The precautionary principle in public health emergency regime: Ethical and legal examinations of Vietnamese and global response to COVID-19.

Responses to the COVID-19 pandemic have been widely criticized for being too delayed and indecisive. As a result, the precautionary principle has been endorsed, applauded, and proposed to guide future responses to global public health emergencies. Drawing from controversial issues in response to COVID-19, especially in Vietnam, this paper critically discusses some key ethical and legal issues of employing the precautionary principle in public health emergencies. Engaging with discussions concerning this principle, especially in environmental law where the precautionary principle first appeared as a guiding principle with objective content(s), this paper formulates the precautionary principle as 'in dubio pro salus', which is about advising, justifying and demanding states to proactively prepare for scenarios arising out of any public health emergency. It distinguishes the precautionary principle into moderate and hard versions. A moderate version largely takes a holistic approach and fulfils a series of criteria specified in this paper, while a hard version either permits restrictive measures to be deployed primarily on a hypothetic basis or expresses an instrumental mentality. The hard version should be rejected because of the ethical and legal problems it raises, including risk-risk tradeoffs, internal paradoxes, unjustified causing of fear and unreasonable presupposition. Ultimately, this paper defends the moderate version.

Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes / 中国药理学通报

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Associations Between Adult Attachment, Maternal Emotion Socialization and Child Behavior.

BACKGROUND: Attachment theories suggest that the adult attachment styles of mothers may influence behavior problems among their children; however, empirical studies examining the direct role of maternal adult attachment styles and the mechanisms through emotion-related parenting are scarce. OBJECTIVE: This study examined the influence of maternal adult attachment styles and emotion-related parenting on child internalizing and externalizing problems. METHODS: The participants were 409 mothers with children aged 4-5 years. A questionnaire survey was conducted to obtain their adult attachment styles to their mothers, maternal emotion socialization, and their children's behavior problems. RESULTS: The results of structural equation modelling (SEM) analyses revealed that maternal adult attachment influenced child behavior problems directly and indirectly through maternal emotion socialization. (1) Maternal attachment anxiety directly affected child externalizing problems, and indirectly affected them via mothers' higher unsupportive emotion socialization (dismissing and dysfunction). Moreover, attachment anxiety influenced child internalizing problems directly, and indirectly via mothers' higher unsupportive emotion socialization (dysfunction). (2) Furthermore, attachment avoidance indirectly impacted child externalizing problems via mothers' lower supportive emotion socialization (coaching). CONCLUSIONS: These results suggested that maternal adult attachment styles and emotion-related parenting have important implications for the development of child behaviors. Future interventions should target parental factors to mitigate the risk of behavior problems among preschoolers.

Nannies Go Rogue? A Call for Research into Nanny-Induced Elderly Abuse in China.

Older people often face varied and vicious abuse from care workers. Situations are often more pronounced for older people who live with additional cognitive or physical difficulties, such as dementia and disabilities, the prevalence of which has been on the rise in China and elsewhere. Recent discoveries of elderly abuse in China, which span from alarming levels of verbal, physical, psychological, financial, to sexual abuse, are all caused by nannies or "bao mu". Different from Western countries, the word nanny is often used to refer to people who offer caregiving help in residential settings at large, regardless of the age of the care recipients. What is also different is the lack of regulations or even rigorous training and evaluation processes for nannies in China: almost anyone could become a nanny-even though a background check is often required for nannies, this process is often highly variable and dependent on the specific labour agencies that nannies are registered with. Yet without structured studies and systematic data, little is known about the extent and severity of nanny-induced elderly abuse in China. To this end, this paper aims to discuss the unique elderly care environment-such as the "721 Rule"-in China, particularly in the post-COVID era, and highlight the critical need for timely and rigorous studies on the potential prevalence and severity of nannies' abuse and neglect of older people.

HOXA1 participates in VSMC-to-macrophage-like cell transformation via regulation of NF-κB p65 and KLF4: a potential mechanism of atherosclerosis pathogenesis.

