Hierarchically Released Liquid Metal Nanoparticles for Mild Photothermal Therapy/Chemotherapy of Breast Cancer Bone Metastases via Remodeling Tumor Stromal Microenvironment.

Currently, the treatment strategy for bone metastasis is mainly to inhibit the growth of tumor cells and the activity of osteoclasts, while ignoring the influence of the tumor stromal microenvironment (TSM) on the progression of bone metastasis. Herein, a dual-target liquid metal (LM)-based drug delivery system (DDS) with favorable photothermal performance is designed to spatially program the delivery of multiple therapeutic agents to enhance the treatment of bone metastasis through TSM remodeling. Briefly, mesoporous silicon-coated LM is integrated into zeolitic imidazolate framework-8 (ZIF-8) with both bone-seeking and tumor-targeting capacities. Curcumin (Cur), a tumor microenvironment modulator, is encapsulated into ZIF-8, and doxorubicin (DOX) is enclosed inside mesoporous silicon. Specific accumulation of the LM-based DDS in bone metastases first relieves the tumor stroma by releasing Cur in response to the acidic tumor microenvironment and then releases DOX deep into the tumor under near-infrared light irradiation. The combined strategy of the LM-based DDS and mild photothermal therapy has been shown to effectively restrain cross-talk between osteoclasts and tumor cells by inhibiting the secretion of transforming growth factor-ß, degrading extracellular matrix components, and increasing infiltration of CD4+ and CD8+ T cells, which provides a promising strategy for the treatment of bone metastases.

Red mud recycling by Fe and Al recovery through the hydrometallurgy method: a collaborative strategy for aluminum and iron industry.

In this work, a collaborative strategy for the aluminum and iron industry based on red mud recycling through the hydrometallurgy method was proposed. In this method, Fe3+ and Al3+ were firstly separated from the red mud by using H2SO4 as a leaching agent, which was by-produced from the sintering process of an iron and steel industry. Multiple influence factors on the leaching process were investigated, with the H2SO4 addition amount showing the strongest influence on the leaching rates of Al and Fe. The main components of the filter residue were CaSO4, TiO2, and SiO2, which could be reused as additives in the building materials. Subsequently, the final Fe recovery product was obtained through the co-precipitation, Fe/Al separation, and Fe(OH)3 calcination. In the final product, the content of Fe2O3 reached 82.87%, and the iron grade was 58.01%, meeting the requirement being raw materials for sinter production.

Combining dual-targeted liquid metal nanoparticles with autophagy activation and mild photothermal therapy to treat metastatic breast cancer and inhibit bone destruction.

Although mild photothermal therapy (mild-PTT) avoids treatment bottleneck of the traditional PTT, the application of mild-PTT in deep and internal tumors is severely restricted due to thermal resistance, limited irradiation area and penetration depth. In addition, bone resorption caused by tumor colonization in distal bone tissue exacerbates tumor progression. Here, a strategy was developed for the treatment of bone metastasis and alleviation of bone resorption, which was based on liquid metal (LM) nanoparticle to resist thermal resistance induced by mild-PTT via autophagy activation. Briefly, LM and autophagy activator (Curcumin, Cur) were loaded into zeolitic imidazolate framework-8 (ZIF-8), which was then functionalized with hyaluronic acid/alendronate (CLALN). CLALN exhibited good photothermal performance, drug release ability under acidic environment, specifical recognition and aggregation at bone metastasis sites. CLALN combined with mild-PPT dramatically inhibited tumor progress by inducing the impaired autophagy and reduced the expression of programmed cell death ligand 1 (PD-L1) protein triggered by mild-PTT, resisting thermal resistance and alleviating the immunosuppression. Besides, CLALN combined with mild-PPT effectively alleviated osteolysis compared with only CLALN or mild-PPT. Our experiments demonstrated that this multi-functional LM-based nanoparticle combined with autophagy activation provided a promising therapeutic strategy for bone metastasis treatment. STATEMENT OF SIGNIFICANCE: Due to the limited light penetration, photothermal therapy (PTT) has limited inhibitory effect on tumor cells colonized in the bone. In addition, nonspecific heat diffusion of PTT may accidentally burn normal tissues and damage peripheral blood vessels, which can block the accumulation of drugs in deep tumors. Here, a multifunctional liquid metal based mild-PTT delivery system is designed to inhibit tumor growth and bone resorption by modulating the bone microenvironment and activating autophagy "on demand". It can overcome the treatment bottleneck of traditional PTT and improve the treatment effect of mild-PTT by resisting photothermal resistance and immune suppression. In addition, it also exhibits favorable heat/acid-responsive drug release performance and can specifically target tumor cells at the site of bone metastases.

