SS-31 mitigates oxidative stress and restores mitochondrial function in cigarette smoke-damaged oral epithelial cells via PINK1-mediated mitophagy.

Smoking is a well-established risk factor for several oral diseases, including oral cancer, oral leukoplakia and periodontitis, primarily related to reactive oxygen species (ROS). SS-31, a mitochondria-targeting tetrapeptide, has exhibited demonstrable efficacy in medical conditions by attenuating mitochondrial ROS production. However, its potential in the treatment of oral diseases remains underexplored. The aim of this study was to investigate the therapeutic potential of SS-31 in mitigating smoking-induced oral epithelial injury. Through in vitro experiments, our results indicate that SS-31 plays a protective role against cigarette smoke extract (CSE) by reducing oxidative stress, attenuating inflammatory response, and restoring mitochondrial function. Furthermore, we found that mitophagy, regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin (Parkin RBR E3 ubiquitin-protein ligase), was critical for the protective role of SS-31. Our findings offer valuable insights into SS-31's therapeutic potential in mitigating CSE-induced oxidative stress, inflammatory response, and mitochondrial dysfunction in oral epithelial cells. This study provides novel intervention targets for smoking-related oral diseases.

Kisspeptin expression during menstruation in PCOS patients undergoing ovulation induction and the correlation with early pregnancy.

PURPOSE: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. MATERIALS AND METHODS: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. RESULTS: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5-3074.5 pg/ml. CONCLUSION: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant.

Prevotella intermedia boosts OSCC progression through ISG15 upregulation: a new target for intervention.

PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects. METHODS: In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups. RESULTS: Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells. CONCLUSION: In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.

Knowledge Mapping of Cowden Syndrome: a Bibliometric Analysis.

OBJECTIVE: To provide a comprehensive overview of the current knowledge structure and research hotspots of Cowden syndrome via bibliometrics. METHODS: The articles and reviews related to Cowden syndrome were included from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace and GraphPad Prism were used to conduct the bibliometric analysis. RESULTS: The number of papers focusing on Cowden syndrome was relatively low initially but increased rapidly from 1997 to 1999, and then maintained small-scale fluctuation. A total of 1,557 papers from 65 countries/regions and 1,762 institutions were identified. The USA was the most productive country, and Ohio State University was the most productive institution. In terms of the number of publications, Human Molecular Genetics ranked first, and Cancer Research was the most frequently cited journal. Eng was the most productive author, and Liaw was the most co-cited author. Phosphatase and tensin homologue (PTEN), germline mutations, gene, cancer, mutations, tumour suppressor gene and breast were high-frequency key words in this field. CONCLUSION: This study was the first comprehensive bibliometric overview of the current state and development of Cowden disease. The mutation of PTEN and associated cancers, especially breast, thyroid and endometrial cancer, could be the focus of future research in this field.

Validation of the 9th edition of the TNM staging system for non-small cell lung cancer with lobectomy in stage IA-IIIA.

OBJECTIVES: The 9th edition of tumour-node-metastasis (TNM) staging for lung cancer was announced by Prof Hisao Asamura at the 2023 World Conference on Lung Cancer in Singapore. The purpose of this study was to externally validate and compare the latest staging of lung cancer. METHODS: We collected 19 193 patients with stage IA-IIIA non-small cell lung cancer (NSCLC) who underwent lobectomy from the Surveillance, Epidemiology and End Results database. Survival analysis by TNM stages was compared using the Kaplan-Meier method and further analysed using univariable and multivariable Cox regression analyses. Receiver operating characteristic curves were used to assess model accuracy, Akaike information criterion, Bayesian information criterion and consistency index were used to compare the prognostic, predictive ability between the current 8th and 9th edition TNM classification. RESULTS: The 9th edition of the TNM staging system can better distinguish between IB and IIA patients on the survival curve (P < 0.0001). In both univariable and multivariable regression analysis, the 9th edition of the TNM staging system can differentiate any 2 adjacent staging patients more evenly than the 8th edition. The 9th and the 8th edition TNM staging have similar predictive power and accuracy for the overall survival of patients with NSCLC [TNM 9th vs 8th, area under the curve: 62.4 vs 62.3; Akaike information criterion: 166 182.1 vs 166 131.6; Bayesian information criterion: 166 324.3 vs 166 273.8 and consistency index: 0.650 (0.003) vs 0.651(0.003)]. CONCLUSIONS: Our external validation demonstrates that the 9th edition of TNM staging for NSCLC is reasonable and valid. The 9th edition of TNM staging for NSCLC has near-identical prognostic accuracy to the 8th edition.

Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment.

BACKGROUND: Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. METHODS: P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. RESULTS: Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. CONCLUSIONS: Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?

BACKGROUND: The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. METHODS: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). RESULTS: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). CONCLUSIONS: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies.

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment. Within this landscape, the innate immune system, a critical sentinel protecting against tumor incursion, is a key player. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has been found to be a linchpin of innate immunity: activation of this signaling pathway orchestrates the production of type I interferon (IFN-α/ß), thus fostering the maturation, differentiation, and mobilization of immune effectors in the tumor microenvironment. Furthermore, STING activation facilitates the release and presentation of tumor antigens, and therefore is an attractive target for cancer immunotherapy. Current strategies to activate the STING pathway, including use of pharmacological agonists, have made substantial advancements, particularly when combined with immune checkpoint inhibitors. These approaches have shown promise in preclinical and clinical settings, by enhancing patient survival rates. This review describes the evolving understanding of the cGAS-STING pathway's involvement in tumor biology and therapy. Moreover, this review explores classical and non-classical STING agonists, providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies. Despite challenges and complexities, the cGAS-STING pathway, a promising avenue for enhancing cancer treatment efficacy, has the potential to revolutionize patient outcomes.

Epidemiological investigation and management of a case of severe Chlamydia psittaci pneumonia / 上海预防医学

ObjectiveTo identify causal factors of a case of severe Chlamydia psittaci pneumonia in Yangpu District and provide a scientific basis for effective prevention and control. MethodsBasic information and epidemiological data of the patient were collected through telephone interviews and field epidemiological surveys. Specimens from the patient， close contacts and the environment were collected for pathogen detection. Metagenomics next-generation sequencing （mNGS） was used to identify unknown pathogens. ResultsA 65-year-old male patient with a history of hypertension and diabetes was admitted to the hospital with symptoms of fatigue， poor appetite for a week， fever and cough for four days. A chest computer tomography （CT） scan showed scattered inflammation in the left lung with infiltration of multiple lobes. Blood gas analysis showed type I respiratory failure. The results of mNGS on the bronchoalveolar lavage fluid of the patient indicated that he was infected with Chlamydia psittaci. Epidemiological investigation showed a clear history of avian exposure， with an incubation period of 30 days. ConclusionThis serious pneumonia is a zoonotic disease caused by Chlamydia psittaci. A clear history of avian exposure and the use of mNGS technology can help in the timely diagnosis of this disease.

Diagnosis and treatment strategies for patients with refractory recurrent aphthous ulcer and systemic diseases / 口腔疾病防治

@#Recurrent aphthous ulcer (RAU) is one of the most common diseases of the oral mucosa. At present, no effective method is available for RAU treatment, especially for refractory RAU, which significantly affects patients’ oral health and quality of life. Research shows that combination with systemic diseases greatly increases the difficulty of curing refractory RAU, making conventional oral ulcer treatment harder to perform effectively. This is probably because dentists commonly only focus on handling oral ulcers but neglect to think about the etiology of oral ulcers from a holistic perspective. Thus, we summarized some conditions of refractory RAU accompanied by systemic diseases, including inflammatory bowel disease, iron deficiency anemia, diabetes mellitus, Behçet’s disease, Reiter’s syndrome, sprue syndrome, Sutton syndrome, and acquired immunodeficiency syndrome. We also outlined the treatment principles of these patients. To be specific, on the one hand, dentists should cooperate with the relevant specialists to treat the systemic diseases, while on the other hand they should take measures including topical/general use of medicine, local physical therapy, Traditional Chinese medicine treatment, and psychotherapy for RAU management. This paper aims to provide clinicians with a more comprehensive understanding of the diagnosis and treatment of refractory RAU, in order to make personalized treatment plans for patients and improve the clinical efficacy of refractory RAU.

Clinical efficacy and safety of transvaginal anterior wall sling release in the treatment of voiding dysfunction after the anterior vaginal wall sling procedure / 中华老年医学杂志