BACKGROUND: Macrophage-like transformation of vascular smooth muscle cells (VSMCs) is a risk factor of atherosclerosis (AS) progression. Transcription factor homeobox A1 (HOXA1) plays functional roles in differentiation and development. This study aims to explore the role of HOXA1 in VSMC transformation, thereby providing evidence for the potential mechanism of AS pathogenesis. METHODS: High fat diet (HFD)-fed apolipoprotein E knockout (ApoE-/-) mice were applied as an in vivo model to imitate AS, while 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POV-PC)-treated VSMCs were applied as an in vitro model. Recombinant adeno-associated-virus-1 (AAV-1) vectors that express short-hairpin RNAs targeting HOXA1, herein referred as AAV1-shHOXA1, were generated for the loss-of-function experiments throughout the study. RESULTS: In the aortic root of AS mice, lipid deposition was severer and HOXA1 expression was higher than the wide-type mice fed with normal diet or HFD. Silencing of HOXA1 inhibited the AS-induced weight gain, inflammatory response, serum and liver lipid metabolism disorder and atherosclerotic plaque formation. Besides, lesions from AS mice with HOXA1 knockdown showed less trans-differentiation of VSMCs to macrophage-like cells, along with a suppression of krüppel-like factor 4 (KLF4) and nuclear factor (NF)-κB RelA (p65) expression. In vitro experiments consistently confirmed that HOXA1 knockdown suppressed lipid accumulation, VSMC-to-macrophage phenotypic switch and inflammation in POV-PC-treated VSMCs. Mechanism investigations further illustrated that HOXA1 transcriptionally activated RelA and KLF4 to participate in the pathological manifestations of VSMCs. CONCLUSIONS: HOXA1 participates in AS progression by regulating VSMCs plasticity via regulation of NF-κB p65 and KLF4. HOXA1 has the potential to be a biomarker or therapeutic target for AS.

It's a family affair: Confucian familist philosophy's potential to improve mental health care for ethnic Chinese in Aotearoa New Zealand.

Many ethnic groups traditionally value familism, which emphasises interdependence and the extended family unit. However, Aotearoa New Zealand's health system remains largely individual-oriented, with the implementation of family-centred care remaining inconsistent. This is known to have negative effects on Maori healthcare experiences and outcomes. Our research, exploring the experiences of ethnic Chinese using mental health services in Aotearoa New Zealand, indicated that this could also be a barrier for ethnic Chinese, who have similarly strong cultural links to familism, accessing mental health care. To balance the cultural importance of family involvement with the protection of individual patient autonomy, we propose a moderate Confucian familist approach, encouraging family involvement and participation in individual patients' care, with patients' consent. The approach acknowledges individual patients as interconnected members of a wider family unit, emphasising their reciprocal, mutual responsibility in maintaining a well-functioning, harmonious family. We highlight Whanau Ora as a potential exemplar for a culturally grounded, family-centred approach to mental health care which could be feasibly implemented and deliver positive outcomes. Parallels between Maori and ethnic Chinese cultural views around whanau, community, and collectivism suggest a Kaupapa Maori approach could also be beneficial to Aotearoa New Zealand's ethnic Chinese populations. However, ethnic Chinese lack the specific legal obligations empowering the implementation of interventions such as Whanau Ora. This is an obstacle which remains to be addressed before mental health services which are sensitive to the needs of ethnic Chinese or of other ethnicities can be effectively implemented.

The Vulnerability of Rural Migrants Under COVID-19 Quarantine in China and its Global Implications: A Socio-Ethical Analysis.

Despite the role of public health interventions in controlling disease transmission and protecting the public during the COVID-19 emergency, the implementation of quarantine restrictions has raised serious ethical concerns, especially in relation to the well-being of vulnerable populations. Drawing on the lived experiences of rural Chinese migrants who are subject to pandemic control, the authors highlight their inadequate capacities to manage the risks associated with the pandemic and adjust to quarantine restrictions. Informed by an ethical discourse of vulnerability, we show that underpinning this group's deficient coping strategies is a range of detrimental social structures and institutions that have developed under the persistent rural-urban divide in China. These structural constraints and pathologies expose rural migrants to serious risks and uncertainties while depriving them of the means and resources necessary to protect their own interests in the process of complying with quarantine restrictions. Understanding the plight of rural Chinese migrants as a structural problem also has implications for the global response to the COVID-19 pandemic. We further suggest a need for state intervention to mitigate structural deficiencies and empower the vulnerable during the COVID-19 era.

