1.Standardization of electronic medical records data in rehabilitation
Yifan TIAN ; Fang XUN ; Haiyan YE ; Ye LIU ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):33-44
ObjectiveTo explore the data standard system of electronic medical records in the field of rehabilitation, focusing on the terminology and coding standards, data structure, and key content categories of rehabilitation electronic medical records. MethodsBased on the Administrative Norms for the Application of Electronic Medical Records issued by the National Health Commission of China, the electronic medical record standard architecture issued by the International Organization for Standardization and Health Level Seven (HL7), the framework of the World Health Organization Family of International Classifications (WHO-FICs), Basic Architecture and Data Standards of Electronic Medical Records, Basic Data Set of Electronic Medical Records, and Specifications for Sharing Documents of Electronic Medical Records, the study constructed and organized the data structure, content, and data standards of rehabilitation electronic medical records. ResultsThe data structure of rehabilitation electronic medical records should strictly follow the structure of electronic medical records, including four levels (clinical document, document section, data set and data element) and four major content areas (basic information, diagnostic information, intervention information and cost information). Rehabilitation electronic medical records further integrated information related to rehabilitation needs and characteristics, emphasizing rehabilitation treatment, into clinical information. By fully applying the WHO-FICs reference classifications, rehabilitation electronic medical records could establish a standardized framework, diagnostic criteria, functional description tools, coding tools and terminology index tools for the coding, indexing, functional description, and analysis and interpretation of diseases and health problems. The study elaborated on the data structure and content categories of rehabilitation electronic medical records in four major categories, refined the granularity of reporting rehabilitation content in electronic medical records, and provided detailed data reporting guidance for rehabilitation electronic medical records. ConclusionThe standardization of rehabilitation electronic medical records is significant for improving the quality of rehabilitation medical services and promoting the rehabilitation process of patients. The development of rehabilitation electronic medical records must be based on the national and international standards. Under the general electronic medical records data structure and standards, a rehabilitation electronic medical records data system should be constructed which incorporates core data such as disease diagnosis, functional description and assessment, and rehabilitation interventions. The standardized rehabilitation electronic medical records scheme constructed in this study can support the improvement of standardization of rehabilitation electronic medical records data information.
2.Effect of acupuncture pretreatment on PINK1/Parkin pathway-mediated mitophagy in rats with exercise-induced muscle damage.
Yulin GUO ; Ming GAO ; Huan CHEN ; Hui LI ; Xun TIAN ; Yuan ZHAO ; Gang XU ; Junling WEN ; Shaoxiong LI
Chinese Acupuncture & Moxibustion 2025;45(11):1617-1626
OBJECTIVE:
Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored.
METHODS:
Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue.
RESULTS:
Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05).
CONCLUSION
The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals
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Ubiquitin-Protein Ligases/genetics*
;
Male
;
Rats
;
Acupuncture Therapy
;
Protein Kinases/genetics*
;
Rats, Sprague-Dawley
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Mitophagy
;
Humans
;
Muscle, Skeletal/metabolism*
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Physical Conditioning, Animal
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Muscular Diseases/physiopathology*
;
Signal Transduction
3.Correlation Between Cardiovascular Events and Traditional Chinese Medicine Syndrome in Patients with Rheumatoid Arthritis:A Cross-Sectional Study
Fuyuan ZHANG ; Quan JIANG ; Jun LI ; Yuchen YANG ; Xieli MA ; Tian CHANG ; Congmin XIA ; Jian WANG ; Xun GONG
Journal of Traditional Chinese Medicine 2025;66(15):1572-1578
ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis(RA) and traditional Chinese medicine(TCM) syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide, in which general information such as name, gender, age, height, body weight, and course of disease were collected by completing a questionnaire; patients were classified into eight types of syndrome according to the information of their four examinations,i.e. wind-dampness obstruction syndrome, cold-dampness obstruction syndrome, dampness-heat obstruction syndrome, phlegm-stasis obstruction syndrome, stasis-blood obstructing collateral syndrome, qi-blood deficiency syndrome, liver-kidney insufficiency syndrome, and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events, they were divided into the occurrence group and the non-occurrence group, and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events, and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included, including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height, gender, insomnia, appetite, white blood cell(WBC), hemoglobin(HGB), platelets(PLT), rheumatoid factor(RF), anti-cyclic peptide containing citrulline(CCP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), γ-glutamyl transpeptidase(GGT), urea creatinine(CREA), and glucose(GLU)(P>0.05). The TCM syndromes between groups showed significant statistic differences(P<0.05). Patients in occurrence group had longer disease duration, heavier body weight, and older age; more severe conditions such as disease activity(DAS-28), number of painful joints(TJC), number of swollen joints(SJC), health questionnaire scores(HAQ), visual analog scores(VAS), restlessness, and fatigue; higher blood sedimentation rate(ESR), low-density lipoprotein(LDL-C), triglyceride(TG), total cholesterol(TC), D-Dimer, and lower high-density lipoprotein(HDL-C)(P<0.05). The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome[OR=5.937, 95%CI (4.434, 7.949), P<0.001]. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes, and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.
