Objective     To evaluate the clinical radiological features combined with circulating tumor cells (CTCs) in the diagnosis of invasiveness evaluation of subsolid nodules in lung cancers. Methods     Clinical data of 296 patients from the First Hospital of Lanzhou University between February 2019 and February 2021 were retrospectively included. There were 130 males and 166 females with a median age of 62.00 years. Patients were randomly divided into a training set and an internal validation set with a ratio of 3 : 1 by random number table method. The patients were divided into two groups: a preinvasive lesion group (atypical adenomatoid hyperplasia and adenocarcinoma in situ) and an invasive lesion group (microinvasive adenocarcinoma and invasive adenocarcinoma). Independent risk factors were selected by regression analysis of training set and a Nomogram prediction model was constructed. The accuracy and consistency of the model were verified by the receiver operating characteristic curve and calibration curve respectively. Subgroup analysis was conducted on nodules with different diameters to further verify the performance of the model. Specific performance metrics, including sensitivity, specificity, positive predictive value, negative predictive value and accuracy at the threshold were calculated. Results     Independent risk factors selected by regression analysis for subsolid nodules were age, CTCs level, nodular nature, lobulation and spiculation. The Nomogram prediction mode provided an area under the curve (AUC) of 0.914 (0.872, 0.956), outperforming clinical radiological features model AUC [0.856 (0.794, 0.917), P=0.003] and CTCs AUC [0.750 (0.675, 0.825), P=0.001] in training set. C-index was 0.914, 0.894 and corrected C-index was 0.902, 0.843 in training set and internal validation set, respectively. The AUC of the prediction model in training set was 0.902 (0.848, 0.955), 0.913 (0.860, 0.966) and 0.873 (0.730, 1.000) for nodule diameter of 5-20 mm, 10-20 mm and 21-30 mm, respectively. Conclusion     The prediction model in this study has better diagnostic value, and is more effective in clinical diagnosis of diseases.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

Component malrotation is one of the major causes of failure in total knee arthroplasty.Based on previous researches,Insall line has excessive external rotation tendency.Although Akagi line is the most recognized anatomical axis at present,it still has a certain tendency of internal rotation.The tibial posterior condylar axis is not suitable for symmetrical component and yet the Curve-on-Curve technique is not suitable for anatomic component.In addition,reference to any fixed anatomical markers cannot ensure the rotation consistency of tibiofemoral component in extension position.Although range of motion technique is beneficial to tibiofemoral rotation synchronization,its clinical effect seems to be unstable.Nevertheless,Patients can obtain good postoperative results with all major techniques.Before the recognized "gold standard" is defined,orthopedic surgeons can determine the rotation alignment of tibial component according to their most accustomed surgical method.With a deeper understanding of knee anatomy,biomechanics and kinematics,digital assistive technology may be expected to become a breakthrough in the tibial rotational alignment.
Arthroplasty, Replacement, Knee/methods* ; Femur/surgery* ; Humans ; Knee Joint/surgery* ; Knee Prosthesis ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular ; Tibia/surgery*

Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.
Alkaloids/biosynthesis* ; Carbolines/metabolism* ; Carbon-Nitrogen Lyases ; Indoles/metabolism* ; Terpenes/metabolism*

As a novel technology, wearable physiological parameter monitoring technology represents the future of monitoring technology. However, there are still many problems in the application of this kind of technology. In this paper, a pilot study was conducted to evaluate the quality of electrocardiogram (ECG) signals of the wearable physiological monitoring system (SensEcho-5B). Firstly, an evaluation algorithm of ECG signal quality was developed based on template matching method, which was used for automatic and quantitative evaluation of ECG signals. The algorithm performance was tested on a randomly selected 100 h dataset of ECG signals from 100 subjects (15 healthy subjects and 85 patients with cardiovascular diseases). On this basis, 24-hour ECG data of 30 subjects (7 healthy subjects and 23 patients with cardiovascular diseases) were collected synchronously by SensEcho-5B and ECG Holter. The evaluation algorithm was used to evaluate the quality of ECG signals recorded synchronously by the two systems. Algorithm validation results: sensitivity was 100%, specificity was 99.51%, and accuracy was 99.99%. Results of controlled test of 30 subjects: the median (Q1, Q3) of ECG signal detected by SensEcho-5B with poor signal quality time was 8.93 (0.84, 32.53) minutes, and the median (Q1, Q3) of ECG signal detected by Holter with poor signal quality time was 14.75 (4.39, 35.98) minutes (Rank sum test,
Algorithms ; Electrocardiography ; Electrocardiography, Ambulatory ; Humans ; Pilot Projects ; Signal Processing, Computer-Assisted ; Wearable Electronic Devices

