Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

Efficient Creation of Ultracold Ground State

We report the creation of ultracold ground state ^{6}Li^{40}K polar molecules with high efficiency. Starting from weakly bound molecules, stimulated Raman adiabatic passage is adopted to coherently transfer the molecules to their singlet rovibrational ground state |X^{1}Σ^{+},v=0,J=0⟩. By employing a singlet stimulated Raman adiabatic passage pathway and low-phase-noise narrow-linewidth lasers, we observed a one-way transfer efficiency of 96(4)%. Held in an optical dipole trap, the lifetime of the ground state molecules is measured to be 5.0(3) ms. The large permanent dipole moment of LiK is confirmed by applying a dc electric field on the molecules and performing Stark shift spectroscopy of the ground state. With recent advances in the quantum control of collisions, our work paves the way for exploring quantum many-body physics with strongly interacting ^{6}Li^{40}K molecules.

[Safety and effectiveness of emergency stenting for acute anterior circulation large artery disease].

Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

[Expression and protective effect of chemerin in idiopathic pulmonary fibrosis].

Objective: To explore the expression and the role of chemerin in idiopathic pulmonary fibrosis (IPF). Methods: Quantitative PCR and Western blotting were used to determine the mRNA and protein levels of chemerin in lung tissues from IPF patients and the controls. Clinical serum level of chemerin was analyzed by enzyme-linked immunosorbent assay. The mouse lung fibroblasts isolated and cultured in vitro were divided into the control, TGF-ß, TGF-ß+chemerin and chemerin groups. Immunofluorescence staining was used to observe the expression of α-smooth muscle actin (α-SMA). C57BL/6 mice were randomly divided into the control, bleomycin, bleomycin+chemerin, and chemerin groups. Masson and immunohistochemical staining were performed to evaluate the severity of pulmonary fibrosis. Expression of epithelial to mesenchymal transition (EMT) markers was detected by quantitative PCR and immunohistochemical staining in the in vitro and in vivo models of pulmonary fibrosis, respectively. Results: Compared with the control group, the expression of chemerin was downregulated in both the lung tissue and the serum of IPF patients. Immunofluorescence showed that treatment of fibroblasts with TGF-ß alone resulted in a robust expression of α-SMA, whereas treatment with TGF-ß and chemerin together exhibited the similar expression levels of α-SMA as the control group. Masson staining indicated that the bleomycin-induced pulmonary fibrosis model was constructed successfully, while treatment of chemerin partially alleviated the damage of lung tissue. Immunohistochemical staining showed that the expression of chemerin in the lung tissue was significantly decreased in the bleomycin group. Quantitative PCR and immunohistochemistry showed that chemerin attenuated EMT induced by TGF-ß and bleomycin both in vitro and in vivo. Conclusions: The expression of chemerin was reduced in patients with IPF. Chemerin may play a protective role in the development of IPF by regulating EMT, providing a new idea for the clinical treatment of IPF.

[Risk stratification and low-density lipoprotein cholesterol goal attainment rates in patients with very high-risk or extreme high-risk atherosclerotic cardiovascular diseases regarding three guidelines].

Objective: To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences. Methods: Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well. Results: A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions: There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

[The association between stress hyperglycemia ratio and outcome of patients with acute ischemic stroke undergoing endovascular treatment].

