1.Hypoxia-inducible factor-prolyl hydroxylase inhibitors in treatment of anemia with chronic disease.
Zuolin LI ; Lan SHEN ; Yan TU ; Shun LU ; Bicheng LIU
Chinese Medical Journal 2025;138(12):1424-1432
Anemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizing HIF and subsequently promoting endogenous erythropoietin (EPO) production and iron absorption and utilization. Thus, HIF-PHIs appear to open a new door for the treatment of ACD patients with a novel mechanism. Here, we comprehensively reviewed the latest advancements in the application of HIF-PHIs in ACD. Specifically, we highlighted the key features of HIF-PHIs on ACD, such as stimulation of endogenous EPO, handling iron metabolism, inflammation-independent, and prolonging lifespan of red blood cells. In conclusion, the success of HIF-PHIs in the treatment of ACD may expand the therapeutic opportunity for other types of anemia beyond renal anemia.
Humans
;
Anemia/metabolism*
;
Chronic Disease
;
Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism*
;
Erythropoietin/metabolism*
;
Prolyl-Hydroxylase Inhibitors/therapeutic use*
;
Animals
;
Renal Insufficiency, Chronic
2.Comparison on odor components before and after processing of Cervi Cornu Pantotrichum based on electronic nose, HS-GC-MS, and odor activity value.
Xiao-Yu YAO ; Ke SHEN ; Di WU ; Xiao-Fei SUN ; Chun-Qin MAO ; Li FU ; Xiao-Yan WANG ; Hui XIE ; Tu-Lin LU
China Journal of Chinese Materia Medica 2025;50(2):421-431
Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis*
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Electronic Nose
;
Gas Chromatography-Mass Spectrometry/methods*
;
Animals
;
Volatile Organic Compounds/analysis*
;
Deer
;
Drugs, Chinese Herbal/chemistry*
3.Effects and mechanisms of total flavones of Abelmoschus manihot combined with empagliflozin in attenuating diabetic tubulopathy through multiple targets based on mitochondrial homeostasis and ZBP1-mediated PANoptosis.
Si-Yu CHA ; Meng WANG ; Yi-Gang WAN ; Si-Ping DING ; Yu WANG ; Shi-Yu SHEN ; Wei WU ; Ying-Lu LIU ; Qi-Jun FANG ; Yue TU ; Hai-Tao TANG
China Journal of Chinese Materia Medica 2025;50(13):3738-3753
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals
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Rats
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Mitochondria/metabolism*
;
Benzhydryl Compounds/administration & dosage*
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Glucosides/administration & dosage*
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Abelmoschus/chemistry*
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Male
;
Homeostasis/drug effects*
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Flavones/administration & dosage*
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Rats, Sprague-Dawley
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Diabetic Nephropathies/physiopathology*
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Drugs, Chinese Herbal/administration & dosage*
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DNA-Binding Proteins/genetics*
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Humans
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Apoptosis/drug effects*
4.Single-position O-arm X-ray navigation assisted oblique lateral interbody fusion combined with minimally invasive percutaneous pedicle nail internal fixation for lumbar spondylolisthesis.
Kai-Kai TU ; Hui FEI ; Yu-Liang LOU ; Can-Feng WANG ; Chang-Ming LI ; Li-Shen ZHOU ; Feng HONG
China Journal of Orthopaedics and Traumatology 2025;38(5):447-453
OBJECTIVE:
To investigate the early clinical efficacy of single-position O-arm navigation-assisted oblique lateral interbody fusion(OLIF) combined with minimally invasive percutaneous pedicle screw fixation(PPS) in the treatment of lumbar spondylolisthesis.
METHODS:
A retrospective analysis was conducted on 22 patients with lumbar spondylolisthesis who underwent OLIF-PPS surgery including 11 males and 11 females with a mean age of (64.6±1.5) years old ranging from 49 to 80 years old between April 2021 and June 2023. All patients presented with lumbosacral pain, lower limb radiating pain, numbness, and had poor responses to conservative treatment. Surgical time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Clinical outcomes were evaluated using the visual analogue scale(VAS) and Oswestry disability index(ODI) preoperatively at 3 days after operation and the final follow-up. Standing lumbar anteroposterior and lateral X-rays were performed to measure disc height(DH), slippage degree, vertebral reduction rate, pedicle screw accuracy, and cage subsidence.
