ABSTRACT Self‐healing materials represent a paradigm shift in designing functional biomedical devices for drug delivery, tissue regeneration, and 3D bioprinting. However, their clinical translation remains limited by challenges such as insufficient mechanical strength, potential cytotoxicity from chemical modifications, and complex activation requirements. Here, we report the development of a self‐healing colloidal gelatin hydrogel engineered as a flowable hemostatic matrix and successfully demonstrate its bench‐to‐bedside translation into a biomedical device (Colloidose). Specifically, amphoteric gelatin sub‐microparticles self‐assemble into an integrated gel network exhibiting a high storage modulus (G’ > 15 kPa) and a healing efficiency exceeding 95%, enabling rapid in situ solidification to accelerate blood clot formation. By benchmarking against conventional flowable matrices composed of coarse hundreds of micrometer‐sized gelatin granules, we demonstrate that Colloidose offers superior hemostatic efficacy in anatomically challenging or pressure‐intolerant sites (e.g., hepatobiliary, otorhinolaryngological, and gynecologic surgeries). Supported by comprehensive preclinical studies and over 300 clinical cases, Colloidose exemplifies the successful translation of an advanced self‐healing biomaterial, establishing its role as a next‐generation hemostat and opening new avenues for injectable and moldable biomedical devices.

The emergence of self-healing materials has brought a paradigm shift in the design of functional biomedical devices for applications such as drug delivery, tissue regeneration, and 3D bioprinting. However, their clinical translation remains limited due to challenges including insufficient mechanical strength, potentially cytotoxic chemical modifications, and complex healing activation conditions. Herein, we present the development of self-healing colloidal gelatin hydrogel as an innovative design of flowable hemostatic matrix, and successfully demonstrate its bench-to-bedside translation into a biomedical device (named as Colloidose). Specifically, amphoteric gelatin submicron particles self-assemble into an integrated gel network exhibiting a high storage modulus (G'> 15 kPa) and a healing efficiency exceeding 95%, enabling rapid in situ solidification to accelerate blood clot formation. By comparing with more conventional design strategy flowable gelatin matrix based on dispersion of hundreds micrometer-sized gelatin granules, we demonstrate that Colloidose are more effective for hemostasis in anatomically challenging or pressure-intolerant sites such as hepatobiliary surgery, otorhinolaryngology, and gynecology based on comprehensive preclinical animal studies and over 300 clinical cases. Overall, Colloidose exemplifies the successful clinical translation of an advanced self-healing biomaterial, establishing its role as a 2nd generation flowable hemostatic matrix and opening new avenues for the development of injectable and moldable biomedical devices. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ChiCTR2500113187 ### Funding Statement This work was funded by National Key Research and Development Program of China (No. 2022YFC2403002), National Natural Science Foundation of China (No.52403152), Natural Science Foundation of Liaoning Province (Grant No. 2024-BSBA-02), Medical-Engineering Interdisciplinary Joint Fund of Dalian University of Technology (Grant No. DUT24YG102). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of West china hospital of Sichuan university gav ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online

Methacrylated gelatin (GelMA) hydrogels have been well-recognized as a widely-used natural polymer for biofabrications due to the adaptability for multiple crosslinking schemes, desirable biocompatibility and biodegradability, and ease of chemical functionalization. With regard to 3D bioprinting, however, GelMA has shown unsatisfactory printing stability and accuracy due to slow sol-gel transition, suboptimal mechanical strength, and strict temperature control for printing. We herein developed an innovative dual-crosslinkable colloidal inks composed of self-assembled GelMA nanospheres with 80 % self-healing efficiency, which outperform the traditional GelMA polymeric inks in terms of enhanced printability and fidelity, broader printing temperature range, adjustable mechanical strength ranging from brain analogue 2.83 kPa to cardiac analogue 52.45 kPa, and improved bio-functionalities evidenced by the elevated hydrophilicity, mass transfer efficiency and prolonged drug release profile. Moreover, the granulation design of GelMA inks unlocked freeform 3D printing modes such as direct multi-ink writing, embedded printing, but also allowed in-situ printing directly at the bleeding wound sites due to the outstanding hemostatic efficacy and network stability of colloidal gels. In general, our nanostructured GelMA colloidal inks present a better replacement for the traditional GelMA polymeric inks in 3D bioprinting, which establishes a foundation for bench-to-bedside translations of 3D printing techniques towards more practical clinical applications.

Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

Bone remodeling is governed by the basic multicellular unit (BMU) and plays a crucial role in both normal bone function and pathological conditions (e.g. osteoporosis). Unfortunately, our understanding of the bone remodeling process is limited as current models do not allow dynamic events in the BMU to be systematically and spatiotemporally analyzed. Leveraging microfluidic and stem cell technologies, we developed an bone-on-a-chip model that enables the dynamic co-culture of osteoblasts (OBs) and osteoclasts (OCs) in a spatiotemporal context. This model faithfully recapitulates critical aspects of the bone remodeling process, including cell migration and differentiation into OBs and OCs, as well as their delicate coupling within the BMU during bone regeneration, homeostasis, and in osteoporotic conditions. RNA sequencing analyses revealed that our bone remodeling-on-a-chip model exhibits more pronounced osteoporotic features compared to conventional OB-OC co-cultures, closely resembling the pathological bone remodeling observed in osteoporotic mice. Notably, our bone remodeling-on-a-chip model accurately predicts the clinically observed antiresorptive effects of two anti-osteoporosis drugs. Therefore, our bone remodeling-on-a-chip model stands poised as an advanced platform to enhance our understanding of bone pathophysiology and offers a promising alternative to current drug testing in bone-related diseases. STATEMENT OF SIGNIFICANCE: Bone remodeling, governed by the basic multicellular unit (BMU), is crucial for bone development. Current models fail to analyze dynamic events within the BMU systematically and spatiotemporally. We developed a microfluidic bone remodeling-on-a-chip model for the co-culture of osteoblasts (OBs) and osteoclasts (OCs). This model replicates key aspects of bone remodeling, including the migration, differentiation, and coupling of OBs and OCs under various conditions. It closely mirrors pathological bone remodeling in osteoporotic mice and demonstrates reliable drug testing for anti-osteoporosis drugs. This advanced platform enhances our understanding of bone pathophysiology and offers a promising drug testing model for bone-related diseases.

Type 2 diabetic osteoporosis (T2DOP) is characterized by impaired bone formation and increased fracture susceptibility; however, the molecular mechanisms linking hyperglycemia to osteoblast dysfunction remain insufficiently defined. In this study, we demonstrate that high glucose (HG) triggers ferroptosis in osteoblasts through activation of the thioredoxin-interacting protein (TXNIP)/thioredoxin-1 (Trx-1)/glutathione peroxidase 4 (GPX4) pathway, leading to reduced cell viability, bioenergetic failure, and impaired osteogenic differentiation. HG exposure induced hallmark ferroptotic features—including excessive intracellular ferrous iron (Fe2⁺), elevated reactive oxygen species (ROS), lipid peroxidation, increased 4-hydroxynonenal (4-HNE), and acyl-CoA synthetase long-chain family member 4 (ACSL4), together with depletion of glutathione (GSH), GPX4, and ferritin heavy chain 1 (FTH1). Transcriptomic profiling identified TXNIP as a key upstream regulator under hyperglycemic conditions. Mechanistically, TXNIP directly interacts with and inhibits Trx-1, suppresses thioredoxin reductase-1 (TrxR1) activity, disrupts redox homeostasis, and ultimately inactivates GPX4, thereby promoting ferroptosis and osteogenic dysfunction. Silencing TXNIP restored antioxidant capacity, mitochondrial respiration, and mineralization in vitro. In a T2DOP rat model, systemic TXNIP knockdown significantly reduced oxidative injury, improved trabecular architecture and bone mineral density, and increased biochemical markers of bone formation. These findings identify TXNIP-dependent ferroptosis as a central mechanism of osteoblast impairment in diabetes and highlight the TXNIP/Trx-1/GPX4 axis as a promising therapeutic target for type 2 diabetic osteoporosis.

3D printing of ceramics or glass typically requires sacrificial organic plasticizers and high-temperature sintering, which is time- and cost-consuming, potentially cytotoxic, and may compromise the bioactivity and functionality of the inorganic components. We herein developed purely inorganic self-healing colloidal gels, consisting of electrostatically attractive silica-based hard nanospheres, to enable 3D printing of highly strong inorganic constructs via additive-free and low temperature sintering (LTS) processing. Through cross-scale analysis of the structural and mechanical features, we quantitatively described the constitutive relationship of attractive colloidal gels based on the integration of colloidal assembly theory with experimental characterizations. This mechanistic understanding further allowed us to develop considerably strong colloidal gels (maximal compressive modulus ∼2.3 MPa) without compromising the self-healing ability. We further demonstrated the excellent printability, shape-fidelity, and reprocessability of the inorganic gels, thereby facilitating additive-free inorganic 3D printing followed by LTS treatment at ∼700 °C. This "green" inorganic 3D-printing strategy enabled cost-efficient and bioactivity-preserved fabrication of bioglass-based bone substitutes, which led to improved in vivo osteogenesis and osteointegrity. In general, this work emphasizes the significance of rationale design and mechanistic understanding of self-healing colloidal gels with outstanding performances as printable inks and provides an avenue for customized fabrication of functional inorganic 3D structures toward applications in biomedical, machinery, energy, and chemical industries.

Cell volume as a characteristic of changes in response to external environmental cues has been shown to control the fate of stem cells. However, its influence on macrophage behavior and macrophage-mediated inflammatory responses have rarely been explored. Herein, through mediating the volume of macrophages by adding polyethylene glycol (PEG), we demonstrated the feasibility of fine-tuning cell volume to regulate macrophage polarization towards anti-inflammatory phenotypes, thereby enabling to reverse macrophage-mediated inflammation response. Specifically, lower the volume of primary macrophages can induce both resting macrophages (M0) and stimulated pro-inflammatory macrophages (M1) to up-regulate the expression of anti-inflammatory factors and down-regulate pro-inflammatory factors. Further mechanistic investigation revealed that macrophage polarization resulting from changing cell volume might be mediated by JAK/STAT signaling pathway evidenced by the transcription sequencing analysis. We further propose to apply this strategy for the treatment of arthritis via direct introduction of PEG into the joint cavity to modulate synovial macrophage-related inflammation. Our preliminary results verified the credibility and effectiveness of this treatment evidenced by the significant inhibition of cartilage destruction and synovitis at early stage. In general, our results suggest that cell volume can be a biophysical regulatory factor to control macrophage polarization and potentially medicate inflammatory response, thereby providing a potential facile and effective therapy for modulating macrophage mediated inflammatory responses. STATEMENT OF SIGNIFICANCE: Cell volume has recently been recognized as a significantly important biophysical signal in regulating cellular functionalities and even steering cell fate. Herein, through mediating the volume of macrophages by adding polyethylene glycol (PEG), we demonstrated the feasibility of fine-tuning cell volume to induce M1 pro-inflammatory macrophages to polarize towards anti-inflammatory M2 phenotype, and this immunomodulatory effect may be mediated by the JAK/STAT signaling pathway. We also proposed the feasible applications of this PEG-induced volume regulation approach towards the treatment of osteoarthritis (OA), wherein our preliminary results implied an effective alleviation of early synovitis. Our study on macrophage polarization mediated by cell volume may open up new pathways for immune regulation through microenvironmental biophysical clues.

Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.

研究在髋关节手术中应用髋关节外科脱位技术的效果以及对患者髋关节功能和预后的影响。 方法:将我院2019年12月—2020年12月收治的72例行髋关节手术的患者作为研究对象,每组各36例。对照组给予传统手术治疗,观察组给予髋关节外科脱位技术治疗,对比2组髋关节功能恢复情况、疼痛评分,并发症发生情况以及术后髋关节改善效果。结果:治疗前2组功能评分并没有明显差别(P>0. 05),治疗后观察组评分明显比对照组高(P<0. 05);观察组各阶段疼痛评分均比对照组低(P<0. 05);观察组改善效果明显优于对照组;观察组并发症发生率明显低于对照组(P<0. 05)。结论:髋关节外科脱位技术在髋关节手术患者当中使用,能够有效改善患者的髋关节功能,提升预后效果,并减少疼痛对患者的影响,加快术后康复的速度,还有助于降低患者的并发症发生率,值得临床推广和应用。

Injectable granular gels consisting of densely packed microgels serving as scaffolding biomaterial have re-cently shown great potential for applications in tissue regeneration, which allow administration via mini-mally invasive surgery, on-target cargo delivery, and high efficiency in nutrient/waste exchange. However, limitations such as insufficient mechanical strength, structural integrity, and uncontrollable differentiation of the encapsulated cells in the scaffolds hamper their further applications in the biomedical field. Herein, we developed a new class of granular gels via bottom-up assembly of cell-laden microgels via photo -triggered imine-crosslinking (PIC) chemistry based on the microfluidic technique. The particulate nature of the granular gels rendered them with shear-thinning and self-healing behavior, thereby functioning as an injectable and adaptable cellularized scaffold for bone tissue regeneration. Specifically, single cell -laden, monodisperse microgels composed of methacrylate-and o-nitrobenzene-functionalized hyaluronic acid and gelatin were prepared using a high-throughput microfluidic technique with a production rate up to 3.7 x 10 8 microgels/hr, wherein the PIC chemistry alleviated the oxygen inhibition on free-radical polymerization and facilitated enhanced fabrication accuracy, accelerated gelation rate, and improved net-work strength. Further in vitro and in vivo studies demonstrated that the microgels can serve as carriers to support the activity of the encapsulated mesenchymal stem cells; these cell-laden microgels can also be used as cellularized bone fillers to induce the regeneration of bone tissues as evidenced by the in vivo experiment using the rat femoral condyle defect model. In general, these results represent a significant step toward the precise fabrication of engineered tissue mimics with single-cell resolution and high cell -density and can potentially offer a powerful tool for the design and applications of a next generation of tissue engineering strategy.

Hyaluronic acid (HA) is an important type of naturally derived carbohydrate polymer with specific polysaccharide macromolecular structures and multifaceted biological functions, including biocompatibility, low immunogenicity, biodegradability, and bioactivity. Specifically, HA hydrogels in a microscopic scale have been widely used for biomedical applications, such as drug delivery, tissue engineering, and medical cosmetology, considering their superior properties outperforming the more conventional monolithic hydrogels in network homogeneity, degradation profile, permeability, and injectability. Herein, we reviewed the recent progress in the preparation and applications of HA microgels in biomedical fields. We first summarized the fabrication of HA microgels by focusing on the different crosslinking/polymerization schemes for HA gelation and the miniaturized fabrication techniques for producing HA-based microparticles. We then highlighted the use of HA-based microgels for different applications in regenerative medicine, including cartilage repair, bioactive delivery, diagnostic imaging, modular tissue engineering. Finally, we discussed the challenges and future perspectives in bridging the translational gap in the utilization of HA-based microgels in regenerative medicine.

Background: The efficacy and safety of anti–nerve growth factor (NGF) antibody therapy used for osteoarthritis (OA) pain are controversial. Purpose: To evaluate the efficacy and safety of anti-NGF antibody therapy via a meta-analysis of randomized controlled trials (RCTs). Study Design: Systematic review; Level of evidence, 1. Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase, and the Web of Science databases were searched for RCTs assessing anti-NGF antibody treatments for hip and knee OA. A total of 623 records were retrieved from the databases. A random-effects model was used to assess primary and secondary outcomes. Bias was assessed using the Cochrane Collaboration tool, funnel plots, and the Egger test. Subgroup analyses were used to assess the efficacy and safety of the independent variables. Sensitivity analysis was conducted to evaluate the effectiveness of tanezumab and the effectiveness of anti-NGF antibodies compared to active comparator drugs. We present the effects of dose, administration mode, and treatment duration on the efficacy and safety of anti-NGF antibody therapy. Results: There were 19 RCTs included in our meta-analysis. Anti-NGF antibody treatment showed significant improvements on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain, physical function, and stiffness as well as on a patient global assessment (PGA). The overall standardized mean differences were as follows: WOMAC pain (–0.31 [95% CI, –0.36 to –0.26]; Z = 11.75; P < .001; I 2 = 38%), WOMAC physical function (−0.36 [95% CI, –0.41 to –0.30]; Z = 12.67; P < .001; I 2 = 44%), WOMAC stiffness (–3.59 [95% CI, –4.87 to –2.30]; Z = 5.47; P < .001; I 2 = 98%), and PGA (−0.28 [95% CI, –0.34 to –0.22]; Z = 9.39; P < .001; I 2 = 50%). Anti-NGF antibody treatment resulted in a greater incidence of adverse events (risk ratio, 1.09 [95% CI, 1.06 to 1.12]; Z = 5.60; P < .001; I 2 = 0%). The incidence of serious adverse events was similar between the treatment and control groups (risk ratio, 1.15 [95% CI, 0.98 to 1.34]; Z = 1.71; P = .09; I 2 = 0%). Conclusion: Anti-NGF antibody treatment significantly relieved pain and improved function in patients with hip and knee OA. However, no conclusion could be drawn regarding the optimal treatment plan for anti-NGF antibodies when all 3 variables (dose, administration mode, and treatment duration) were combined in the analyses.

Current techniques for the generation of cell-laden microgels are limited by numerous challenges, including poorly uncontrolled batch-to-batch variations, processes that are both labor- and time-consuming, the high expense of devices and reagents, and low production rates; this hampers the translation of laboratory findings to clinical applications. To address these challenges, we develop a droplet-based microfluidic strategy based on metastable droplet-templating and microchannel integration for the substantial large-scale production of single cell-laden alginate microgels. Specifically, we present a continuous processing method for microgel generation by introducing amphiphilic perfluoronated alcohols to obtain metastable emulsion droplets as sacrificial templates. In addition, to adapt to the metastable emulsion system, integrated microfluidic chips containing 80 drop-maker units are designed and optimized based on the computational fluid dynamics simulation. This strategy allows single cell encapsulation in microgels at a maximum production rate of 10 ml h(-1) of cell suspension while retaining cell viability and functionality. These results represent a significant advance toward using cell-laden microgels for clinical-relevant applications, including cell therapy, tissue regeneration and 3D bioprinting.

Cell microenvironment is a collection of dynamic biochemical and biophysical cues which functions as the key factor in determining cell behavior. Encapsulating single cell into micrometer-scale hydrogels which mimics the cell microenvironment can be used for single cell analysis, cell therapies, and tissue engineering. Here, we developed a microfluidics-based platform to engineer the niche environment at single cell level using alginate microgels crosslinked by different metal ions to regulate stem cell behavior for bone regeneration. Specifically, we revealed that Ca2+ in the engineered microenvironment promoted osteogenic differentiation of encapsulated stem cells and substantially accelerated the matrix mineralization compared to Sr2+in vitro. However, the superior osteoinductive capacity of Ca2+ compared with Sr2+ led to comparable bone healing in a rat bone defect model. This attributed to Sr2+ in microgels to inhibit the osteoclast activity and bone resorption after implantation. In summary, the present study demonstrates metal ions as a critical factor in the environmental cues to affect cell behavior and influence the efficacy of stem cell-based therapy in tissue regeneration, and provides new insights to engineer an expecting microenvironment for regenerative medicine.

The encapsulation of cells in microscale hydrogels can provide a mimic of a three-dimensional (3D) microenvironment to support cell viability and functions and to protect cells from the environmental stress, which have been widely used in tissue regeneration and cell therapies. Here, a microfluidics-based approach is developed for continuous encapsulation of mesenchymal stem cells (MSCs) at the single-cell level using alginate microgels. This microfluidic technique integrated on-chip encapsulation, gelation, and de-emulsification into a one-step fabrication process, which enables scalable cell encapsulation while retaining the viability and functionality of loaded cells. Remarkably, we observed MSCs encapsulated in Ca-alginate microgels at the single-cell level showed significantly enhanced osteogenesis and accelerated mineralization of the microgels which occurred only after 7 days of induction. Furthermore, MSCs laden in alginate microgels displayed significantly enhanced bone formation compared to MSCs mixed with microgels and acellular microgels in a rat tibial ablation model. To conclude, the current microfluidic technique represents a significant step toward continuous single cells encapsulation, fabrication, and purification. These microgels can boost bone regeneration by providing a controlled osteogenic microenvironment for encapsulated MSCs and facilitate stem cell therapy in the treatment of bone defects in a minimally invasive delivery way. Statement of significance The biological functions and therapeutic activities of single cells laden in microgels for tissue engineering remains less investigated. Here, we reported a microfluidic-based method for continuous encapsulation of single MSCs with high viability and functionality by integrating on-chip encapsulation, gelation, and de-emulsification into a one-step fabrication process. More importantly, MSCs encapsulated in alginate microgels at the single-cell level showed significantly enhanced osteogenesis, remarkably accelerated mineralization in vitro and bone formation capacity in vivo. Therefore, this single-cell encapsulation technique can facilitate stem cell therapy for bone regeneration and be potentially used in a variety of tissue engineering applications.

Moli Wu* Danyang Song* Hui Li Yang Yang Xiaodong Ma Sa Deng Changle Ren Xiaohong Shu 1College of Pharmacy, Dalian Medical University, Dalian 116044, People’s Republic of China; 2College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, People’s Republic of China; 3Surgery Department of Dalian Municipal Central Hospital, Dalian Medical University, Dalian 116033, People’s Republic of China

STAT3 is the most ubiquitous member of the STAT family and involved in many biological processes, such as cell proliferation, differentiation, and apoptosis. Mounting evidence has revealed that STAT3 is aberrantly activated in many malignant tumors and plays a critical role in cancer progression. STAT3 is usually regarded as an effective molecular target for cancer treatment, and abolishing the STAT3 activity may diminish tumor growth and metastasis. Recent studies have shown that negative regulators of STAT3 signaling such as PIAS, SOCS, and PTP, can effectively retard tumor progression. However, PIAS, SOCS, and PTP have also been reported to correlate with tumor malignancy, and their biological function in tumorigenesis and antitumor therapy are somewhat controversial. In this review, we summarize actual knowledge on the negative regulators of STAT3 in tumors, and focus on the potential role of PIAS, SOCS, and PTP in cancer treatment. Furthermore, we also outline the STAT3 inhibitors that have entered clinical trials. Targeting STAT3 seems to be a promising strategy in cancer therapy.

目的 观察术前血清C反应蛋白(CRP)水平对老年肥胖患者全膝关节置换(TKA)术后膝关节功能恢复的影响.方法 回顾性分析自2009-01-2017-12行TKA手术治疗的124例老年肥胖膝关节骨性关节炎.记录术前CRP水平,以及术后第3天患者下床活动及膝关节屈曲至90°的情况.术后第7天进行膝关节功能AKS评分和HSS评分,AKS评分与HSS评分≥70分定义为膝关节功能恢复较好,AKS与HSS评分＜70分定义为膝关节功能恢复较差.结果 术后至开始下床活动时间＜3 d、术后至膝关节屈曲90°时间＜3 d、术后第7天AKS评分≥70分、术后第7天HSS评分≥70分的患者术前CRP水平更低,差异有统计学意义(P＜0.05).术前CRP＜0.53 mg/dl组术后至开始下床活动时间＜3 d、术后至膝关节屈曲90°时间＜3 d、术后第7天AKS评分≥70分、术后第7天HSS评分≥70分患者的比例更高,差异有统计学意义(P＜0.05).COX回归分析结果显示,术前CRP≥0.53 mg/dl可能是术后膝关节功能恢复较差的危险因素.结论 老年肥胖患者术前血清CRP水平可能是评估TKA术后膝关节功能恢复情况的有效指标,术前CRP升高可能不利于患者膝关节功能恢复,因此临床医师可根据情况早期采取措施干预.