Transoral Endoscopic Thyroidectomy by Vestibular Approach for Papillary Thyroid Carcinoma with Tumor Size ≥2 cm.

Background: The transoral endoscopic thyroidectomy by vestibular approach (TOETVA) has been developed for papillary thyroid carcinoma (PTC) treatment with satisfactory results. However, there were few malignant thyroid nodules ≥2 cm in previous studies of TOETVA. Therefore, we conducted this study to evaluate the results of treatment by TOETVA for PTC with tumor size ≥2 cm. Materials and Methods: The clinical characteristics and surgical outcomes of 10 PTC patients with tumor size ≥2 cm who underwent TOETVA in our center from June 2018 to August 2021 were, respectively, reviewed. Results: All 10 included PTC patients successfully underwent TOETVA and the mean tumor size was 2.5 ± 0.5 cm. The mean number lymph nodes dissected was 9.6 ± 2.9, and 3.1 ± 3.3 positive lymph nodes were discovered. Postoperatively, transient hypoparathyroidism was recorded in 2 patients (20%), transient recurrent laryngeal nerve injury was noted in 1 patient (10%), transient superior laryngeal nerve injury was noted in 1 patient (10%), and numb chin was identified in 1 patient (10%). The postoperative complications aforementioned recovered within 6 months. During a median follow-up of 23.8 ± 13.1 months, no other complications or tumor recurrence were found. Conclusions: TOETVA is feasible for PTC patients with tumor size ≥2 cm and satisfactory short-term surgical outcomes have achieved in this study. We suggested that experienced surgeons can gradually expand the indications for TOETVA.

Characteristics of whole genome analysis of severe acute respiratory syndrome coronavirus 2 during different epidemic periods in Wuxi City / 中华传染病杂志

Objective:To understand the genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike protein variations during different epidemic periods in Wuxi City.Methods:Nucleic acid was extracted from the nasopharyngeal swab samples of six local cases of coronavirus disease 2019 (COVID-19) (from January to February, 2020) and 13 imported cases of COVID-19 (from March to September, 2021) in Wuxi City, and the whole genome was amplified to construct the sequencing library. The second-generation sequencer was used for sequencing. The CLC Genomics Workbench (21 version) software was used to analyze the offline data with NC_045512.2 as the reference strain, and MEGA 7.0 software was used to construct the phylogenetic tree.Identification of type was conducted by Nextstrain typing method and phylogenetic assignment of named global outbreak lineages (Pangolin) typing method.Results:There were five subtypes in Nextstrain and seven subtypes in Pangolin of the nineteen patients with COVID-19. Compared with NC_045512.2, the median nucleotide mutation sites were 29 (range 0 to 42) and amino acid mutation sites were 20 (range 0 to 34). The six local and 13 imported cases had no common nucleotide mutation sites and were in different evolutionary branches. The sequences of the six local cases were highly homologous with the reference strain sequences (NC_045512.2) at the early stage of the pandemic, and the evolutionary distance was close to that of the reference strain. The 13 imported cases were obviously divided into three evolutionary branches (Alpha, Beta, Delta variant).The four Beta variants shared eight amino acid mutation sites in spike protein, and the two Alpha variants shared eight amino acid mutation sites in spike protein, and the seven Delta variants shared five amino acid mutation sites in spike protein.Conclusions:New mutations of SARS-CoV-2 are constantly emerging during the epidemic. The increase of the nucleotide sites number may result in the change of spike protein amino acid. Therefore, the whole-genome sequencing analysis plays an important role in the accurate tracing of epidemic origin and adjustment of prevention and control measures.

Study on method of osthole loaded by exosomes / 中国药理学通报

Aim To construct a drug delivery system of osthole loaded by exosomes. Methods Osthole could inhibit the proliferation of ovarian cancer cells by literature. SKOV3 cells were treated with 80 (µnol • L

A novel hybrid approach for "Scarless" (at the neck) lateral neck dissection for papillary thyroid carcinoma: A case series and literature review.