RESULTS:
All surgeries were successfully completed with a mean follow-up of (27.1±2.2) months (range 18 to 36 months). The mean surgical time was (76.1±12.2) min (range 60 to 93 min), intraoperative blood loss was (86.3±32.2) ml (range 40 to 113 ml), and hospital stay was (7.1±1.2) days. Postoperative VAS significantly improved from (7.2±0.7) preoperatively to (2.3±0.5) at 3 days after operation and (1.7±0.2) at the final follow-up (P<0.05). ODI decreased from (68.5±7.2)% preoperatively to (30.3±3.1)% at 3 days after operation and (16.6±1.6)% at the final follow-up (P<0.05). DH increased from (8.5±1.7) mm preoperatively to (18.1±1.4) mm at 3 days after operation and (17.2±1.1) mm at the final follow-up (P<0.05). Slippage degree improved from (24.1±4.6)% preoperatively to (10.3±4.2)% at 3 days after operation and (10.1±3.2)% at the final follow-up (P<0.05). A total of 88 pedicle screws were implanted with an excellent rate of 98% (86/88). Complications included transient left hip flexion weakness (2 cases) and left anteromedial thigh pain (1 case), all resolved during follow-up. No incision hematoma, infection, screw loosening, or cage subsidence occurred.
CONCLUSION
Single-position O-arm navigation-assisted OLIF combined with PPS demonstrates satisfactory early clinical efficacy for lumbar spondylolisthesis, with advantages including minimal invasiveness, significant pain relief, effective vertebral reduction, and low complication rates.
Humans
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Male
;
Female
;
Spondylolisthesis/diagnostic imaging*
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Middle Aged
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Aged
;
Spinal Fusion/methods*
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Lumbar Vertebrae/diagnostic imaging*
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Minimally Invasive Surgical Procedures/methods*
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Pedicle Screws
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Aged, 80 and over
;
Retrospective Studies
5.Diagnosis and treatment of special type of laryngeal foreign body with granuloma in children.
Dezhen TU ; Zongtong LIN ; Ling SHEN ; Deping CHEN ; Zhongjie YANG ; Qiaoyu LIAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(2):163-167
Objective:This article explores the diagnosis and treatment of a special type of laryngeal foreign body with granuloma in children, providing a clinical reference for standardized diagnosis and treatment. Methods:This article retrospectively analyzes one case admitted to our department and five other cases reported in relevant literature involving a special type of laryngeal foreign body with granuloma in children. It summarizes the clinical characteristics of this disease and explores its diagnosis and treatment. Results:①A total of 6 cases were misdiagnosed and had a long course of illness. Five cases had no clear history of foreign body at the first visit. One case had foreign body history but no foreign body was found. ②The clinical symptoms were diverse, which could be hoarseness, cough, wheezing, dyspnea, or no symptoms. ③A total of 3 cases were diagnosed by laryngoscopy, and 3 cases were diagnosed by laryngoscopy and imaging examination. ④Foreign bodies that were not wrapped in granulomas, were removed first and then the granulomas were treated; foreign bodies wrapped in granulomas were removed after the removal of granulomas. Conclusion:A special type of laryngeal foreign body with granuloma may lack of accurate foreign body history, resulting in long-term retention of foreign bodies, leading to granuloma formation and misdiagnosis. Electronic laryngoscopy combined with CT examination contribute to early diagnosis. Low temperature plasma under endoscope and anesthetic laryngoscope is conducive to the exposure and precise removal of foreign bodies and avoids tracheotomy to a certain extent.
