Vascular aging refers to arterial functional, structural, and mechanical changes that occur with aging or age-related metabolic diseases within the cardiovascular system (Ryder et al., 2020; Singam et al., 2020). The prominent structural changes in aging vessels include increased arterial stiffness, reduced compliance, diminished vascular repair and regeneration capacity, and impaired endothelial cell function, ultimately leading to the development of atherosclerosis and calcification (Gopcevic et al., 2021). The inflammation, oxidative stress, autophagy, and the accumulation of AGEs are associated with the entire process of vascular aging.

Oxidative stress is currently recognized as the "ultimate common pathway" for many chronic age-related diseases (Pitocco et al., 2013), as it can disrupt cellular metabolism and homeostasis, leading to endothelial cell damage. Reactive oxygen species (ROS) serve as the major drivers of oxidative stress. T2DM leads to excessive ROS production through various pathways. Early research suggested that glucose could directly stimulate excessive ROS production (Du et al., 1999), but later studies found that high glucose (HG) activates various enzymatic cascades in mitochondria (Rizwan et al., 2020), including the activation of NADPH oxidase (Jansen et al., 2013), NO synthase uncoupling (Sasaki et al., 2008), and the stimulation of xanthine oxidase (Hernandez-Hernandez et al., 2022). Similarly, elderly individuals often have comorbidities such as dyslipidemia and hypertension, which can also induce ROS production.

AGEs are non-enzymatically formed through the condensation of the carbonyl group of reducing sugars with free amino groups in nucleic acids, proteins, or lipids. These compounds then undergo further rearrangement, producing stable and irreversible end products that can alter tissue function and mechanical properties (Twarda-Clapa et al., 2022). AGEs are associated with many age-related diseases and accumulate in various tissues, exerting cytotoxic effects. Research has shown that the AGEs/Receptor for Advanced Glycation End Products (RAGE) signaling pathway plays a central role in diabetic-related atherosclerosis and narrowing processes (Soro-Paavonen et al., 2008; Kopytek et al., 2020). Elevated glucose levels in T2DM patients can promote the late glycation end-product and collagen cross-linking, resulting in stiff and less hydrolysable collagen proteins, thereby increasing vascular wall stiffness (Aronson, 2003; Reddy, 2004). AGEs stimulate endothelial cells to produce ROS through RAGE activation, and these signaling molecules can activate the NF-κB and downstream signaling pathways (Dorenkamp et al., 2023; Shu et al., 2023). AGEs also inhibit the phagocytic action of macrophages by binding to AGEs receptors, thus promoting inflammation (Du et al., 2023). Additionally, HG-induced AGEs dysregulate the chromatin remodeling through DNA methyltransferases (DNMTs), DNMT1-ten-eleven translocations (TETs), histone modifications, miRNAs, and lncRNAs. This leads to changes in chromatin structure and persistent vascular damage through metabolic memory, ultimately resulting in a chronic inflammatory state and vascular complications (Dhawan et al., 2022).

Autophagy is a critical regulator of cellular metabolism and intracellular homeostasis, playing a crucial role in maintaining the normal function of vascular cells. Autophagy dysfunction has been observed in some age-related diseases such as T2DM (Sehrawat et al., 2023). Reduced autophagic activity not only leads to the delayed and abnormal accumulation of denatured proteins and dysfunctional organelles but also, through various pathways, results in endothelial dysfunction and intimal thickening, exacerbating vascular aging. Autophagy has been shown to play roles in the homeostasis of β-cells, IR, clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues (Sehrawat et al., 2023).

Moreover, the activation of the inflammasome via the NOD (nucleotide-binding oligomerization domain)-like receptor family, pyrin domain containing 3 (NLRP3) pathway during T2DM can also promote chronic inflammation and exacerbate vascular endothelial cell aging and endothelial dysfunction (Gora et al., 2021).

Cognitive impairment is increasingly recognized as a significant comorbidity of diabetes. Diabetes-related cognitive impairment progresses through different stages. The more severe stages, particularly mild cognitive impairment and dementia, often accompanied by progressive deficits, predominantly manifest in elderly individuals (Biessels and Despa, 2018).

