reconstruction. The short axis image of the heart matched with MR image was obtained by multiplanar reconstruction. Based on the data of spectral based image, the IDD map was reconstructed for the calculation of myocardial CT-ECV during the late iodine enhancement. ECV of infarcted myocardium, salvageable myocardium and remote myocardium based on CT and MRI were calculated respectively. Bland-Altman consistency test and intra group correlation coefficient analysis (ICC) were used to compare the consistency of two measurements and different methods. The correlation between CT-ECV and MRI-ECV was compared by Spearman method.Results:The CT-ECV values of infarcted, salvageable, and remote myocardium were 51.21 (49.27, 53)%, 38.64 (36.17, 40)%, and 51.21 (49.27, 53)%, respectively. The difference was statistically significant ( H= 43.17, P<0.01). The CT-ECV value of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=-24.60, 35.40, P<0.01), but there was no significant difference between salvageable myocardium and remote myocardium ( Z= 10.80, P=0.15). The T 1 values of infarcted myocardium, salvageable myocardium and remote myocardium were (1 554.85±70.94), (1 443.85±67.28) and (1 307.05±91.73) ms respectively, the difference was statistically significant ( F=51.35, P<0.01). The T 1 value of infarcted myocardium was higher than that of salvageable myocardium and remote myocardium ( t=-5.07, 9.55, P<0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( t=5.38, P<0.01). The MRI-ECV values of infarcted myocardium, salvageable myocardium and remote myocardium were 55.00 (49.27, 57.75)%, 33.50 (29.00, 35.00)%,and 27.00 (26.00, 29.00)%, respectively. The difference was statistically significant ( Z= 47.12, P<0.01). MRI-ECV of infarcted myocardium was significantly higher than that of salvageable myocardium and remote myocardium ( Z=37.45, -20.30, P< 0.01), and salvageable myocardium was significantly higher than that of remote myocardium ( Z = 17.15, P<0.05). The difference between CT-ECV and MRI-ECV measured by two physicians was good. The bias of Bland-Altman analysis was -0.1% (95% CI:-5.5%-5.2%), 0.8% (95% CI:-9.8%-8.2%), and the ICC values were 0.92 and 0.94, respectively. The bias of Bland-Altman analysis in CT-ECV and MRI-ECV consistency test was 4.00% (95% CI:-9.0%-16.9%) and ICC value was 0.88, which had a good correlation ( r=0.75, P=0.001). Conclusions:The iodine density based ECV fromdual-layer spectral detector CT can be used to quantitatively evaluate the changes of extracellular space after acute STEMI, which is helpful to quantitatively evaluate the histological changes after myocardial ischemia.

The prognostic significance of dynamic monitoring of minimal residual disease (MRD) status in patients with newly-diagnosed multiple myeloma / 中华血液学杂志

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

Adverse effects of double-hit combining ISS-Ⅲ stage and 1q gain or del (17p) on prognosis of patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.

Prognostic analysis of 182 newly diagnosed multiple myeloma patients with high risk cytogenetic abnormalities / 中华血液学杂志

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.

Research advances in the effect of environmental stress in the neonatal intensive care unit on the neurodevelopment of preterm infants and its epigenetics / 中国当代儿科杂志

Adverse environmental stimulation in the neonatal intensive care unit (NICU) can affect neurodevelopment through epigenetic modification and thus has adverse effects on the long-term developmental outcome of preterm infants. Developmental care can reverse epigenetic changes in genes and promote neurodevelopment in preterm infants. This article reviews the influence of environmental stress in the NICU and developmental care on neurodevelopment in preterm infants, as well as related epigenetic effects, in order to provide a reference for epigenetic studies of preterm infants.