Child
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Child, Preschool
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Female
;
Humans
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Infant
;
Male
;
Foreign Bodies/surgery*
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Granuloma, Foreign-Body/therapy*
;
Larynx/pathology*
;
Retrospective Studies
6.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
7.Traditional Chinese Medicine in Regulating Crown-like Structures for Treatment of Obese PCOS: A Review
Wenyan TU ; Liqun YE ; Muyang LI ; Yihong YIN ; Ying SHEN ; Qidi LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):296-307
Polycystic ovary syndrome (PCOS), a common reproductive endocrine disorder in women, is one of the leading causes of ovulatory infertility in women of reproductive age. Due to its heterogeneous etiology, complex symptoms, and challenging treatment, PCOS has become a focal point of research in gynecological and reproductive medicine globally. The pathogenesis of PCOS is complex and may involve regulatory mechanisms such as inflammatory responses, oxidative stress, and cellular autophagy. Crown-like structures (CLSs) refer to pro-inflammatory microenvironments formed by macrophages engulfing adipocytes. The inflammatory disorders induced by CLSs are one of the key factors contributing to the development of PCOS and its complications. Current studies have indicated that the obese status in PCOS accelerates the formation of CLSs, and the density of CLSs can predict the progression of metabolic disorders and influence the outcomes of various metabolic diseases. Traditional Chinese Medicine (TCM) offers the unique advantages of a holistic view, four diagnostic methods, and syndrome differentiation and treatment to ameliorate the symptoms and signs of PCOS through multiple levels, pathways, and targets. Although studies on the mechanisms of metabolic diseases and CLS formation have been reported in China and abroad, there is still a lack of literature on the correlation between CLSs and PCOS, as well as reviews on TCM interventions targeting CLSs for treating this disease. Therefore, this paper summarized the correlation between obese PCOS and CLSs and reviewed recent studies on TCM interventions based on CLS formation (adipose tissue-macrophage inflammatory crosstalk) in the treatment of obese PCOS, aiming to provide new research perspectives for the prevention and treatment of PCOS using TCM.
8.Traditional Chinese Medicine in Regulating Crown-like Structures for Treatment of Obese PCOS: A Review
Wenyan TU ; Liqun YE ; Muyang LI ; Yihong YIN ; Ying SHEN ; Qidi LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):296-307
Polycystic ovary syndrome (PCOS), a common reproductive endocrine disorder in women, is one of the leading causes of ovulatory infertility in women of reproductive age. Due to its heterogeneous etiology, complex symptoms, and challenging treatment, PCOS has become a focal point of research in gynecological and reproductive medicine globally. The pathogenesis of PCOS is complex and may involve regulatory mechanisms such as inflammatory responses, oxidative stress, and cellular autophagy. Crown-like structures (CLSs) refer to pro-inflammatory microenvironments formed by macrophages engulfing adipocytes. The inflammatory disorders induced by CLSs are one of the key factors contributing to the development of PCOS and its complications. Current studies have indicated that the obese status in PCOS accelerates the formation of CLSs, and the density of CLSs can predict the progression of metabolic disorders and influence the outcomes of various metabolic diseases. Traditional Chinese Medicine (TCM) offers the unique advantages of a holistic view, four diagnostic methods, and syndrome differentiation and treatment to ameliorate the symptoms and signs of PCOS through multiple levels, pathways, and targets. Although studies on the mechanisms of metabolic diseases and CLS formation have been reported in China and abroad, there is still a lack of literature on the correlation between CLSs and PCOS, as well as reviews on TCM interventions targeting CLSs for treating this disease. Therefore, this paper summarized the correlation between obese PCOS and CLSs and reviewed recent studies on TCM interventions based on CLS formation (adipose tissue-macrophage inflammatory crosstalk) in the treatment of obese PCOS, aiming to provide new research perspectives for the prevention and treatment of PCOS using TCM.
9.Surgical treatment for trichiasis caused by eyelid aging
Xifei QIAN ; Jingyi TU ; Jue HOU ; Chongxiang FAN ; Yirui PAN ; Haiyan SHEN ; Qinyuan ZHAO ; Jufang ZHANG
Chinese Journal of Plastic Surgery 2025;41(5):524-528
Senile trichiasis is primarily manifested by eyelid laxity, decreased horizontal elasticity and tension of the eyelids, leading to friction between the eyelashes and the cornea, which subsequently causes corneal damage and vision decline. Surgical intervention remains the most effective therapeutic approach for senile trichiasis. This article elaborates on the epidemiological characteristics, pathological mechanisms, and clinical manifestations of senile trichiasis and systematically reviews the surgical treatment method for upper and lower eyelid trichiasis, including traditional surgical techniques and emerging minimally invasive procedures combined with personalized therapies. Through a literature review, the effectiveness and recurrence rates of surgical treatment are summarized, emphasizing the importance of preoperative assessment and individualized treatment. Additionally, strategies and recommendations for preventing senile trichiasis are proposed.
