1.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
2.Incremental effectiveness of two-dose of mumps-containing vaccine in chidren
Chinese Journal of School Health 2025;46(6):883-887
Objective:
To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies.
Methods:
A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE).
Results:
There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years.
Conclusions
The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.
3.Biological principles for "homotherapy for heteropathy"
Wei-jia KONG ; Yu-huan LI ; Jian-dong JIANG
Acta Pharmaceutica Sinica 2024;59(2):269-278
Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.
4.Mechanism of Cigarette Smoke-induced Injury to Alveolar Epithelial Cells
Jian-Lu TIAN ; Hong-Juan WANG ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2024;51(9):2144-2155
Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD+ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.
5.Effect of recombinant bovine basic fibroblast growth factor gel combined with silver ion dressing on the donor site in patients with hand trauma undergoing skin grafting
Ying YE ; Cheng WANG ; Huan LIU ; Jian LI
Chinese Journal of Primary Medicine and Pharmacy 2024;31(4):565-569
Objective:To investigate the efficacy of combined repair therapy using recombinant bovine basic fibroblast growth factor (R-bFGF) gel and silver ion dressing on the donor site of patients with hand trauma undergoing skin grafting.Methods:Eighty patients with hand trauma who underwent skin grafting at Lishui Central Hospital between October 2020 and October 2021 were enrolled in this study. Using a simple random grouping method, the patients were randomly assigned to a control group and an observation group in a 1:1 ratio, with 40 patients in each group. The control group received conventional vaseline gauze treatment, while the observation group was treated with a combination of R-bFGF gel and silver ion dressing. After 2 weeks of treatment, the repair effects of both groups were evaluated. Before and after treatment, the Connor-Davidson Resilience Scale (CD-RISC) scores and Visual Analog Scale (VAS) scores were compared between the control and observation groups. Additionally, wound healing time, granulation tissue growth time, wound epithelium formation time, and dressing change times as well as total active motion of the fingers were evaluated and compared between the two groups.Results:The repair effect in the observation group was significantly superior to that in the control group ( Z = 4.92, P < 0.05). Furthermore, the recovery of hand function in the observation group was notably better than that in the control group ( Z = 4.31, P < 0.05). The CD-RISC score in the observation group was significantly higher than that in the control group [(77.54 ± 11.35) points vs. (70.61 ± 9.72) points, t = 2.93, P < 0.05]. Additionally, the VAS score, wound healing time, granulation tissue growth time, wound epithelium formation time, and dressing change times in the observation group were significantly lower or fewer than those in the control group [(4.95 ± 1.13) points vs. (5.52 ± 1.24) points, (10.43 ± 1.65) days vs. (15.54 ± 1.71) days, (7.42 ± 2.35) days vs. (11.56 ± 2.71) days, (10.25 ± 2.47) days vs. (12.82 ± 2.64) days, and (2.12 ± 0.63) times vs. (3.35 ± 0.86) times, t = -2.15, -13.60, -7.30, -4.50, -7.30, all P < 0.05]. Conclusion:The combined use of R-bFGF gel and silver ion dressing effectively enhances the repair outcomes of skin donor sites, thereby improving the psychological well-being and reducing pain perception in patients with hand trauma. This therapeutic approach markedly promotes the prognosis and functional recovery of these patients, offering valuable clinical reference for the treatment of hand injuries.
6.Analysis of TCM Syndrome Distribution Characteristics of Pulmonary Hypertension Based on Cross-Sectional Clinical Investigation
Zhengwei DONG ; Huan ZHAO ; Jian ZHANG ; Qingyong HE ; Guanwei FAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):2009-2015
Objective To clarify the predominant symptoms of PH and their correlation with clinical indicators by collecting Chinese medicine clinical syndromic data of patients with pulmonary hypertension(PH).To provide a basis for the clinical diagnosis and treatment of Chinese medicine.Methods Adopting a cross-sectional study method,from January 2020 to July 2021,the cardiovascular ward of Guang'an men Hospital of the China Academy of Traditional Chinese Medicine was in line with the patients with the diagnosis of PH.A total of 298 patients'data were collected,and 236 patients were included in this study by excluding factors such as incomplete data and repeated hospitalization.The clinical data of the patients were organized,analyzed and counted.The distribution pattern of symptoms and syndrome types of PH was derived,and the correlation between syndrome elements and hemodynamics,cardiac function,and coagulation function was explored.Results The eight syndrome elements of PH in this study were,in descending order,blood stasis>Qi deficiency>water stagnation>phlegm turbidity>blood deficiency>yang deficiency>yin deficiency>qi stagnation;The eight syndrome types were in the order of high to low:Qi deficiency and blood stasis,spleen and lung deficiency,blood stasis and water stagnation,phlegm and water stagnation,phlegm and blood stasis stagnation,phlegm and water stagnation,yang deficiency and water stagnation,phlegm and turbid obstruction of lungs,and deficiency of both qi and yin;Qi deficiency was negatively correlated with Systolic pulmonary artery pressure(SPAP),and water stagnation was positively correlated with SPAP;Qi deficiency was negatively correlated with cardiac function grading,and water stagnation and phlegm turbidity evidence were positively correlated with cardiac function grading.Conclusion Blood stasis is the core pathogenesis of PH,and the clinical manifestations and symptoms of PH patients gradually transformed from qi deficiency through blood stasis to phlegm turbidity and water stagnation."Stasis"is present throughout the course of PH disease and has a significant impact on the progression of PH.
7.Case report of children with Addison′s disease complicated by torsades de pointes
Juanli WANG ; Jian LI ; Hongyu XIAO ; Huan LI ; Xi LEI ; Tao WANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(10):783-785
This article retrospectively analyzes the clinical data of a patient with Addison′s disease complicated by torsades de pointes treated in Children′s Hospital Affiliated to Xi′an Jiaotong University in July 2021.The patient, female, aged 12 years, was hospitalized multiple times due to recurrent seizures, syncope, and coma, and had been successively diagnosed with fulminant myocarditis, supraventricular tachycardia, etc.She was later transferred to Children′s Hospital Affiliated to Xi′an Jiaotong University, where during hospitalization, electrocardiogram (ECG) monitoring revealed torsades de pointes associated with the attacks.The ECG between attacks showed a prolonged Q-T interval, with the longest Q-Tc of 564 ms.Echocardiography suggested a slight enlargement of the left ventricle and reduced left ventricular ejection fraction.After a comprehensive examination, she was diagnosed with Addison′s disease.Treatment with intravenous Hydrocortisone for 3 days, followed by oral Hydrocortisone tablets, was administered sequentially.After treatment, symptoms such as syncope did not recur, and the Q-T interval gradually returned to normal.After continued treatment for 1 year, echocardiography revealed no abnormality.This report aims to enhance pediatricians′ understanding and research on the relationship between pediatric endocrine diseases and arrhythmias.
8.Effect of TCM Constitution Correction on Early Asymptomatic Diabetic Peripheral Neuropathy
Yan LONG ; Huan JING ; Shuai-Li HUANG ; Rong FU ; Jian-Fang HU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1136-1143
Objective To observe the clinical efficacy and safety of traditional Chinese medicine(TCM)constitution correction based on the theory of preventive treatment of disease on the patients with early asymptomatic diabetic peripheral neuropathy(DPN).Methods A total of 87 patients with early asymptomatic DPN were randomly divided into the control group with 43 cases and the trial group with 44 cases.The control group was required to have standard diet,do exercises and take medicines for diabetes.On the basis of treatment for the control group,the trial group was given the corresponding TCM constitution correction regimen according to the predominated constitution types of the patients.The course of treatment for the two groups lasted for 48 weeks.Before and after intervention,the two groups were observed in the alteration of TCM constitution types,and the changes of body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and nerve conduction velocity(NCV).Moreover,the safety of the two groups was evaluated.Results(1)After the intervention,the constitution of 17 patients in the trial group was transformed into the balanced constitution,while only the constitution of 5 patients in the control group was transformed into balanced constitution.There was a statistically significant difference in the distribution of TCM constitution between the two groups(P<0.05).