1.Analysis of the incidence and mortality trends of type 2 diabetic nephropathy in China from 1990 to 2021
Xuewei DOU ; Wenfei CUI ; Ling NIU ; Binglei YIN ; Jinjin WANG
Acta Universitatis Medicinalis Anhui 2026;61(1):176-182
ObjectiveTo analyze the long-term trend of incidence and mortality of type 2 diabetic kidney disease (DKD) in China from 1990 to 2021. MethodsThe Joinpoint regression model was used to analyze the average annual percentage change (AAPC) of standardized incidence rate and standardized mortality rate, and the age-period-cohort (APC) model was constructed to analyze the longitudinal age change, period and cohort effect risk ratio (RR). ResultsFrom 1990 to 2021, the standardized incidence rate of type 2 DKD in males and females showed an overall upward trend, with AAPC of 0.08% and 0.36%, respectively. The age-standardized mortality rate of the total population and female showed a downward trend, with AAPC of -0.61% and -1.03%, respectively. However, there was no significant difference in males. APC model showed that the age effect existed: the peak age was 75-79 years old, the mortality rate of females increased, and the mortality rate of males decreased after 80-84 years old. For the effect of time period, the risk of type 2 DKD incidence in females in 2017—2021 was 1.05 times that in 2002—2006, and the risk of death in males and females in 2017—2021 was 0.84 and 0.71 times that in 2002—2006, respectively. For cohort effects, the highest risk of disease was seen in men and women born in 1967—1971, and the highest risk of death was seen in men born in 1952—1956 and women born in 1912—1916. ConclusionFrom 1990 to 2021, the standardized incidence rate of type 2 DKD in China shows an upward trend, and the standardized mortality rate shows a downward trend. It is necessary to strengthen the health behavior publicity and education of type 2 DKD, and actively carry out early screening to reduce the disease burden.
2.Key Information Research and Modern Clinical Application of Xiaofengsan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Ningli WANG ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):238-249
Employing bibliometric methods and adhering to principles of textual research, this study systematically investigated prescription source, formula name, composition evolution, dose evolution, origin, processing, ancient and modern applications of Xiaofengsan. Xiaofengsan, also known as Renshen Xiaofengsan and Chantui Xiaofengsan, was first recorded in the Taiping Huimin Hejijufang(hereafter referred to as Jufang) of the Southern Song dynasty. The formula composition included Schizonepetae Spica, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoptery Rhizoma et Radix, Bombyx Batryticatus, Saposhnikoviae Radix, Poria, Cicadae Periostracum, Pogostemonis Herba, Ginseng Radix et Rhizoma, Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium, a total of 12 medicinal materials. In terms of the evolution of formula composition, formulas across dynasties largely aligned with those recorded in Jufang, with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages:Schizonepetae Spica of 82.6 g, Glycyrrhizae Radix et Rhizoma of 82.6 g, Chuanxiong Rhizoma of 82.6 g, Notoptery Rhizoma et Radix of 82.6 g, Bombyx Batryticatus of 82.6 g, Saposhnikoviae Radix of 82.6 g, Poria of 82.6 g, Cicadae Periostracum of 82.6 g, Pogostemonis Herba of 82.6 g, Ginseng Radix et Rhizoma of 82.6 g, Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g, the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder(pass through the No.5 sieve), and 8.26 g was taken for each dose, which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily, 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat, eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases, predominantly affecting the upper body, especially the head and face. The diseases involved in modern applications were mostly dermatological diseases, including urticaria, eczema, atopic dermatitis and others. In this paper, by combing the relevant ancient literature, the key information of Xiaofengsan was textual researched, in order to provide reference for the modern application and development of this formula.
3.Immunotherapy and radiotherapy: An effective combination in cancer treatment.
Xuewei LI ; Chen WANG ; Haiou YANG ; Wenhui XUE ; Yaqian DING ; Na WU ; Beibei PEI ; Xiaoyan MA ; Wenhui YANG
Chinese Medical Journal 2025;138(20):2527-2539
Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans
;
Neoplasms/radiotherapy*
;
Immunotherapy/methods*
;
Combined Modality Therapy
;
Radiotherapy/methods*
4.Associations between per- and polyfluoroalkyl substance exposure and the prevalence of myopia in adolescents: the mediating role of serum albumin.
Xuewei LI ; Xiaodong CHEN ; Yixuan ZHANG ; Tonglei ZHENG ; Lvzhen HUANG ; Yan LI ; Kai WANG
Environmental Health and Preventive Medicine 2025;30():50-50
BACKGROUND:
The objective of this study was to investigate the potential link between myopia in adolescents and exposure to per- and polyfluoroalkyl substances (PFASs).
METHODS:
This investigation included 1971 subjects with accessible PFAS level data, myopia status, and associated variables from four cycles of the National Health and Nutritional Examination Survey (NHANES). The investigation focused on specific PFAS compounds found in the serum, including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), chosen for their frequent detection. Owing to the skewed nature of the PFAS level data, the PFAS levels were log-transformed (Ln-PFAS) prior to analysis. Logistic regression, restricted cubic spline modeling, subgroup analysis, and sensitivity analysis were used to examine the associations between exposure to PFASs and the onset of myopia.
