[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

Study on the construction of nomogram prediction model for prognostic assessment of heart failure patients based on serological markers and echocardiography.

OBJECTIVE: We aimed to construct a nomogram prediction model for prognostic assessment of patients with heart failure (HF) based on serological markers and echocardiography. PATIENTS AND METHODS: A total of 200 HF patients admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to January 2020 were selected as the research objects. According to the New York Heart Association (NYHA) cardiac function classification, they were divided into 3 groups, including 65 cases of grade II, 97 cases of grade III, and 38 cases of grade IV. Three groups of echocardiographic parameters were compared [including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], differences in serum markers brain natriuretic peptide (BNP), soluble growth-stimulating expression gene 2 (sST2) and the Modified Early Warning Score (MEWS). The patients were divided into two groups according to their clinical outcomes during the follow-up period, including 52 cases in the death group and 148 cases in the survival group. The clinical data of the two groups were compared, and multi-factor logistic regression analysis was performed to screen out the independent risk factors affecting the patient's death. A nomogram model of the patient's mortality risk was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the discrimination and accuracy of the nomogram model. RESULTS: As the cardiac function class of elderly chronic heart failure (CHF) patients increases, LVEDD, LVESD, sST2, and MEWS increase and LVEF decreases (p<0.05). Multifactor analysis results showed that LVEF, LVEDD, sST2, and MEWS were independent factors affecting the clinical outcome of patients. The AUCs predicted using LVEF, LVEDD, sST2, and MEWS alone were 0.738, 0.775, 0.717, 0.831, and 0.768, respectively. There is a certain degree of discrimination, and the model has extremely high accuracy. CONCLUSIONS: MEWS, LVEDD, and sST2 increase as the NYHA cardiac function grade of HF patients increases and LVEF decreases, which can reflect the severity of the disease to a certain extent. Additionally, the nomogram model established based on this has a high predictive value for the long-term prognosis of patients and can formulate effective intervention measures for quantitative values.

Labile assembly of a tardigrade protein induces biostasis.

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins, which also function to prevent perturbations induced by drying in vitro and in heterologous systems. CAHS proteins have been shown to form gels both in vitro and in vivo, which has been speculated to be linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of fibrillization and gelation for CAHS D similar to that of intermediate filament assembly. We show that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fibrillar networks during osmotic stress. Fibrillar networking of CAHS D improves survival of osmotically shocked cells. We observe two emergent properties associated with fibrillization; (i) prevention of cell volume change and (ii) reduction of metabolic activity during osmotic shock. We find that there is no significant correlation between maintenance of cell volume and survival, while there is a significant correlation between reduced metabolism and survival. Importantly, CAHS D's fibrillar network formation is reversible and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

HMGN1 down-regulation in the diabetic kidney attenuates tubular cells injury and protects against renal inflammation via suppressing MCP-1 and KIM-1 expression through TLR4.

BACKGROUND: Renal tubular injury, accompanied by damaging inflammation, has been identified to drive diabetic kidney disease (DKD) toward end-stage renal disease. However, it is unclear how damage-associated molecular patterns (DAMPs) activate innate immunity to mediate tubular epithelial cell (TEC) injury, which in turn causes with subsequent sterile inflammation in diabetic kidneys. High mobility group nucleosome-binding protein 1 (HMGN1) is a novel DAMP that contributes to generating the innate immune response. In this study, we focused on determining whether HMGN1 is involved in DKD progression. METHODS: Streptozotocin (STZ)-induced diabetic mice model was established. Then we downrergulated HMGN1 expression in kidney with or without HMGN1 administration. The renal dysfunction and morphological lesions in the kidneys were evaluated. The expressions of KIM-1, MCP-1, F4/80, CD68, and HMGN1/TLR4 signaling were examined in the renal tissue. In vitro, HK2 cells were exposed in the high glucose with or without HMGN1, and further pre-incubated with TAK242 was applied to elucidate the underlying mechanism. RESULTS: We demonstrated that HMGN1 was upregulated in the tubular epithelial cells of streptozotocin (STZ)-induced type 1 and type 2 diabetic mouse kidneys compared to controls, while being positively correlated with increased TLR4, KIM-1, and MCP-1. Down-regulation of renal HMGN1 attenuated diabetic kidney injury, decreased the TLR4, KIM-1, and MCP-1 expression levels, and reduced interstitial infiltrating macrophages. However, these phenotypes were reversed after administration of HMGN1. In HK-2 cells, HMGN1 promoted the expression of KIM-1 and MCP-1 via regulating MyD88/NF-κB pathway; inhibition of TLR4 effectively diminished the in vitro response to HMGN1. CONCLUSIONS: Our study provides novel insight into HMGN1 signaling mechanisms that contribute to tubular sterile injury and low-grade inflammation in DKD. The study findings may help to develop new HMGN1-targeted approaches as therapy for immune-mediated kidney damage rather than as an anti-infection treatments.