(2)Before intervention,there were no significant differences in the levels of BMI,SBP,DBP,FPG,HbA1c,TC,TG,HDL-C and LDL-C between the two groups(P>0.05).After intervention,the levels of BMI,SBP and DBP in the two groups and the levels of HbA1c,TC,TG and LDL-C in the trial group were lower than those before intervention(P<0.05 or P<0.01),while the levels of FPG and HDL-C in the control group were higher than those before intervention(P<0.05 or P<0.01).The intergroup comparison showed that the levels of FPG,HbA1c,TG and LDL-C in the trial group were significantly lower than those in the control group(P<0.05 or P<0.01).(3)After the intervention,10 cases in the control group had typical clinical symptoms of DPN,while only 6 cases in the trial group had the clinical symptoms of DPN.Before intervention,there was no significant difference in the motor nerve conduction velocity(MNCV)of bilateral tibial nerve and common peroneal nerve and in the sensory nerve conduction velocity(SNCV)of bilateral sural nerve and superficial peroneal nerve between the two groups(P>0.05).After intervention,the MNCV of bilateral tibial nerve and common peroneal nerve and the SNCV of bilateral sural nerve and superficial peroneal nerve in the control group were slower than those before intervention(P<0.05),while the above indicators of nerve conduction velocity in the trial group were mildly increased compared with those before intervention,but the differences were not significant(P>0.05).The intergroup comparison showed that the MNCV of bilateral tibial nerve and SNCV of bilateral sural nerve and superficial peroneal nerve in the trial group were higher than those in the control group,and the differences were statistically significant(P<0.05).(4)During the intervention,no obvious adverse reactions occurred in the two groups,with high safety.Conclusion The TCM constitution correction can adjust the biased constitution of patients with early asymptomatic DPN,and has certain protective effect on the glucose and lipid metabolism,MNCV of tibial nerve,and SNCV of bilateral sural nerve and superficial peroneal nerve.
9.Zuoguiwan Prevent Decreased Ovarian Reserve in Prenatal Stressed Offspring Rats via TLR4/NF-κB p65 Signaling Pathway
Yinjuan LYU ; Weiheng ZHANG ; Siyi CHEN ; Wenjing TIAN ; Jian GONG ; Yuhao MENG ; Huan HE ; Xiaocui JIANG ; Min ZHAO ; Min XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):67-76
ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress (PS) and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 (TLR4/NF-κB p65) signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups (n=8): control, model, Zuoguiwan (18.9 mg·kg-1), and vitamin E (1.44 mg·kg-1). Except the control group, the other three groups were subjected to chronic unpredictable mild stress (CUMS) from day 11 of pregnancy, and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test, open field test, and serum corticosterone (CORT) level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence (IF) assay. The expression of TLR4, NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group, the model group showed reduced primordial follicles in the offspring on the day of birth (P<0.01) as well as disturbed estrous cycle, decreased ovary index and uterus index (P<0.01), reduced corpus luteum, increased atretic follicles (P<0.01), lowered serum levels of AMH and E2 (P<0.01), elevated serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and up-regulated protein levels of TLR4, NF-κB p65, recombinant myeloid differentiation factor 88 (MyD88), and phosphorylated NF-κB inhibitor (p-IκBα) (P<0.01) in the 75-day-old offspring rats. Compared with the model group, Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth (P<0.01). Moreover, they resumed the estrous cycle, increased the ovary and uterine indices (P<0.05, P<0.01) and corpus luteum (P<0.01), reduced atretic follicles (P<0.01), elevated the serum levels of AMH and E2 (P<0.05, P<0.01), lowered the serum levels of LH, FSH, IL-1β, and TNF-α (P<0.05, P<0.01), and down-regulated the expression of TLR4, NF-κB p65, MyD88, and p-IκB-α (P<0.05, P<0.01) in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.
10.Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation
Peng MEI ; Min En DING ; Yang Hao YIN ; Xue Xue DING ; Huan WANG ; Feng Jian WANG ; Lei HAN ; Dong Heng ZHANG ; Li Bao ZHU
Biomedical and Environmental Sciences 2024;37(4):354-366
Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.


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