Research progress on targeted therapy of breast cancer with low expression of HER2 / 国际肿瘤学杂志

Breast cancer has become the malignant tumor with the highest incidence rate among women, of which human epidermal growth factor receptor 2 (HER2) positive breast cancer accounts for about 15%-20%. With the development of anti HER2 targeted drugs, the survival and prognosis of HER2 positive breast cancer has significantly benefited. About 45%-55% of breast cancer patients have low HER2 expression, and these patients usually do not receive anti HER2 treatment. However, there is a significant difference between the biological behavior and prognosis of breast cancer with low HER2 expression and breast cancer with zero HER2 expression. It is helpful to differentiate and adopt corresponding treatment strategies to improve the prognosis of patients. At present, there have been many advances in targeted therapy of breast cancer with low HER2 expression, which provides a useful reference for precision treatment of breast cancer with low HER2 expression.

Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Progress of targeted drugs for treatment of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphoma. The relapsed/refractory DLBCL patients have poor outcomes and DLBCL is still lack of effective treatment standard regimens. How to effectively treat relapsed/refractory DLBCL patients has become a research hotspot, and the current treatment methods include bispecific antibody therapy, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates (ADC) therapy. This paper reviews the progress of targeted drugs/cell treatment for DLBCL at the 64th American Society of Hematology annual meeting.

Survey on the current situation and influencing factors of humanistic care ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City / 中华劳动卫生职业病杂志

Objective: To investigate the humanistic care consciousness and ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City. Methods: In June 2021, a total of 345 outpatient and emergency nurses from 6 tertiary Grade A hospitals in Zhengzhou City were selected as the survey objects by random number table method. The humanistic care ability of outpatient and emergency nurses was investigated. Multiple linear regression analysis was used to analyze the related factors influencing the humanistic care ability of outpatient and emergency nurses. Results: The total score of humanistic care ability of outpatient and emergency nurses in Zhengzhou tertiary Grade A hospital was (194.18±30.53). The scores of humanistic care ability of outpatient and emergency nurses with different gender, age, educational background, professional title, length of service, night shift frequency, marital status, children's status, employment patterns and average monthly household income were significantly different (P<0.05). Regression analysis showed that education background, length of service, professional title and night shift frequency were independent influencing factors for outpatient and emergency nurses' humanistic care ability (β=0.243, 0.139, 0.163, -0.126, P<0.05) . Conclusion: At present, the humanistic care ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City is still low. Education, length of service, professional title and night shift frequency are independent influencing factors affecting the humanistic care ability of nurses.

Research progress of histone acetylation in prevention and treatment of heart failure and new ideas based on traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) has become a worldwide public health problem due to its high morbidity and mortality, which seriously endangers people's lifespan and quality of life. In recent years, the treatment strategy of CHF has shifted its emphasis on short-term improvement and transformation of hemodynamics to long-term repair as well as improvement of the biological properties of heart failure. At present, with the continuous deepening of medical research, it has been found that histone acetylation is closely related to the occurrence and development of CHF. Traditional Chinese medicine, via regulating histone acetylation, delays ventricular remodeling, improves energy metabolism, inhibits fibrosis and cardiomyocyte hypertrophy, and intervenes in the development process of heart failure, thus reducing the mortality and the readmission rate and ultimately improving long-term prognosis. Therefore, this study reviewed the mechanism of histone acetylation in the treatment of heart failure as well as its prevention and treatment with traditional Chinese medicine, to provide reference for clinical treatment of CHF.

Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Effect of neuroelectrophysiological changes on the clinical manifestations and surgical outcomes of lumbar degenerative diseases / 中国骨伤