Insulin and Insulin-like Growth Factor receptors (IGF) receptors, akin to insulin-like peptides, are expressed in neurons and glial cells, with insulin receptor (IR), insulin-like growth factor 1 (IGF1R), and insulin-like growth factor 2 (IGF2R) signaling through their respective receptors well-expressed in regions such as the hippocampus, striatum, hypothalamus, cerebral cortex, and olfactory bulb (Duarte et al., 2012). In elderly individuals with diabetes, alterations in insulin levels and/or signaling pathways in the brain occur due to cerebral IR. This results in neuronal loss, disruption of peripheral metabolism, and synaptic dysfunction (Wijesekara et al., 2018). Studies have found that impaired brain insulin-PI3K-AKT signaling may promote neurodegeneration in Alzheimer’s disease (AD) by downregulating O-GlcNAcylation, subsequently promoting abnormal tau hyperphosphorylation and neurofibrillary degeneration (Liu et al., 2011b). Intravenous or intranasal insulin administration has improved memory function in both humans and animals (Chapman et al., 2018; Wu et al., 2023b), indicating that compromised insulin signaling pathways may be a primary defect linking AD and T2D.

Currently, a substantial body of research suggests that AD primarily results from an imbalance between the generation and clearance of Aβ, promoting Aβ accumulation in the central nervous system and triggering AD (Hardy and Selkoe, 2002; Selkoe and Hardy, 2016). Hyperglycemic states contribute to cerebral endothelial damage, promote atherosclerosis, affecting cerebral perfusion and function while impeding the clearance of brain metabolites. This may impair the Aβ clearance system, further promoting Aβ deposition in the brain (Hamzé et al., 2022).

Sarcopenia is a progressive, systemic skeletal muscle disorder that is associated with an increased risk of adverse outcomes such as falls, fractures, physical disability, and mortality (Schaap et al., 2018).

In elderly patients with T2DM, the pro-inflammatory pathway is activated during the aging process of skeletal muscle. However, due to a decrease in the activity of antioxidant enzymes, the number of mitochondria decreases, and their anti-oxidative capacity decreases, thereby leading to an increase in intracellular accumulation of reactive oxygen species and oxidative stress levels in skeletal muscle (Crescioli, 2020). Besides, low muscle mass is linked to poor blood glucose control (Alabadi et al., 2023). This appears to be a bidirectional relationship, where prolonged exposure of cells and tissues to high blood glucose levels promotes the accumulation of AGEs in skeletal muscle, leading to increased oxidative stress, mitochondrial dysfunction (Ritov et al., 2010; Tabara et al., 2019), and impaired insulin synthesis and metabolism (Gougeon, 2013). All of these factors contribute to muscle damage and a lack of physical activity, ultimately resulting in the loss of muscle mass and function, referred to as muscle wasting syndrome. Therefore, T2DM is also considered a significant predictive factor for sarcopenia (Cruz-Jentoft et al., 2019). In addition, age-related insulin-mediated impaired glucose uptake is related to the gradual deterioration of skeletal muscle structure and function. In the human body, skeletal muscle accounts for over 80% of glucose uptake following oral glucose load, and insensitivity of this organ can lead to IR and elevated blood glucose levels (Merz and Thurmond, 2020). Muscle mass plays a pivotal role in facilitating glucose disposal mediated by insulin, and its reduction can further exacerbate IR (Maliszewska et al., 2019). Potential mechanisms include mitochondrial dysfunction, increased low-grade inflammation, lipid accumulation, and oxidative stress in intramuscular cells, as well as accumulation and decreased autophagy and enzyme activity in aging cells (Jiao and Demontis, 2017; Kalinkovich and Livshits, 2017; Crescioli, 2020; Shou et al., 2020).

The musculoskeletal system is a comprehensive and interconnected system, and diabetic patients with muscle wasting syndrome are more prone to developing osteoporosis, and lower muscle mass and strength, along with higher fat content, can impair bone quality (Herrmann et al., 2020). Due to the long-term blood glucose fluctuations, elderly T2DM patients may experience metabolic disturbances which are unfavorable for bone matrix (HICKMAN et al., 2018). Furthermore, HG levels can lead to osmotic diuresis, and disturbances in calcium-phosphorus metabolism, causing significant loss of trace elements such as calcium and phosphorus, resulting in decreased bone density, decreased levels of bone growth factors and bone remodeling function (Seyfizadeh et al., 2018; Sinnott-Armstrong et al., 2021). Poor long-term blood glucose control leads to an increase in AGEs which can also lead to abnormalities in bone organic matter metabolism (Zhang et al., 2023).