10.Clinical characteristics and risk factors of delayed viral clearance in 562 Chikungunya fever patients in Shunde region, Guangdong Province, 2025
Zuning REN ; Guotao LYU ; Qun LIN ; Zhifeng HONG ; Shuichun WAN ; Feng KANG ; Yanling OUYANG ; Chunhua TU ; Guo RAO ; Hua LIANG ; Yawei LIU ; Yan ZHU ; Jie PENG ; Jie SHEN ; Hong LI
Chinese Journal of Infectious Diseases 2025;43(8):449-456
Objective:To analyze the clinical characteristics of the Chikungunya fever outbreak in Shunde District, Foshan City, Guangdong Province in July 2025 and the risk factors associated with delayed viral RNA clearance.Methods:A total of 562 patients with Chikungunya fever admitted to three designated hospitals in Shunde District from July 10 to 30, 2025 were enrolled. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into four age groups including minors (<18 years), young adults (18 to 39 years), middle-aged adults (40 to 64 years) and elderly adults (≥65 years). The differences of clinical characteristics among these age groups were analyzed. Intergroup comparisons were performed using chi-square test, one-way analysis of variance, or Kruskal-Wallis H test. Pairwise comparisons between groups were conducted using the Bonferroni or Games-Howell or Dunn method. Binary logistic regression was employed to analyze risk factors associated with delayed viral RNA clearance (>7 days). Results:The mean age of the 562 enrolled Chikungunya fever patients was (44.8±21.3) years. Fever, arthralgia and rash were the three core symptoms, with incidence rates of 87.5% (492/562), 88.4%(497/562) and 69.6%(391/562), respectively. At discharge, only 54.1%(304/562) of patients achieved complete symptom resolution, while 26.5%(149/562) still had arthralgia and 36.1%(203/562) had residual rash. Significant differences were observed among age groups in the incidence of fever ( χ2=9.43, P=0.024), peak body temperature ( F=6.54, P<0.001), incidence of arthralgia ( χ2=26.89, P<0.001), duration of arthralgia ( F=12.68, P=0.001), incidence of rash ( χ2=68.99, P<0.001), rate of residual rash at discharge ( χ2=32.37, P<0.001), lymphocyte count ( F=12.94, P<0.001), platelet count ( F=14.95, P<0.001), and C-reactive protein levels (CRP) ( H=94.18, P<0.001). Further pairwise comparisons revealed that compared to the middle-aged and elderly groups, the minor group had a higher incidence of fever and a lower incidence of arthralgia, and the duration of arthralgia was shorter than the elderly group (all P<0.008 3). Compared with the other three groups, the elderly group had lower incidence and residual rate of rash, and lower platelet counts (all P<0.008 3), and higher levels of CRP (all P<0.05). The elderly group had lower lymphocyte counts compared to the minor and young adult groups (both P<0.05). Significant differences were found among age groups in the time to viral RNA clearance ( F=5.77, P=0.003) and length of hospital stay ( F=11.64, P<0.001), with the elderly group having significantly longer duration for both compared to the other three groups (all P<0.05). Multivariate analysis showed that advanced age (odds ratio ( OR)=1.049, 95% confidence interval ( CI) 1.015 to 1.083), longer duration of fever ( OR=1.529, 95% CI 1.086 to 2.155) and longer duration of arthralgia ( OR=1.927, 95% CI 1.318 to 2.817) were independent risk factors for delayed viral RNA clearance (all P<0.05). Conclusions:Patients with Chikungunya fever in Shunde District primarily present with fever, arthralgia and rash. The incidence and characteristics of these three core symptoms show age-related variations. Elderly patients and those with longer durations of fever or arthralgia are more likely to experience delayed viral clearance.

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