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Background Osteoarthritis is a common chronic disease in middle-aged and elderly people, which seriously affects their quality of life. Carrying out community-based management of osteoarthritis is conducive to the optimization of healthcare resource allocation and the improvement of the overall prevention and treatment level of osteoarthritis. However, current community-based management of osteoarthritis has many problems and is not effectively. Objective To perform a review and comparative analysis of the developments in foreign and domestic community-based management of osteoarthritis, and strategies addressing the existing problems, providing evidence for improving strategies regarding community-based management of osteoarthritis to improve the treatment and prognosis of osteoarthritis patients in China. Methods From October 2020 to January 2021, Studies related to osteoarthritis management in Chinese published from January 1, 2010 to January 1, 2020 were searched from databases of CNKI, Wanfang Data and CQVIP using "骨关节炎" plus "管理", "骨关节炎" plus "模式", "骨关节炎" plus "策略" as the search terms, and those in English published during the same period were searched from databases of PubMed, Web of Science, and the Cochrane Library using osteoarthritis and management, mode or strategy as the search terms. After excluding duplicates or those about self-management of osteoarthritis, the enrolled studies about community-based management of osteoarthritis were analyzed using systematic analysis. Results Altogether, 2 695 studies were retrieved, 2 642 of them were excluded, and the other 53 were included. Five studies were about surveys on the management of osteoarthritis in the community, all of which revealed the lack of coordination and purpose in community-based management of osteoarthritis at home and abroad, and the key treatments are relieving symptoms, delaying cartilage degradation, and reducing the possibility of developing deformities, but the efficacies of such treatments were unsatisfactory, and symptoms often recurred. Moreover, community-based management modes of osteoarthritis in China were undiversified, mostly were various types of health education. Six studies proposed that the management of osteoarthritis in the community may be influenced by insufficient understanding of osteoarthritis in patients and their families, insufficient understanding and undervaluing of osteoarthritis in some primary care physicians, and uncoordinated healthcare resources, and put forward that a variety of factors led to the lack of coordination and purpose in the management of osteoarthritis in the community. There were three articles referring the significance of community-based osteoarthritis management, which highlighted that community-based osteoarthritis management could relieve pain, delay disease progression, and improve the quality of life in patients, and improve patients' satisfaction with treatment and services by healthcare professionals, as well as optimize the use of healthcare resources. There were 39 studies related to the strategies for community-based osteoarthritis management, 22 of which involved systematic management strategies, including 18 studies of multi-disciplinary or integrated management models and four studies of hierarchical management. As a whole, China's successful experience of managing diabetes and hypertension in the community has provided new ideas for the prevention and treatment of osteoarthritis, but most of the strategies were in the developmental stage, and their applications in practice needed further research. The remaining 17 studies involved various non-systematic community-based management strategies of osteoarthritis, including eight centering on health education, three focusing on internet-based management approaches, two involving telephone-based management, two focusing on non-drug management, and two focusing on written guidance. Conclusion There are problems in the community-based management strategies of osteoarthritis, including uncoordinated management, unsound methods, and imperfect systems. The referential community-based management strategies for osteoarthritis include: multidisciplinary or comprehensive management, hierarchical management and other systematic management strategies; making full use of medical techniques and tools (such as e-health, remote management, and health manuals) ; optimizing resource allocation (such as adding osteoarthritis management as a national essential public health project, and increasing government policy support for osteoarthritis management) .