[WU Xu's experience of sequential therapy for peripheral facial paralysis].

The paper introduces professor WU Xu 's experience of sequential therapy for peripheral facial paralysis. The sequential therapy refers to a staging treatment, but not rigidly adheres to it. With this therapy, the acupuncture- moxibustion regimen is modified flexibly in line with the specific symptoms of illness. At the acute phase of peripheral facial paralysis, warm acupuncture at Wangu (GB 12) is predominated and electroacupuncture is not recommended at the acupoints on the face. At the recovery phase, warm acupuncture at Zusanli (ST 36) is the main therapy and electroacupuncture is applied to the acupoints on the face appropriately. Besides, for the intractable case, the tapping technique with plum-blossom needle or skin needle should be combined and exerted in the local affected region. At the sequelae phase, in order to shorten the duration of illness, depending on the different types of facial paralysis, i.e. stiffness type, spasmodic type and flaccid type, the corresponding needling techniques are provided, i.e. bloodletting and moxibustion, strong stimulation with contralateral acupuncture and the technique for promoting the governor vessel and warming up yang.

Development and assessment of machine learning models for predicting recurrence risk after endovascular treatment in patients with intracranial aneurysms.

Intracranial aneurysms (IAs) remain a major public health concern and endovascular treatment (EVT) has become a major tool for managing IAs. However, the recurrence rate of IAs after EVT is relatively high, which may lead to the risk for aneurysm re-rupture and re-bleed. Thus, we aimed to develop and assess prediction models based on machine learning (ML) algorithms to predict recurrence risk among patients with IAs after EVT in 6 months. Patient population included patients with IAs after EVT between January 2016 and August 2019 in Hunan Provincial People's Hospital, and an adaptive synthetic (ADASYN) sampling approach was applied for the entire imbalanced dataset. We developed five ML models and assessed the models. In addition, we used SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. A total of 425 IAs were enrolled into this study, and 66 (15.5%) of which recurred in 6 months. Among the five ML models, gradient boosting decision tree (GBDT) model performed best. The area under curve (AUC) of the GBDT model on the testing set was 0.842 (sensitivity: 81.2%; specificity: 70.4%). Our study firstly demonstrated that ML-based models can serve as a reliable tool for predicting recurrence risk in patients with IAs after EVT in 6 months, and the GBDT model showed the optimal prediction performance.

Protective effect of Dachengqi decoction on the pancreatic microcirculatory system in severe acute pancreatitis by down-regulating HMGB-TLR-4-IL-23-IL-17A mediated neutrophil activation by targeting SIRT1.