Objectives: To investigate the correlation between stress hyperglycemia ratio (SHR) and outcomes in patients with acute ischemic stroke treated with endovascular treatment. Methods: In a multicenter registration study for RESCUE-RE (a registration study for critical care of acute ischemic stroke after recanalization), eligible patients with large vessel occlusion stroke within 24 hours after onset who received endovascular treatment between July 2018 and May 2019 were enrolled. SHR was calculated as the fasting glucose concentration divided by the estimated average glucose concentration and then categorized into four groups according to the quartiles (group Q1, group Q2, group Q3 and group Q4). The primary outcome was poor neurological outcomeat day 90 fromstroke onset [defined as modified Rankin scale (mRS) of 3-6]. Secondary outcomes included early neurological deterioration (END), death within 3 months after stroke onset, and symptomatic intracranial hemorrhage.Multivariable logistic and Cox regression modelswere used to assess the correlation between quartiles of SHR and prognosis in patients with endovascular treatment. Results: A total of 592 patients were enrolled in the study, with a mean age of (63±12) years, and 68.07% were male.The median National Institute of Health stroke scale(NIHSS) score on admission was15(11, 20), and the median SHR was 1.23 (1.07, 1.47), with SHR<1.07 in group Q1, 1.07≤SHR<1.23 in group Q2, 1.23≤SHR<1.47 in group Q3 and SHR≥1.47 in group Q4, respectively. The rate of complete recanalization was lower in group Q4 than that of group Q1 (70.27% vs 83.67%, P=0.026). After fully adjusted for potential covariates, the risk of poor neurological outcome at day 90 from stroke onset in group Q4 was 2.38 folds that of group Q1(adjusted OR= 2.38, 95%CI: 1.57-3.57,P=0.003). The risk of death within 3 months of patients in group Q4 was 1.80 times that of the patients in group Q1, but the difference was not statistically significant(adjusted HR=1.80, 95%CI: 0.90-3.62, P=0.098). Conclusion: Higher SHR was correlated with poor neurological outcome at 3 months in large artery occlusion related acute ischemic stroke patients receiving endovascular therapy.

[Clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma of the breast].

Objective: To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma (MSCC) of the breast. Methods: A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from January 2010 to December 2021 were reviewed. The clinical information (including the follow-up data of HER2 positive patients) and pathological features were collected and analyzed. Results: All of the patients were female. Among the 47 cases, 25 were pure squamous cell carcinoma (PSCC) and 22 were mixed metaplastic carcinoma with squamous cell component (MMSC). The median age of the patients was 54 years (range, 29-84 years). The maximum diameter of the mass ranged from 0.8 to 10.0 cm, with a mean value of 3.3 cm, 85.7% (24/28) of the cases were smaller than 5 cm, and only 4 cases were larger than or equal to 5 cm. 89.5% of the MMSC presented with a solid mass. Cystic changes were more commonly found in the PSCC group (50%, P<0.05) than the MMSC group. 36.7% (11/30) of the patients had lymph node metastasis at the time of diagnosis. The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63, p40 and CK5/6. 55.3% (26/47) of the cases showed triple-negative phenotype. Among the 7 HER2-positive patients, 6 were MMSC group, which had a significantly higher rate of HER2-positivity than that in the PSCC group (1 case). In 1 MMSC case, immunohistochemistry showed HER2 2+in the invasive ductal carcinoma component and HER2 negativity (0) in the squamous cell carcinoma component, but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component. Six HER2-positive MSCC patients received anti-HER2-targeted therapy, including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery. One patient achieved pathological complete remission, while the other achieved partial remission (the residual tumors were squamous cell carcinoma components). After 9-26 months of follow-up, four patients had no disease progression, two patients developed pulmonary metastases, and one patient showed local recurrence. Conclusions: MSCC is a group of heterogeneous diseases. PSCC and MMSC may be two different entities. Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component. Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy, but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.

[Investigation on occupational hazard factors in teaching and research places of a university].

Objective: To investigate and monitor the occupational hazards in the Teaching and Research Laboratory (hereinafter referred to as the place) of a university, so as to provide basis for the occupational health work in the university. Methods: November 2014, 46 places in a university were selected by stratified random sampling, and the occupational health risk factors were investigated. Results: Indoor temperature, humidity, sulfur dioxide, nitrogen dioxide, carbon monoxide and carbon dioxide were detected in 21 sites, xylene and hydrofluoric acid were detected in 6 sites, and colony count was detected in 18 sites, the power frequency electric field intensity was measured in 23 places, and the x-ray radiation dose was measured in 4 places. Noise was measured at 21 sites, with 7 sites exceeding the standards accounting for 33.3% (7/21) ; 21 sites were detected for illumination and 10 sites for nonconformity accounting for 47.6% (10/21) ; 10 sites for Microwave Radiation and 3 sites exceeding the standards accounting for 30% (3/10) ; and 25 sites were detected for outdoor air volume and air velocity, the percentage of unqualified was 72% (18/25) in 18 sites, among which the wind velocity was statistically significant in teaching, research and experimental sites (P=0.010) . Conclusion: The occupational hazards in the teaching and research places of a university should be paid attention to, and the engineering protection and personal protection should be strengthened in the experiment.

[Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases].

Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy,and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology by February 4, 2020 were retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.

[Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy].

Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.

[Pathological changes of the spleen in ten patients with coronavirus disease 2019(COVID-19) by postmortem needle autopsy].

Objective: To study the pathological changes of the spleen in patients with COVID-19 and to analyze the relationship between the weakened immune system and splenic lesions. Methods: Postmortem needle autopsies from the spleen were carried out on 10 patients who died from COVID-19 in Wuhan. Routine hematoxylin and eosin (HE) staining was used to observe the pathological changes. The changes of lymphocytes were studied further with immunohistochemistry.RT-PCR was used to detect 2019-nCoV RNA in the spleen. In addition,the Epstein-Barr virus (EBV) was detected by in situ hybridization, and coronavirus particles were detected by transmission electron microscopy in 2 cases. Results: There were 7 males and 3 females, with an average age of 68.3 years.Of the 10 cases, 4 had cancer history and another 4 had other underlying diseases respectively.Cough, fever, malaise and dyspnea were the main clinical symptoms.The time from onset to death was 15-45 days.Ten cases patients had normal or slight increase in peripheral blood leukocyte count in the early stage of the disease, 6 cases had significant increase before death. Five patients' peripheral blood lymphocyte count decreased in the early stage of the disease, and 10 patients' peripheral blood lymphocyte count decreased significantly before the disease progressed or died. Seven cases were treated with corticosteroid (methylprednisolone ≤40 mg/d, not more than 5 days). Histopathological examination showed that the cell composition of the spleen decreased, white pulp atrophied at different levels, meanwhile lymphoid follicles decreased or absent;in addition, the ratio of red pulp to white pulp increased with varying degrees. In 7 cases, more neutrophil infiltration was found, and in 5 cases, scattered plasma cell infiltration was found. Macrophage proliferation and hemophagocytic phenomena in a few cells were found in a case. Meanwhile, necrosis and lymphocyte apoptosis were detected in 2 cases, small artery thrombosis and spleen infarction in 1 case, and fungal infection in 1 case. The results of immunohistochemistry showed that the T and B lymphocyte components of the spleen in all cases decreased in varying degrees. CD20(+) B cells were found to accumulate in the lymphoid sheath around the splenic artery in 8 cases. However, CD20 and CD21 immunostaining in 2 cases showed that the number of white pulp was almost normal, and splenic nodules were atrophic. CD3(+), CD4(+) and CD8(+)T cells were decreased. In 9 cases,CD68(+) macrophages were no significant changes in the distribution and quantity. While more CD68(+) cells were found in the medullary sinuses of 1 case (related to fungal infection). Few CD56(+) cells were found. EBV was negative by in situ hybridization. RT-PCR was used to detect the nucleic acid of 2019-nCoV. One of 10 cases was positive, 39 years old,who was the youngest patient in this group, and the other 9 cases were negative. Coronavirus particles were found in the cytoplasm of macrophage under electron microscope in 2 cases. Conclusions: The death of COVID-19 occurs mainly in the elderly, and some cases have no underlying diseases. Spleen may be one of the organs directly attacked by the virus in some patients who died from COVID-19. T and B lymphocyte in the spleen decrease in varying degrees, lymphoid follicles are atrophied, decreased or absent, and the number of NK cells do not change significantly. And the pathological changes of the spleen are not related to the use of low dose corticosteroid, which may be related to the direct attack of virus and the attack of immune system on its own tissues.

[Preliminary study of a mask filtration test device with respiratory simulation].

