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.

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4⁺T lymphocytes (CD4) counts >500 cells/μl (compared with having recent CD4 counts <200 cells/μl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adolescent ; Adult ; Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; HIV Infections/epidemiology* ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Marriage ; Young Adult

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 investigate the neuroimaging relationship between tau protein deposition and brain atrophy, and assess their relationships with cognitive decline in Alzheimer′s disease (AD) patients.Methods:From April 2017 to October 2019, 26 AD patients (12 males, 14 females, age (70.7±12.2) years) and 19 cognitively normal controls (CN; 9 males, 10 females, age (65.6±8.1) years) in Chinese PLA General Hospital were retrospectively enrolled. All subjects received (S)-6-[(3- 18F-fluoro-2-hydroxy)propoxy]-2-(4-methylaminophenyl)quinoline ( 18F-THK5317) PET/MR and the standardized uptake value ratio (SUVR) and gray matter volume (GMV) were measured. General linear model (GLM) was used to evaluate the differences of SUVR and GMV between two groups. Pearson correlation analysis was used to assess the relationships between SUVR and GMV, and relationships of SUVR and GMV with Mini-Mental State Examination (MMSE) scores in AD patients. Results:Compared with CN, the AD patients showed significantly increased 18F-THK5317 retention in lateral temporal, frontal, posterior cingulated/precuneus and occipital cortex with significant differences of SUVR between two groups (2.18±0.54 vs 1.78±0.09, 2.13±0.50 vs 1.82±0.06, 2.03±0.45 vs 1.69±0.08, 2.18±0.57 vs 1.76±0.10, t values: 2.58-6.57, all P<0.001). The AD patients also showed decreased GMV in medial temporal, posterior cingulated/precuneus and orbitofrontal cortex ( t values: 3.67-8.85, all P<0.001). In AD patients, SUVR was negatively associated with GMV in bilateral lateral temporal cortex, pre-frontal cortex and orbital frontal cortex ( r values: from -0.52 to -0.43, all P<0.05). Both SUVR ( r=-0.599, P=0.001) and GMV ( r=0.443, P=0.023) were significantly correlated with MMSE scores in AD patients. Conclusion:AD patients have neocortical 18F-THK5317 abnormal uptake and GMV reduction, which are significantly correlated with cognitive decline.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

OBJECTIVETo investigate the effect of MicroRNA-3963(miR-3963) on the adipogenic differentiation of mouse bone-derived mesenchymal stem cells(MSC).

METHODSMSCs were isolated from C57BL/6 mice bone fragment and transfected with miR-3963 mimic, miR-3963 inhibitor and negative control. The expression of miR-3963 and transfection efficiency were detected by q-PCR. These transfected cells were induced to adipocytes and stained with oil red O after 14 days culture. q-PCR and Western blot were used to detect the expression of adipogenic differentiation marker genes C/EBPα and PPARγ at transcriptional level and protein level.

RESULTSThe results of q-PCR revealed that miR-3963 expression level was up-regulated after transfection with miR-3963 mimic (P<0.0001), and down-regulated after transfection with miR-3963 inhibitor (P<0.0001). After oil red staining, overexpression of miR-3963 in MSCs could promote the formation of lipid droplet. The q-PCR and Western blot analyses showed the significant increase of expression of adipogenic marker genes C/EBPα and PPARγ in MSC transfected with miR-3963 mimic. Additionally, compared with the control group, miR-3963 inhibitor could decrease adipogenic differentiation of MSC.

CONCLUSIONmiR-3963 can regulate and promote adipogenic differentiation of mouse bone-derived MSC.

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.
Adolescent ; Adult ; Aged ; Child ; Female ; Hodgkin Disease ; Humans ; Male ; Middle Aged ; PTEN Phosphohydrolase/analysis* ; Prognosis ; Programmed Cell Death 1 Receptor/analysis* ; Retrospective Studies ; Young Adult

OBJECTIVETo assess the early curative effect of epidural or intravenous administration of steroids during a percutaneous endoscopic lumbar discectomy (PELD).

METHODS28 consecutive patients who underwent PELD due to large lumbar disc herniation between November 2014 and January 2016 were followed up for 6 months. These patients were divided into two groups according to the treatment they received after PELD. 14 patients (Group A) were treated by PELD and epidural steroids, while the other 14 patients (Group B) were treated by PELD and intravenous steroids. We evaluated the effectiveness by the preoperative and postoperative visual analogue scale (VAS) scores for back and leg pain, and the postoperative Oswestry disability index (ODI) at 3 weeks after surgery via the clinical charts and telephone interview. Postoperative hospital stay and time return to work were investigated as well.

RESULTSThere is a significant decrease in VAS (back, leg), ODI, and time return to work (p < 0.05). For VAS (back), Group A showed a significant decrease compared with Group B at 1 day and 1 week after surgery (p = 0.011, p = 0.017). As for VAS (leg), Group A showed a significant decrease compared with Group B at 1 day, 1 week, 3 weeks, and 3 months follow-up examinations (p = 0.002, p = 0.006, p < 0.001, p < 0.001). For ODI, Group A showed a notable decrease compared with Group B (p < 0.001). The postoperative hospital stay in two groups was not statistically different (p = 0.636). But the time return to work in Group A was significantly shorter than that in Group B (p = 0.023).

CONCLUSIONPatients who underwent PELD with epidural steroid administration for large lumbar disc herniation showed favorable curative effect compared with those who underwent PELD with intravenous steroid administration.

Adult ; Betamethasone ; administration & dosage ; Diskectomy, Percutaneous ; methods ; Endoscopy ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Injections, Epidural ; Injections, Intravenous ; Intervertebral Disc Displacement ; surgery ; Length of Stay ; Lumbar Vertebrae ; surgery ; Male ; Pain Measurement ; Retrospective Studies

PURPOSETo investigate the usefulness of three-dimensional (3D) printing in complex spinal surgery.

METHODSThe study was conducted from October 2014 to March 2015 in Shenzhen Second Peoples' Hospital and 4 cases of complex severe spinal disorders were selected from our department. Among them one patient combined with congenital scoliosis, one with atlas neoplasm, one with atlantoaxial dislocation, and the rest one with atlantoaxial fracture-dislocation. The data of the diseased region was collected from computerized tomography scans for 3D digital reconstruction and rapid prototyping to prepare photosensitive resin models, which were applied in the treatment of these cases.

RESULTSThe use of 3D models reduced operating time and intraoperative blood loss as well as the risk of postoperative complications. Furthermore, no pedicle penetrations or screw misplacement occurred according to the postoperative planar radiographic images.

CONCLUSIONThe tactile models from 3D printing allow direct observation and measurement, helping the orthopedists to have accurate morphometric information to provide personalized surgical planning and better communication with the patient and coworkers. Moreover, the photosensitive resin models can also guide the actual surgery with the drilling of pedicle screws and safe resection of tumor.

Aged ; Child ; Humans ; Male ; Precision Medicine ; Printing, Three-Dimensional ; Scoliosis ; surgery ; Spinal Diseases ; surgery ; Spinal Fractures ; surgery ; Spinal Neoplasms ; surgery