ObjectiveTo investigate the effects of licoflavone A on the proliferation and glycolysis of gastric cancer cells in the hypoxic environment. MethodHuman gastric cancer AGS cells were classified into five groups： Normoxia， hypoxia， and low-， medium-， and high-dose （25， 50， 100 μmol·L^-1， respectively） licoflavone A. The cells in other groups except the normoxia group were cultured in the environment with 5% O₂ for 48 h. The cell counting kit-8 （CCK-8） and colony formation assay were employed to examine the proliferation of AGS cells. Cell migration was detected by the scratch assay. The protein and mRNA levels of hypoxia-inducible factor 1-alpha （HIF-1α）， glucose transporter 1 （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and hexokinase Ⅱ （HK2） in AGS cells were measured by Western blotting and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. The corresponding kits were used to determine glucose uptake and HK activity. ResultThe CCK-8 results showed that compared with the hypoxia group， the high- and medium-dose licoflavone A groups showed decreased proliferation rate of AGS cells at the time point of 24 h （P<0.01） and all the licoflavone A groups demonstrated decreased proliferation rate at the time point of 48 h （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased number of clone formation of AGS cells （P<0.01）， which was decreased after the treatment with licoflavone A at high， medium， and low doses （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased migration of AGS cells （P<0.01）， which was attenuated by the high， medium， and low doses of licoflavone A （P<0.01）. Compared with the normoxia group， the hypoxia group showed up-regulated mRNA levels of GLUT1， LDHA， PKM2， and HK2 （P<0.05， P<0.01）. Compared with those in the hypoxia group， the mRNA levels of GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group， GLUT1， LDHA， and HK2 in the medium-dose licoflavone A group， and HK2 in the low-dose licoflavone A group were down-regulated （P<0.05， P<0.01）. The protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the hypoxia group were higher than those in the normoxia group （P<0.05， P<0.01）. Compared with those in the hypoxia group， the protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group and HK2 in the medium- and low-dose licoflavone A groups were down-regulated （P<0.05， P<0.01）. The glucose uptake and HK activity were elevated in the hypoxia group compared with those in the normoxia group （P<0.01）. Compared with the hypoxia group， high-dose licoflavone A decreased the glucose uptake and HK activity， and medium-dose licoflavone A decreased the HK activity （P<0.01）. ConclusionLicoflavone A inhibits the proliferation of AGS cells under hypoxic conditions by regulating glycolysis in gastric cancer.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

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.

Objective    To explore the clinical effect of tubeless 3 mm ultra-fine thoracoscope combined with needle electrocoagulation hook thoracic sympathicotomy in the treatment of primary palmar hyperhidrosis. Methods    The clinical data of 77 patients with primary palmar hyperhidrosis who underwent surgery in the First Hospital of Lanzhou University from September 2017 to July 2021 were retrospectively analyzed, including 50 males and 27 females, with an average age of 23.60±5.60 years. A total of 36 patients were treated with tubeless 3 mm ultra-fine thoracoscopic electrocoagulation hook thoracic sympathicotomy (an observation group), and 41 patients were treated with conventional thoracoscopic thoracic sympathicotomy (a control group). The baseline data, perioperative data and the results of 12 hours after operation were compared between the two groups. Results    All the 77 patients completed the operation successfully, no conversion to thoracotomy, no intraoperative bleeding, and no conversion to endotracheal intubation in the observation group. In the observation group, the time of anesthesia before operation [19.00 (17.00, 23.75) min vs. 25.00 (21.00, 27.00) min, P=0.001] and postoperative hospital stay [2.00 (1.00, 2.00) d vs. 2.00 (1.00, 3.00) d, P=0.012] were shorter than those in the control group. The operation time [22.50 (21.00, 25.75) min vs. 26.00 (23.50, 28.50) min, P=0.001], intraoperative blood loss [5.00 (2.25, 5.00) mL vs. 6.00 (5.00, 10.00) mL, P=0.003], postoperative pain index [2.00 (1.00, 2.00) vs. 3.00 (2.00, 3.00), P=0.001], hospitalization cost (14 246.58±879.28 yuan vs. 15 085.90±827.15 yuan, P<0.001) and postoperative inflammation index: white blood cell count [(12.96±2.32)×109/L vs. (14.47±2.05)×109/L, P=0.003], percentage of neutrophils (76.31%±5.40% vs. 79.97%±7.12%, P=0.014) were significantly lower or less than those in the control group. There was no significant difference in the incidence of major postoperative complications or adverse consequences between the two groups (P>0.05). In the evaluation of 12 hours after operation, the time of getting out of bed [2.00 (1.00, 2.00) h vs. 2.00 (2.00, 3.00) h, P=0.017], the time of drinking water after operation [1.50 (1.00, 2.00) h vs. 2.00 (1.00, 3.00) h, P=0.005], and the heart rate (80.25±14.42 bpm vs. 91.07±15.08 bpm, P=0.002), the incidence of dizziness, nausea and other uncomfortable symptoms (5.6% vs. 25.0%, P=0.040) at 12 hours after operation were shorter or lower than those in the control group. There was no significant difference in blood oxygen saturation (non-inhaled oxygen state) 12 hours after the operation between the two groups [97.00% (95.25%, 98.00%) vs. 97.00% (96.00%, 98.00%), P=0.763]. Conclusion    Compared with conventional thoracoscopic thoracic sympathicotomy, tubeless 3 mm ultra-fine thoracoscopic electrocoagulation hook thoracic sympathicotomy can significantly shorten the operation time, reduce postoperative pain and promote postoperative recovery, in line with the concept of accelerated rehabilitation surgery and minimally invasive surgery, and is worth popularizing in clinical practice.