Imaging features of temporomandibular joint synovial chondromatosis with associated osseous degenerative changes.

Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare benign disease associated with the formation of multiple cartilaginous nodules in the synovial tissue of the TMJ. This can result in pain, swelling, clicking, limited mouth opening, and osseous degenerative joint changes. A retrospective cross-sectional study was performed to summarize the clinical features, radiographic findings, and surgical and histopathological findings of TMJ SC patients who underwent open surgery over a 24-year period. A radiographic scoring system was used to evaluate osseous changes and correlate condyle and joint fossa degeneration. The study included 38 patients and focused on 38 joints. All 38 of these joints showed degenerative changes in the condyle, while 37 showed osseous degenerative changes in the articular fossa. The degree of condylar degenerative changes was related to the duration of the chief complaints (r = 0.342, P = 0.036) and the histopathological stage of the TMJ SC (r = 0.440, P = 0.006), while the degree of joint fossa degenerative changes was associated with the radiographic extent of the SC (r = 0.504, P = 0.001), type of calcification (r = 0.365, P = 0.024), and the histopathological stage (r = 0.458, P = 0.004).

Diffusion-weighted imaging of the orbit.

Orbital lesions compose a heterogeneous group of pathologies that often present with non-specific imaging findings on conventional magnetic resonance imaging (MRI) sequences (T1-and T2-weighted). Accordingly, the application of diffusion MRI offers an opportunity to further distinguish between lesions along this spectrum. Diffusion-weighted imaging (DWI) represents the simplest and most frequent clinically utilised diffusion imaging technique. Recent advances in DWI techniques have extended its application to the evaluation of a wider spectrum of neurological pathology, including orbital lesions. This review details the manifestations of select orbital pathology on DWI and underscores specific situations where diffusion imaging allows for increased diagnostic sensitivity compared to more conventional MRI techniques. These examples also describe preferred management for orbital lesions identified by DWI.

Determination of DNA architecture of bacteria under various types of stress, methodological approaches, problems, and solutions.

Actively growing cells maintain a dynamic, far from equilibrium order through metabolism. Under starvation stress or under stress of exposure to the analog of the anabiosis autoinducer (4-hexylresorcinol), cells go into a dormant state (almost complete lack of metabolism) or even into a mummified state. In a dormant state, cells are forced to use the physical mechanisms of DNA protection. The architecture of DNA in the dormant and mummified state of cells was studied by x-ray diffraction of synchrotron radiation and transmission electron microscopy (TEM). Diffraction experiments indicate the appearance of an ordered organization of DNA. TEM made it possible to visualize the type of DNA ordering. Intracellular nanocrystalline, liquid-crystalline, and folded nucleosome-like structures of DNA have been found. The structure of DNA within a cell in an anabiotic dormant state and dormant state (starvation stress) coincides (forms nanocrystalline structures). Data suggest the universality of DNA condensation by a protein Dps for a dormant state, regardless of the type of stress. The mummified state is very different in structure from the dormant state (has no ordering within a cell). It turned out that it is possible to visualize DNA conformation in toroidal and liquid crystal structures in which there is either no or a very small amount of the Dps protein. Observation of the DNA conformation in nanocrystals and folded nucleosome-like structures so far has been inconclusive. The methodological advances described will facilitate high-resolution visualization of the DNA conformation in the near future.

[Vaginal microbiota abnormalities in women with unexplained infertility and its treatment].

The vaginal microbiota is a complex and dynamic environment that plays an important role in the healthy reproduction of women. The mechanism of unexplained infertility is not yet clear, and the imbalance and low stability of vaginal microbiota may be related to unexplained infertility. Taking probiotic composite preparations to restore normal vaginal microbiota may be a safe and natural method for treating unexplained infertility. This article reviews the probiotic composite preparations used in the treatment of unexplained infertility both domestically and internationally, including the isolation site of the bacterial species, the use method of the composite preparation, the course of treatment, and the final therapeutic effect, aiming to provide a basis for the clinical application of probiotic composite preparations in the treatment of unexplained infertility.