4.Integration and innovation of wet granulation and continuous manufacturing technology: a review of on-line detection, modeling, and process scale-up.
Guang-di YANG ; Ge AO ; Yang CHEN ; Yu-Fang HUANG ; Shu CHEN ; Dong-Xun LI ; Wen-Liu ZHANG ; Tian-Tian WANG ; Guo-Song ZHANG
China Journal of Chinese Materia Medica 2025;50(6):1484-1495
Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation*
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Technology, Pharmaceutical/methods*
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Drugs, Chinese Herbal/chemistry*
;
Models, Theoretical
5.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
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Humans
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Male
;
Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
;
Retrospective Studies
6.Isolation,identification and treatment effectiveness evaluation of resistant Acinetobacter baumannii phage Abgy202162
Xun TIAN ; Wencai TAN ; Bi YANG ; Xiang LIU ; Wenfeng YU ; Xiaolan QI ; Yinhui JIANG
Acta Universitatis Medicinalis Anhui 2024;59(10):1742-1751
Objective To isolate a Acinetobacter baumannii(Ab)phage from underground sewage,study its prop-erties,and to provide a theoretical basis for phage treatment of Ab infection.Methods Double-layer agar tech-nique was used to isolate phages by using Ab GY-6 as the host strain.Biological characterization and therapeutic effect of the phage was tested.Genetic information of the phage was analyzed.Results Ab phage Abgy202162 was isolated.Transmission electron microscopy(TEM)analysis showed that the morphology of Abgy202162 exhibited an icosahedral structure.Biological characteristic analysis showed that the optimal multiplicity of infection was 1,the latent period was 5 min,and the burst size was approximately 520 PFU per cell.In addition,Abgy202162 re-mained stable at different concentrations of chloroform,pH,and temperatures.Sodium dodecyl sulfate-polyacryl-amide gel electrophoresis(SDS-PAGE)analysis showed that it contained 10 proteins with molecular weights ran-ging from 15 to 100 ku.The double-stranded(ds)DNA genome of Abgy202162 consisted of 40 889 bp and its G+C content was 38.85%.It contained 47 open reading frames(ORFs),of which 26 had specific functions,but no virulence related genes or antibiotic resistance genes were found.Phylogenetic analysis showed that Abgy202162 was a new phage in the Autographiviridae family,Beijerinkvirinae subfamily,and Friunavirus genus.Abgy202162 showed the ability to prevent Ab infection in the Galleria mellonella in vivo model.Conclusion The phage Ab-gy202162 has strong environmental tolerance and high safety,indicating its potential as an antibiotic alternative used in the treatment of infections caused by Ab.
7.Hyperthyroidism Induces Ventricular Remodeling via Activating β-catenin/FoxO1 in Rat Cardiomyocytes
Xun YUAN ; Li BAN ; Songlin TIAN ; Qiulian ZHU ; Guiping ZHANG ; Yuan QIN ; Li PAN ; Ning HOU
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):393-411
[Objective]To explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes.[Methods]Hyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine(T4)at 0.1 mg/kg for 30 days.β-catenin inhibitor MSAB(14 mg/kg)was admin-istrated for 30 days.We used western blot to detect the expression of myocardial hypertrophy marker ANP,β-catenin and FoxO1;immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1.Hyperthy-roidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine(T3)into cul-tured primary neonatal rat cardiomyocytes for 24 hours.β-catenin siRNA(30 nmol/L)was used to down-regulate β-catenin expression in cardiomyocytes.Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy.[Results]Following Wnt/β-catenin activation,β-catenin was found increased nuclear expression,to bind to the nuclear transcriptional factors and regulate the gene ex-pression.β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats,but no change was found in the expression of typical transcriptional factor TCF7l2.Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling.Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes.[Conclusions]β-catenin/FoxO1 is activated in hyperthy-roidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyo-cyte hypertrophy.