Lateral neck dissection (LND) is a necessary treatment for thyroid cancer with lateral lymph node metastasis. However, the defect created during open surgery leaves a visible scar on the neck. With advancements in surgical technology, many robotic and endoscopic surgical techniques have been reported as alternatives to open surgery. In this study, we present a case series demonstrating the successful application of a novel hybrid approach for endoscopic LND and a review of different surgical approaches for "scarless" (at the neck) LND. We performed endoscopic LND via a combined chest and transoral approach in 24 patients between January 2021 and March 2022. The surgery was completed successfully in all patients with an average operation time of 298.1 ± 72.9 min. The numbers of positive/retrieved lymph nodes at levels II, III-IV, and VI were 0.7 ± 0.9/8.4 ± 4.1, 3.6 ± 2.7/19.5 ± 6.8, and 4.9 ± 3.9/10.3 ± 4.5, respectively. Complications included transient hypoparathyroidism in 10 patients, transient recurrent laryngeal nerve injury in 1 patient, internal jugular vein (IJN) injury in 1 patient, IJN sacrifice due to cancer invasion in 1 patient, and chyle leak in 1 patient, and no cases of tumor recurrence were observed during follow-up. The present case series indicates that the combined chest and transoral approach is feasible and effective for performing LND. Our review of different approaches for "scarless" (at the neck) LND identified advantages and disadvantages for all techniques. Our novel approach has unique advantages, and thus, it can provide an ideal surgical procedure for specific papillary thyroid carcinoma patients.

Safety and feasibility of the transoral endoscopic thyroidectomy vestibular approach with neuroprotection techniques for papillary thyroid carcinoma.

BACKGROUND: This study aimed to evaluate the feasibility and safety of the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) with neuroprotection techniques for the surgical management of papillary thyroid carcinoma (PTC). METHODS: Patients with PTC who underwent TOETVA between December 2016 and July 2020 were included in this study, and their relevant clinical characteristics, operational details, and surgical outcomes were reviewed and extracted from their medical records for further analysis. RESULTS: A total of 75 patients successfully underwent TOETVA with zero conversions. Unilateral lobectomy with isthmectomy and total thyroidectomy were completed for 58 and 17 patients, respectively, all using our unique neuroprotective procedure and ipsilateral central neck dissection (CND). The mean number of retrieved lymph nodes versus positive lymph nodes was 6.8 ± 3.7 vs. 1.5 ± 2.3. Postoperative complications included three cases of transient superior laryngeal nerve (SLN) palsy (4.0%), five cases of transient recurrent laryngeal nerve (RLN) palsy (6.7%), 14 cases of transient hypoparathyroidism (18.7%), two cases of numb chin (2.7%) and two cases of flap perforation (2.7%). The follow-up period for patients with PTC lasted for 15.6 ± 10.9 months, during which no other complications or tumor recurrence were observed. CONCLUSION: TOETVA can be safely performed for patients with PTC with satisfactory results during the short-term follow-up period. Our neuroprotection techniques can be integrated into TOETVA, which is worth recommending for PTC patients who desire better cosmetic surgical outcomes.

Endoscopic thyroidectomy via the combined trans-oral and chest approach for cT1-2N1bM0 papillary thyroid carcinoma.

BACKGROUND: Recent years there have been witnessed considerable advances in endoscopic selective lateral neck dissection (LND). However, dissection of lymph nodes at level IV and level VI via the chest approach is inherently challenging. In this study, we used combined trans-oral and chest approach for endoscopic thyroidectomy in patients with cT1-2N1bM0 papillary thyroid carcinoma (PTC). METHODS: Clinical characteristics and surgical outcomes of ten patients with cT1-2N1bM0 PTC who underwent endoscopic thyroidectomy via combination of trans-oral and chest approach between September 2020 and September 2021 were retrospectively reviewed. RESULTS: All 10 patients successfully underwent total thyroidectomy and selective LND via chest approach, while central neck dissection (CND) and supplementary dissection of lymph nodes at level IV were performed via the trans-oral approach. The mean number of positive/retrieved level II, III-IV, and VI lymph nodes were 0.6 ± 1.0/9.8 ± 5.0, 4.6 ± 2.8/23.1 ± 4.7, and 4.9 ± 3.4/10.3 ± 4.6, respectively. Four patients developed transient hypoparathyroidism which spontaneously resolved within 1 month. Five patients developed numbness of lateral neck and ear and one patient experienced limb lift restriction. No other complications or tumor recurrence occurred during follow-up. CONCLUSION: It is feasible to perform total thyroidectomy, CND, and selective LND via combined trans-oral and chest approach, and satisfactory short-term outcomes were observed in this cohort. This approach may offer one more option for cT1-2N1bM0 PTC patients, especially those in whom metastatic lymph nodes at level IV or level VI are detected by preoperative examination.

