[Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses].

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

There "ain't no mountain high enough"?: The drivers, diversity and sustainability of China's Rhodiola trade.

ETHNOPHARMACOLOGICAL RELEVANCE: Across Asia, Rhodiola species have been used in Bhutanese, Mongolian, Nepalese, Kazakh, Kyrgyz and Uzbek traditional medical systems. China is globally significant in terms of Rhodiola species diversity, with over 60% (55 species) of the world's 90 Rhodiola species, including 16 species found nowhere else in the world. Since the late 1980's there has been a shift from relatively low demand for infusions using chopped dried Rhodiola roots, to high 21st century demand for a wide variety of processed products. China's trade in Rhodiola products is now very diverse, with use in cosmetics and foods in addition to herbal products. Rhodiola crenulata (Hook.f. & Thomson) H.Ohba is the most widely traded species in China. In addition to R. crenulata and Rhodiola rosea L., 19 Rhodiola other species are used. AIMS OF THE STUDY: These were to: (i) better understand why adulteration occurs in Rhodiola products; (ii) become more aware of what drives the growing market demand for Rhodiola products in China; (iii) find out whether increased demand is reflected in wholesale prices for Rhodiola raw materials traditional medicine markets; (iv) to examine Rhodiola supply chains and (v) given that wild populations are the primary supply source, to review the implications of growing demand for conservation and sustainable use. MATERIALS AND METHODS: Firstly, we assessed growth in the diversity of Rhodiola products using three approaches: (i) by assessing patent applications for Rhodiola products in China (1990-2019); (ii) in 2018, through on-line searches of CFDA (China Food and Drug Administration) records for medicines and dietary supplements that had Rhodiola as an ingredient and (iii) by visiting retail stores in 2018 and 2019 to assess the diversity of commercial Rhodiola based products in trade. Secondly, we visited traditional medicine markets in Yunnan, Sichuan, and Qinghai provinces to investigate the trade in Rhodiola (folk taxonomy, trade names, prices, source areas, levels of processing and grading). Thirdly, we analysed the wholesale price data for Rhodiola raw materials in trade over a 16-year period (2002-2018). Fourthly, as most products come from wild collected Rhodiola species, we documented the extent of Rhodiola cultivation in China. RESULTS: International exports of Rhodiola products from China, particularly extracts, is a major driver of commercial trade. One proxy indicator of Rhodiola product diversification in China has been the rapid rise in patent applications from single applications in 1990 and 1991, to a peak of 1017 patent applications in 2015. Wholesale price data from 2002 to 2018 shows a steady increase in wholesale prices. As the growing market for Rhodiola products in China is currently supplied entirely from wild collection, there are justifiable concerns about sustainability. Commercial cultivation needs to expand to meet future demand. CONCLUSIONS: In contrast to Europe and North America, where R. rosea is the focal species in commerce, the trade in Rhodiola products in China is much more diverse. In the face of growing demand, both effective conservation of wild populations and cultivation are needed.

Paris in the spring: A review of the trade, conservation and opportunities in the shift from wild harvest to cultivation of Paris polyphylla (Trilliaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: P. polyphylla Smith is used in traditional medicine in China, India and Nepal and is likely to be similarly used through most of its geographic range. China is at the centre of demand for P. polyphylla where it is used as an ingredient in several very successful Chinese medicinal herbal formulations. The Chinese e-commerce platform 'alibaba.com', for example, lists 97 P. polyphylla items offered by 46 Asian suppliers, of which 21 are situated in the Chinese mainland, 12 in Nepal, 7 in India, 2 in Pakistan, and 1 each in Bhutan, Hong Kong, Thailand, and Vietnam. Products offered include the crude drug (dried whole or cut rhizomes), extracts and formulations containing this herbal drug. AIMS OF THE REVIEW: The aims of this review were to assess the scale of the P. polyphylla trade, reviewing evidence on the impacts of wild harvest on P. polyphylla populations and on the role of cultivation as an alternative to wild harvest. MATERIALS AND METHODS: Firstly, we reviewed published information on Paris population biology and studies on impacts of wild P. polyphylla harvest from across the geographic range of this species. Secondly, global trade data for P. polyphylla were analysed. Thirdly, we reviewed published information on P. polyphylla cultivation and made field visits to P. polyphylla cultivation areas in Yunnan and Sichuan. RESULTS: Since the 1980s, there has been a 400-fold increase in the market price paid in China for P. polyphylla rhizomes, from 2.7 Chinese Yuan (CNY) per kg in the 1980s to market prices up to 1100 CNY per kg in 2017. Cross-border trade in dried P. polyphylla rhizomes occurs at three different scales. Firstly, an internal, national trade of P. polyphylla rhizomes within countries (such as India, Nepal and China). Secondly, trade in P. polyphylla rhizomes from Nepal (and possibly from Bhutan) to the two range states that have the largest traditional medicine trade in the world: China and India. Thirdly, trade in processed herbal products. In China, for example, P. polyphylla is widely used as an ingredient in several very successful herbal products, including a famous first aid treatment to stop bleeding. Some of these products are exported globally, in addition to entering into regional trade. Trade data in our review shows that c. 800-1050 t of P. polyphylla rhizomes are sold annually, significantly more than recorded in earlier studies. China is the only country where P. polyphylla is cultivated on a significant scale, although small-scale cultivation is taking place in India and Nepal. CONCLUSIONS: Based on the criteria for the inclusion of species in CITES Appendix II (Art. IV 2(a)), there is compelling evidence for adding Paris polyphylla. At the same time, cultivation of P. polyphylla outside of high conservation value habitats needs to be encouraged and supported. One way of doing this may be to develop separate, traceable supply chains for cultivated supplies in order to distinguish them from wild harvested stocks.