Norovirus outbreaks in hospitals in China: a systematic review.

BACKGROUND: Norovirus outbreaks in hospitals can potentially impair patient care and result in significant financial expenses. There is currently limited information on hospital norovirus outbreaks in the Chinese mainland. AIM: To systematically review the published literature to describe the characteristics of norovirus outbreaks in Chinese mainland hospitals to facilitate prompt identification and control of outbreaks. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards. Databases including PubMed, Web of Science, and Chinese Journals Online databases (China National Knowledge Infrastructure (CNKI), Chinese Wan Fang digital database (WANFANG) were searched from inception to July 18th, 2022. FINDINGS: A total of 41 norovirus Chinese hospital outbreaks occurring before July 18th, 2022 were reported in 32 articles. Most reported outbreaks were from Shanghai and Beijing, and occurred in December and January. Cases were mainly adults. The male:female ratio was 1.22:1. The majority of cases in norovirus outbreaks were hospitalized patients (56.82%); medical staff were affected in 15 outbreaks. Norovirus outbreaks occurred in both private and public hospitals, and in secondary and tertiary care centres, and occurred mainly in internal medicine and geriatric departments. Person-to-person transmission was the primary transmission mode and GII was more prevalent. CONCLUSION: Norovirus outbreaks in hospitals can affect both patients and healthcare workers, sometimes causing serious financial losses. In order to have a more complete understanding of the disease burden caused by norovirus outbreaks, surveillance needs to be established in hospitals.

[Identification and preliminary validation of potential biomarkers in the peripheral blood mononuclear cells of atopic dermatitis].

Objective: To explore the difference of peripheral blood mononuclear cells (PBMC) transcripts between atopic dermatitis (AD) and healthy controls, and to screen and preliminarily validate potential biomarkers of AD. Methods: From January 2021 to May 2022, blood samples from 9 AD patients and 10 healthy controls were collected from the Dermatology and Cosmetic Center of the Third Affiliated Hospital of Chongqing Medical University, ribonucleic acid-sequencing (RNA-seq) was used to determine the transcriptome and relative expression of PBMC, the differentially expressed genes (DEGs) were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction networks (PPI) analysis, and the potential biomarkers were identified by quantitative real-time PCR (qRT-PCR). Results: The age of patients in the AD group [M (Q1, Q3)] was 26.50 (22.75, 30.50) years old, and the course of disease [M (Q1, Q3)] was 15 (10, 20) years,and the age of the healthy control group [M (Q1, Q3)] was 37.00 (27.75, 40.25) years old. Compared with healthy controls, 1 044 DEGs were detected in PBMC samples in AD group, including 668 up-regulated genes and 376 down-regulated genes. Differential variable splicing (AS) showed that mutually exclusive exons (46.74%) and skipped exon (31.01%) accounted for a large proportion. GO and KEGG enrichment analysis revealed that AD is closely linked to DEGs implicated in the inflammatory response and cytokine interaction and signal pathway. Comprehensive enrichment analysis and PPI analysis selected the expression of 8 candidate genes (CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20, LY96), which was confirmed by qRT-PCR and were consistent with that of RNA-seq. Conclusions: CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20 and LY96 might be potential biomarkers of AD, participating in the occurrence and development of AD.

Contralateral needling at the foot of unaffected side combining with rehabilitation treatment for motor dysfunction of hand after ischemic stroke: study protocol for a randomized controlled pilot trial.

This pilot study is to assess the feasibility and the effect of a combination therapy of rehabilitation treatment and contralateral needling, which is manipulated at the foot of the unaffected side, for the recovery of the paretic hand post-stroke. This prospective pilot clinical trial will recruit 72 stroke patients with paretic hands and a disease course of 14 to 90 d. Patients will be randomized into two groups: the control group will receive conventional Xingnao Kaiqiao acupuncture and basic treatment for the stroke; based on the control group, the observation group will receive the contralateral needling at the foot of the unaffected side combined with the rehabilitation movement of the paretic hand. 12 sessions will be administrated for 2 weeks. The primary outcome, Fugl-Meyer Assessment, and the secondary outcomes, the handgrip strength, the range of motion, the modified Barthel index, and the Brunnstrom recovery stages, will be measured the recovery of the hand motor function during the 2 weeks' intervention. This study aims to investigate the instant effect of contralateral needling at the foot of the unaffected side combined with the rehabilitation treatment movement for patients with the paretic hand of Poststroke motor dysfunction and provide the previous evidence for the future large sample studies.

Importance of oxygen tension in human ovarian tissue in vitro culture.