BACKGROUND: Dachengqi decoction (DCQD), one of classic prescription of Chinese herbal medicine has been widely used in clinic to treat severe acute pancreatitis (SAP). The damage of pancreatic microcirculation plays key pathogenesis of SAP. However, little is known about the molecular pharmacological activity of DCQD on pancreatic microcirculation in SAP. METHODS: Sodium taurodeoxycholate and cerulein were used to establish model of SAP in vitro and in vivo, respectively. The pancreatic pathological morphology, wet weight ratio, myeloperoxidase (MPO) activity, cell viability and microcirculatory function of the pancreas, as well as serum lipase and amylase expressions were evaluated. The expression levels of SIRT1, acety-HMGB1, TLR-4, HMGB1, IL-23, IL-17A, neutrophil chemokines (KC, LIX, and MIP-2), and inflammation-related factors (IL-6, IL-1ß, and TNF-α), the translocation of HMGB1 and the interaction of SIRT-HMGB1 in the pancreas and serum were determined by ELISA real-time PCR, western blotting and immunoprecipitation. RESULTS: In vivo studies showed that DCQD or neutralizing antibody (anti-23p19 or anti-IL-17A) could all significantly decrease lipase, amylase activity, down-regulate the expression of CD68, Myeloperoxidase (MPO), wet/weight, IL-1ß, IL-6, TNF-α, and neutrophil chemokines (KC, LIX, MIP-2), alleviate pathological injury and improve pancreatic microcirculatory function in rats with SAP. Furthermore, DCQD remarkably increased SIRT1 expression, promoted SIRT1 and HMGB1 combination, reduced HMGB1 translocation from nuclear to cytoplasm, and alleviated the expression of acetyl-HMGB1, HMGB1, IL-17A, TLR-4, and IL-23 in vitro and in vivo with SAP. However, the intervention with EX527 (SIRT1 inhibitor) or r-HMGB1 (recombinant HMGB1) obliviously reverses the above mentioned influence mentioned above of DCQD in SAP. In vitro, we confirmed that DCQD could decrease HMGB1 acetylation, migration, and release, and improve the decline of cell viability, SIRT1 expression and SIRI-HMGB1 combination induced by cerulean with promoting macrophage to release IL-23 by relying on the HMGB1/TLR-4 way. CONCLUSIONS: DCQD treatment improves SAP-induced pancreatic microcirculatory dysfunction by inhibiting neutrophil-mediated inflammation via inactivating HMGB1-TLR-4-IL-23-IL-17A signaling by targeting SIRT1.

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice.

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe-/- ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe-/- mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe-/- mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.

A Single Molecule Drug Targeting Photosensitizer for Enhanced Breast Cancer Photothermal Therapy.

Targeting is one of the most important strategies for enhancing the efficacy of cancer photothermal therapy (PTT) and reducing damage to surrounding normal tissues. Compared with the traditional targeting approaches, the active targeting of breast cancer cells in PTT using chemotherapeutic drugs, such as tamoxifen (TAM), in combination with single-molecule photothermal photosensitizers has superior selectivity and therapeutic effects. However, single-molecule drug-targeting photosensitizers for improved PTT efficacy are not widely reported. Accordingly, herein, a near-infrared induced small-molecule photothermal photosensitizer (CyT) is developed that actively targets the estrogen receptors (ERs) of breast cancer cells as well as targets mitochondria by structure-inherent targeting. Cell uptake and cytotoxicity studies using different types of cells show that CyT enhances the efficiency of TAM-based PTT by targeting ER-overexpressing breast cancer cells and selectively killing them. In vivo experiments demonstrate that CyT can be used as a photothermal agent for fluorescence imaging-guided PTT. More importantly, the intravenous injection of CyT results in better targeting and efficiency of tumor inhibition compared with that achieved with the TAM-free control molecule Cy. Thus, the study presents an excellent small-molecule photothermal agent for breast cancer therapy with potential clinical application prospects.

Systematic investigation of the mechanism of Cichorium glandulosum on type 2 diabetes mellitus accompanied with non-alcoholic fatty liver rats.