Overall, the underlying pathophysiological mechanism of bone fragility in diabetes is very complex, including hyperglycemia, oxidative stress, and the accumulation of advanced glycosylation end products, which will damage the characteristics of collagen, increase bone marrow obesity, release inflammatory factors and adipokines from visceral fat, and may change the function of bone cells. Other factors include treatment-induced hypoglycemia, some antidiabetic drugs (such as thiazolidinediones) that have a direct impact on bone and mineral metabolism, and an increased tendency to fall, all of which will lead to an increased risk of fracture in diabetes patients (Napoli et al., 2017).

Clinical research shows that for older patients with diabetes, the result of an intensive hypoglycemic treatment strategy is that the risk of hypoglycemia in patients with T2DM is significantly increased, and the mortality rate with cardiovascular events is increased (Gerstein et al., 2011). As is well known, hypoglycemia is the main cause of myocardial infarction and cardiovascular events, and the regulatory mechanism of hypoglycemia, especially in elderly people, is weakened (Ishikawa et al., 2018). In elderly patients with diabetes, the secretion of incretin is reduced, the storage and release function of glycogen is weakened, the ability of self-regulating hypoglycemia is reduced, the liver and kidney functions are reduced, and multi-drug treatment caused by various chronic comorbidities (including heart disease, stroke, and chronic kidney disease) can increase the risk of severe hypoglycemia (Corsonello et al., 1999; Lipska et al., 2016). The consequences of recurrent hypoglycemic episodes include acute and long-term cognitive changes, arrhythmia and myocardial infarction, severe falls, weakness, and death; For elderly diabetes patients with sympathetic nerve dysfunction, the induction of hypoglycemia is reduced, and asymptomatic hypoglycemia, nonspecific neurological symptoms (improper speech, confusion of thinking, strange behavior) or direct hypoglycemic coma may occur.

TCM may treat elderly diabetes by regulating the proliferation and apoptosis of pancreatic islet cells. A TCM formulation known as Shenqi Compound (SQC), composed of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma, has been found to significantly control blood glucose levels, inhibit IR, reduce hyperinsulinemia, and protect pancreatic islet hypertrophy. It accomplishes this through alleviating oxidative stress and suppressing inflammation, as well as inhibiting the apoptosis and senescence of β-cells (Yang et al., 2023). Fufang-zhenzhu-tiaozhi formula (FTZ), a patented TCM preparation, has been demonstrated to promote β-cell regeneration by protecting the islets from inflammatory cell invasion, maintaining the number of pancreatic β-cells, and increasing the expression of key markers of new β-cell formation, such as PDX-1, MAFA, and NGN3 (Chen et al., 2023). Research has revealed that Puerarin, an isoflavone derived from the root of Pueraria lobata (Willd.) Ohwi, significantly improves blood glucose stability in high-fat diet-induced diabetic mice by promoting β-cell neogenesis.

Puerarin has demonstrated a significant improvement in blood glucose homeostasis in HFD-induced diabetic mice. Additionally, during the treatment of HFD-fed mice with puerarin, the pancreatic ducts exhibited the presence of markers of new β-cell formation, including insulin, PDX1 (Pancreatic and Duodenal Homeobox 1), and Ngn3 (Neurogenin 3). Moreover, this treatment induced the expression of insulin and PDX1 in the pancreatic ducts, along with the upregulation of GLP-1R expression, followed by the activation of β-catenin proteins and STAT3 (Wang et al., 2020a).

Cellular aging is a critical factor in the development of elderly diabetes, while vascular aging is a degenerative condition that occurs in the cardiovascular system as one ages. Research has shown that extracts derived from ginseng, sanqi, and chuanxiong may potentially slow down endothelial cell aging induced by high glucose and high fat (Wang et al., 2020b). This is achieved by enhancing cellular autophagy activity, elevating mitochondrial membrane potential, and reducing the accumulation of DNA damage caused by ROS generation (Wang et al., 2020b). Furthermore, another study discovered that these extracts can lower random blood glucose levels in aging diabetic mice, inhibit the expression of proteins related to the AMPK/mTOR pathway, improve cardiac aging in mice, reduce vascular calcification, and delay vascular aging (Hu et al., 2020).