Objective: To develop an air particulate protective mask filter test device that can simulate the dynamics process of human breathing. Methods: The new device used two air pumps working alternately to simulate the dynamics process of human breathing. On March 4th to 17th, 2017, the new device and the traditional one-way airflow mask filtration test device were used to measure the internal and external particle levels of 39 masks of 13 models of 6 brands, and then the filtration efficiency of the mask was calculated and the test results were compared. Results: For the mask without breathing valve, there was no statistically significant difference between the filter efficiency test results of the new device and the traditional unidirectional airflow filter performance test device (P>0.05) . For masks with breathing valves, the new device detected that three of them had lower filtration efficiency (99.50% vs 98.63%, P<0.01) . After sealing the mask breathing valve with glue, the filtering efficiency of the mask with a breathing valve detected by the new device significantly improved (98.63% vs 99.50%, P<0.01) . Conclusion: This new device can simulate the dynamic process of human exhalation and inhalation, and measure the filtration efficiency of the mask. For masks with breathing valves, the new device makes it easier to detect the decrease in the filtering efficiency of the mask caused by the breathing valve.

Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis.

As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable clinical success. However, high inter-individual variability and unpredictable toxicity continue to challenge its use in clinical practices. Some studies suggest this variation is associated with a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in pediatric patients with malignancy. We found significant associations of the MTHFR C677T polymorphism with hepatotoxicity (grade ⩾2; CC vs CT/TT: risk ratio (RR): 0.82, 95% confidence interval (CI): 0.67-0.99; P=0.04), hematological toxicity (grade 3-4; CC vs CT/TT: RR: 0.65, 95% CI: 0.44-0.97; P=0.03) in a dominant genetic model and mucositis (grade ⩾3) in all models (CC vs CT/TT: RR: 0.18, 95% CI: 0.04-0.87; P=0.03; CC/CT vs TT: RR: 0.10, 95% CI: 0.03-0.32; P⩽0.0001; CC vs TT: RR: 0.10, 95% CI: 0.02-0.50; P=0.005). No significant association was found with the MTHFR A1298C polymorphism. For children with malignancy, genotyping of the MTHFR C677T polymorphism is expected to be a useful tool in reducing toxicity and improving outcome in personalized MTX therapy.

Optimization of reverse chemical ecology method: false positive binding of Aenasius bambawalei odorant binding protein 1 caused by uncertain binding mechanism.

Odorant binding proteins (OBPs) are considered as the core molecular targets in reverse chemical ecology, which is a convenient and efficient method by which to screen potential semiochemicals. Herein, we identified a classic OBP, AbamOBP1 from Aenasius bambawalei, which showed high mRNA expression in male antennae. Fluorescence competitive binding assay (FCBA) results demonstrated that AbamOBP1 has higher binding affinity with ligands at acid pH, suggesting the physiologically inconsistent binding affinity of this protein. Amongst the four compounds with the highest binding affinities at acid pH, 2, 4, 4-trimethyl-2-pentene and 1-octen-3-one were shown to have attractant activity for male adults, whereas (-)-limonene and an analogue of 1-octen-3-ol exhibited nonbehavioural activity. Further homology modelling and fluorescence quenching experiments demonstrated that the stoichiometry of the binding of this protein to these ligands was not 1: 1, suggesting that the results of FCBA were false. In contrast, the apparent association constants (Ka) of fluorescence quenching experiments seemed to be more reliable, because 2, 4, 4-trimethyl-2-pentene and 1-octen-3-one had observably higher Ka than (-)-limonene and 1-octen-3-ol at neutral pH. Based on the characteristics of different OBPs, various approaches should be applied to study their binding affinities with ligands, which could modify and complement the results of FCBA and contribute to the application of reverse chemical ecology.

[Totally endoscopic sublay repair (TES)--a novel approach to repair midline ventral hernia].