"There is a huge need, and it's growing endlessly": perspectives of mental health service providers to ethnic Chinese in Aotearoa New Zealand.

AIM: Little is known about the experiences of ethnic Chinese accessing mental health services in Aotearoa New Zealand, resulting in uncertainty around their service preferences, and facilitators or barriers to their mental health help-seeking. This paper investigated the experiences of providers of specific mental health services for ethnic Chinese in Aotearoa, their opinions regarding their patients' experience, and their suggestions to improve the system. METHOD: Sixteen health professionals with experience and expertise delivering mental health services for ethnic Chinese were interviewed at 12 organisations across Aotearoa. Interviews were recorded, transcribed and analysed using general inductive methods and thematic analysis. RESULTS: Practitioners' experiences revolved heavily around cultural brokerage, which is vital for culturally appropriate care, but this is time-consuming and receives little formal support. Practitioners thought the patient experience was inadequate, with a lack of language- and culturally appropriate services leading to delays in help-seeking. Practitioners' suggestions for system improvement included increasing resourcing for research, and for expanding the availability of language and culturally appropriate services. CONCLUSION: Current mental health service provision is inadequate for ethnic Chinese seeking help in Aotearoa, and is causing harm by delaying mental health help-seeking. Decisive Government leadership and deeper collaboration between non-Government organisations (NGOs) will be key to improving mental health service accessibility and outcomes.

Qin's seven steps for endoscopic selective lateral neck dissection via the chest approach in patients with papillary thyroid cancer: experience of 35 cases.

BACKGROUND: Endoscopic thyroidectomy is widely performed as it does not result in neck scar. However, there is a paucity of reports pertaining to completely endoscopic lateral neck dissection (LND). In this study, we introduce our step-wise approach for performing endoscopic selective LND via the chest-breast approach. We refer to this approach as Qin's seven steps. METHODS: The Qin's seven steps are: (1) establishment of working space range; (2) dissection of lymph nodes between the SCM and the sternohyoid muscle (level IV) and exposure of omohyoid; (3) dissection of lymph nodes at level IV; (4) dissection of lymph nodes at level III; (5) dissection of lymph nodes at carotid triangle (level III); (6) exposure of accessory nerve and dissection of lymph nodes at level II a; (7) dissection of lymph nodes at level II b. We reviewed the clinical data of 35 patients with papillary thyroid cancer (PTC) who were operated using the Qin's seven steps. RESULTS: All 35 patients successfully underwent LND; bilateral LND was performed in 5 patients. The mean tumor size was 1.8 ± 1.0 cm; seven patients had multiple lesions. The mean number of retrieved lymph nodes in level II, III and IV were 8.8 ± 5.6, 6.1 ± 4.0 and 9.3 ± 5.1, respectively. As for complications, there were 3 cases of accessory nerve injury and 1 case of hypoglossal nerve injury. Internal jugular vein injury, cervical plexus injury and lymphatic leakage occurred in 2, 7, and 1 patients, respectively. CONCLUSION: The Qin's seven steps for performing endoscopic selective LND could be safely used in PTC patients with lateral lymph node metastasis. Satisfactory results were achieved in the short-term follow-up period. We recommend the use of Qin's seven steps for PTC patients who are not desirous of neck scar.

