The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem. Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity, good drug-loading ability and sustained drug release properties. As a typical example, hyaluronic acid dressing (Healoderm) has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers. However, the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment. Due to the intricacy of diabetic wounds, antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice, although these medications are easily hindered by the hostile environment. In this case, scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds (such as high glucose and low pH) or combined with external stimuli (such as light or magnetic field) to achieve controllable drug release, gel degradation, and microenvironment improvements in order to overcome these clinical issues. These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings. Here, we review recent advances on responsive-hydrogel dressings towards diabetic wound healing, with focus on hydrogel structure design, the principle of responsiveness, and the behavior of degradation. Last but not least, the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed. We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

Hypoxic-ischemic injury is a common pathological dysfunction in clinical settings. Mitochondria are sensitive organelles that are readily damaged following ischemia and hypoxia. Dynamin-related protein 1 (Drp1) regulates mitochondrial quality and cellular functions via its oligomeric changes and multiple modifications, which plays a role in mediating the induction of multiple organ damage during hypoxic-ischemic injury. However, there is active controversy and gaps in knowledge regarding the modification, protein interaction, and functions of Drp1, which both hinder and promote development of Drp1 as a novel therapeutic target. Here, we summarize recent findings on the oligomeric changes, modification types, and protein interactions of Drp1 in various hypoxic-ischemic diseases, as well as the Drp1-mediated regulation of mitochondrial quality and cell functions following ischemia and hypoxia. Additionally, potential clinical translation prospects for targeting Drp1 are discussed. This review provides new ideas and targets for proactive interventions on multiple organ damage induced by various hypoxic-ischemic diseases.

G-protein coupled receptors (GPCRs) are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying mechanism.

The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation (BDL) for 21 d or carbon tetrachloride (CCl₄) for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65’s action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated.

We found that hepatic macrophage (HM)-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL- and CCl₄-induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation (BMT) experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages (BMMs). Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), all of which subsequently promoted the activation of hepatic stellate cells (HSCs) and the damage of hepatocytes (HCs). Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-α and IL-6 via the Gαq-Ca²⁺-JNK/NF-κB pathways, while promoted the expression of TGF-β through the Gαq-Ca²⁺-MLK3-MKK7-JNK pathway. Notably, pharmacological GPR65 inhibition retarded the development of inflammation, HCs injury and fibrosis in vivo.

GPR65 is a major regulator that modulates the progression of liver fibrosis. Thus, targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines (CPGs) limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scafolds to promote bone regeneration.

In this study, a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO₃, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.

The incorporation of BaTiO₃ into the scafold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.

The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids. Serving as three-dimensional (3D) models that mimic human skin, these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional (2D) systems and ethical concerns. The inherent plasticity of skin organoids allows for their construction into physiological and pathological models, enabling the study of skin development and dynamic changes. This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages. Furthermore, it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques, such as 3D printing and microfuidic devices. The review also summarizes and discusses the diverse applications of skin organoids in developmental biology, disease modelling, regenerative medicine, and personalized medicine, while considering their prospects and limitations.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and anti-fibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EV-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6–18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95%CI 3.3–3.5 million) experiencing their first-ever stroke and another 2.3 million (95%CI 2.2–2.4 million) dying as a result. Additionally, approximately 12.5% (95%CI 12.4%–12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95%CI 2.1–2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age±standard error (SE) was (65.700±0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80.0% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean±SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6±16.3), ranging from (13,310.1±12.8) in IS to (81,369.8±260.7) in SAH, and out-of-pocket expenses were (5788.9±8.6), ranging from (4449.0±6.6) in IS to (30,778.2±156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95%CI 9.2%–9.2%), ranging from 6.4% (95%CI 6.4%–6.5%) for IS to 21.8% (95%CI 21.8%–21.9%) for ICH. From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT+MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95%CI 3.2%–3.3%), 7.7% (95%CI 7.5%–8.0%), and 12.9% (95%CI 12.3%–13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95%CI 8.8%–9.0%), 16.5% (95%CI 16.2%–16.9%), and 16.8% (95%CI 16.2%–17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [%(95%CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95%CI 14.6%–15.0%) and 14.0% (95%CI 13.8%–14.2%), respectively. The mortality rate [%(95%CI)] of stroke at 3-month and 12-month was 4.2% (95%CI 4.1%–4.3%) and 8.5% (95%CI 8.4%–8.6%), respectively. The recurrence rate [%(95%CI)] of stroke at 3-month and 12-month was 3.6% (95%CI 3.5%–3.7%) and 5.6% (95%CI 5.4%–5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.