Effect of age factor on sedative efficacy of propofol given by closed-loop infusion in patients undergoing gynecological laparoscopic surgery / 中华麻醉学杂志

Objective To evaluate the effect of age factor on the sedative efficacy of propofol given by closed-loop infusion in patients undergoing gynecological laparoscopic surgery.Methods A total of 100 patients,weighing 55-75 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective gynecological laparoscopic surgery under general anesthesia,were divided into 2 groups (n =50 each) according to age:middle-aged group (45-64 yr) and elderly group (65-75 yr).Propofol was given by closed-loop infusion,and the target plasma concentration was automatically regulated to maintain bispectral index (BIS) value within the target range of 45-55.Remifentanil was given by target-controlled infusion at a target plasma concentration of 2-6 ng/ml to maintain anesthesia,and cisatracurium was injected intermittently to maintain muscle relaxation.The total consumption of propofol and remifentanil,regulating frequency of propofol,time ratio of BIS40-60,global score reflecting performance of closed-loop infusion system,emergence time and extubation time were recorded.Results Compared with middle-aged group,the time ratio of BIS40-60 was significantly increased,global score was decreased,the total consumption of propofol and remifentanil was significantly decreased,the regulating frequency of propofol was increased (P＜0.05),and no significant change was found in emergence time or extubation time in elderly group (P＞0.05).Conclusion The sedative efficacy of propofol given by closed-loop infusion is influenced by age factors when used for gynecologic laparoscopic surgery,and the stability in elderly patients is superior to that in middle-aged patients.

Predictors of cerebral infarction in patients with ruptured anterior communicating artery aneurysms / 中华放射学杂志

Objective To investigate the incidence and predictors of cerebral infarction in patients with ruptured ACoA aneurysms, and to provide diagnostic and therapeutic information.Methods A total of 319 patients with ruptured ACoA aneurysms in our hospital from January 2009 to February 2015 were reviewed in this study. The author collected data regarding clinical characteristics, and measured the aneurysm morphologies on CTA images. Age, flow angle, vessel angle were analyzed by independent-samples t tests in patients with or without cerebral infarction. Mann-Whitney U tests were used for aneurysm size, aneurysm height, perpendicular height, neck size, size ratio, aspect ratio, aneurysm angle , World Federation of Neurosurgical Societies (WFNS) grade at admission and Fisher grade. Chi-square tests and Fisher's exact tests were used for sex, histories of hypertension, smoking and stroke, treatment modalities, anterior cerebral A1 segment configuration and angiographic vasospasm on CTA images. The multivariate logistic regression analyses were used to determine the independent risk factors of cerebral infarction using the stepwise regression method. Results Of the 319 patients, there were 253 without and 66 patients with cerebral infarction. Differences of age(53±11 vs 57±12,respectively;t=-2.415, P=0.016), Fisher grade [Ⅰ 23(9.1%), Ⅱ 27(10.7%), Ⅲ 74(29.2%), Ⅳ 129(51.0%) vs Ⅰ 1(1.5%), Ⅱ 7 (10.6% ), Ⅲ 13(19.7% ), Ⅳ 45(68.2% ), respectively;Z=-2.541, P=0.035] and treatment modalities [endovascular coil embolization 155(61.3% ), neurosurgical clipping 98(38.7% ) vs endovascular coil embolization 23(34.8%), neurosurgical clipping 43(65.2%), respectively;χ2=14.810, P<0.001] reached statistical significance. Multivariate analysis showed that Fisher grade Ⅳ(OR=10.36,95%CI 1.34-80.29, P=0.025) and neurosurgical clipping (OR=3.28, 95% CI 1.84-5.86,P<0.001)still had statistical significance. Conclusions Cerebral infarction in patients with ruptured ACoA aneurysms may be associated with Fisher grade and treatment modalities. Although there is difference between the two groups in age, it is not a predictor of the occurrence of cerebral infarction.

Effects of different depths of sedation on postoperative cognitive function in elderly patients with mild cognitive impairment / 中华麻醉学杂志