A considerable number of active components derived from TCM have been demonstrated to inhibit the NLRP3 inflammasome. Published data suggest that many candidate drugs from traditional herbal sources exert anti-inflammatory effects by inhibiting upstream signals of NLRP3, including TXNIP and NF-κB, or by combating oxidative stress, such as promoting Nfr2 signal transduction. Ultimately, these interventions may lead to targeted inhibition of the NLRP3 inflammasome, resulting in the amelioration of oxidative stress, endoplasmic reticulum stress (ERS), inflammatory pathways, and the suppression of pro-inflammatory cytokines. This approach holds promise for improving diabetes and its complications (Bai et al., 2021).

Extensive research has confirmed the significant therapeutic effects of TCM on diabetes-related cognitive dysfunction (DCD). Most TCM and their active ingredients can ameliorate DCD by reducing IR, microvascular dysfunction, abnormal gut microbiota composition, inflammation, and damage to the blood-brain barrier, cerebral blood vessels, and neurons under hyperglycemic conditions (Meng et al., 2021). Specifically, the underlying mechanisms involve the regulation of various signaling pathways, such as PI3K/Akt/GSK-3β signaling pathways (Guo et al., 2023), RhoA/ROCK/moesin and Src signaling pathways (Li et al., 2018b), AGEs/RAGE (Wang et al., 2012), NLRP3 inflammasome (Tian et al., 2023), ERS (Chen et al., 2018), and Nrf2/ARE (Liu et al., 2019), among others. These pathways collectively improve IR, synaptic plasticity, and exert anti-inflammatory, antioxidant, anti-ERS, and anti-neuronal apoptosis effects.

Recent studies have shown that Danshinone IIA (TAN) lowers fasting blood glucose (FBG) levels and enhances cognitive and memory function in HFD and streptozotocin (STZ)-induced diabetic animals. The potential mechanism may be related to the modulation of the gut microbiota by TAN. TAN regulates neuronal biomarkers, reduces serum levels of LPS and TNF-α, corrects the reduced abundance of specific microbial taxa in diabetic rats, regulates the abundance of specific microbial taxa to control pathways related to fatty acid lipid metabolism and biosynthesis, and significantly restores decreased levels of isobutyric acid and butyric acid (Zheng et al., 2022a). Similar studies have also demonstrated the beneficial effects of dendrobium mixture (consisting of Dendrobii Caulis, Astragali Radix, and Rehmanniae Radix) in alleviating DCD by regulating gut microbiota composition (Zheng et al., 2022b).

Diabetic osteoporosis (DOP) is a chronic bone metabolic disorder induced by diabetes, and research has shown that TCM can treat DOP by improving bone metabolism and differentiation. In a recent study, Epimedium brevicornum, mainly composed of Epimedium brevicornum polysaccharides, was found to promote bone formation and ameliorate apoptosis by regulating the Bax/Bcl-2 signaling pathway, thus accelerating osteogenesis in osteoblasts in a HG-induced DOP model (Lei et al., 2023). Arabinoxylans (PPCP-1) isolated from the bark of Phedendron chinense Schneid were shown to downregulate the expression of AGEs receptors induced by streptozotocin in the tibia of diabetic rats, thereby improving diabetes-associated osteoporosis (Wang et al., 2021). Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herbal compound has been shown to effectively lower fasting blood glucose levels in diabetic rats, reverse the osteoporotic phenotype, significantly improve trabecular area percentage, trabecular thickness, and trabecular number in vertebral bodies, and reduce trabecular separation (Xu et al., 2022). Another research has found that the AR/PCC herbal compound improved osteogenesis, promoted neurite outgrowth, and enhanced angiogenesis (Fu et al., 2023) by reducing the overexpression of Nlrp3, Asc, Caspase1, Gsdmd, and IL-1β, thus alleviating abnormal activation of apoptosis in vertebral osteoblasts of diabetic rats (Fu et al., 2023). Additionally, it upregulated the antioxidant response protein Nrf2, activating the antioxidant pathway, while simultaneously reducing its negative feedback regulator Keap1 (Fu et al., 2023). Ligustroflavone, an active compound in Ligustrum lucidum (Scrophulariaceae), has been found elevate parathyroid hormone (PTH) levels in diabetic mice, regulate calcium metabolism, and prevent osteoporosis (Feng et al., 2019). Rehmannia glutinosa (Scrophulariaceae) regulated alkaline phosphatase activity and bone alkaline phosphatase levels in diabetic rats, enhancing bone density and improving bone microstructure. Catalpol (CAT), acteoside (ACT), and echinacoside (ECH) extracted from Rehmannia glutinosa promoted bone formation by regulating the IGF-1/PI3K/mTOR signaling pathway (Gong et al., 2019).