Background Osteoarthritis is a chronic disease commonly seen in community settings, and the management of which is associated with numerous inter-related factors. Due to lack of appropriate healthcare-seeking perceptions and behaviors in osteoarthritis patients, it is difficult to diagnose, treat and manage osteoarthritis. Objective To understand healthcare-seeking perceptions and behaviors in community-living osteoarthritis patients, providing evidence for improving the diagnosis and treatment of such patients in the community. Methods This was a mixed-methods study. From May to June 2019, interviews for understanding osteoarthritis patients' healthcare-seeking perceptions and behavior-related factors, as well as management were conducted with a purposive sample of five orthopedic physicians and five general practitioners (GPs) from a general hospital in a regional healthcare consortium in Shanghai's Yangpu District, and a convenience sample of 12 GPs and 12 osteoarthritis patients from six community health centers (CHCs) in the same consortium. Then from June 2019 to December 2020, 425 patients with osteoarthritis were chosen from three randomly selected CHCs of the above-mentioned six ones to attend a survey using a quantitative questionnaire developed based on the themes derived from the above-mentioned interviews (excluding some highly subjective and less quantifiable indicators) for understanding their socio-demographic information, disease status, healthcare-seeking perceptions and behaviors, self-management and utilization of the APP for chronic disease management. Binary Logistic regression was used to analyze the influencing factors of healthcare-seeking behaviors in patients with osteoarthritis. Results The following themes were extracted from the interviews: patients' insufficient awareness of osteoarthritis, lack of management of osteoarthritis and influencing factors of patients' healthcare-seeking behavior. Three hundred and ninety-seven of the 425 cases (93.4%) who effectively completed the questionnaire were included for quantitative analysis. One hundred and fifty-two (38.3%) respondents understood osteoarthritis, and 79 (52.0%) of them acquired relevant knowledge from the media, and other 50 (32.9%) from ward-mates. Two hundred (50.4%) respondents knew the treatments for osteoarthritis, including 91 (45.5%) knowing exercise and physical therapies, and 105 (52.5%) knowing treatment with painkillers. The healthcare-seeking behaviors in osteoarthritis patients varied significantly by sex, BMI, pain level, impact of pain on sleep quality, and previous healthcare-seeking experience (P

To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology. [ABSTRACT FROM AUTHOR]

The current paradigm of joint detection and tracking still requires a large amount of instance-level trajectory annotation, which incurs high annotation costs. Moreover, treating embedding training as a classification problem would lead to difficulties in model fitting. In this paper, we propose a new self-supervised multi-object tracking based on the real-time joint detection and embedding (JDE) framework, which we termed as self-supervised multi-object tracking (SS-MOT). In SS-MOT, the short-term temporal correlations between objects within and across adjacent video frames are both considered as self-supervised constraints, where the distances between different objects are enlarged while the distances between same object of adjacent frames are brought closer. In addition, short trajectories are formed by matching pairs of adjacent frames using a matching algorithm, and these matched pairs are treated as positive samples. The distances between positive samples are then minimized for futher the feature representation of the same object. Therefore, our method can be trained on videos without instance-level annotations. We apply our approach to state-of-the-art JDE models, such as FairMOT, Cstrack, and SiamMOT, and achieve comparable results to these supevised methods on the widely used MOT17 and MOT20 challenges. [ABSTRACT FROM AUTHOR]

Global change and environmental pollution have reawakened ecologists to the great threat of multi-stress interactions to different growth stages of plants. Sophora alopecuroides L., a dune plant, has been widely studied for its medicinal components and strong salinity tolerance. S. alopecuroides seeds, obtained from the desert steppe of Yanchi, Ningxia, China, were used to analyze the effects of sand burial, salinity, drought, and their interactions on seed germination (germination percentage, germination energy, and germination index). The results showed that sand burial and salinity stress had significant effects on the seed germination ability of S. alopecuroides, and drought stress had no significant effect, but the interaction of the three stresses had a significant effect. Under different drought-stress treatments, the interaction of no sand burial and a certain degree of salinity stress significantly improved the germination ability of S. alopecuroides, and the overall intensity of the effects of the three stresses showed that sand burial > salinity > drought. Considering the germination percentage, germination energy, and germination index of S. alopecuroides under various stress interactions, the treatment of no sand burial × 1% soil saline-alkali content × 18–20% soil water content was adopted to maximize the germination ability of S. alopecuroides. In the desert steppe area of Yanchi, Ningxia, sand burial stress was still the most limiting factor for seed germination of S. alopecuroides, and soil saline-alkali content should be increased moderately, and soil moisture should be ensured to obtain the best germination ability. [ABSTRACT FROM AUTHOR]