Objective:To analyze the clinical efficacy and safety of surgical excision of slings in the treatment of voiding dysfunction after the midurethral sling(MUS)procedure.Methods:A retrospective analysis was conducted on postoperative patients with voiding dysfunction after MUS from January 2016 to June 2021.The ages of the patients ranged from 47 to 73 years, with an average of(61.3±8.2)years.The patients were followed up for preoperative and postoperative urinary flow rates and PVR, and results from the ICI-Q-SF were collected from patients for statistical analysis.Results:The shortest time from the first sling procedure to the occurrence of voiding dysfunction was 2 months and the longest was 7 months, with an average of(3.8±1.8)months.The earliest surgical excision was performed 5 months after MUS and the latest was done 24 months after MUS, with an average of(12.3±6.6)months.Among the 12 patients, symptoms of 11 patients after surgical excision of slings were significantly improved, compared with pre-surgery data.The urinary flow rate was 9.3(3.7, 13.2)ml/s before surgery and 21.5(15.7, 34.2)ml/s after surgery, P=0.004; The residual urine volume before surgery: 315(200, 377)ml, after surgery: 0(0, 80)points, P<0.001, both with statistical significance; preoperative ICI-Q-SF: 0(0, 5)points, postoperative: 4(0, 8)points, There was no significant difference between before and after operation( P=0.348). Conclusions:Surgical excision of slings is safe and effective in the treatment of voiding dysfunction after MUS.

Epidemic characteristics of local cases infected with SARS-CoV-2 in Yangpu District of Shanghai， China / 上海预防医学

Objective:To analyze the incidence and epidemic characteristics of local cases infected with SARS-CoV-2 in Yangpu District of Shanghai， China， and provide scientific evidence for the prevention and control of coronavirus disease-19 （COVID-19）. Methods:Descriptive epidemiological methods were applied to analyze the epidemic data of all the patients tested positive for SARS-CoV-2 RNA in Yangpu District of Shanghai， China. Results:A total of 9 local cases （7 males and 2 females） were documented in Yangpu District from January 30， 2020 to February 29， 2020. The average age was （48.56±13.85） years old. According to the body mass index， the patients with overweight and obesity accounted for 44.44% of the total cases. All the patients had fever at the onset and radiological findings of pneumonia by CT examination. They were diagnosed during January 24 and February 8， 2020. The median incubation period of the COVID-19 was 9 days and the median course was 22 days. Six cases had travel history in the epidemic areas and the other 3 cases had history of contact with confirmed cases. There were two familial clusters， both of which were husband-wife relationships. One cluster had a clear temporal sequence of onset， while the other one might be co-exposed or mutually infected. No new local case infected with SARS-CoV-2 was evident since February 8， 2020. Conclusion:All the local COVID-19 cases in Yangpu District have clear epidemiological exposure history. It warrants further attention to the family clustering SARS-CoV-2 transmission. Currently， containment of imported cases is crucial for the prevention and control of COVID-19 epidemic.

Effects of linagliptin on blood glucose, islet function and liver stiffness measurement in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus / 中国医师进修杂志

Objective:To explore the effects of linagliptin on blood glucose, islet function and liver stiffness measurement (LSM) in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).Methods:During the period from January 2019 to April 2020, 102 patients with NAFLD and T2DM in the Second Affiliated Hospital of Suzhou University were enrolled and divided into study group and control group according to different treatment methods, with 51 cases in each group. The control group was treated with metformin, while study group was treated with linagliptin and metformin. The clinical curative effect on fatty liver was observed and compared between the two groups. The levels of fasting blood glucose (FBG), glycated hemoglobin (HbA 1c), homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of islet insulin cell function index β (HOMA-β), alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), glutamyl transpeptidase (GGT) and LSM before and after treatment were compared between the two groups. The occurrence of adverse reactions during treatment in both groups was recorded. Results:The total response rate of fatty liver treatment in study group was significantly higher than that in control group: 96.1% (49/51) vs. 82.4% (42/51), and there was statistical difference ( P<0.05). After treatment, levels of FBG, HbA 1c, HOMA-IR, serum ALT, AST, GGT and LSM in study group were significantly lower than those in control group: (7.1 ± 1.0) mmol/L vs. (7.9 ± 0.9) mmol/L, (7.5 ± 0.7)% vs. (7.9 ± 1.0)%, 3.2 ± 0.2 vs. 4.7 ± 0.3, (56.7 ± 10.4) U/L vs. (62.8 ± 8.2) U/L, (73.2 ± 6.8) U/L vs. (81.1 ± 6.7) U/L, (56.4 ± 10.2) U/L vs. (62.3 ± 8.1) U/L, (10.5 ± 3.3) kPa vs. (13.4 ± 1.6), the level of HOMA-β was significantly higher than that in control group: 48.5 ± 8.3 vs. 41.2 ± 7.1, and there were statistical differences ( P<0.05). The incidence of adverse reactions during treatment was low in both groups, and the difference was not statistically significant between the two groups ( P>0.05). Conclusions:Linagliptin can improve clinical curative effect on fatty liver in patients with NAFLD and T2DM, control blood glucose level, and improve islet function, liver function and liver fibrosis, with higher medication safety.