Cichorium glandulosum(CG) can treat various diseases with multiple targets effectively. It has been widely used in folk medicine to treat nonalcoholic fatty liver disease (NAFLD) as well as type 2 diabetes mellitus (T2DM). However, the active compounds and underlying mechanisms of CG on T2DM accompanied with NAFLD (T2DM-NAFLD) remain unclear. In this study, a systems pharmacology method was used to explain the pharmacology mechanism of CG for treatment of T2DM-NAFLD. Twenty four main compounds were detected by UPLC-Q-TOF-MS, of which 13 showed favorable pharmacokinetic profiles. We demonstrated with target fishing and pathway analysis that CG has protective effects on T2DM-NAFLD, probably through the regulation of 88 targets and 86 pathways. Forty nine targets were related to T2DM, and 39 were related to NAFLD, while 27 targets, primarily involved in insulin resistance and inflammation were common to T2DM and NAFLD related pathways. A NF-κB signaling pathway was chosen to validate the impacts of CG on T2DM-NAFLD because CG can ameliorate T2DM-NAFLD by regulating the NF-κB signaling pathway according to animal experiments. These findings systematically interpreted the active compounds and mechanism of the efficiency of CG for treating T2DM-NAFLD. This study not only laid a basis for understanding the active compounds and action mechanism of CG, but also provides a reference for a study of the mechanism of a herbal medicine for the treatment of multiple diseases.

GZFLW Induces Apoptosis of Ectopic Endometrial Stromal Cells via Promoting VPS53 Protein Stability.

Endometriosis is still a major problem in obstetrics and gynecology. While GZFLW (Gui Zhi Fu Ling Wan) has been originally used for treating gynecological diseases, however, the molecular mechanism that GZFLW acts on endometriosis is not clear. To investigate the molecular mechanism that GZFLW plays role on endometriosis, iTRAQ (isobaric tags for relative and absolute quantification) proteomics and human endometrial stromal cells (Y14) obtained from a patient with endometriosis were used in in vitro study. Our results demonstrated that GZFLW decreased Y14 cells proliferation while increased cells apoptosis. The differential expression protein VPS53 (Vacuolar protein sorting 53 homolog) was predicted by iTRAQ coupled LC-MS/MS and further identified by western blot. Besides, GZFLW induced VPS53 protein level by promoting its stabilization. Our findings highlight a novel role for VPS53 in gynecology and provide a potent therapeutic strategy against endometriosis.

Ping-Chong-Jiang-Ni Formula Induces Apoptosis and Inhibits Proliferation of Human Ectopic Endometrial Stromal Cells in Endometriosis via the Activation of JNK Signaling Pathway.

Endometriosis is a common gynecological condition in childbearing age women and its therapy in modern medicine achieves usually temporary cure. Ping-Chong-Jiang-Ni formula (PCJNF), a Chinese herbal medicine (CHM), was shown to be clinically effective on endometriosis. Meanwhile, c-Jun N-terminal kinase (JNK) signaling pathway was involved in the therapeutic process of CHM on endometriosis. Here, we explored the effect of PCJNF on the ectopic endometrial stromal cells (EESCs) from endometriosis and test whether JNK signaling was involved. After being treated with PCJNF-containing serum obtained from Sprague Dawley rat, cell proliferation, migration, invasion, and apoptosis were evaluated in EESCs, and the total and phosphorylated JNK, ERK, and p38 proteins were detected. Our results showed that PCJNF could suppress cell proliferation, migration, and invasion and induce apoptosis in EESCs. The suppressed proliferation and increased apoptosis were dependent on JNK activation. Additionally, PCJNF caused cell cycle arrest at G2/M phase and this effect was mediated by JNK signaling, while the decreased cell migration and invasion treated by PCJNF were independent of JNK signaling. In summary, our results provided the first evidence that PCJNF could suppress cell proliferation, migration, and invasion, while increasing apoptosis in EESCs, and the suppressed proliferation and enhanced apoptosis were mediated by JNK signaling.

Unconventional Superconductivity in the Layered Iron Germanide YFe(2)Ge(2).