Objective To evaluate the effects of different depths of sedation on postoperative cognitive function in elderly patients with mild cognitive impairment.Methods A total of 100 patients with mild cognitive impairment before surgery,aged 65-75 yr,weighing 55-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective gynecological surgery under general anesthesia,were divided into Ⅰ and Ⅱ groups (n =50 each) using a random number table method.Propofol was given by closed-loop target-controlled infusion,and the target plasma concentration was automatically regulated.The bispectral index value was maintained at 40-50 in group Ⅰ and at＞50-60 in group Ⅱ.Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate the cognitive function at 1 day before operation (T0) and 7 days after operation (T1),and the development of postoperative cognitive dysfunction (POCD) was recorded.Venous blood samples were collected at T0 and T1 for determination of the concentrations of serum interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) by enzyme-linked immunosorbent assay.Results Compared with the baseline value at T0,MoCA and MMSE scores were significantly decreased at T1,and the serum concentrations of IL-10 and TNF-α were increased in both groups (P＜0.05).Compared with group Ⅰ,MoCA and MMSE scores were significantly decreased at T1,and the incidence of POCD was increased,the serum concentration of TNF-α was increased,and the serum concentration of IL-t0 was decreased in group Ⅱ (P ＜ 0.05).Conclusion Maintaining BIS value at 40-50 during operation can decrease the development of POCD in elderly patients with mild cognitive impairment,which may be related to reduced systemic inflammatory responses.

Simultaneous determination of four constituents in Hydnocarpus anthelmintica by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of four constituents in Hydnocarpus anthelmintica Pierre.METHODS The analysis of 60％ ethanol extract from H.anthelmintica was carried out on a 35 ℃ thermostatic Diamonsil C18column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of 80％ acetonitrile-0.1％ phosphoric acid flowing at 1.0 mL/min in a gradient manner,and the detection wavelength was set at 347 nm.RESULTS Luteolin,hydnocarpusol,chrysoeriol and hydnocarpin showed good linear relationships within the ranges of 0.0523 6-1.047 μg (r =0.999 9),0.011 24-0.224 8 μg (r =0.999 9),0.029 46-0.589 2 μg (r =0.999 9) and 0.130 5-2.609 μg (r =0.999 9),whose average recoveries were 102.45％ (RSD=1.9％),98.66％ (RSD=1.8％),97.60％ (RSD=1.6％) and 97.88％ (RSD=1.4％),respectively.CONCLUSION This simple,accurate and sensitive method can be used for the quality control of H.anthelmintica.

Diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions / 中华超声影像学杂志

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 .

Analysis of components in plasma from effective fractions of Inula cappa based on UHPLC/Q-TOF/MS / 中国药理学通报

Aim To analyze the main components of effective fractions of Inula cappa in rat plasma with UHPLC/Q-TOF/MS technology and serum pharmacochemistry theory.Methods After gavage administration with Inula cappa extracts,blood was collected from abdominal aorta,and the protein in plasma sample was precipitated by methanol.Eclipse Plus C18 RRHD (2.1 mm × 100 mm,1.8 μm) was used,with 0.1％ formic acid agueous solution (A)-0.1％ formic acid and acetonitrile (B) as the mobile phase for gradient elution,and the flow rate was 0.3 mL ·min-1 Detected at negative ion mode,and with the help of Metabolite Tools software from Bruker Corporation,components in plasma were defined.Results A total of 16 compounds were identified,including 9 prototypes and 7 metabolites.Main metabolites were isomerization,methylation,glucuronidation and recombination of caffeoylquinic acid.Conclusions Therefore,our study has comprehensively expounded Inula cappa extracts' constituents migrating to rat plasma,and provided a reference for further studies for in vivo metabolic process and effective material base of Inula cappa.

Observation on therapeutic effect of acupuncture at points Daling (PC 7) and "Shimian" in 48 cases of refractory insomnia / 中国针灸

<p><b>OBJECTIVE</b>To find the best method for increasing clinical therapeutic effect on refractory insomnia.</p><p><b>METHODS</b>Ninty-one cases of refractory insomnia were randomly divided into an observation group (n = 48) and a routine acupuncture group (n = 43). The observation group were treated by acupuncture at acupoints Daling (PC 7) and "Shimian", and the routine acupuncture group by routine acupoints. After treatment of 4 courses, their therapeutic effects were compared.</p><p><b>RESULTS</b>The cured rate was 81.25% in the observation group and 34.88% in the routine acupuncture group, the observation group being significantly better than the routine acupuncture group (P < 0.01). And the cured rate of one course in the observation group was significantly higher than that in the routine acupuncture group (P < 0.01).</p><p><b>CONCLUSION</b>The therapeutic effect of acupuncture at Daling (PC 7) and "Shimian" is significantly better than that of acupuncture at routinely selected acupoints.</p>