STUDY QUESTION: Is there any difference between 20% and 5% oxygen (O2) tension in vitro culture (IVC) on the viability and quality of human follicles contained in cultured ovarian cortex? SUMMARY ANSWER: An O2 tension of 5% yields higher follicle viability and quality than does 20% O2 tension after 6 days of IVC. WHAT IS KNOWN ALREADY: The primordial follicle (PMF) pool resides within the ovarian cortex, where the in vivo O2 tension ranges between 2% and 8%. Some studies suggest that lowering O2 tension to physiological levels may improve in vitro follicle quality rates. STUDY DESIGN, SIZE, DURATION: This prospective experimental study included frozen-thawed ovarian cortex from six adult patients (mean age: 28.5 years; age range: 26-31 years) who were undergoing laparoscopic surgery for non-ovarian diseases. Ovarian cortical fragments were cultured for 6 days at (i) 20% O2 with 5% CO2 and (ii) 5% O2 with 5% CO2. Non-cultured fragments served as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cortical fragments were used for the following analyses: hematoxylin and eosin staining for follicle count and classification; Ki67 staining to evaluate PMF proliferation; cleaved caspase-3 immunostaining to identify follicle apoptosis; 8-hydroxy-2-deoxyguanosine and gamma-H2AX (γH2AX) immunolabeling to detect oxidative stress damage and DNA double-strand breaks (DSBs) in oocytes and granulosa cells (GCs); and ß-galactosidase staining to assess follicle senescence. Droplet digital PCR was also performed to further explore the gene expression of superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4) from the antioxidant defense system and cyclin-dependent kinase inhibitors (p21 and p16) as tissue senescence-related genes. MAIN RESULTS AND THE ROLE OF CHANCE: Apoptosis (P = 0.002) and follicle senescence (P < 0.001) rates were significantly lower in the 5% O2 group than in the 20% O2 group. Moreover, GCs in follicles in the 20% O2 group exhibited significantly (P < 0.001) higher oxidative stress damage rates than those in the 5% O2 group. DNA DSB damage rates in GCs of follicles were also significantly higher (P = 0.001) in the 20% O2 group than in the 5% O2 group. SOD2 expression was significantly greater in the 5% O2 group compared to the 20% O2 group (P = 0.04) and the non-cultured group (P = 0.002). Expression of p21 was significantly increased in both the 20% O2 (P = 0.03) and 5% O2 (P = 0.008) groups compared to the non-cultured group. Moreover, the 20% O2 group showed significantly greater p16 expression (P = 0.04) than the non-cultured group, while no significant variation was observed between the 5% O2 and no culture groups. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study focuses on improving follicle outcomes during the first step of ovarian tissue IVC, where follicles remain in situ within the tissue. The impact of O2 tension in further steps, such as secondary follicle isolation and maturation, was not investigated here. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that 5% O2 tension culture is a promising step toward potentially solving the problem of poor follicle viability after IVC. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR T.0064.22, CDR J.0063.20 and grant 5/4/150/5 awarded to M.M.D.). The authors have nothing to disclose.

[Status and associated factors of pre-exposure prophylaxis use among men who have sex with men in 24 cities in China].

Objective: To understand the cognition and medication use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in China and its associated factors. Method: From August 25 to September 5, 2021, 2 447 MSM were recruited in 24 cities to complete the online questionnaire through a male social interaction platform, Blued 7.5 software. The survey contents included demographic information of the respondents, PrEP awareness and usage, and risk behaviors. Descriptive analysis and multi-level logistic regression were performed for data analysis. SPSS 24.0 and SAS 9.4 software were used for statistical analysis. Results: Among the 2 447 respondents of MSM, 1 712 (69.96%) had heard of PrEP, 437 (17.86%) ever used PrEP, 274 (11.20%) were on PrEP, and 163 (6.66%) had discontinued PrEP; among the 437 cases (whoever used PrEP), more than 61.88% (388/627) adopted emtricitabine/tenofovir disoproxil fumarate regimen, and most of them adopted on-demand regimen. The average PrEP dosage reported in the past year is 1.12 tabletsper person per week. PrEP purchase was primarily via an online channel, and the most concerned factor was the PrEP effectiveness on HIV prevention. The most common reasons for discontinuing PrEP, reported by 163 cases, were the lack of HIV risk perception, the use of a condom to prevent HIV, and the economic burden of PrEP use. The logistic regression analysis showed that PrEP use among MSM in 24 cities was statistically associated with age, monthly income, ever having unprotected anal sex in the past year, used sexual drugs and sexually transmitted disease (STD) diagnosis in the past year. Compared with MSM aged 18-24, the proportion of MSM was relatively lower among those aged 25-44, who discontinued the PrEP (aOR=0.54,95%CI:0.34-0.87) or never used PrEP (aOR=0.62,95%CI:0.44-0.87). The proportion of unprotected anal sex among MSM currently on PrEP use was higher than those who have stopped PrEP and never used PrEP (all P<0.05). Those MSM group, with monthly income higher than 5 000 Yuan, used sexual drugs and STD diagnosis in the past year were more likely to have a higher rate for PrEP usage (all P<0.05). Conclusions: Currently, pre-exposure prophylaxis in the MSM group is primarily obtained via the online channel and adopted in an on-demand mode. Although the PrEP users have reached a certain proportion, it is still necessary to strengthen health education on the PrEP effects and side effects of MSM and to improve the awareness and use rate, especially for young MSM group, which can be combined with the advantages of the internet targeting its needs and use barriers.

