Exploring the mechanism of Si-Miao-Yong-An decoction on heart failure based on molecular docking and network pharmacology.

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

[Spatiotemporal Distribution and Source Analysis of Heavy Metals in Surface Sediments in Lake Ulansuhai Based on PCA-APCS-MLR Model].

To explore the spatial and temporal distribution characteristics of heavy metals in the surface sediments of lakes in cold regions during ice-sealing and non-ice-sealing periods, we analyzed the potential ecological risk degree and the pollution sources. A total of 20 sampling sites in Lake Ulansuhai in cold regions were collected from 2020 to 2021, and 120 surface sediment samples were collected during different periods. The contents of As, Cd, Cr, Cu, Ni, Pb, Zn, and Hg were determined. Correlation analysis, principal component analysis, and the absolute factor score-multiple linear regression (APCS-MLR) receptor model were used to trace the source of heavy metal pollution. The results showed that:① the distribution of heavy metals in lake surface sediments was different between the ice-sealing period and the non-ice-sealing period. The distribution of heavy metals during the ice-sealing period was higher in the north and lower in the south. Cd and Hg were mainly distributed in the central and southern lakes during the non-glacial period. ② Hg, Cd, and As were moderately polluted, and Ni was mildly polluted in the surface sediments of the lake. The overall performance was at a high risk level, and the pollution level during the non-ice-sealing period was higher than that during the ice-sealing period. The main environmental risk factors were Hg and Cd, which showed high risk and moderate risk, respectively. ③ The sources of heavy metals in lake surface sediments were mainly industrial sources from mining and transportation, agricultural sources, and natural sources. As, Ni, Pb, and Hg were mainly affected by industrial sources, with contribution rates of 62.67%, 75.31%, 77.47%, and 80.11%, respectively. The main sources of Cu and Zn were natural sources, and Cd was greatly affected by agricultural sources. The contribution rate was 81.57%. The source of Cr was mainly affected by natural factors, and the influence of human activities and unknown sources require further attention.

[Significance of herbal/botanical monograph in international registration of Chinese medicine].

Herbal/botanical monograph, first emerging abroad, includes the scientific conclusions on safety and effectiveness of herbal medicine/botanical medicine, as it is often compiled by drug regulatory authorities. It is designed to unify the related technologies in this field and evaluation standards for review. Thus, herbal/botanical monograph is vital for the internationalization of Chinese medicine and being inscribed into the herbal/botanical monograph of target country is the first step for drug registration there. At the moment, there are few domestic studies on international herbal/botanical monographs, let alone the importance of the monographs in international registration of Chinese medicine preparations. This study first described international monographs on herbal/botanical medicine, then discussed the similarities and differences between international monographs and Chinese Pharmacopoeia, and finally analyzed the significance and value of the monographs in the international registration of Chinese medicine. On this basis, this study underscored the research on herbal/botanical monographs of key candidate countries for Chinese medicine registration, with a view to enhancing international recognition and laying the foundation for international registration and related policy formulation.

[Deposition Law of Low-Density Microplastics Aggregation in Wuliangsu Lake].

Deposition is the main migration process of low-density microplastic aggregation in lakes. In order to explore the deposition law of low-density microplastic aggregation in Wuliangsu Lake, a microplastic trap was designed and applied to examine the deposition process based on the similarities and differences between microplastics and naturally occurring suspended solids. The deposition processes of different sizes and shapes of low-density microplastic aggregation were quantified in Wuliangsu Lake. The results showed that the deposition fluxes of all types of low-density microplastic aggregation increased with wind speed. The deposition of flux of low-density microplastic aggregations with a similar shape of fiber and with a size ranging from 0.05-0.5, 0.5-2, and 2-5 mm had better correlation with wind speed. The correlation coefficient changed from 0.218 to 0.836. The deposition of flux of low-density microplastic aggregations with a similar shape of fiber, fragment, grain, and film and with size ranging from 0.05-0.5, 0.5-2, and 2-5 mm under different wind speeds at different experiment sites changed from 0-(1458±284), 0-(368±144), 0-(71±37), and 0-(85±65)n·(m2·d)-1, respectively. Furthermore, we found that, when shape was held constant, larger low-density microplastic aggregations were more likely to be deposited, whereas smaller low-density microplastic aggregations were more likely to be transported. When size was held constant, fragmentary low-density microplastic aggregations were more likely to be deposited than fibrous and film microplastic.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Liraglutide Lowers Body Weight Set Point in DIO Rats and its Relationship with Hypothalamic Microglia Activation.