In a casing-cement sheath-formation system, the cement–formation interface is usually weakly cemented for the residual of drilling mud, in which a leakage path would easily form, threatening the safe operation of underground energy exploitation and storage. To evaluate the compressive and shear mechanical behavior of the cement–formation interface, cement–rock composite cylindrical specimens were prepared. Uniaxial and triaxial compression and direct shear tests were implemented. The flushing efficiency of the rock surface, compressive strength, interface incompatible deformation, parameters of shear strength, and morphology of shear failure surface were acquired and analyzed. Results show that the flushing efficiency of shale surface decreases from 76.7% to 64.2% with the surface roughness increasing from 0 to 2 mm. The flushing efficiency of sandstone is only 44.7%, remarkably lower than that of shale. With the stress condition transforming from uniaxial to triaxial compression, the feature of the stress–strain curves changes from elastic-brittle to elastoplastic, and the compressive strength increases from 20.6~60.1 MPa to 110~120 MPa. The cement part presents noteworthy plastic deformation and several micro shear fractures develop. There is incompatible deformation between cement and rock, which induces interface debonding for almost all the composite specimens. The internal friction angle and cohesive strength both decrease with the increase in pollution degree of drilling mud, and increase with the rise in surface roughness. The shear facture surface is not exactly the rock–cement interface, but usually manifests as a shear zone, in which the rock, cement, and interface all contribute to the final shear failure. The above findings would be valuable for the revealing of cement–formation interface failure mechanism. [ABSTRACT FROM AUTHOR]

In single-port thoracoscopic lobectomy, surgical instruments are likely to collide and interfere with each other. We used magnetic anchor technique to design an anchoring device suitable for thoracoscopic surgery, and verified the safety and feasibility of its use in animal experiments. Ten Beagles were used as models, and magnetic anchor technology was used to assist thoracoscopic lobectomy. During the operation, a self-designed magnetic anchored internal grasper was used in place of the traditional laparoscopic grasping forceps. The operation time, intraoperative blood loss, incidence of postoperative complications, and the effect of intraoperative use of the device were analyzed. All 10 beagles were successfully operated; the mean operation time was 19.7 ± 3.53 min (range 15–26 min), and the postoperative blood loss was < 10 mL. No surgical complications occurred. During the operation, the internal grasper was firmly clamped, the auxiliary operation field was well exposed, and the interference of the main operation hole instruments was effectively reduced. We provide preliminary experimental evidence of the safety and feasibility of magnetic anchor technique-assisted thoracoscopic lobectomy. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the use of laser bandwidth may mitigate the growth of stimulated Raman scattering (SRS) in laser plasma interaction experiments, in particular, when the spectrum of the driving (or pump) laser is composed of uniformly distributed frequency components with a well-chosen bandwidth [for example, Luo et al., Phys. Plasmas 29, 032102 (2022); Wen et al., ibid. 28, 042109 (2021); and Follett et al., ibid. 26, 062111 (2019)]. Here, we investigate the effects of frequency chirp in the pump laser on backward SRS in inhomogeneous plasmas, taking into account kinetic effects associated with the nonlinear detuning of the parametric resonance due to high-amplitude electron plasma waves (EPW). Through theoretical considerations and numerical simulations, using a multi-dimensional particle-in-cell (PIC) code, it is shown that positive frequency chirp rates lead to a displacement of the resonance in the plasma profile. For a sufficiently strong positive chirp rate, such that the resonance displacement is faster than the EPW group velocity, the EPWs prove to remain limited in amplitude such that SRS is suppressed. The required frequency chirp rate corresponds to a laser bandwidth of about 1%–2%. [ABSTRACT FROM AUTHOR]

This paper analyzes how imitation and innovation strategies of high-tech small and medium-sized enterprises (SMEs) impact their sustainable performances and also the whole business ecosystem with the NK-model that mimics the fitness landscape and simulates enterprises' choice of technological strategy in response to causal ambiguity and environmental complexity. Our study yielded three findings: (1) When the imitation barriers are low, the imitation strategy of high-tech SMEs has a better effect on the performance improvement in the early stage of the operation than the innovation strategy. In the long run, high-tech SMEs exhibit innovation, which plays a greater and more lasting role in enhancing sustainable performance. On the contrary, it is always difficult for imitators to realize significant performance improvement, (2) In a simple environment, imitation strategy plays a more effective role in improving high-tech SMEs' performance, whereas in a complex environment, innovation strategy is more conducive to discovering opportunities, and it issues from high levels of competition, and (3) more importantly, the simulation finds that the innovation of high-tech SMEs contributes more to the performance of the business ecosystem as a whole. The introduction of the NK-model simulation method in the research of technological strategies and the new scope of looking at the strategies in the business ecosystem provide new research venues for the literature. [ABSTRACT FROM AUTHOR]