The iron-based intermetallic YFe_{2}Ge_{2} stands out among transition metal compounds for its high Sommerfeld coefficient of the order of 100 mJ/(mol K^{2}), which signals strong electronic correlations. A new generation of high quality samples of YFe_{2}Ge_{2} show superconducting transition anomalies below 1.8 K in thermodynamic, magnetic, and transport measurements, establishing that superconductivity is intrinsic in this layered iron compound outside the known superconducting iron pnictide or chalcogenide families. The Fermi surface geometry of YFe_{2}Ge_{2} resembles that of KFe_{2}As_{2} in the high pressure collapsed tetragonal phase, in which superconductivity at temperatures as high as 10 K has recently been reported, suggesting an underlying connection between the two systems.

Inhibitory Effects of Lanthanum Chloride on Wear Particle-Induced Osteolysis in a Mouse Calvarial Model.

Osteolysis is a bone disorder associated with progressive destruction of bone tissues. However, the effects of lanthanum chloride (LaCl3) on osteolysis remain unknown. Therefore, the aim of this study was to determine the effects of LaCl3 on osteolysis in vivo. In a mouse calvarial model, C57BL/6J mice were injected with wear particles with or without LaCl3. Microcomputed tomography, hematoxylin and eosin staining, and tartrate-resistant acid phosphatase staining were performed for the pathological characterization of calvariae, and eight calvariae per group were prepared for the assay of TNF-α, IL-1ß, and RANKL secretion using quantitative enzyme-linked immunosorbent assay (ELISA). In mice treated with high-dose LaCl3, particle-induced osteolysis and inflammatory reaction were reduced compared with that in the vehicle-treated control. Moreover, treatment with high-dose LaCl3 suppressed the wear particle-induced decrease in bone mineral content, bone mineral density, and bone volume fraction. Bone destruction and resorption were higher in the LaCl3-treated group than in the saline-treated group but lower than those in the wear particle group. Finally, our results showed that treatment with a high dose of LaCl3 suppressed osteoclastogenesis. Thus, LaCl3 may represent a novel therapeutic agent for the treatment or prevention of wear particle-induced osteolysis and aseptic loosening.

[Variation of Locations of Baliao Acupoints in 290 Volunteer Subjects Analyzed by Using Computed Tomography-aided Three-dimensional Reconstruction Technique].

OBJECTIVE: To observe the variation of sacral vertebrates and foramen involving the bilateral Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34, Baliao acupoints), so as to provide an anatomic basis of acupoint needling in clinical practice. METHODS: A total of 290 patients[161 men and 129 women, mean age and standard devia-tion, (63.6±13.3)years old and (59.5±13.3) years old, respectively] with intact pelvic structure were recruited in the present study. Computed tomography (CT) scans of intact pelves were taken using a SOMATOM Definition AS 128 and the acquired signals were imported into Siemens Syngo Inspace platform for 3 D reconstruction, followed by identification, classification and analysis of the variation of sacral foramen (Baliao acupoint). RESULTS: The total variation rate of posterior sacral foramen (Baliao acupoint) was 20.34%(59/290). The detected three types of variation were sacral vertebrae number variation (4 sacral vertebraes, 6 sacral vertebraes), fusion variant (lumbosacral fusion, sacrococcygeal fusion, lumbosacral & sacrococcygeal fusion, and lumbosacral fusion & S 4 variation) and mixed type. CONCLUSIONS: Variations of sacral vertebrae including the number and fusion exist in the human body, suggesting an increase of the difficulty of acupoint needling. Since posterior iliac spine does not change generally, it is recommended to be used as a reference point for locating the Baliao acupoint.

[Development of Researches on the Underlying Mechanism of Acupuncture Stimulation of Baliao-points for Improving Outlet Obstruction Constipation].