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter

The laccase (PpLAC) gene family members in peach fruit were identified and the relationship between their expression pattern and chilling induced browning were investigated. The study was performed using two varieties of peaches with different chilling tolerance, treated with or without exogenous γ-aminobutyric acid (GABA) during cold storage. Twenty-six genes were screened from the peach fruit genome. These genes were distributed on 6 chromosomes and each contained 5-7 exons. The PpLAC gene family members shared relatively similar gene structure and conserved motifs, and they were classified into 7 subgroups based on the cluster analysis. Transcriptome sequencing revealed that the expression levels of PpLAC7 and PpLAC9 exhibited an increasing pattern under low temperature storage, and displayed a similar trend with the browning index of peach fruit. Notably, GABA treatment reduced the degree of browning and inhibited the expression of PpLAC7 and PpLAC9. These results suggested that PpLAC7 and PpLAC9 might be involved in the browning of peach fruit during cold storage.
Food Storage ; Fruit/genetics* ; Laccase/genetics* ; Prunus persica/genetics*

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.
Autoimmune Diseases/drug therapy* ; B-Cell Activating Factor/therapeutic use* ; B-Lymphocytes ; Humans ; Interleukin-4 ; Lupus Erythematosus, Systemic/drug therapy*

Objective:To compare the differences of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa) positive rate and postoperative complications between transperineal cognitive prostate biopsy (COG-TPBx) and transrectal cognitive prostate biopsy (COG-TRBx) based on biparametric magnetic resonance imaging (bpMRI).Methods:The data of 276 patients undergoing prostate biopsy from January 2019 to June 2021 in the First Affiliated Hospital of Nanjing Medical University were retrospectively reviewed. 157 patients underwent COG-TPBx(TPBx group) and 119 patients underwent COG-TRBx (TRBx group). The average age [(66.39 ± 8.31) vs. (66.30 ± 8.42)years], body mass index (BMI) [(23.85±2.49) vs. (23.68±2.61) kg/m 2], PSA values [9.43(1.47-19.80) vs. 8.94(0.66-19.99) ng/ml], prostate volume [37.92(13.99-167.40) vs. 40.78(11.67-188.21) cm 3], PSA density [0.21(0.04-1.17) vs. 0.20(0.04-1.04) ng/(ml·cm 3)], and suspicious digital rectal examination [17.20% (27/157) vs. 21.10% (25/119) ] were not significantly different between TPBx group and TRBx group. The positive rate of PCa, CsPCa, as well as post-biopsy complications of the two groups were compared. Results:There were no significant differences in the positive rate of PCa [49.68%(78/157) vs. 47.06%(56/119), P=0.666] and CsPCa [38.22%(60/157) vs. 34.45%(41/119), P=0.520] between the two groups. In stratification analysis, TPBx group has a significantly higher positive rate of both PCa [54.69%(35/64)] and CsPCa[43.75%(28/64)] in apex zone than TRBx group[39.62%(21/53) and 20.75%(11/53), all P<0.05). Moreover, the postoperative complications were not significantly different in TPBx group compared to that in TRBx group [10.19% (16/157) vs. 12.61%(15/119), P= 0.567]. Conclusions:Our investigations revealed that the overall positive rate of PCa, CsPCa, and the complications were not statistically different between COG-TPBx and COG-TRBx. COG-TPBx has a significantly higher positive rate of both PCa and CsPCa in apex zone.

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.
Angiotensin-Converting Enzyme 2 ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism* ; Protein Binding ; SARS-CoV-2 ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus/metabolism*

Objective:To investigate the clinical feasibility of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in the quantitative assessment of blood perfusion of hepatocellular carcinoma (HCC).Methods:Between January 2020 and August 2021, 36 HCC patients (39 lesions in total) confirmed by pathology and clinical diagnosis without any treatment from Zhongshan Hospital, Fudan University were enrolled and underwent both 2D-CEUS and 3D-CEUS examinations. Each examination last for 150 s and all images were recorded, and then the data were analyzed. A region of interest was manually drawn along the margin of the whole tumor and then the time-intensity curve (TIC) generated. The following perfusion parameters were extracted: peak intensity (PI), peak time (TTP), ascending slope (AS), mean transit time (MTT) and area under the curve (AUC). After calculating the quality of fit (QOF) of the curve, the intraobserver agreement of the 3D-CEUS quantitative parameters obtained by the same doctor between two times were assessed, and the consistency of the 3D-CEUS and 2D-CEUS quantitative parameters was evaluated when QOF>75%. The differences of the quantitative parameters between different groups (divided by depth of 8 cm and necrosis rate of 50%, respectively) in 3D-CEUS were compared.Results:There were 38 lesions (97.4%, 38/39) with QOF>75% in 3D-CEUS. The intraobserver agreement was excellent, the intraclass correlation efficient(ICC) values was 0.85-0.99. The consistency of the time quantitative parameters (TTP and MTT) were high (the ICC values of 0.87 and 0.91), and the correlation of intensity quantitative parameters were substantial, the rs values were 0.71, 0.72 and 0.71. The differences in 3D-CEUS quantitative parameters of the two groups of lesions with different depths were statistically significant (all P<0.05); but there were no significant differences in quantitative parameters between the two groups with different necrosis rate (all P>0.05). Conclusions:Quantitative 3D-CEUS is an useful and creditable tool in evaluating the blood perfusion of HCC, especially when the depth of lesion was less than 8 cm.