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

【Objective】 To analyze the effects of IgG subtypes(IgG 1 and IgG3) of antibodies contained in infant serum and erythrocyte eluates on hemolytic disease of the newborn(HDN), so as to provide reference for its early clinical diagnosis and treatment. 【Methods】 49 newborns with HDN in our hospital from June 2019 to March 2020 were detected for three hemolytic tests(direct antiglobulin test, elution test and indirect antiglobulin test), as well as the components of IgG1 and IgG3 in eluates. The correlation analysis was conducted by combining birth hours (physiological jaundice) and hemolytic degrees (total bilirubin, indirect bilirubin, and hemoglobin). 【Results】 In the 44 cases of IgG1 and IgG3 subtype detection of infant RBC eluates, regression equations could be established between total bilirubin, indirect bilirubin and birth hours, and between hemoglobin and elution test, and linear regression relationships were found (P<0.05). In the 28 cases of IgG1 and IgG3 subtype detection of infant serum, regression equations could be established between total bilirubin, indirect bilirubin, birth time and IgG3 subtype, and between hemoglobin and IgG1 subtype (P<0.05), and linear regression relationships were found (all P<0.05). Three infants, presenting IgG1 and IgG2 subtypes(+ ) and three hemolysis tests(-), were all second pregnancy, constituted by Rh-HDN of 2 case and other-system-HDN 1. 【Conclusion】 The degree of HDN is directly related to IgG1 and IgG3 antibodies in infant blood plasma. In addition to the total bilirubin and indirect bilirubin, the changes of IgG3 antibodies in infant plasma and IgG1 antibody in anemic infants should be monitored. If IgG1 and IgG3 antibodies are yielded even with all negative ABO-HDN hemolysis tests, non-ABO-HDN should be considered in time to achieve accurate diagnosis and treatment.

Sequencing technology has been greatly improved in terms of throughput and cost. The single-molecule nanopore DNA sequencing, one of the major branches of the third-generation sequencing technology, has made great contributions in the fields of medicine and life sciences due to its advantages of ultra-long reading length, real-time detection and direct detection of base methylation modification, etc. This article briefly describes the principle of nanopore sequencing technology, and discusses its application in clinical, animal, plant, bacterial and virus fields and its future development direction.
Animals ; Base Sequence ; DNA ; chemistry ; genetics ; Humans ; Nanopore Sequencing ; trends ; Nanopores ; Research ; trends ; Sequence Analysis, DNA ; trends

BACKGROUND: Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART). METHODS: From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group. RESULTS: From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course. CONCLUSIONS This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).
CD4 Lymphocyte Count ; HIV Infections/therapy* ; HIV-1 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy ; Killer Cells, Natural ; Prospective Studies ; Viral Load

Steroid associated-osteonecrosis (SAON) is non-trauma induced osteonecrosis, which is induced by long-term or high dose of corticosteroid indicated for inflammatory or immune diseases, etc. Subchondral collapse at late stage of SAON usually needs to be treated with joint replacement, while the costs and the prognosis of the surgery are challenge. It is important to perform the fundamental researches on the hip preservation treatments of SAON at early stage, and it is necessary to establish suitable animal models for studying the mechanisms of SAON and evaluating the potential treatments for the SAON. Rabbit SAON model is the most frequently used animal model. It is extensively used in studies on etiology and pathology of SAON. Furthermore, it is possible to evaluate potential drugs for preventing SAON and improving osteogenic repair of mid-stage SAON to prevent joint collapse. Because of bi-pedal, emu has the similar mechanical properties with human. Thus, it can be a suitable animal model for studying preventions and treatments of subchondral collapse of SAON, such as core-decompression with biodegradable materials for bone regeneration. In conclusion, this review updates the current animal SAON models with similar pathology to clinical SAON. These typical models could be used as clinical references for investigating drugs in prevention of early-stage of SAON and biomaterials in hip-preservation surgery for mid-stage of SAON.