Outlet obstruction constipation (OOC) is a common clinical problem affecting many people's daily life quality nowadays. Acupuncture therapy is effective in easing OOC to reduce patients' sufferings by stimulation of Baliao-points i. e., bilateral Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34), which has been confirmed repeatedly in clinical practice. In the present paper, the authors reviewed development of studies on the underlying mechanisms of acupuncture stimulation of Baliao-points for OOC from: 1) lowering the sensitivity of intraganglionic laminar nerve endings (rIGLEs) to rectal mechanical distension during defecation, 2) raising the level of circulating cholecystokinin (CCK) to improve the sensory threshold of the rectum, 3) lowering the excitability of γ-motor neurons in the spinal anterior horns controlling the slow contraction of the rectal sphincter muscle, 4) inhibiting the excitability of sympathetic output from the spinal lateral horns, 5) easing the tonic contraction of the pelvic muscles to reduce the release of 5-hydroxy tryptamine (5-HT), histamine, and other related chemical mediators due to local ischemia. Moreover, further study on the mechanism of acupuncture stimulation of Baliao-points underlying improving OOC may help up find more specific and effective therapeutic targets and provide more reliable experimental foundation and theoretical basis.

[From Biological Effects of Local Cutaneous Thermal Stimulation to Moxibustion Therapy].

Moxibustion is one of the major external therapies of traditional Chinese medicine (TCM) and exerts a definite favorable effect in the treatment of patients with different problems. In the present paper, the authors reviewed 38 papers about somatic thermal intervention therapy published in recent 15 years and analyzed its biological functions from local, distal, and whole body effects. The local effects include 1) improving cutaneous inflammatory illnesses as verruca, herpes simplex, Leishmania infection, cutaneous necrosis, wound disunion, and promoting percutaneous absorption of some medicines, swelling pain; 2) reliving sports fatigue and muscular injury, eliminating inflammation and pain reactions, probably by lowering local reactive oxygen species, superoxide dismutase,catalase, glutathione, etc. levels, and strengthening the flexibility of the knee-joint, and anterior and posterior cruciate ligaments; 3) increasing blood perfusion of the regional arteriola, micrangium to eliminate accumulated subcutaneous blood cells, inflammatory mediators and other metabolic products. The distal effects contain 1) increase of the distal cutaneous blood flow and suppression of the arterial stenosis; and 2) improvement of the visceral functions including the heart (ischemia), liver, gastrointestinal blood flow and smooth muscles, uterus smooth muscular tension, etc. The whole body effects include raising immunoability against cancer, and reducing tumor blood flow to damage the blood vessels in the tumor tissue, etc. In addition, the effects of thermal stimulation are affected by the temperature, stimulating duration and the stimulated positions. These research results may help us to comprehensively understand the effects and mechanisms of moxibustion therapy in the treatment of different clinical disorders.

[Distribution characteristics and erosion risk of nitrogen and phosphorus in soils of Zhuangmu town in Lake Wabuhu basin].

To understand the loss risk of soil erosion in the Zhuangmu town in Lake Wabuhu watershed, concentration and spatial distribution of nitrogen and phosphorus in 162 surface soil samples collected from the farmlands in ten administrative villages of the town were investigated. The risk assessment was conducted by using the nitrogen and phosphorus index method after speciation analysis of soil nitrogen and phosphorus. Based on ArcGIS technology, the spatial interpolation of total nitrogen (TN), total phosphorus (TP), and bioavailable nitrogen and phosphorus contents as well as nitrogen and phosphorus index values were performed by means of Kriging interpolation. The results show that, generally, average contents of TN and TP were obtained at 1.67 g x kg(-1) and 0.71 g x kg(-1), respectively. And the mean concentration of bioavailable nitrogen and phosphorus were estimated at 0.26 g x kg(-1) and 0.33 g x kg(-1), accounting for 14.93% and 47.30% of TN and TP contents, respectively. Spatially, the samples with high concentration of TN were mostly from Houji, Yangwan and Liuqian villages, whereas the samples sites with higher contents of TP located in Houji, Yangwan and Zaolin villages. The mean values of nitrogen index (NI) and phosphorus index (PI) for the whole town are 2.11 and 2.13, respectively. According to the numeric size of NI and PI, ten villages ranged in the order of Yangwan > Zhuangmu > Xueqiao > Liuqian > Lizhuang > Jinqiao > Zaolin > Zhangwei > Houji > Xugang village. In general, the soil nitrogen loss is dominated by low and medium risks in the Zhuangmu town, and high risk sporadically appears in local area of the Yangwan village. Like the nitrogen, soil phosphorus loss risk also gives priority to low, and above medium risk concentrates in the Yangwan village as well.