8.Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma
Yan BIAN ; Ye GAO ; Chaojing LU ; Bo TIAN ; Lei XIN ; Han LIN ; Yanhui ZHANG ; Xun ZHANG ; Siwei ZHOU ; Kangkang WAN ; Jun ZHOU ; Zhaoshen LI ; Hezhong CHEN ; Luowei WANG
Chinese Medical Journal 2024;137(14):1724-1735
Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.
9.Study on the changes of serum vitamin in different inflammatory states based on CRP levels
Jing-Jing WANG ; Ying WANG ; Xiao-Xiao TIAN ; Chen NIU ; Yu-Mei QI ; Guo-Xun LI
Parenteral & Enteral Nutrition 2024;31(5):262-267,274
Objective:To investigate the correlation between C-reactive protein(CRP)and vitamin levels,and to Elucidate that inflammation is a crucial cause of vitamin deficiency.Methods:The clinical data of 551 patients treated by the Department of Nutrition of Tianjin Third Central Hospital were retrospectively analyzed from September 2021 to July 2023.Based on CRP levels,the patients were categorized into three groups:the no/mild inflammation group(89 cases,CRP<10 mg/L),the moderate inflammation group(148 cases,10 mg/L≤CRP<50 mg/L),and the severe inflammation group(314 cases,CRP≥50 mg/L).Clinical characteristics and serum vitamin levels of the three groups were compared to further Investigate the effects of inflammation on serum vitamin concentrations.Results:A total of 551 patients were included in the analysis of nine water-soluble vitamins and four fat-soluble vitamins.CRP levels were negatively correlated with serum vitamin C,vitamin B3,vitamin B9,vitamin A,25-OH vitamin D3 and 25-OH vitamin D,and the correlation coefficients were as follows:-0.33,-0.11,-0.16,-0.33,-0.09,-0.12.Conversely,CRP was positively correlated with serum vitamin B6,and the correlation coefficient was 0.16.Analysis of the three inflammatory subgroups revealed that serum levels of vitamin C,vitamin B9,vitamin A,25-OH vitamin D3 and 25-OH vitamin D were progressively decreased with the severity of inflammation(P<0.001).With the exacerbation of inflammation,the serum vitamin B3 level decreased significantly only in the condition of severe inflammation(P<0.01).Serum levels of vitamin B2,vitamin B5 and vitamin B6 in moderate to severe inflammation group were higher than those in no/mild inflammation group(P<0.001).Levels of Vitamin B7,vitamin B12,vitamin E and vitamin K levels were not correlated with CRP,and no statistical significance was observed in the analysis of inflammation subgroups among the three groups(P>0.05).Conclusions:Certain vitamin levels are influenced by the body's inflammatory state.When clinically found abnormal increase in inflammatory indicators,the serum levels of vitamin C,B9,B3,A,and D should be further monitored to be vigilant against vitamin deficiency.