Effects of curcumin on cognitive function and hippocampal cell apoptosis in rats with cerebral hemorrhage / 中风与神经疾病杂志

@#Objective　Currently,drugs used to treat intracerebral hemorrhage can only relieve the symptoms of patients,but cannot delay the development of the disease or cure the disease.In order to find more effective and less toxic drugs or nutritional supplements against cerebral hemorrhage,curcumin was selected as the active factor in this study to establish a rat model of cerebral hemorrhage to evaluate the effect of curcumin on cognition and hippocampal cell apoptosis in the rat model of cerebral.Methods　C57BL/6 male rats were selected to establish the animal model of spontaneous intracerebral hemorrhage.They were divided into negative control group (0.005% ethanol/normal saline) and curcumin group (120 mg/kg,480 mg/kg),Morris water maze test was used to evaluate the spatial learning and memory ability of rats；Apoptotic ratio was determined by apoptosis morphology combined with TUNEL analysis；RNA isolation in rat brain tissue carried out to determine caspase-3 mRNA expression；Western blotting was used to analyze the expression of bcl-2 and Bax proteins in PC12 cells.Results　Morris water maze test confirmed that the rats treated with curcumin had a shorter escape incubation period compared with the rats in the sick group.In addition,the percentage of crossing times,residence time and total distance in the platform quadrant significantly increased (P<0.05).Curcumin significantly decreased the expression of caspase-3 mRNA and Bax protein in diseased mice,and increased the ratio of bcl-2/Bax and the expression of bcl-2 protein.Conclusion　Curcumin could significantly improve the cognitive function of rats with cerebral hemorrhage.The potential mechanism of action may play a role in preventing neuron injury by inhibiting the neuronal apoptosis signaling pathway.

Clinical assessment of tension-free vaginal tape surgery for the treatment of recurrent stress urinary incontinence in women / 中华老年医学杂志

Objective:To analyze the clinical efficacy and safety of the retropubic tension-free vaginal tape(TVT)procedure for postoperative recurrent urinary incontinence in women.Methods:Retrospective analysis was conducted on twenty-two patients who had developed recurrent urinary incontinence after mid-urethral sling(MUS)surgery and received the retropubic TVT procedure via the middle urethra from January 2016 to June 2020.Patients were between 44 and 74 years old, with a mean age of 61.2±10.2.They were initially treated with the TVT and inside-out trans-obturator(TVT-O)procedures and were followed up by using the International Consultation on Incontinence Questionnaire-Short Form(ICI-Q-SF). Then statistical analysis was performed.Results:No bladder or urethral puncture wounds were observed in the 22 patients during cystoscopy.No pain, sling, vaginal or urethral erosion, or postoperative sling infection was found in any of the patients during a long-term follow-up.Considerable improvement was achieved in frequency of leakage[pre-operation: 4(4, 5) vs.post-operation: 1(1, 2), P<0.001], urine leakage volume[pre-operation: 6(4, 6)ml vs.post-operation: 2(2, 2)ml, P<0.001], impact on quality of life[pre-operation: 10(8, 10) vs. post-operation: 2(1, 3), P<0.001]and ICI-Q-SF[pre-operation: 20(18, 21) vs. post-operation: 5(3, 7), P<0.001]after TVT. Conclusions:TVT is safe and effective for the treatment of recurrent urinary incontinence after MUS surgery.

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. We here reported Nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin converting enzyme 2 (ACE2) with SARS-CoV-2-RBD-variants, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 g/mL. Nb11-59 can be produced on a large-scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/242867v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@e4434org.highwire.dtl.DTLVardef@9fee79org.highwire.dtl.DTLVardef@1e15bb1org.highwire.dtl.DTLVardef@4adb0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

The value of MRI in assessment of the functional disorders of stress urinary incontinence in women / 中华放射学杂志