T2DM in the elderly can lead to a decline in muscle mass and grip strength. Skeletal muscle, as one of the largest organs in the human body, is responsible for up to 80% of postprandial glucose uptake (Merz and Thurmond, 2020). Impairments in skeletal muscle glucose uptake and utilization play a critical role in the development of T2DM. Previous research has demonstrated that the combination of Astragalus membranaceus and Dioscorea opposita improves diabetic muscle atrophy by addressing mitochondrial dysfunction mediated by the Rab5a/mTOR pathway (She et al., 2023). Another herbal combination, AR/PCC reverses muscle atrophy in diabetic mice through the Akt/mTOR/FoxO3 signaling pathway (Zhang et al., 2014b).

Relevant studies were identified by searching for papers published from January 2000 to November 2023 in the following databases: Web of Science, Pubmed, Embase, Cochrane Library, Sinomed, China National Knowledge Internet, Wanfang and VIP. Search terms included the following: (“diabetes” or “diabetes mellitus” or “diabetes nephropathy” or“diabetes retinopathy” or “diabetes peripheral neuropathy” or “diabetic cardiomyopathy” or “diabetic gastroparesis” or “diabetic foot” or “diabetes and osteoporosis” or “diabetes and sarcopenia” or “diabetes and coronary heart disease” or “diabetes and arteriosclerosis” or “diabetes and cognitive impairment”) and (older or elderly or senile) and (“randomized controlled trial” or “controlled clinical trial” or “random” or “randomly” or “randomized” or “control” or “RCT”) and (“TCM” or “traditional Chinese medicine” or “Chinese medicinal herb” or “Chinese herbal medicine” or “decoction” or “formula” or “prescription” or “powder” or “Chinese patent medicine” or “Chinese patent drug” or “Chinese herbal compound prescription” or “granule” or “pill” or “tablet” or “capsule” or “admixture” or “Chinese medicine extract” or “extractive” or “glycosides” or “polysaccharide” or “oil”). The authors of the identified papers were contacted for additional information if necessary.

We included clinical studies that satisfied the following criteria: (a) Study participants were diagnosed with elderly diabetes, with or without diabetes nephropathy, diabetes peripheral neuropathy, diabetes retinopathy, diabetes cardiomyopathy, diabetes gastroparesis, diabetes foot, cognitive impairment, osteoporosis, sarcopenia, coronary heart disease, and arterial sclerosis. (b) Sample size ≥60; (c) The study follow-up ≥12 weeks.

We excluded clinical studies with the following features: (a) Studies that were non-randomized; (b) Patients that were enrolled with no definite. (c) Sample size <60; (d) The study follow-up <12 weeks; (e) Non-oral Chinese medicine treatment; (f) TCM treatment based on syndrome differentiation, the therapeutic drugs are uncertain; (g) The control group was not a western drug or the placebo; (h) studies that reported only symptomatic changes in patients without objective laboratory measurements or physical examination; (i) Conference papers or dissertations; (j) Full text not found.

According to the above design, two reviewers (Qiqi Zhang and Shiwan Hu) searched the online databases listed above and assessed the eligibility of these articles and made decisions on every research (inclusion or exclusion) independently. If they did not reach the same decision, the concerned articles were discussed with a third reviewer (Zishan Jin). Three reviewers (Qiqi Zhang, Shiwan Hu and Zishan Jin) extracted data independently from each study. Differences of extracted data were solved after discussion with a fourth reviewer (Boxun Zhang).