High altitude species, high profits: Can the trade in wild harvested Fritillaria cirrhosa (Liliaceae) be sustained?

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillaria cirrhosa D. Don bulbs contain alkaloids and are one of the most intensively exploited alpine Himalayan medicinal species. In terms of proprietary medicines, our study shows that 210 F. cirrhosa products are offered by 46 suppliers, most of which (44) are situated in China and two in Nepal. A widespread commercial use is as one of the main ingredients in cough syrups. A well known example is "Nin Jiom Pei Pa Koa Herbal Cough & Throat Syrup", which typically contains more F. cirrhosa than any other herbal ingredient in the formulation. The biggest market for F. cirrhosa bulbs is China, where demand exceeds supply of this wild harvested species for use in traditional Chinese medicine (TCM). Cross-border trade from Nepal to China occurs in significant quantities. Bhutan also imports F. cirrhosa bulbs from Nepal. In addition, F. cirrhosa is registered as an active ingredient in traditional herbal medicinal preparations in Australia, Canada, Hong Kong SAR, Malaysia, Republic of Korea, Singapore and Taiwan. There is also an export trade in F. cirrhosa to Europe. Assessing how much F. cirrhosa is traded is complex, however, due to a "look-alike" challenge, as nine Chinese Fritillaria species are traded in Europe (Fritillaria cirrhosa, F. delavayi, F. hupehensis, F. pallidiflora, F. przewalskii, F. thunbergii, F. unibracteata, F. ussuriensis and F. walujewii). AIMS OF THE STUDY: The aims of this review were to assess the scale of the global trade in F. cirrhosa, and to synthesise studies of the impacts of wild harvest on F. cirrhosa populations and on the extent of emerging cultivation initiatives as an alternative to wild harvest. METHODS: Firstly, we reviewed published information on studies on impacts of wild F. cirrhosa harvest from across the geographic range of this species. Secondly, global trade data for F. cirrhosa were analysed. RESULTS: The principal demand for F. cirrhosa bulbs is in China, where hundreds of different companies produce Fritillaria preparations. Trade data also show that in 2013, China exported over 44 tonnes of F. cirrhosa bulbs to Taiwan and 26.7 tonnes to the Republic of Korea. Extensive commercial use and limited wild stocks result in a high price (2000 - 3800 CNY per kg (around US$ 303 -560 per kg in 2017)) for F. cirrhosa bulbs. Prices of cultivated Fritillaria bulbs are much lower (600-680 CNY per kg in 2017) than wild harvested bulbs. But due to very specific growth requirements of F. cirrhosa, cultivation is not yet able to meet total demand. The consequence is continued exploitation of wild stocks. At the same time, however, an increasing proportion of the demand is met by cultivation of alternative Fritillaria species that are easier to grow than F. cirrhosa. The air-dry mass of F. cirrhosa bulbs varies between 0.0917 and 0.1116 g per bulb. This represents 8960 - 10,900 bulbs/kg or 8.9 - 10.9 million bulbs per tonne. Current demand therefore represents billions of bulbs per year. CONCLUSIONS: Demand for F. cirrhosa bulbs, particularly from China, makes this species one of the most intensively harvested alpine Himalayan medicinal bulbs. Although F. cirrhosa is listed as a Class III protected species in China, billions of these tiny, wild harvested bulbs are sold per year. Due to demand exceeding supply, the price of F. cirrhosa bulbs has increased dramatically. Between 2002 and 2017, for example, the price of wild harvested F. cirrhosa bulbs increased over nine-fold, from the equivalent of US$60 in 2002 to US$560 per kg in 2017. To date, cultivation has been unable to meet the entire market demand for F. cirrhosa bulbs, although other Fritillaria species are successfully cultivated on a larger scale.