Effect of Activated Immunocompetent Cells on the Content of Multipotent Stromal Cells in Splenic Transplants of CBA and CBA/N Mice Administered with Polyvinylpyrrolidone.

One day after intraperitoneal injection of polyvinylpyrrolidone (PVP) to recipient CBA and CBA/N mice, the count of multipotent stromal cells (MSC) in the 4-month-old splenic transplants was minimum in CBA/N→CBA/N group in comparison with the transplants of intact recipients (0.6 from the control level), but increased by 2.3, 3.2, and 3.7 times in CBA/N→CBA, CBA→CBA, and CBA→CBA/N groups, respectively. In the blood serum of recipient CBA/N mice with 4-month splenic transplants of CBA donors, the levels of some cytokines (IL-5, TNFα, and IL-2) was significantly increased 1 and 24 h after PVP injection in contrast to mice with bone marrow transplants, which attests to activation of the innate immunity mechanisms in this (splenic) transplantation variant. Probably, this phenomenon can be explained by the fact that the splenic transplants contain a sufficient number of CD+B-1a lymphocytes that can restore the response of recipient CBA/N mice to PVP. Thus, similar to bone marrow transplants [5], MSC count in splenic transplants increased only in groups, where the recipients were capable of responding to PVP. In other words, after injection of PVP to recipient mice, MSC counts in the spleen and bone marrow at this moment are determined by availability of activated immunocompetent cells. Overall, the novel data attest to close relationships between the stromal tissue of hematopoietic and lymphoid organs, on the one hand, and immune system, on the other.

One-Stage Shifted Laplacian Refining for Multiple Kernel Clustering.

Graph learning can effectively characterize the similarity structure of sample pairs, hence multiple kernel clustering based on graph learning (MKC-GL) achieves promising results on nonlinear clustering tasks. However, previous methods confine to a "three-stage" scheme, that is, affinity graph learning, Laplacian construction, and clustering indicator extracting, which results in the information distortion in the step alternating. Meanwhile, the energy of Laplacian reconstruction and the necessary cluster information cannot be preserved simultaneously. To address these problems, we propose a one-stage shifted Laplacian refining (OSLR) method for multiple kernel clustering (MKC), where using the "one-stage" scheme focuses on Laplacian learning rather than traditional graph learning. Concretely, our method treats each kernel matrix as an affinity graph rather than ordinary data and constructs its corresponding Laplacian matrix in advance. Compared to the traditional Laplacian methods, we transform each Laplacian to an approximately shifted Laplacian (ASL) for refining a consensus Laplacian. Then, we project the consensus Laplacian onto a Fantope space to ensure that reconstruction information and clustering information concentrate on larger eigenvalues. Theoretically, our OSLR reduces the memory complexity and computation complexity to O(n) and O(n2) , respectively. Moreover, experimental results have shown that it outperforms state-of-the-art MKC methods on multiple benchmark datasets.

[Analysis of time for diagnosis of nontuberculous mycobacterial lung disease and its associated factors in a tuberculosis-designated hospital in Shanghai].