[Location of disease: acupoint view from the angle of clinic].

Doctor WANG Zhi-zhong in the Southern Song Dynasty proposed the acupoint view of "location of disease", which explained the connotation of acupoints from the angle of clinic. Its meaning included two levels, one level meant pathological change on the body surface, that was the location of acupuncture diagnosis-treatment, and the other one indicated that the body surface which was the reflecting point of pathological change on the distal area or inside the body was the location of acupuncture diagnosis-treatment. The specific connotations of clinical acupoints were: location of pathogenic factors or reflection of pathogenic factors, regularity between acupoints un- der disease and specific organ, morphological differences and positioning variability after acupoints under disease, and acupoints examination, diagnosis and treatment.

Changes in ruminal fermentation, milk performance and milk fatty acid profile in dairy cows with subacute ruminal acidosis and its regulation with pelleted beet pulp.

The aims of the experiment were to investigate the variation in ruminal fermentation, milk performance and milk fatty acid profile triggered by induced subacute ruminal acidosis (SARA); and to evaluate the ability of beet pulp (BP) as a replacement for ground maize in order to alleviate SARA. Eight Holstein-Friesian cows were fed four diets (total mixed rations) during four successive periods (each of 17 d): (1) without wheat (W0); (2) with 10% finely ground wheat (FGW) (W10); (3) with 20% FGW (W20); (4) with 20% FGW and 10% pelleted BP (BP10). Inducing SARA by diet W20 decreased the daily mean ruminal pH (6.37 vs. 5.94) and the minimum ruminal pH (5.99 vs. 5.41) from baseline to challenge period. Ruminal concentrations of total volatile fatty acid, propionate, butyrate, valerate and isovalerate increased with the W20 compared with the W0 and W10 treatments. The substitution of BP for maize increased the minimum ruminal pH and molar percentage of acetate and decreased the molar percentage of butyrate. The diets had no effect on dry matter intake (DMI) and milk yield, but the milk fat percentage and yield as well as the amount of fat-corrected milk was reduced in the W20 and BP10 treatments. The cows fed the W20 diet had greater milk concentrations of C11:0, C13:0, C15:0, C14:1, C16:1, C17:1, C18:2n6c, C20:3n6, total polyunsaturated fatty acids (FA) and total odd-chain FA, and lower concentrations of C18:0 and total saturated FA compared with the cows fed the W0 diet. Therefore, it can be concluded that changes in ruminal fermentation, milk fat concentration and fatty acid profile are highly related to SARA induced by feeding high FGW diets, and that the substitution of BP for maize could reduce the risk of SARA in dairy cows.

[Chemical constituents from Astilbe myriantha].

OBJECTIVE: To study the chemical constituents from Astilbe myriantha. METHODS: The constituents were isolated and purified by column chromatography methods and recrystallization. Their structures were identified on the basis of physiochemical properties and special analysis. RESULTS: Ten compounds were isolated from 95% ethanol extract of Astilbe myriantha and their structures were identified as: beta-sitosterol (1), methyl p-hydroxy benzoate (2), ferulic acid (3), bergenin (4), gallic acid (5), (+)-catechin (6), 3beta-acetoxy-6beta-hydroxyolean-12-en-27-oic acid (7), 3beta-hydroxyolean-12-en-27-oic acid (8),3beta,6beta-dihydrolean-12-en-27-oic acid (9) and 3beta-hydroxyurs-12-en-27-oic acid (10). CONCLUSION: Compounds 1-7 are isolated from this plant for the first time.