Objective:To investigate the application value of MRI in evaluating the disorders of pelvic floor in female stress urinary incontinence (SUI).Methods:From January 2017 to January 2019, the patients in the SUI group and the control group of Beijing Chaoyang Hospital, Capital Medical University were prospectively collected. Some patients in the SUI group were treated with tension-free vaginal tape (TVT). The dynamic MR was performed in both SUI patients and volunteers, and the following functional MR parameters were assessed between two groups: the urethral length and urethral hypermobility; the opening of urethral and bladder neck; and the pelvic organ prolapse. For SUI patients, the functional changes of the pelvic floor on MRI after TVT was also analyzed. Chi-square test, rank-sum test and t test were used. Results:Comparing with the control groups ( n=25), the urethral hypermobility, shortening functional urethral length, bladder neck funneling and urethra opening were significantly associated with SUI group ( n=33). Thirty one patients were treated with TVT, 12 of them were reexamined with MRI at 3 to 6 months after operation. Postoperative MR showed that SUI patients had lower risk of the urethral opening and bladder neck funneling ( P<0.05). There were significant differences in the length of functional urethra, angle of urethra movement, H-line, M-line, bladder funnel sign, urethra opening and bladder prolapse between the two groups ( P<0.05). There was a significant difference between the bladder funnel sign and urethra open sign before and after TVT ( P<0.05). There was no significant difference in the degree of bladder prolapse and uterus prolapse, length of urethra and angle of urethra movement between the two groups ( P>0.05). Conclusion:MRI can accurately evaluate pelvic floor function of SUI patients. However, TVT did not significantly improve weak pelvic supporting structures and pelvic organ prolapse.

Effects of celecoxib combined with radiotherapy on immune function in patients with malignant glioma of brain / 天津医药

Objective To study the clinical effect of celecoxib combined with radiotherapy in the treatment of malignant glioma tumor of brain. Methods A total of 80 patients diagnosed as brain malignant tumor were randomly divided into control group (n=40) and observation group (n=40). The control group received three-dimensional conformal radiotherapy for 5 times a week, with dosage 4-6 Gy each time. Base on control group, the observation group received celecoxib 0.2 g/time twice a day during treatment.After 6 weeks,the clinical efficacy,immune function,quality of life and the serum levels of metalloprotease-9 (MMP-9), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) were compared between two groups of patients. Results After 6 weeks of the current therapy, the total effective rate was better in observation group than that of control group(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+increased in the both groups.The level of CD8+decreased,and the changes of CD3+,CD4+and CD4+/CD8+were significantly higher after treatment in the observation group than those of control group, but CD8+was lower in the observation group than that of control group (P < 0.05). Meanwhile, the levels of MMP-9, TGF-β and VEGF were significantly decreased after treatment in both two groups.The levels of MMP-9,TGF-β and VEGF were significantly lower after treatment in the observation group(P<0.05).The life quality was significantly better and the overall efficiency of the improvement of the disease was higher in observation group than those of control group(P<0.05).Conclusion Celecoxib can enhance the radiosensitivity of glioma patients.The combined treatment can improve the clinical efficacy and quality of life of patients.Moreover,it improves patients'immune function and reduces the levels of VEGF,TGF-β and MMP-9.

MRI analysis of cerebral infarction of hematopathy patient / 医疗卫生装备

Objective To enhance the diagnosis of cerebral infarction of the hematopathy patient by analyzing its causes and MRI manifestations.Methods Totally 36 hematopathy patients with cerebral infarction from April 2010 to November 2015 had their data discussed retrospectively on involved vessel,anatomic distribution and MRI manifestations.Results Of the 36 patients,12 ones had only an artery involved in and 24 ones had multi arteries affected,31 ones had multi cerebral infarction foci and 5 ones had single focus.The foci had high or slighdy high signals in T2WI and very high signals in DWI,and there were no enhancement or only gyrus-like enhancement around the foci found by enhanced scan.Conchusion MRI gains advantages over CT when used to diagnose and find the hematopaty patient with cerebral infarction,when it has to be differentiated with cerebral early infection and parenchymal infiltration.It's suggested that the hematopathy patient has to undergo MRI examination in case central nervous system symptoms especially cerebral infarction occur.

MRI analysis of cerebral infarction of hematopathy patient / 医疗卫生装备

Objective To enhance the diagnosis of cerebral infarction of the hematopathy patient by analyzing its causes and MRI manifestations.Methods Totally 36 hematopathy patients with cerebral infarction from April 2010 to November 2015 had their data discussed retrospectively on involved vessel,anatomic distribution and MRI manifestations.Results Of the 36 patients,12 ones had only an artery involved in and 24 ones had multi arteries affected,31 ones had multi cerebral infarction foci and 5 ones had single focus.The foci had high or slighdy high signals in T2WI and very high signals in DWI,and there were no enhancement or only gyrus-like enhancement around the foci found by enhanced scan.Conchusion MRI gains advantages over CT when used to diagnose and find the hematopaty patient with cerebral infarction,when it has to be differentiated with cerebral early infection and parenchymal infiltration.It's suggested that the hematopathy patient has to undergo MRI examination in case central nervous system symptoms especially cerebral infarction occur.