Objective: To investigate the pathogenic characteristics, bacteriological diagnosis time and its associated factors among patients with nontuberculous mycobacterial (NTM) lung disease in a large tuberculosis-designated hospital in Shanghai from 2020 to 2021, in order to improve diagnosis efficiency and formulate precision treatment. Methods: On the basis of the Tuberculosis Database in Shanghai Pulmonary Hospital, NTM patients diagnosed by the Department of Tuberculosis between January 2020 and December 2021 were screened. Demographic, clinical and bacterial information were retrospectively collected. Chi-square test, paired-sample nonparametric test and logistic regression model were used to analyze the factors associated with the diagnosis time of NTM lung disease. Results: A total of 294 patients with bacteriologically confirmed NTM lung disease were included in this study, 147 males and 147 females with a median age of 61(46, 69) years. Of them, 227 (77.2%) patients had comorbidity of bronchiectasis. Species identification results showed that Mycobacterium Avium-Intracellulare Complex was the main pathogen of NTM lung disease (56.1%), followed by Mycobacterium kansasii (19.0%) and Mycobacterium abscessus (15.3%). Species such as Mycobacterium xenopi and Mycobacterium malmoense were rarely identified, accounting for a total proportion of only 3.1%. Positive culture rates for sputum, bronchoalveolar lavage fluid and puncture fluid were 87.4%, 80.3% and 61.5%, respectively. Paired-sample analysis showed that the positive rate of sputum culture was significantly higher than that of smear microscopy (87.1% vs. 48.4%, P<0.01), while no statistical difference was observed between sputum and bronchoalveolar lavage fluid on positive culture rate (78.7% vs. 77.3%, P>0.05). Patients with cough or expectoration were observed with 4.04-fold (95%CI 1.80-9.05) or 2.95-fold (95%CI 1.34-6.52) higher probability of positive sputum culture, compared to those without. Regarding bronchoalveolar lavage fluid, female or patients with bronchiectasis had a 2.82-fold (95%CI 1.16-6.88) or 2.38-fold (95%CI 1.01-5.63) higher probability to achieve a positive culture. The median time to diagnosis of NTM lung disease was 32 (interquartile range: 26-42) days. The results of multivariable analysis showed that patients with symptom of expectoration (aOR=0.48, 95%CI 0.29-0.80) needed a shorter diagnosis time in comparison with patients without expectoration. With Mycobacterium Avium-Intracellulare Complex as a reference, lung disease caused by Mycobacterium abscessus needed shorter diagnosis time (aOR=0.43, 95%CI 0.21-0.88), whereas those caused by rare NTM species were observed to require a longer diagnosis time (aOR=8.31, 95%CI 1.01-68.6). Conclusion: The main pathogen causing NTM lung disease in Shanghai was Mycobacterium Avium-Intracellulare Complex. Sex, clinical symptoms and bronchiectasis had an impact on the positive rate of mycobacterial culture. The majority of patients in study hospital were timely diagnosed. Clinical symptoms and NTM species were associated with the bacteriological diagnosis time of NTM lung disease.

Chronological and Replicative Aging of CD51+/PDGFR-α+ Pulp Stromal Cells.

As a crucial source of mesenchymal stromal cells, CD51+/PDGFR-α+ human dental pulp stromal cells (hDPSCs) are promising seeding cells for regenerative medicine. Cellular senescence hinders the translational application of hDPSCs. However, it remains unclear whether chronological and replicative senescence results in distinct outcomes for hDPSCs. To investigate the influence of senescence on DPSCs, we used transgenic lineage tracking, immunofluorescence, flow cytometry, and various molecular experiments to depict the dynamic pattern of hDPSCs in mice and humans during chronological and replicative senescence. The data demonstrated that CD51+/PDGFR-α+ cells were decreased in chronological senescence. Impaired self-renewal and higher ossificatory differentiation were observed in chronologically senescent hDPSCs. Regarding replicative senescence, a decreased CD51+ but upregulated PDGFR-α+ population was observed in culture. Furthermore, weakened self-renewal and osteogenic differentiation were observed in replicatively senescent hDPSCs. In summary, CD51+/PDGFR-α+ hDPSCs decrease in chronologically aged pulp, with self-renewal that is impaired without impaired osteogenic differentiation. However, replicative senescence has a different impact: self-renewal and ossific differentiation are impaired and CD51 expression is reduced, but PDGFR-α expression remains. These findings demonstrate the different outcomes of chronological and replicative senescence in CD51+/PDGFR-α+ hDPSCs. Furthermore, we revealed that impaired self-renewal is the core dysfunction for both types of cellular aging and that osteogenic differentiation capability differs between them. This study provides insights into the influence of chronological and replicative senescence on the characteristics and capabilities of hDPSCs. These advances provide fundamental knowledge to alleviate cellular aging of CD51+/PDGFR-α+ hDPSCs and promote their translational applications.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.