OBJECTIVE@#To evaluate the effects of electromyography on the clinical manifestations and prognosis after posterior lumbar interbody fusion(PLIF) of degenerative lumbar diseases.@*METHODS@#A retrospective analysis was performed on 68 patients with degenerative lumbar diseases, including 29 males and 39 females, aged 21 to 84 years old, who underwent electromyogram (EMG) from January 2018 to October 2019. The patients were divided into negative and positive groups according to whether theresults of EMG was normal or abnormal, PLIF surgery was performed in both groups. The preoperative duration of illness, postoperative recovery time, operative time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) of low back and lower limb, the Japanese Orthopedic Association(JOA) score before and after operation.@*RESULTS@#All patients were follow-up from 26 to 39 months. The subjective symptoms, clinical signs, daily activities and JOA total scores after operation in two groups were significantly higher than those before preoperation(P<0.05);the clinical signs score and total JOA score in the negative group at 3 months after operation were higher than those in the positive group(P<0.05). The VAS score of leg pain in the negative group after 1 and 3 months was less than that in the positive group(P<0.05). Patients 's illness time, postoperative recovery time, hospitalization time and implantation time in the negative group were shorter than those in the positive group(P<0.05). At other time points, there was no significant difference in low pain VAS, leg pain VAS, JOA scores in the two groups(P>0.05). There was no significant difference in the operation time and intraoperative bleeding volume between the two groups(P>0.05).@*CONCLUSION@#Patients with normal electromyography had shorter disease duration than ones with abnormal electromyography in lumbar degenerative disease;after PLIF, patients with normal electromyography recovered faster than ones with abnormal electromyography, but the results of electromyography had no effect on the final prognosis of PLIF surgery.

Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism / 中国中药杂志

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Utilizing ultra-small volume graft in auxiliary liver transplantation for portal hypertension / 中华外科杂志

Objective: To examine the clinical effect of auxiliary liver transplantation with ultra-small volume graft in the treatment of portal hypertension. Methods: Twelve cases of portal hypertension treated by auxiliary liver transplantation with small volume graft at Liver Transplantation Center,Beijing Friendship Hospital, Capital Medical University between December 2014 and March 2022 were studied retrospectively. There were 8 males and 4 females,aged 14 to 66 years. Model for end-stage liver disease scores were 1 to 15 points and Child scores were 6 to 11 points. The grafts was derived from living donors in 9 cases,from split cadaveric donors in 2 cases,from whole cadaveric liver of child in 1 case. The graft recipient body weight ratios of 3 cadaveric donor livers were 0.79% to 0.90%, and of 9 living donor livers were 0.31% to 0.55%.In these cases, ultra-small volume grafts were implanted. The survivals of patient and graft, complications, portal vein blood flow of residual liver and graft, abdominal drainage and biochemical indexes of liver function were observed. Results: All the grafts and patients survived. Complications included outflow tract torsion in 2 cases, acute rejection in 1 case, bile leakage in 1 case, and thyroid cancer at the later stage of follow-up in 1 case, all of which were cured. The torsion of outflow tract was attributed to the change of anastomotic angle after the growth of donor liver. After the improvement of anastomotic method, the complication did not recur in the later stage. There was no complication of portal hypertension. The measurement of ultrasonic portal vein blood flow velocity showed that the blood flow of residual liver decreased significantly in the early stage after operation, and maintained a very low blood flow velocity or occlusion in the long term after operation, and the blood flow of transplanted liver was stable. Conclusions: Auxiliary liver transplantation can implant ultra-small donor liver through compensation of residual liver. This method may promote the development of living donor left lobe donation and split liver transplantation. However, the auxiliary liver transplantation is complex, and it is difficult to control the complications. Therefore, this method is currently limited to centers that are skilled in living related liver transplantation and that have complete ability to monitor and deal with complications.

Combination of anlotinib and irinotecan in the second-line treatment of metastatic colorectal cancer: a multicenter phase 1/2 trial / 中华肿瘤杂志

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.

Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft / 中华心血管病杂志

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

Construction and management model practice of a patient-derived xenograft model platform / 中华医学科研管理杂志

Objective:In the era of precision medicine, there is an urgent need for a preclinical evaluation method with a high cost-benefit ratio to improve the effectiveness and value of clinical trials.Methods:Taking clinical needs and scientific research purposes as the starting point, the platform focused on four aspects of project management, information retrieval, quality control, and practical application, and introduced in detail the management practice of building a patient-derived xenograft model platform system.Results:With the support of the institutional system, quality control system, and information system, the patient-derived xenograft model platform was formed with standardization as the core. With the assistance of this platform and scientific research management, as of December 2021, there are 48 animal models of patient-derived xenograft in the database. In total of 6 SCI scientific and technological articles were published using these animal models, with a total impact factor of 36.77 (the highest single article was 7.333). In total of 6 direct industrial projects, 6 clinical trial-related projects, and 4 NSFC projects were approved with a total research fund of 1.5 million yuan.Conclusions:Continuous construction and improvement of the existing platform will help promote the development of basic research translation and clinical research in the field of oncology, and accelerate the development of new oncological diagnosis and treatment models, thereby benefiting more patients.