RESULTS:
PFOA levels were significantly associated with myopia risk (OR: 1.33; 95% CI: 1.05-1.69; P = 0.019). More specifically, with respect to the first quartile, the second quartile (ORQ2: 1.69; 95% CI: 1.16-2.46; P = 0.007), third quartile (ORQ3: 1.45; 95% CI: 1.03-2.03; P = 0.035), and highest quartile (ORQ4: 1.58; 95% CI: 1.12-2.21; P = 0.010) of participants presented with increased myopia risk. Mediation analysis revealed that PFOA and myopia risk were partially mediated by serum albumin (ALB), with a mediation percentage of 22.48% (P = 0.008). A nonlinear inverted U-shaped relationship was identified between the level of PFOA and myopia risk (P for nonlinearity = 0.005).
CONCLUSION
Our findings suggest a potential link between exposure to PFOA and the likelihood of myopia development in young individuals and a mediating effect of serum ALB on this relationship. Notably, PFOA was identified as a key PFAS significantly contributing to the observed link between PFAS exposure and myopia risk. The potential threat of PFOA to myopia should be examined further.
Humans
;
Fluorocarbons/adverse effects*
;
Myopia/blood*
;
Adolescent
;
Male
;
Female
;
Prevalence
;
Environmental Exposure/adverse effects*
;
Nutrition Surveys
;
Environmental Pollutants/adverse effects*
;
United States/epidemiology*
;
Alkanesulfonic Acids/blood*
;
Caprylates/blood*
;
Serum Albumin/metabolism*
;
Child
;
Sulfonic Acids
5.Urban-Rural Disparities in Activities of Daily Living Among Older Adults in Sichuan Province and the Influencing Factors
Ting SONG ; Huan XU ; Xuewei TANG ; Xueli ZHANG ; Linya HUANG ; Bing GUO ; Juying ZHANG
Journal of Sichuan University (Medical Sciences) 2025;56(2):478-483
Objective To investigate the disparities in the activities of daily living(ADL)among older adults living in urban and rural areas of Sichuan Province,China and the influencing factors,and to provide a basis for promoting the health of older adults and formulating relevant policies.Methods Using data from the Seventh Health Services Survey of Sichuan Province,we enrolled 7 369 older adults from urban and rural areas and analyzed their ability to perform ADL and the relevant influencing factors.All participants were aged 60 years or older.Chi-square tests and logistic regression were performed to identify the influencing factors.Results The ADL impairment rate among older adults living in urban areas of Sichuan Province was 17.7%,which was higher than the rate of 13.8%among older adults living in rural areas.According to the results of logistic regression analysis,age≥80 years(odds ratio[OR]=3.725;95%CI,2.460-5.639),accidental injuries(OR=2.375;95%CI,1.597-3.532),and good sleep quality(OR=0.420,95%CI:0.289-0.612)were factors influencing ADL among older adults living in urban areas,while age ≥ 80 years(OR=1.867;95%CI,1.459-2.390),being married(OR=0.805;95%CI,0.664-0.976),accidental injuries(OR=1.936;95%CI,1.564-2.397),and participation in social activities(OR=0.417;95%CI,0.352-0.495)were factors influencing ADL among older adults living in rural areas.Conclusion There are differences in ADL impairment rates and the relevant influencing factors between urban and rural older adults in Sichuan Province.These findings underscore the need to consider urban-rural differences when adopting relevant policies and measures.