Periodontal disease severity is associated with micronutrient intake.

BACKGROUND: This study aimed to examine if specific micronutrients were associated with periodontal disease using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. METHODS: Participants who were aged 30 years or more and received complete periodontal examinations were included. Regression analyses were performed to determine associations of variables of interest with periodontal disease. RESULTS: Data of 6415 NHANES participants were included in the analysis. Multivariable analysis revealed that less intake of vitamin A (adjusted odds ratio (aOR) = 1.784), vitamin B1 (aOR = 1.334), vitamin C (aOR = 1.401), vitamin E (aOR = 1.576), iron (aOR = 1.234), folate (aOR = 1.254) and phosphorus (aOR = 1.280) was associated with increased severity of periodontal disease. Compared with the highest level of vitamin D intake, the second highest level of vitamin D intake was associated with lower severity of periodontal disease (aOR = 0.727). CONCLUSIONS: Insufficient intake of vitamin A, B1, C and E, iron, folate and phosphorus was significantly associated with severity of periodontal disease. Results of the present study suggest that the above micronutrients may be increased in the diet or taken as dietary supplements in order to reduce severity of periodontal disease.

Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: involvement of mitogen-activated protein kinase pathway.

Osthole, a bioactive simple coumarin derivative extracted from many medicinal plants such as Cnidium monnieri (L.) Cusson, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The aim of this study was to investigate the potential neuroprotective role of osthole against ischemic injury in vitro, as well as the potential mechanism. Cultured cortical neurons were exposed to oxygen and glucose deprivation (OGD) for 4 h followed by a 24 h reperfusion. Osthole exhibited remarkable neuroprotection in a dose-dependent manner and the effect required presence of osthole during both OGD and reperfusion phases. Western blot was used to examine the activation of three members of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). We found that osthole prolonged activation of ERK1/2 and prevented activation of JNK. Furthermore, we investigated the effects of MAPKs inhibitors on osthole-induced protection. The results demonstrated that the protection of osthole was partly reversed by PD98059, a selective inhibitor of ERK1/2, but further enhanced by the JNK inhibitor SP600125. In addition, osthole-induced reduction of neuronal apoptosis was abrogated by the ERK1/2 inhibitor PD98059, whereas the total neuronal death was further decreased by the JNK inhibitor SP600125. In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.

[Identification of Panax quinquefolius, P. ginseng and P. notoginseng by protein fingerprints].

Establish the way of protein fingerprints to identify P. quinquefolius, P. ginseng and P. notoginseng of genus Panax by SDS-PAGE, Tris-tricine and Western blot. The fingerprints of Panax species from 28 KD to 58 KD and 55 KD are in common. Very different fingerprints of P. quinquefolius are found below 28 KD. The fingerprints above 58 KD seemed to be peculiar for P. ginseng. Hence the approach may be used as a means to authenticate the concerned Panax species, especially for identification of P. quinquefolius.

[Protection mechanism of huanshaodan decoction in the brain].

OBJECTIVE: To observe the protective effect of Huanshaodan (HSD) in mouse brain in a steady ischemia-reperfusion model. METHODS: Step-through experiment, receptor binding test and choline acetyl-transferase (CAT) activity determination was performed. RESULTS: After HSD treatment, mice made much less mistakes in step-through experiment than sham groups. Meanwhile the 3H-MK801 binding of cerebral cortex and hippocampus tissues was significantly decreased. CAT activity of cerebral cortex and hippocampus tissue were increased respectively. CONCLUSION: HSD might antagonize ischemia injury of brain through modulating excessive activation of glutamate N-methyl-D-Aspartic acid receptors.

Ultrastructural basis for synaptic transmission between jaw-muscle spindle afferents and trigeminothalamic neurons in the rostral trigeminal sensory nuclei of the rat.

