Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

Objective To understand the experience of fall alertness in elderly patients with rheumatoid arthritis and to provide references for the development of targeted nursing intervention strategies.Methods 13 elderly patients with rheumatoid arthritis,who were admitted to the Department of Rheumatology and Immunology of a tertiary hospital in Guizhou Province from February to April 2024,were selected through purposive sampling.Phenomenological qualitative research methods were used,with semi-structured in-depth interviews.Data were analyzed using Colaizzi's seven-step method,and themes were extracted.Results 3 main themes and 9 sub-themes were identified:the process of fall risk perception(reshaping fall risk cognition,establishing emotional coping mechanism,enhancing fall alertness effect),behavioral responses to fall alertness(creating a safe living environment,regularizing daily routine plan),and needs for fall prevention support(need for fall prevention knowledge,home rehabilitation care needs,intelligent device usage needs,psychosocial support needs).Conclusion Clinical medical staff should pay attention to the transformation process of fall risk perception in elderly rheumatoid arthritis patients,accurately identify patients'fall support needs in practice,and guide patients to adopt appropriate fall alert response behaviors through innovative fall demand support interaction paths and the construction of social support network systems,in order to improve patients'fall alertness and reduce their fall risk.

Objective To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula(YYHT)against high glucose-induced injury in mouse renal podocytes(MPC5 cells)and the possible mechanism.Methods Adult Wistar rats were treated with 19,38,and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose(30 mmol/L)prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic.The changes in miR-21a-5p expressions and the mRNA levels of FoxO1,PINK1,and Parkin in the treated cells were detected with qRT-PCR,and the protein levels of nephrin,podocin,FoxO1,PINK1,and Parkin were detected with Western blotting.Autophagic activity in the cells were evaluated with MDC staining.The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.Results MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression,lowered expressions of FoxO1,PINK1,and Parkin1 mRNAs,and reduced levels of FoxO1,PINK1,parkin,nephrin,and podocin proteins and autophagic activity.Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin,inhibited the expression of miR-21a-5p,increased the mRNA and protein expressions of FoxO1,PINK1 and Parkin,and upregulated autophagic activity of the cells.Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells,and these effects were obviously attenuated by treatment with YYHT-medicated sera.Conclusion YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

Objective To investigate the requirement of blood sugar management in elderly patients with Type Ⅱ diabetes and to provide a reference for development of a program in management of blood sugar.Methods Using interpretive decriptive phenomenological research,an interview outline based on the theoretical domain framework was developed and face-to-face semi-structured interviews were conducted with 16 aged patients who had Type Ⅱ diabetes in the Department of Endocrinology and Metabolism of a Grade ⅢA hospital in Jiangxi Province.The participants were selected by purposive sampling.Colaizzi 7-step analytical method,in conjunction with Nvivo 11 software,was used to analyse,summarise and extract the themes.Results Seven themes related to the theoretical domain framework were extracted,which included knowledge,skills,environmental context and resources,behavioural adjustment,motivation and goals,emotions and self-efficacy.After refinement,nine sub-themes on major requirement for blood glucose management were extracted,which included the requirements for knowledge and skills in blood sugar management,support from the community and healthcare resources,support from the family,changes in maladaptive behaviours,individualised blood sugar management,motivation for self-management,clarity in goals of blood sugar control,emotional support and psychological adjustment,and support for strengthened beliefs(9 sub-themes).Conclusion Elderly patients with Type Ⅱ diabetes have diverse and individualised needs in management of blood sugar.In the future,healthcare staff should develop appropriate strategies or programs to meet the individual needs of patients by addressing the actual needs of patients,improving the self-management behaviours of patients so as to improve the effects of the blood sugar control.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Objective To investigate the requirement of blood sugar management in elderly patients with Type Ⅱ diabetes and to provide a reference for development of a program in management of blood sugar.Methods Using interpretive decriptive phenomenological research,an interview outline based on the theoretical domain framework was developed and face-to-face semi-structured interviews were conducted with 16 aged patients who had Type Ⅱ diabetes in the Department of Endocrinology and Metabolism of a Grade ⅢA hospital in Jiangxi Province.The participants were selected by purposive sampling.Colaizzi 7-step analytical method,in conjunction with Nvivo 11 software,was used to analyse,summarise and extract the themes.Results Seven themes related to the theoretical domain framework were extracted,which included knowledge,skills,environmental context and resources,behavioural adjustment,motivation and goals,emotions and self-efficacy.After refinement,nine sub-themes on major requirement for blood glucose management were extracted,which included the requirements for knowledge and skills in blood sugar management,support from the community and healthcare resources,support from the family,changes in maladaptive behaviours,individualised blood sugar management,motivation for self-management,clarity in goals of blood sugar control,emotional support and psychological adjustment,and support for strengthened beliefs(9 sub-themes).Conclusion Elderly patients with Type Ⅱ diabetes have diverse and individualised needs in management of blood sugar.In the future,healthcare staff should develop appropriate strategies or programs to meet the individual needs of patients by addressing the actual needs of patients,improving the self-management behaviours of patients so as to improve the effects of the blood sugar control.