OBJECTIVE: This study aimed to investigate the effects of liraglutide on the body weight set point (BWSP) in diet-induced obese rats and to determine the relationship between BWSP and hypothalamic arcuate nucleus (ARC) microglial activation. METHODS: Diet-induced obesity (DIO) rats were divided into three groups: continuous high-fat diet (HFD) plus saline, HFD with liraglutide, and HFD with liraglutide pair feeding. Body weight, BWSP, inflammatory cytokines, suppressor of cytokine signaling 3, orexigenic/anorexigenic proteins, apoptosis, and microglia in the ARC were assessed. The effect of liraglutide on the Notch-1 signaling pathway and its relationships with  nuclear factor-κB and p38 mitogen-activated protein kinase were also investigated in a lipopolysaccharide (LPS)-induced microglia activation model. RESULTS: Liraglutide reduced BWSP; reversed adverse changes in hypothalamic inflammation, suppressor of cytokine signaling 3, and apoptosis; and diminished microgliosis in DIO rats. The BWSP showed a linear correlation with ARC microglial density. Liraglutide inhibited LPS-induced M1 microglial polarization and promoted microglial polarization to the M2 phenotype, diminishing inflammatory cytokine expression. Liraglutide inhibited Notch-1 signaling pathway activation and decreased nuclear factor-κB and p38 mitogen-activated protein kinase pathway activation in LPS-stimulated microglia. CONCLUSIONS: Liraglutide can reduce BWSP in DIO rats. There is a linear correlation between hypothalamic microgliosis and BWSP. Liraglutide reduces excessive microglial activation and inflammation, which may contribute to BWSP reduction.

[Effect of environmental factors on photosynthetic physiology and flavonoid constituent of Scutellaria baicalensis].

To discuss the effect of environmental factors and photosynthesis on the growing of plant and the content of active components in Scutellaria baicalensis, the photosynthetic physiology index and diurnal changes of flavonoid constituent of S. Baicalensis were observed and tested in flowering and fruiting stages, and in the meantime environmental parameters were recorded. The obtained data were analyzed data by using path analysis and gray correlation analysis. The results showed that PAR and SWC were important environmental factors impacting on photosynthesis of S. baicalensis. SWC, RH and Ca were important environmental factors impacting on baicalin content. PAR, Po and Ta were important environmental factors impacting on baicalein content.

[Effect of bushen tiaojing recipe on the quality of the oocytes and reproductive hormones in the follicular fluid in IVF-ET patients].

OBJECTIVE: To explore the effect of Bushen Tiaojing Recipe (BTR) on the quality of oocytes, reproductive hormones, and the expression of bone morphogenetic protein-15 (BMP15) of in vitro fertilization-embryo transfer (IVF-ET) patients. METHODS: Sixty infertility patients who prepared for IVF-ET were assigned to two groups according to the treatment order, the treatment group [20 cases, treated with BTR + controlled ovarian hyperstimulation (COH)] and the control group (treated with COH alone, 40 cases). Age, the time limit for infertility, basal follicle-stimulating hormone (bFSH) concentration, usage days and the dosage of gonadotropins (Gn), serum levels of estradiol (E2), luteotropic hormone (LH), and progesterone (P) on the HCG injection day, the number of retrieved occytes, the fertilization rate, the number of embryos, the high quality embryo rate, and the clinical pregnancy rate were compared. Concentrations of follicle-stimulating hormone (FSH), LH, E2, testosterone (T), and P in the follicular fluid were detected via chemiluminescence microparticle immunoassay. The mRNA and protein expression of BMP-15 in mature granulosa cells was detected by real-time fluorescent PCR and Western blot. RESULTS: Thirty-two patients were pregnant and the total pregnancy rate was 53.3%. Of them, 19 were pregnant and the total pregnancy rate was 47.5% in the control group, while 20 were pregnant and the total pregnancy rate was 65.0% in the treatment group. But there was no statistical difference between the two groups (P > 0.05). Compared with the control group, the Gn dosage was lower and the high quality embryo rate was higher in the treatment group, showing statistical difference (P < 0.05). There was no statistical difference in serum concentrations of E2, LH, or P on the HCG injection day, the number of retrieved oocytes, or the fertilization rate (P > 0.05). Compared with the control group, FSH concentrations in the follicular fluid were significantly lower and LH concentrations were significantly higher in the treatment group (P < 0.05). The LH concentrations in the follicular fluid were significantly higher in pregnant patients than non-pregnant patients, showing statistical difference (P < 0.05).There was no statistical difference in E2, T, or P concentrations (P > 0.05). The mRNA and protein expression of BMP-15 in granulosa cells was higher in the treatment group than in the control group (P < 0.05). It was also higher in pregnant patients than non-pregnant patients, showing statistical difference (P < 0.05). CONCLUSION: During the IVF-ET process, BTR could elevate the quality of oocytes, and increase the sensitivity of ovarian follicles to exogenous Gn, which was correlated with the mRNA and protein expression of BMP-15 in granulosa cells, and changing concentrations of FSH and LH.

N-methyl-d-aspartate inhibits cerebellar Purkinje cell activity via the excitation of molecular layer interneurons under in vivo conditions in mice.