6.The effect of dexmedetomidine on intracranial pressure after interventional embolization of intracranial aneurysms
Honglin FU ; Jingna HU ; Xuewei ZHANG ; Lihong HU
Journal of Interventional Radiology 2025;34(3):296-300
Objective By using ultrasonography to calculate the ratio of optic nerve sheath diameter(ONSD)at 3 mm behind eyeball to the eyeball transverse diameter(ETD),based on which to evaluate the effect of dexmedetomidine on intracranial pressure(ICP)in patients with intracranial aneurysm after receiving interventional embolization under general anesthesia.Methods A total of 40 patients with intracranial aneurysm,who were scheduled to receive interventional embolization under general anesthesia at the Affiliated Lihuili Hospital of Ningbo University of China from May 2023 to November 2023,were selected for this study.By using random number table method,the patients were divided into control group(group C)and dexmedetomidine group(group D)with 20 patients in each group.Standardized anesthesia strategy was adopted in both groups.For patients of group D,a loading dose of dexmedetomidine was pumped at a velocity of 1 μg/(kg·h)for 10 min before the surgery,the pumping was continued at 0.5 μg/(kg·h)velocity during the operation,and the pumping stopped half an hour before the end of the operation.For patients of group C,the same anesthesia strategy was used,while no any special treatment was given.At the different time points,including before awakening(T0),immediately after extubation(T1),and 5 min(T2),10 min(T3),15 min(T4)after extubation,ONSD at 3 mm behind eyeball and ETD were measured by transorbital ultrasonography,and ONSD/ETD ratio was calculated to evaluate ICP.The mean arterial pressure(MAP),heart rate(HR),blood oxygen saturation(SPO2),severity of cough,and extubation time were recorded at the time to remove the catheter.Results Compared with the data obtained at T0,the ONSD/ETD ratios obtained at T1 and T2 were increased in both groups(P<0.05),while the ONSD/ETD ratios obtained at other time points were not significantly different from the ONSD/ETD ratio obtained at T0(P>0.05).Compared with Group C,in Group D the ONSD/ETD ratios obtained at T1 and T2 were smaller,the differences were statistically significant(P<0.05).The incidence of moderate to severe cough in Group D was lower than that in Group C(P<0.05).Compared with Group C,in Group D the HR and MAP determined at the time of removing catheter were lower(P<0.05).The extubation time in Group D was longer than that in group C,the difference was statistically significant(P<0.05).Conclusion ONSD/ETD ratio calculated by ultrasono-graphy can objectively reflect the changes of ICP during the extubation period.Dexmedetomidine can reduce the elevation degree of ICP through effectively inhibiting cough reflex and circulatory fluctuation during tracheal extubation.However,dexmedetomidine may increase the incidence of adverse events such as bradycardia,delayed extubation,etc.
7.Growth and Development of Atractylodes chinensis and Microecological Response of Cultivated Soil Mediated by Two Microbial Fertilizers
Xuewei LIU ; Chunping XIAO ; Lili WENG ; Zhaoyang LI ; Xinxing HU ; Bo LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):157-165
ObjectiveThe effects of two microbial fertilizers (Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer) on the growth and development, the accumulation of active ingredients, and the microbial community diversity of rhizosphere soil of Atractylodes chinensis were investigated. MethodsA field experiment was carried out with two-year-old Atractylodes chinensis as the test material. Plant samples were collected during the wilt stage (September 26, 2023) to determine the general agronomic traits of Atractylodes chinensis. High-performance liquid chromatography (HPLC) was utilized to evaluate the effects of microbial fertilizers on the synthesis and accumulation of four active ingredients (atractylodin, atractylon, β-eudesmol, and atractylenolide Ⅰ) in Atractylodes chinensi. PacBio Sequel sequencing technology was used to explore the differences in bacterial community structures and diversity in the rhizosphere soil of Atractylodes chinensis treated with different microbial fertilizers. ResultsThe two microbial fertilizers had significant growth-promoting effects on Atractylodes chinensis. Compared with those of the CK group, the stem diameter, stem and leaf dry and fresh weight, and rhizome dry and fresh weight of Atractylodes chinensis significantly increased by 0.47-1.07 times (P<0.05) after the application of the Bacillus subtilis fertilizer (16 kg/667 m2), and those significantly increased by 0.62-0.96 times (P<0.05) after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer (1.5 kg/667 m2). The effect on plant height was not significant. The application of two microbial fertilizers was beneficial to the accumulation of atractylodin, atractylon, β-eudesmol, and atractylenolide Ⅰ (P<0.01), and the effect of the Bacillus subtilis fertilizer on the accumulation of active ingredients of Atractylodes chinensis was better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The results of high-throughput sequencing showed that compared with the CK group, the Bacillus subtilis fertilizer (8 kg/667 m2) could significantly increase the diversity of rhizosphere bacterial species by regulating the Simpson index and Shannon index (P<0.05), and the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer significantly reduced the bacterial diversity (P<0.05). The relative abundance of dominant bacteria was compared at the phylum and genus levels. The relative abundance of Proteobacteria (45.73%) and Burkholderia_Caballeronia_Paraburkholderia (9.98%) significantly increased after the application of the Bacillus subtilis fertilizer (P<0.01), and the relative abundance of Acidobacteriota (20.53%) and Sphingomonas (3.63%) increased significantly (P<0.01) after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The relative abundance of beneficial bacteria in the Bacillus subtilis fertilizer was slightly higher than that in the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. Pearson correlation analysis showed that Burkholderia_Caballeronia_Paraburkholderia and Sphingomonas were positively correlated with the content of atractylodin, atractylon, β-eudesmol, and atractylenolide Ⅰ (P<0.05). ConclusionThe application of the Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer can increase the yield of medicinal materials and promote the synthesis and accumulation of active ingredients by regulating the rhizosphere microecological diversity of Atractylodes chinensis, and the application effect of the Bacillus subtilis fertilizer is better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer.
8.A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide
Leilei GONG ; Xiaoxia WANG ; Xuewei FENG ; Xinlei LI ; Han ZHAO ; Xueyan ZHANG ; Xin FENG
Laboratory Animal and Comparative Medicine 2025;45(4):403-410
ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E2 levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.
9.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.
10.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.

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