All the studies were divided into three subgroups of Traditional Chinese Prescription, Traditional Chinese patent medicines and Traditional Chinese Medicine Extracts for analysis. If there were ≥5 studies included, the frequency of using TCM will be statistically analyzed. For adverse reactions, the frequency and number of symptoms in the control group and intervention group were separately counted. The above analyses were conducted in Microsoft Excel.

Quality assessment of all the trials included in this review was independently evaluated by three reviewers (Qiqi Zhang, Shiwan Hu and Zishan Jin) using Jadad Scale (Jadad et al., 1996). Any disagreement was resolved by discussions with a fourth reviewer (Boxun Zhang).

Two researchers (Qiqi Zhang and Shiwan Hu) evaluated all studies on traditional Chinese medicine extracts using the guidelines outlined in the ConPhyMp statement (Heinrich et al., 2022). If there is any dispute, it shall be determined by the third researcher (Zishan Jin).

We searched 26,303 articles from eight databases, and after deleting duplicates, the number of articles was reduced to 18,187. According to the title and abstract of the articles, we excluded 17,254 articles for reasons including animal experiments, case reports or reviews, and not related to TCM treatment of elderly diabetes. Subsequently, we downloaded the full text of the remaining 933 articles for further screening, and according to the inclusion and exclusion rules, we finally included 160 articles. Articles on elderly diabetic gastroparesis were excluded because they were all followed up for less than 12 weeks. An article on elderly diabetes with sarcopenia was also excluded due to its study size <60 participants. The flow chart of the study selection process is shown in Figure 3.

All the included 160 studies were conducted in China, of which 159 were published in Chinese and 1 in English. The control group in 159 trials were oral western medicine or insulin injection therapy, and the control group in 1 trial was placebo.

Two studies explored the effect of TCM on DCM in the elderly and included studies of Traditional Chinese Prescription only. A total of 146 participants aged between 60 and 80 years were included in the study. The intervention period was 12 weeks (Table 3; Supplementary Table S10). Xing et al. (2023) applied Yangyin Yiqi Huoxue Recipe to treat elderly DCM complicated with heart failure and found that Yangyin Yiqi Huoxue Recipe could improve heart function while lowering blood sugar, and its mechanism might be related to regulating VEGF expression. Chen (2021) treated the elderly diabetic patients complicated with heart arrhythmia with Zhigancao Decoction and found that it could improve the cardiac autonomic nerve function and reduce the level of inflammation.

Adverse reactions were reported in 72 studies, of which 23 reported no adverse reactions. Among the adverse events studies, there were 48 adverse events in the control group, including 30 symptoms, involving 222 subjects, and common adverse events included hypoglycemia (13 RCTs, 42 subjects), gastrointestinal discomfort (7 RCTs, 19 subjects), dizzy (13 RCTs, 18 subjects), loss of appetite (8 RCTs, 18 subjects), diarrhea (9 RCTs, 17 subjects), vomit (9 RCTs, 16 subjects), nausea (9 RCTs, 13 subjects), headache (8 RCTs, 11 subjects); Adverse events occurred in 47 studies in the intervention group, with 26 symptoms and involving 167 participants. Common adverse events included gastrointestinal discomfort (9 RCTs, 24 subjects), dizzy (11 RCTs, 22 subjects), nausea (12 RCTs, 18 subjects), hypoglycemia (10 RCTs, 17 subjects), diarrhea (9 RCTs, 14 subjects), vomit (9 RCTs, 13 subjects), loss of appetite (5 RCTs, 10 subjects), rash (5 RCTs, 9 subjects) (Supplementary Table S16).

Jadad scale was used to evaluate the treatment of literatures, and there were 1 study with a score of 5, 13 studies with a score of 4, 61 studies with a score of 3, 82 studies with a score of 2, and 3 studies with a score of 1. Not use blind methods, failure to report dropout and loss of follow-up, and failure to explain the way of randomization performed were the main reasons for the low Jadad score (Supplementary Table S17).

Nine studies about Traditional Chinese Medicine Extracts were evaluated by the ConPhyMP statement. Zea mays L. [Poaceae, corn silk] was identified as type B extracts because corn silk was not included in Pharmacopoeia of the People’s Republic of China 2020 (Committee, 2020). Other extracts were identified as type A extracts. Detailed evaluation results were shown in the Supplementary Table S18–26.