BACKGROUND: Daptomycin is an effective clinical drug for treating Staphylococcus aureus bacteraemia. Daptomycin and its derivatives are essential resources for antimicrobial screening and drug development. The daptomycin nucleus is a critical intermediate for producing daptomycin and its derivatives; it is catalysed by deacylase from Actinoplanes utahensis. However, the yield of the daptomycin nucleus was low by the original strain. RESULTS: In this study, the deacylase gene was overexpressed in the heterologous hosts of three different Streptomyces strains, and the efficiency of recombinant Streptomyces coelicolor was higher than that of the other two strains. Daptomycin and its nucleus were isolated, their structures were identified by nuclear magnetic resonance (NMR) and liquid chromatography‐mass spectrometry (LC–MS), and its bioconversion was confirmed by high‐performance liquid chromatography (HPLC). The optimal conditions were a phosphate buffer with 0.2 mol L−1 KCl, pH 7.0, and temperature of 40 °C, with a reaction time >4 h; in these conditions, the bioconversion efficiency increased from 71.04% to 85.02%, which is an increase of 16.44%. In addition, daptomycin nucleus yield could reach 4.36 g L−1 when 8 g L−1 daptomycin was added to the 200 mL reaction system by recombinant S. coelicolor, and the yield was 1.23 g L−1 when 6 g L−1 of daptomycin was introduced into wild‐type strain in a preliminary study for further industrialization applications. CONCLUSION: These results are helpful for enhancing daptomycin nucleus production in recombinant Streptomyces. Our work could make it possible to commercialise the daptomycin nucleus‐overproducing stains and provide a library of chemical substances for antibacterial screening and drug development. © 2021 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Genetic polymorphisms of NEIL1 and NEIL2 maybe change protein function, and increased carcinogenesis. In this study, seven NEIL1 SNPs and three NEIL2 SNPs were selected. 400 CSCCs, 400 CIN III, and 1200 normal healthy controls were genotyped by mismatch amplification PCR. mRNA and protein expression of NEIL2 was measured in 92 freshly-obtained CSCC tumor tissues. The association between homozygote CC genotype of NEIL2 rs804270 with susceptible risk was gradually increased in CIN III (OR = 1.44) and CSCC (OR = 2.22). Carriers of C-allele (GC + CC) at rs804270 had a high risk of CSCC (OR = 1.46). The heterozygote GT genotype of rs8191664 was also closely related to the higher risk of CINIII (OR = 1.59) and CSCC (OR = 2.54). Carriers of T-allele (GT + TT) at rs8191664 had a high risk for CIN III (OR = 1.55) and CSCC (OR = 2.34). The genotypes of NEIL2 rs804270 (G/C) and rs8191664 (G/T) that were related to the higher risk for CIN III were CC-GG (OR = 1.42) and CC-GT (OR = 2.07). More notably, there was a greater risk for CSCC with the GC-GT (OR = 1.91), CC-GG (OR = 1.67), and CC-GT (OR = 6.18) genotypes. NEIL2 mRNA expression in CSCCs with the rs804270-CC genotype was lower expression than those in CSCCs with the rs804270-GG and rs804270-GC genotypes. Similarly, NEIL2 protein expression was significantly decreased in CSCCs with the rs804270-CC genotype. In summary, the two genetic polymorphisms (rs804270 and rs8191664) of NEIL2 gene were significantly associated to the increased susceptibility of CIN III or CSCC. This increased susceptibility maybe due to altered NEIL2 repair activity through altered protein expression, or changed structure of the functional domain. The genotypes of GC-GT, CC-GG, and CC-GT of rs804270 and rs8191664 of NEIL2 gene could act as a genetic predictive biomarker of susceptibility to CIN III and CSCC. [ABSTRACT FROM AUTHOR]