10.Effects of advanced platelet-rich fibrin/chitosan thermosensitive hydrogel on full-thickness skin defect wound healing in diabetic rats
Haoyi XUN ; Xiaowei SU ; Fangchao HU ; Xiangyu LIU ; Yushou WU ; Tian LIU ; Ran SUN ; Hongjie DUAN ; Yunfei CHI ; Jiake CHAI
Chinese Journal of Burns 2024;40(5):451-460
Objective:To prepare advanced platelet-rich fibrin (A-PRF)/chitosan thermosensitive hydrogel (hereinafter referred to as composite hydrogel) and explore the effects of composite hydrogel on full-thickness skin defect wound healing in diabetic rats.Methods:This study was an experimental study. The composite hydrogel with porous mesh structure and thermosensitive characteristics was successfully prepared, containing A-PRF with mass concentrations of 10, 15, 20, 50, and 100 g/L. Diabetic model was successfully established in male Sprague-Dawley rats aged 6-8 weeks by intraperitoneal injection of streptozotocin, and 4 full-thickness skin defect wounds were established on the back of each rat (finally the model was successfully established in 36 rats). Three wounds of each rat were divided into blank group (no drug intervention), positive control group (dropping recombinant human granulocyte-macrophage stimulating factor gel), and chitosan hydrogel group (dropping chitosan hydrogel solution). Thirty rats were collected, and the remaining one wound of each rat (totally 30 wounds) was divided into 10, 15, 20, 50, and 100 g/L composite hydrogel groups, with 6 wounds in each group, which were dropped with composite hydrogel solution containing 10, 15, 20, 50, and 100 g/L A-PRF, respectively. Taking the remaining six rats, the remaining one wound from each rat was dropped with composite hydrogel solution containing 100 g/L A-PRF. On 14 d after injury, 6 rats with one wound dropped with composite hydrogel containing 100 g/L A-PRF were selected for hematoxylin-eosin (HE) staining to observe the inflammation, hemorrhage, or necrosis of the heart, liver, spleen, lung, and kidney. On 10 d after injury, 6 rats with one wound dropped with composite hydrogel containing 15 g/L A-PRF were selected to observe the blood perfusion of wounds in the four groups (with sample size of 6). On 7 and 14 d after injury, the wound healing rates in the eight groups were calculated. On 14 d after injury, the wound tissue in the eight groups was taken for HE and Masson staining to observe the formation of new epithelium and collagen formation, respectively; the positive expressions of CD31 and vascular endothelial growth factor A (VEGFA) were detected by immunohistochemistry, and the percentages of positive areas were calculated; the protein expressions of CD31 and VEGFA were detected by Western blotting; the mRNA expressions of CD31 and VEGFA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction method (with all sample sizes of 4).Results:On 14 d after injury, no obvious inflammation, hemorrhage, or necrosis was observed in the heart, liver, spleen, lung, and kidney in the 6 rats. On 10 d after injury, the blood perfusion volume of wound in 15 g/L composite hydrogel group was significantly more than that in blank group, positive control group, and chitosan hydrogel group, respectively (with P values all <0.05). On 7 and 14 d after injury, the wound healing rates of blank group were (26.0±8.9)% and (75.0±1.8)%, which were significantly lower than those of positive control group, chitosan hydrogel group, and 10, 15, 20, 50, and 100 g/L composite hydrogel groups, respectively ((45.8±3.2)%, (49.8±3.7)%, (51.2±2.9)%, (68.5±2.4)%, (68.8±1.5)%, (72.7±2.1)%, (75.0±3.7)% and (79.1±1.9)%, (77.2±1.7)%, (82.3±1.3)%, (89.6±1.9)%, (89.8±1.3)%, (87.3±1.1)%, (87.9±1.3)%), P<0.05; the wound healing rates of positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group were significantly lower than those of 15, 20, 50, and 100 g/L composite hydrogel groups ( P<0.05). On 14 d after injury, the wound epithelialization degrees of 15, 20, 50, and 100 g/L composite hydrogel groups were higher than those of the other 4 groups, the new microvascular situation was better, and the collagen was more abundant and arranged more neatly. On 14 d after injury, the percentages of CD31 and VEGFA positive areas in wounds in positive control group and the percentage of VEGFA positive area in wounds in chitosan hydrogel group were significantly higher than those in blank group ( P<0.05), the percentage of VEGFA positive area in wounds in 10 g/L composite hydrogel group was significantly higher than that in blank group, chitosan hydrogel group, and positive control group (with P values all <0.05), and the percentages of CD31 and VEGFA positive areas in wounds in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05). On 14 d after injury, the protein and mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group, positive control group, and 10 g/L composite hydrogel group were significantly higher than those in blank group ( P<0.05); the protein expression of VEGFA in wound tissue in 10 g/L composite hydrogel group was significantly higher than that in positive control group ( P<0.05), and the mRNA expressions of CD31 and VEGFA in wound tissue in 10 g/L composite hydrogel group were significantly higher than those in positive control group and chitosan hydrogel group ( P<0.05); the protein and mRNA expressions of CD31 and VEGFA in wound tissue in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05); the mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group were significantly lower than those in positive control group ( P<0.05). Conclusions:The composite hydrogel has high biological safety, can improve wound blood perfusion, effectively promote the formation of blood vessels and collagen in wound tissue, thus promoting the wound healing of full-thickness skin defects in diabetic rats. 15 g/L is the optimal mass concentration of A-PRF in composite hydrogel.


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