Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective:To investigate whether glycated haemoglobin A1c (HbA1c) can be used as a predictor of mortality risk in patients with influenza pneumonia.Methods:This study was a single-center retrospective study, and enrolled patients with influenza pneumonia in the Emergency Department and in-patient departments of Beijing Chaoyang Hospital, Capital Medical University from 2017 to 2019. Gender, age, underlying diseases, influenza virus nucleic acid or antigen results, chest X-ray or chest CT reports, routine blood test, biochemical indicators, HbA1c and procalcitonin (PCT) were collected, and all subjects were divided into survival and death groups based on 28-day mortality. The differences between the two groups were compared and Cox regression was used to analyze risk factors for 28-day mortality.Results:In this study, 122 patients with influenza pneumonia were included, and 94 (77.0%) cases were divided into the survival group and 28 (23.0%) cases into the death group. Univariate analysis showed that lymphocyte counts [0.49 (0.33, 0.73) vs. 0.77 (0.49, 1.23) ×10 9/L, Z= -3.008, P=0.003] were lower and HbA1c levels [6.5 (6.1, 7.1) vs. 6.1 (5.7, 6.8) %, Z= 2.203, P= 0.028] and PCT levels [0.64 (0.20, 6.43) vs. 0.16 (0.05, 0.87) μg/L, Z=2.594, P=0.009] were higher in dead patients compared with those in the survivors. Cox multivariate regression and survival analysis found that after adjusting for age, lymphocyte counts ( HR=0.260, 95% CI: 0.087-0.773, P=0.015) and HbA1c levels ( HR=1.295, 95% CI:1.007-1.666, P=0.044) were independent risk factors for 28-day mortality. Conclusions:HbA1c is an independent risk factor for predicting 28-day mortality in patients with influenza pneumonia.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.
Humans ; Moxibustion ; Acupuncture Therapy ; Acupuncture ; Brain Diseases/therapy* ; Neuroimaging

Objective:To explore the clinical value of arterial partial pressure of carbon dioxide (PaCO 2) combined with Wells score in predicting acute pulmonary embolism (PE). Methods:Patients with suspected acute PE admitted to Emergency Department of Beijing Chaoyang Hospital, Capital Medical University from January 1, 2016 to August 31, 2021 were screened. Patients with positive computed tomography pulmonary angiography (CTPA) results were classified as the PE group, and those with negative CTPA results were classified as the non-PE group. Demographic characteristics, symptoms, vital signs, underlying diseases, risk factors for venous thrombosis, arterial blood gas analysis and Wells scores were statistically analyzed and compared between the two groups, and the clinical efficacy of PaCO 2 combined with Wells score in predicting acute PE was evaluated. Results:A total of 1 869 patients with suspected acute PE were screened, and 1 492 patients were finally selected. There were 537 cases in the PE group and 955 cases in the non-PE group. The frequency of chest pain, dyspnea, unilateral lower limb edema, history of PE or deep venous thrombosis, history of surgery or immobilization within 3 months, history of fracture within 3 months, active malignant tumor, elevated Wells score and reduced PaCO 2 in the PE group was significantly higher than that in the non-PE group (all P< 0.05). The area under receiver operating characteristic (ROC) curve (AUC) of Wells score was 0.784 (95% CI: 0.758-0.810), and the sensitivity and specificity of predicting acute pulmonary embolism were 61.64% and 88.48%, respectively. The AUC of reduced PaCO 2 was 0.679 (95% CI: 0.651-0.707), and the sensitivity and specificity of predicting acute pulmonary embolism were 79.89% and 55.92%, respectively. The AUC of reduced PaCO 2 combined with Wells score was 0.837 (95% CI: 0.816-0.858), and the sensitivity and specificity of predicting acute pulmonary embolism were 74.12% and 77.07%, respectively. The AUC of reduced PaCO 2 combined with Wells score was significantly greater than the AUC of Wells score ( P<0.001) and the AUC of reduced PaCO 2 ( P<0.001). Conclusions:The efficacy of PaCO 2 reduction combined with Wells score in predicting acute PE was superior to that of either of them alone. This was a beneficial supplement to the screening of patients with acute PE, and would also help reduce the abuse of CTPA in the emergency department.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

BACKGROUND: Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals. METHODS: From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured. RESULTS: Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P < 0.001). Between-group comparisons were performed, and the PD group showed a higher SN positivity rate than the ET (χ2 = 94.898, P < 0.017), MSA (χ2 = 57.619, P < 0.017), and PSP (χ2 = 37.687, P < 0.017) groups. SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases, collectively or individually. The incidences of lenticular hyperechoic area significantly differed among the four patient groups (χ2 = 38.904, P < 0.001). Next, between-group comparisons were performed. The lenticular hyperechoic area was higher in the PD group than in the ET (χ2 = 6.714, P < 0.017) and MSA (χ2 = 18.680, P < 0.017) groups but lower than that in the PSP group (χ2 = 0.679, P > 0.017). CONCLUSION SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population.
Diagnosis, Differential ; Humans ; Multiple System Atrophy/diagnostic imaging* ; Parkinson Disease/diagnostic imaging* ; Substantia Nigra/diagnostic imaging* ; Supranuclear Palsy, Progressive

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity

Objective: To analyse the clinical application of thoracodorsal artery perforator flaps (TDAPF) in the repair of head and neck defects. Methods: A retrospective review was conducted on 38 patients with oral and maxillofacial head and neck malignant tumors who underwent radical resection of oral and oropharyngeal carcinoma and TDAPF repair in the Department of Oral and Maxillofacial Head and Neck Oncology of the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to November 2018. Among them, 32 were males and 6 were females, aged 30-74 years. Flap size, vessel pedicle length, diameter and number of perforators, and flap fat thickness were recorded and counted. Elasti Meter and Skin Fibro Meter were applied to measure the skin elasticity and hardness in the donor areas of 4 kinds of skin flaps before the flap preparation. SPSS 19.0 statistical software was used for statistical analysis of the data. Results: All the flaps survived (100%). The mean elasticity of TDAPF [(41.2±12.9) N/m] was significantly lower than that of anterolateral thigh [(77.6±23.3) N/m, χ²=88.89, P<0.05], anterolateral thigh [(62.6±17.7) N/m, χ²=59.99, P<0.05] and or forearm flap [(51.7±8.6) N/m, χ²=37.82, P<0.05]. The hardness of TDAPF [(0.037±0.016) N] was also significantly lower than that of anterolateral femoral [(0.088±0.019) N, F=93.27, P<0.05], anteromedial femoral [(0.059±0.020) N, F=25.71, P<0.05] or forearm flap [(0.062±0.016) N, F=29.11, P<0.05]. Follow-up period ranged from 2 to 14 months. The 38 patients treated with TDAPF had a good recovery of the functions in the recipient areas, and the scars of the donor areas were not obvious after surgery, without serious complications. Conclusion: TDAPF is suitable for reconstruction of head and neck defect, with ductile texture and good recovery of the morphology and function of head and neck.
China ; Female ; Femoral Artery/surgery* ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Thigh/surgery*

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies