1.Comparative Analysis of Clinical Efficacy of Traditional Chinese Medicine Manipulative Reduction Combined with Small Splint Fixation Versus Surgical Treatment for Type A Distal Radius Fracture
Yang SHAO ; Zihan WANG ; Jianwei WANG ; Guoda DAI ; Hengyan CUI ; Zhen HUA ; Tingchen ZHU ; Shaoshuo LI ; Jun MAO ; Fenghua CHEN ; Shuai TAO ; Mao WU
Journal of Traditional Chinese Medicine 2026;67(10):1078-1085
ObjectiveTo compare the clinical efficacy of traditional Chinese medicine (TCM) manipulative reduction combined with small splint fixation versus surgical treatment for type A distal radius fracture (DRF) and to explore the factors influencing the choice of treatment. MethodsA multi-center retrospective study was conducted, collecting data from 1237 type A DRF patients treated in 11 hospitals in Jiangsu province from September, 2023 to April, 2025. Among them, 851 patients in the TCM group received manipulative reduction combined with small splint fixation, and 386 patients in the surgical group underwent open reduction and internal fixation. Visual analog scale (VAS) scores for pain and radiographic indicators including palmar tilt, ulnar deviation, and radial height were compared before treatment, 5-7 days after treatment, and 4-6 weeks after treatment. The wrist joint function scores including Dienst and Gartland-Werley scores at 12 weeks after treatment were recorded. Subgroup analysis was conducted for the excellent rate of Dienst and Gartland-Werley scores, stratified by age (<50, 50-59, 60-69, ≥70 years old) and AO subtypes (A1, A2, A3). A multivariate logistic regression model was used to identify independent factors influencing treatment choice. ResultsOn 5-7 days after treatment, the surgical group had lower VAS scores than the TCM group, while 4-6 weeks after treatment, the TCM group showed lower VAS scores than the surgical group (P<0.01). In terms of radiographic indicators, except for the palmar tilt before treatment being higher in the surgical group than in the TCM group (P<0.01), there were no significant differences in palmar tilt, ulnar deviation, and radial height at other timepoints (P>0.05). Twelve weeks after treatment, the surgical group had a higher average Gartland-Werley score and the excellent rate than the TCM group (P<0.01). Subgroup analysis showed that in patients with A2 type DRF aged 50-59 and 60-69 years old, the excellent rates of Dienst and Gartland-Werley scores in the TCM group were higher than those in the surgical group (P<0.05). Multivariate logistic regression analysis revealed that age, palmar tilt, ulnar deviation, and the degree of swelling on the affected side were independent factors influencing the choice of treatment (P<0.05). ConclusionBoth TCM manipulative reduction combined with small splint fixation and surgical treatment for type A DRF can achieve good therapeutic effects. TCM manipulative reduction combined with small splint fixation has certain advantages in medium- and long-term pain relief, especially in elderly patients, where wrist joint function recovery is more stable. Age, palmar tilt, ulnar deviation, and swelling degree are the main factors influencing the treatment choice.
2.Advancements in Gas-releasing Micro/Nanoplatforms for Overcoming MDR Bacterial Infections in Diabetic Wounds
Ruo-Can LIU ; Yu-Qian WANG ; Shuai ZHANG ; Shao-Zhi ZUO ; Yun-Di WU ; Xi-Long WU
Progress in Biochemistry and Biophysics 2026;53(5):1356-1375
Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H2S significantly accelerates endothelial cell migration for neovascularization, and H2 acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.
3.Advancements in Gas-releasing Micro/Nanoplatforms for Overcoming MDR Bacterial Infections in Diabetic Wounds
Ruo-Can LIU ; Yu-Qian WANG ; Shuai ZHANG ; Shao-Zhi ZUO ; Yun-Di WU ; Xi-Long WU
Progress in Biochemistry and Biophysics 2026;53(5):1356-1375
Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H2S significantly accelerates endothelial cell migration for neovascularization, and H2 acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.
4.Relationship between serum endocan, 8-OHdG and restless leg syndrome in patients with end-stage renal disease on hemodialysis
Shuai HAN ; Bing SHAO ; Wei YANG ; Yanning ZHANG
Journal of Chinese Physician 2025;27(2):195-200
Objective:To investigate the relationship between serum endothelia cell-specific molecules (endocan), 8-hydroxy-2′deoxyguanosine (8-OHdG) and restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD) on hemodialysis.Methods:A total of 180 ESRD hemodialysis patients admitted to the Shenyang First People′s Hospital, the Liaoning Electric Power Center Hospital and the Northern Theater Command General Hospital of the Chinese People′s Liberation Army from May 2021 to May 2023 were prospectively selected and divided into RLS group (41 cases) and non-RLS group (139 cases) according to whether RLS occurred. According to the International RLS Rating Scale (IRLS), the patients with RLS were divided into mild group (12 cases), moderate group (19 cases) and severe group (10 cases). Serum endocan and 8-OHdG levels were detected by enzyme-linked immunosorbent assay. Pearson correlation was used to analyze the correlation between serum endocan, 8-OHdG levels and IRLS scores in RLS patients. Multivariate logistic regression model was used to evaluate the influencing factors of RLS in ESRD hemodialysis patients. The diagnostic value of serum endocan and 8-OHdG levels in ESRD hemodialysis patients was analyzed by receiver operating characteristic (ROC) curve.Results:Comparing with the non-RLS group [(4.03±1.23)ng/ml, (0.38±0.13)ng/ml], the levels of serum endocan in the RLS group [(6.10±1.95)ng/ml], 8-OHdG [(0.53±0.14)ng/ml] were higher ( t=8.180, 6.379, P<0.001). The levels of serum endocan of the RLS patients in the mild, moderate and severe groups [(3.61±1.01)ng/ml, (6.39±1.41)ng/ml, (8.54±2.68)ng/ml], 8-OHdG [(0.39±0.07)ng/ml, (0.51±0.05)ng/ml, (0.74±0.08)ng/ml] were increased successively ( F=23.065, 83.013, P<0.001). Pearson correlation analysis showed that serum endocan and 8-OHdG levels were positively correlated with IRLS scores in RLS patients ( r=0.813, 0.830, P<0.001). Multivariate logistic regression analysis showed that long dialysis time, elevated serum endocan and 8-OHdG were independent risk factors for RLS in ESRD hemodialysis patients, and elevated ferritin was independent protective factor (all P<0.05). ROC curve analysis showed that the area under the curve of RLS in ESRD hemodialysis patients diagnosed with serum endocan and 8-OHdG combined was 0.919 (95% CI: 0.870-0.955), which was larger than in patients diagnosed with serum endocan and 8-OHdG alone 0.791 (95% CI: 0.724-0.848), 0.780 (95% CI: 0.712-0.838). Conclusions:The increase of serum endocan and 8-OHdG is related to the occurrence and severity of RLS in ESRD hemodialysis patients. The combined detection of serum endocan and 8-OHdG levels is of high diagnostic value in the occurrence of RLS in ESRD hemodialysis patients.
5.Genetic variation analysis in three cases of acute generalized exanthematous pustulosis caused by hydroxychloroquine
Yi SHAO ; Shuai ZHANG ; Jinfa DOU ; Lu BIAN ; Xing FAN ; Ming LI ; Hongwei LIU ; Jianbo WANG ; Jianguo LI
Chinese Journal of Dermatology 2025;58(8):767-770
To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.
6.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
7.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
8.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
9.The treatment of moderate and severe glabellar lines by W-shaped excision of glabellar lines combined with botulinum toxin type A injection
Xue DONG ; Shuai SHAO ; Kejia ZHANG
Chinese Journal of Plastic Surgery 2025;41(10):1008-1015
Objective:To evaluate the efficacy of W-shaped excision of glabellar lines combined with botulinum toxin type A (BTX-A) injection for treating moderate to severe glabellar lines.Methods:A retrospective analysis was conducted on the clinical data of patients at the Department of Plastic and Cosmetic Surgery, the First Hospital of Jilin University, from June 2021 to June 2024. All the patients had noticeable dynamic and static glabellar lines—primarily featuring vertical, depressed wrinkles. All of them underwent W-shaped glabellar excision combined with BTX-A injection. All the depressed wrinkles were completely removed during the operation, followed by suturing the bilateral tissues towards the center to improve the underlying tissue depression. Immediately following surgery, 20 units of BTX-A were administered into the glabellar muscle complex using the standardized five-point injection technique. Patients were instructed to receive repeat BTX-A injections at regular intervals of 4 to 6 months. Postoperative assessments were conducted at 6 and 12 months to evaluated both surgical efficacy and patient-reported satisfaction. Surgical outcomes were assessed by three independent physicians who evaluated the severity of glabellar lines at rest using a four-grade scale (none, mild, moderate, or severe). The consensus rating was determined by majority agreement. Patient satisfaction was assessed using a three-point Likert-type scale, categorized as very satisfied, satisfied, or dissatisfied.Results:The study cohort comprised 37 patients (12 males and 25 females), aged between 29 and 59 years (mean age, 42.4 years). All patients exhibited moderate to severe glabellar lines characterized by vertical depressed wrinkles. All incisions achieved primary healing without hematoma, infection, or other complications. During a follow-up period of 12 to 24 months, with an average of 13.7 months, all patients presented various degrees of improvement in glabellar lines. At 6 months postoperatively, 54.1% (20/37) of patients exhibited no visible lines, 40.5% (15/37) had mild static lines, and 5.4% (2/37) had moderate static lines; no cases of severe static lines were observed. The overall patient satisfaction rate (very satisfied and satisfied) was 94.6% (35/37). At 12 months postoperatively, 95.2% (20/21) of patients in the regular injection group (≥2 injections) maintained a status of no or mild static lines, whereas 43.8% (7/16) of patients in the single-injection group developed moderate to severe static lines. The patient satisfaction survey showed that the proportion of patients reporting "very satisfied" or "satisfied" was 100% (21/21) in the regular injection group and 87.5% (14/16) in the single-injection group. No serious complications were observed throughout the follow-up period.Conclusion:The combination of W-shaped excision and BTX-A injection provides satisfactory clinical result for moderate to severe glabellar lines. Patients who adhere to a regimen of regular injections demonstrate longer-lasting surgical effects.
10.Treatment and diagnosis of generalized pustular psoriasis: advances, challenges, and prospects
Chinese Journal of Dermatology 2025;58(11):1015-1019
Generalized pustular psoriasis (GPP) is a rare and life-threatening autoinflammatory disorder. Recent advances in genetics, immunology, and targeted therapies have made its pathogenesis increasingly clear and led to refinements in diagnostic criteria and treatment strategies. Nonetheless, several challenges remain unresolved, including the heterogeneity of clinical phenotypes and therapeutic responses, as well as the prediction and control of disease relapse. Future research will focus on dissecting the immune mechanisms and pivotal inflammatory signaling pathways underlying GPP, identifying novel therapeutic targets, and developing more effective and durable treatment regimens based on research findings.

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