Nursing care of a patient with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy combined with coronary artery bypass grafting / 中国实用护理杂志

Objective:To summarize the nursing experience of a patient with refractory hypoxia, septic shock and delirium after pulmonary endarterectomy combined with coronary artery bypass grafting for severe chronic thromboembolic pulmonary hypertension.Methods:An elderly patient with severe chronic thromboembolic pulmonary hypertension admitted to China-Japan Friendship Hospital in December 2020 was given nursing measures in terms of hemodynamic management, anticoagulant management, nursing of intractable hypoxia and balloon pulmonary arterioplasty, infection prevention and control, lung rehabilitation, early functional exercise and transitional nursing etc.Results:After multiple consultations with multidisciplinary experts inside and outside the hospital, the patient′s diagnosis and treatment plan was refined. After individualized and comprehensive nursing, the patient recovered well after surgery and was transferred back to the common ward 57 days after surgery, and discharged successfully 73 days after surgery.Conclusions:The individual and comprehensive nursing measures for this patient have effectively improved the prognosis of the patient and improved the quality of life of the patient.

Regulatory role of Slc1a2 on the maturation and function of dendritic cells / 国际生物医学工程杂志

Objective:To investigate the regulatory effects of nuclear factor-κB (NF-κB) on dendritic cell (DC) maturation and function through solute carrier family 1 member 2 (Slc1a2).Methods:Mouse bone marrow-derived DCs were transfected with Slc1a2-specific siRNA and an overexpression Slc1a2 eukaryotic expression vector. The real-time fluorescence quantitation (RT-PCR) and Western Blot methods were used to detect knockdown and overexpression efficiency. The expression of surface molecules (CD40, CD80) and major histocompatibility complex Ⅱ (MHCⅡ) of DCs was detected by flow cytometry. ELISA was used to detect the secretion of the cytokines interleukin (IL)-12, IL-6, and transforming growth factor-β (TGF-β). The effects of knockdown of Slc1a2 on DC maturation and function and the effects of overexpression of Slc1a2 on DC maturation and function were reflected by the above assay results. A mixed lymphocyte culture assay was used to investigate the effect of Slc1a2 on T cell proliferation, and an ELISA was used to detect the lavel of IL-17A. Changes in the relative fluorescence intensity of FITC in DCs were analyzed by flow cytometry to investigate the ability of Slc1a2 overexpression on antigen phagocytosis. Finally, DCs were pretreated with an NF-κB inhibitor, toluoylphenylalanine chloromethyl ketone (TPCK), and the effect of TPCK on the expression of Slc1a2 in DCs and DC maturation was examined.Results:Slc1a2 expression was found to be high in DC treated with lipopolysaccharides (LPS) ( P<0.001). The knockdown of Slc1a2 decreased DC maturation and ability to stimulate the proliferation of CD4 + T cells ( P<0.001) and inhibited IL-17 secretion ( P<0.01). Overexpression of Slc1a2 promoted DC maturation and ability to stimulate the proliferation of CD4 + T cells(all P<0.01) Pretreatment of DC with the NF-κB inhibitor TPCK inhibited the expression of Slc1a2 at mRNA and protein levels induced by LPS. Conclusions:NF-κB regulates Slc1a2 expression, which affects the maturation and function of DC.

miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.

Syndecan 4 contributes to osteoclast differentiation induced by RANKL through enhancing autophagy.

Periodontitis is a common chronic disease. Osteoclast differentiation contributes to alveolar bone resorption which is a distinct phenomenon during periodontitis. Syndecan 4 (SDC4), a member of the syndecan family, was found to be highly expressed during periodontitis. However, little is known about its role in periodontitis. Herein, we explored the role of SDC4 in osteoclast differentiation. An experimental periodontitis rat model was established by ligating the right first molar. The SDC4 expression in periodontium was detected by western blot and immunofluorescence. Our study demonstrated that SDC4 was highly expressed in the periodontium of periodontitis rats. It was positively transcriptionally regulated by NF-κB. SDC4 silencing abrogated osteoclast differentiation induced by RANKL, while SDC4 overexpression enhanced osteoclast differentiation. Moreover, SDC4 enhanced autophagy induced by RANKL. 3-MA, an autophagy inhibitor, was employed to explore whether SDC4 impacts osteoclast differentiation through activating autophagy. Treatment with 3-MA abolished osteoclast differentiation which was enhanced by SDC4, indicating that SDC4 promotes osteoclast differentiation through activating autophagy. This study reveals that SDC4 may contribute to osteoclast differentiation during periodontitis through activating autophagy. It sheds light on the important role of SDC4 in periodontitis.