Application and design of lymphoma dataset based on real-world research / 中华医学科研管理杂志

Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.

Predictive value of single high-sensitivity cardiac troponin Ⅰ level on the 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome / 中华检验医学杂志

Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.

CHESS endoscopic ruler in objective measurement of diameter of esophageal varices in liver cirrhosis and portal hypertension: a prospective multicenter study / 中华消化杂志

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice / 南方医科大学学报

OBJECTIVE@#To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.@*METHODS@#Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.@*RESULTS@#Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.@*CONCLUSIONS@#Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Application of prospective respiratory gating based on 4D-CT in precise radiotherapy for lung cancer / 中华放射肿瘤学杂志

Objective:The respiratory waveform of lung cancer patients based on 4D-CT respiratory gating was analyzed to evaluate the accuracy of gating during radiotherapy, and to explore the off-target in the 4D-CT respiratory gating radiotherapy.Methods:Clinical data of 18 patients with lung cancer admitted to Radiotherapy Department of Jiangsu Cancer Hospital were collected to obtain the respiratory waveform data during 4D-CT respiratory gating radiotherapy. The waveform in each treatment working cycle was compared with the waveform in 4D-CT scan to study whether there was a possibility of the off-target in the treatment of lung cancer patients.Results:There were 154 treatment sessions and 20,790 treatment breathing cycles in 18 patients, among which the threshold of gated opening beam miss amplitude (Δm-en) was greater than 0 in 95 treatment breathing cycles in 7 patients, accounting for 0.46% of all breathing cycles, and the threshold of gated closing beam miss amplitude (Δm-dis) was greater than 0 in 1419 treatment breathing cycles in 13 patients, accounting for 6.83% of all cycles. Among the 13 patients withΔm-dis greater than 0, actual tumor range of motion (R G) was greater than the sum of the value of target margin (M) and the value of plan tumor range of motion (R T) in 7 patients, R G was more than 1.5 times of M+R T in 7 patients, and there were also 7 patients in the phase of rapid rise and fall of respiratory curve. The correlation efficients between R G-M-R T and the percentage of beam on miss phase (T en%) and the percentage of beam closing off phase (T dis%) were 0.41 and 0.57, respectively. Conclusion:When R G is more than 1.5 times of M+R T value and the gating beam on phase contains the phases in the rapid rise and fall of the respiratory curve, the possibility of the off-target during radiotherapy is significantly increased.

Characteristic Analysis on Human-Machine Interaction Force of Lower Limb Exoskeleton / 医用生物力学

Objective To propose a human-machine coupling dynamics modeling method based on virtual muscles, so as to quantitatively analyze the characteristics of human-computer interaction force and muscle activation of the musculoskeletal system. Methods First, in the gait experiment of wearing exoskeleton, the human motion capture system and self-developed mechanical monitoring device were used to obtain the wearer’s walking dynamics, electromyography (EMG) signals, exoskeleton drive status and local human-computer interaction information. The human-machine coupling model was established in modeling environment of the bone system, and the gait experiment data and the exoskeleton joint torques were used as driving information of the coupling model to perform inverse mechanical calculations. Finally, by adjusting strength and stiffness parameters of the virtual muscles, the real data of the model was compared with the experimental test result, to quantitatively evaluate effectiveness of the human-machine coupling model of the lower extremity exoskeleton. Results The normal interaction force calculated by inverse dynamics of the coupled model and the activation of lower limb muscles had a good consistency in response curve trend compared with measurement results of the gait experiment, and the interaction force results had a high degree of correlation (r=0.931, P<0.01), the root mean square error was small, and the peak error of lower limb muscle activation was lower than 5%. Conclusions The human-machine coupling model proposed in this study can effectively calculate the interaction force between human and exoskeleton. The establishment of the coupling model provides a theoretical basis for verification and iteration of the exoskeleton structure optimization and control algorithm, as well as performance evaluation on mobility assistance effects of the exoskeleton.