Objective: Investigating a novel approach to treat a midline ventral hernia--totally endoscopic sublay repair (TES). The procedure will be described in detail and the safety and efficacy evaluated. Methods: During July and December 2017, eleven consecutive cases of primary and secondary epigastric midline ventral hernias were repaired using the TES procedure. A large mesh should be placed in the retrorectus position using this minimally invasive procedure. The indications for this procedure include umbilical, epigastric and incisional hernia equal in length to the rectus diastasis. Results: All operations were successful without open conversion. The mean operation time was 120 mins(80-205 min), postoperative pain was mild and the mean VAS was 2.5 on first postoperative day. The average postoperative stay in hospital was 3.3 days (2-5 days). 2 cases experienced postoperative seroma but without adverse effect on the final outcome and no recurrences during the follow-up period of 1 to 6 months. Conclusions: TES procedure is safe, practical and minimally invasive requiring no specific device and highly reproducible. Besides there is no need for expensive anti-adhesion mesh and fixation tacker which make it more cost effective. TES is a good technique for the surgical treatment of midline ventral hernia.

[Expression of platelet miR-223 in coronary artery disease patients and its clinical significance].

Objective: To investigate the correlation of the expression of platelet microRNA-223 (miR-223) with the degree of platelet activation and the severity of coronary lesions in patients with coronary artery disease (CAD). Methods: A total of 204 consecutive patients underwent coronary artery angiography (CAG) at Beijing Anzhen Hospital between April and December 2016 were enrolled. According to CAG results, all the patients were divided into two groups: 112 patients in CAD group and 92 patients in control group. Real-time fluorescent quantitative PCR was used to detect the expression level of platelet miR-223 and mRNA of its target gene P2Y12. Flow cytometry was performed to detect the expression of platelet associated complement-1 (PAC-1). Results: Compared with control group, the expression level of platelet miR-223 in CAD group was higher [(1.27 (1.17, 1.32) vs 0.73 (0.64, 0.79), P<0.001], while the expression level of P2Y12 mRNA was lower [0.75 (0.51, 0.96) vs 1.00 (0.80, 1.64), P<0.001]. The positive expression rate of PAC-1 of CAD group was higher than that of control group (P<0.001). The expression level of platelet miR-223 was negatively correlated with the expression of P2Y12 (r=-0.39, P=0.02), but positively correlated with the expression of PAC-1 (r=0.50, P<0.001). The platelet miR-223 expression level had a positive correlation with the Gensini score in CAD group (r=0.90, P<0.001), but had no significant correlation with platelet aggregation (r=-0.06, P=0.36). Conclusion: The expression level of platelet miR-223 in patients with CAD may be an indicator for monitoring platelet activation and assessing the severity of CAD.

[HER2 status in gastric adenocarcinoma of Chinese: a multicenter study of 40 842 patients].

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions: HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Evaluation of attenuation correction in cardiac PET using PET/MR.

BACKGROUND: Simultaneous acquisition Positron emission tomography/magnetic resonance (PET/MR) is a new technology that has potential as a tool both in research and clinical diagnosis. However, cardiac PET acquisition has not yet been validated using MR imaging for attenuation correction (AC). The goal of this study is to evaluate the feasibility of PET imaging using a standard 2-point Dixon volume interpolated breathhold examination (VIBE) MR sequence for AC. METHODS AND RESULTS: Evaluation was performed in both phantom and patient data. A chest phantom containing heart, lungs, and a lesion insert was scanned by both PET/MR and PET/CT. In addition, 30 patients underwent whole-body 18F-fluorodeoxyglucose PET/CT followed by simultaneous cardiac PET/MR. Phantom study showed 3% reduction of activity values in the myocardium due to the non-inclusion of the phased array coil in the AC. In patient scans, average standardized uptake values (SUVs) obtained by PET/CT and PET/MR showed no significant difference (n = 30, 4.6 ± 3.5 vs 4.7 ± 2.8, P = 0.47). There was excellent per patient correlation between the values acquired by PET/CT and PET/MR (R 2 = 0.97). CONCLUSIONS: Myocardial SUVs PET imaging using MR for AC shows excellent correlation with myocardial SUVs obtained by standard PET/CT imaging. The 2-point Dixon VIBE MR technique can be used for AC in simultaneous PET/MR data acquisition.