Trigeminothalamic neurons were retrogradely labeled by injection of horseradish peroxidase into the ventroposteromedial nucleus of the thalamus in rats. Jaw-muscle spindle afferent axons were then physiologically identified and intracellularly stained with biotinamide. The ultrastructure of labeled spindle afferent boutons was then studied in the caudolateral supratrigeminal region (Vsup) and dorsomedial trigeminal principal sensory nucleus (Vpdm). A total of 418 stained spindle afferent boutons were identified in Vsup and Vpdm; approximately 75% of these synapsed with dendrites, 10% synapsed with somata, and 15% synapsed with axons. Most jaw-muscle spindle afferent boutons were postsynaptic to unlabeled P-type boutons. Reciprocal synapses between spindle afferent boutons and unlabeled boutons were occasionally observed. A few dendrites in Vsup and Vpdm received synapses from multiple spindle afferent boutons. Conversely, some large (from 3 x 6 to 4 x 8 microns) and giant (from > 4 x 8 to 5 x 10 microns) spindle afferent boutons simultaneously contacted two to five dendrites and/or somata. Jaw-muscle spindle afferent boutons also formed synapses with retrogradely labeled trigeminothalamic neurons in Vsup and Vpdm. Numerous unlabeled S-and F-type boutons converged onto the same trigeminothalamic dendrite or soma contacted by a spindle afferent bouton. A small number of synaptic triads consisting of an unlabeled P-type bouton, a spindle afferent bouton, and either a dendrite or soma were also encountered. These data indicate that sensory feedback from the masticatory muscles is subject to presynaptic inhibition and integration prior to reaching the thalamus. This pathway is likely to be important in the relay of proprioceptive and kinesthetic information from the muscles of mastication to the thalamus.

Inputs from identified jaw-muscle spindle afferents to trigeminothalamic neurons in the rat: a double-labeling study using retrograde HRP and intracellular biotinamide.

Projections from physiologically identified jaw-muscle spindle afferents onto trigeminothalamic neurons were studied in the rat. Trigeminothalamic neurons were identified by means of retrograde transport of horseradish peroxidase from the ventroposteromedial nucleus of the thalamus. Labeled neurons were found contralaterally in the supratrigeminal region (Vsup), the trigeminal principal sensory nucleus, the ventrolateral part of the trigeminal subnucleus oralis, the spinal trigeminal subnuclei interpolaris and caudalis, the reticular formation, and an area ventral to the trigeminal motor nucleus (Vmo) and medial to the trigeminal principal sensory nucleus (AVM). Jaw-muscle spindle afferents were physiologically identified by their increased firing during stretching of the jaw muscles and intracellularly injected with biotinamide. Axon collaterals and boutons from jaw-muscle spindle afferents were found in Vmo; Vsup; the dorsomedial part of the trigeminal principal sensory nucleus (Vpdm); the dorsomedial part of the spinal trigeminal subnuclei oralis, interpolaris (Vidm) and caudalis; the parvicellular reticular formation (PCRt); and the mesencephalic trigeminal nucleus. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, PCRt, and AVM were associated with axon collaterals and boutons from intracellularly stained jaw-muscle spindle afferents. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, and PCRt were closely apposed by one to 14 intracellularly labeled boutons from jaw-muscle spindle afferents, suggesting a powerful input to some trigeminothalamic neurons. These data demonstrate that muscle length and velocity feedback from jaw-muscle spindle afferents is projected to the contralateral thalamus via multiple regions of the trigeminal system and implicates these pathways in the projection of trigeminal proprioceptive information to the cerebral cortex.

The anatomical evidence of recurrent axonal collaterals of the thalamus projecting neurons of the rostral pole of the trigeminal sensory nuclear complex in the rat.

Thalamus projecting neurons and their recurrent axonal collaterals were observed in the dorsomedial part of the trigeminal principal sensory nucleus (Vpdm) and the caudolateral part of supratrigeminal nucleus (Vsup CL) after injection of horseradish peroxidase (HRP) into the contralateral ventrobasal complex of the thalamus (VBm) by using the HRP retrogradely tracing-Golgi-like staining method. About 7% (8/120) parent axons of the labeled cells gave rise to recurrent axon collaterals. However, no retrogradely labeled cells were observed in the VBm after injection of HRP into the Vpdm and Vsup CL. In an electron microscopic study, the terminals of recurrent axon collaterals made synapses with the dendrites of the thalamus projecting neurons or non-labeled neurons in the neuropil of the Vpdm and Vsup CL. It is suggested that the recurrent axon collaterals might play a role of negative feedback in transmission of the proprioceptive message from the jaw-closing muscle spindles to the thalamus.