Summary: The mitochondrial unfolded protein response (UPRmt), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPRmt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPRmt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking. In this study, we devised three experimental approaches that enable us to monitor quiescent and proliferating hematopoietic stem cells (HSCs) and provided the direct evidence that the UPRmt is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAb) directed against CD20, either unmodified or in radiolabeled forms, have been successfully used in clinic as effective therapeutic agents in the management of non-Hodgkin''s B-cell lymphoma. Despite all clinical success the exact mechanisms of action of various anti-CD20 antibodies remains mostly unclear. Several mechanisms have been proposed to be responsible for the therapeutic activity of anti-CD20 antibodies, including antibody-dependent cell-mediated cytotoxicity, complement-mediated cytotoxicity, and direct inhibition of tumor growth via induction of apoptosis. We previously produced an anti-CD20 mAb, HI47, and showed that the antibody effectively blocked human B-cell proliferation in vitro and inhibited xenografted B-cell lymphoma in nude mice. In this study, we engineered the chimeric versions of both the Fab and F(ab)′2 fragments of HI47 and produced the fragments in E. coli. Both fragments competed efficiently with HI47 for binding to CD20+ B cells, and inhibited proliferation of B-lymphoma cells in a dose-dependent manner. Mechanistic studies revealed that both antibody fragments induced significant degree of B-cell apoptosis that is independent of any cross-linking agents. Further, both the F(ab)′2 and Fab fragments when administered in vivo significantly inhibited the growth of human B-cell lymphoma xenografts in nude mice. The bivalent F(ab)′2 fragment showed consistently better efficacy compared to its monovalent Fab counterpart in inducing apoptosis and inhibiting B-cell lymphoma growth both in vitro and in vivo. Taken together, these observations suggest that HI47 and its fragments most likely exert their antitumor activity through induction of cell apoptosis, and cross-linking/dimerization of CD20 molecules on B- cell surface is an important, but not essential, process for therapeutic efficacy of HI47 and its fragments. [Copyright &y& Elsevier]

Objective. This study characterized the activation of platelet integrin αIIbβ3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4. Method. Using [SUP125]I-labeled human fibrinogen(Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin αIIbβ3 by the two mAbs. Results. HI117 and SJ9A4 (10 μg/ml and 20 μg/ml) induced evident specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin αIIbβ3. Further study indicated that HI117 and SJ9A4 induced integrin αIIbβ3 activation independent of platelet Fe-receptors, and that HI117 and SJ9A4-induced integrin αIIbβ3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. Conclusion. The anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin αIIbβ3 activation independent of Fe-receptors. Three signaling pathways, i.e., thromboxane, secreted ADP, and cAMP pathways may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways. [ABSTRACT FROM AUTHOR]

Chemotherapy-resistant breast cancer displays aggressive clinical behavior, is poorly differentiated and is associated with the occurrence of epithelial-mesenchymal transition and the presence of cancer stem cells. The anthelmintic drug niclosamide has been shown to have numerous clinical applications in the treatment of malignant tumors, in addition to its traditional use in tapeworm disease. Our previous study demonstrated that niclosamide had an antiproliferative effect and could inhibit the stem-like phenotype of the breast cancer cells, suggesting that it might have the potential to be used in the treatment of triple-negative breast cancer. However, the specific function and underlying mechanism of action of niclosamide in chemoresistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer remain unknown. The present study aimed to determine whether niclosamide can inhibit cell proliferation, invasion and epithelial-to-mesenchymal transition, as well as the stem-like phenotype in cisplatin-resistant HER2-positive breast cancer. Alamar Blue and Annexin V/7-AAD staining, mammosphere formation and Transwell assays were performed to assess the viability, apoptosis, stem-like phenotype and invasion ability of breast cancer cell lines, respectively. Signaling molecule expression was detected via western blotting and a xenograft model was used to verify the inhibitory effect of niclosamide in vivo. The results from the present study demonstrated that niclosamide inhibited the resistance of HER2-positive breast cancer to cisplatin both in vitro and in vivo. Furthermore, niclosamide combined with cisplatin could inhibit breast cancer cell invasion, epithelial-mesenchymal transition and cell stemness. The inhibitory effect of niclosamide was mediated by apoptosis induction and Bcl-2 downregulation. Taken together, the results of the present study suggested that niclosamide combined with cisplatin may be considered as a novel treatment for chemoresistant HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]