N-methyl-d-aspartate (NMDA) receptors play a key role in synaptic transmission, and are widely expressed on the membrane of granule cells, parallel fibers, and molecular layer interneurons (MLIs) in the cerebellar cortex of mammals. In cerebellar slices, activation of NMDA receptors increases inhibitory postsynaptic currents (IPSCs) of Purkinje cells (PCs). However, the effects of NMDA on the cerebellar network under in vivo conditions are currently unclear. In the present study, we examined the effects of NMDA on the spontaneous activity of PCs and MLIs in urethane-anesthetized mice by electrophysiological, pharmacological, and juxtacellular labeling methods. Our results revealed that cerebellar surface application of NMDA (5-200µM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. Application of GABAA receptor antagonist, SR95531 (20µM) abolished NMDA-induced inhibition of PCs spontaneous activity, and revealed NMDA-induced excitation of cerebellar PCs. NMDA receptor antagonist, DAP-V (250µM) did not affect the mean frequency of SS firing, but the SS firing rate of PCs became more regular than the control. In addition, NMDA increased the spike firing of both basket-type and stellate-type MLIs. Overall, these results indicated that NMDA-induced excitation of MLIs at the cerebellar surface may inhibit PC activity. Thus, NMDA receptors of MLIs may play a key role in regulating the spontaneous activity of PCs, and in information transmission and integration in cerebellar cortex.

Properties of 4 Hz stimulation-induced parallel fiber-Purkinje cell presynaptic long-term plasticity in mouse cerebellar cortex in vivo.

Cerebellar parallel fiber-Purkinje cell (PF-PC) long-term synaptic plasticity is important for the formation and stability of cerebellar neuronal circuits, and provides substrates for motor learning and memory. We previously reported both presynaptic long-term potentiation (LTP) and long-term depression (LTD) in cerebellar PF-PC synapses in vitro. However, the expression and mechanisms of cerebellar PF-PC synaptic plasticity in the cerebellar cortex in vivo are poorly understood. In the present study, we studied the properties of 4 Hz stimulation-induced PF-PC presynaptic long-term plasticity using in vivo the whole-cell patch-clamp recording technique and pharmacological methods in urethane-anesthetised mice. Our results demonstrated that 4 Hz PF stimulation induced presynaptic LTD of PF-PC synaptic transmission in the intact cerebellar cortex in living mice. The PF-PC presynaptic LTD was attenuated by either the N-methyl-D-aspartate receptor antagonist, D-aminophosphonovaleric acid, or the group 1 metabotropic glutamate receptor antagonist, JNJ16259685, and was abolished by combined D-aminophosphonovaleric acid and JNJ16259685, but enhanced by inhibition of nitric oxide synthase. Blockade of cannabinoid type 1 receptor activity abolished the PF-PC LTD and revealed a presynaptic PF-PC LTP. These data indicate that both endocannabinoids and nitric oxide synthase are involved in the 4 Hz stimulation-induced PF-PC presynaptic plasticity, but the endocannabinoid-dependent PF-PC presynaptic LTD masked the nitric oxide-mediated PF-PC presynaptic LTP in the cerebellar cortex in urethane-anesthetised mice.

[Effect of bushen tiaojing recipe on the expressions of Smad1, Smad5, Smad8, and Smad4 in human mural granulosa cells].

OBJECTIVE: To explore the effect of Bushen Tiaojing Recipe (BTR) on the expressions of drosophila mothers against decapentaplegic protein (Smadl), Smad5, Smad8, and Smad4 on human mural granulosa cells. METHODS: Sixty-six patients undergoing in vitro fertilization-embryo transfer (IVF-ET) were randomly assigned to two groups in the ratio of 1:2, the treatment group and the control group. Twenty-three patients in the treatment group were treated with BTR and GnRHa/FSH/hCG, while forty-three patients in the control group were treated with GnRHa/FSH/hCG. The mRNA expressions of Smad1, Smad5, Smad8, and Smad4 on mural granulosa cells of the mature follicle were detected by real-time PCR on the ovum retrieval day. The expressions of Smad1, Smad5, Smad8, and Smad4 at the protein level were observed using cell immunofluorescence method. RESULTS: The mRNA and protein expressions of Smadl in the granulosa cells were significantly higher in the treatment group than in the control group (P <0.05). There was no statistical difference in the mRNA and protein expressions of Smad5, Smad8, and Smad4 between the two groups. CONCLUSION: The mechanisms of BTR for improving the pregnancy rate and the ovarian functions might be correlated with up-regulating mRNA and protein expressions of Smadl of human mural granulosa cells.

Unveiling ontogenesis of herbal medicine in plant chemical profiles by infrared macro-fingerprinting.

Given that harvesting time has a great impact on the quality of herbal medicine, knowing the ontogenesis in the chemical profile aspect is essential to determine the optimal harvesting season. A high-throughput and versatile approach (herbal infrared macro-fingerprinting) harmonizing with the character of herbal medicine and providing the whole chemical profile (entirety), group analogues (part), and single compounds (major components) is developed to rapidly disclose the variation rule of the full chemical profile of herbal medicine over a growing season without extraction pretreatments, and thus to determine the optimal harvesting period in respect to groups of chemical compounds using Scutellaria baicalensis as a demonstration. IR macro-fingerprints of Scutellaria baicalensis harvested in the same period have a high similarity (> 0.91) despite small variations, suggesting that IR macro-fingerprinting can faithfully reflect the spectacle of "disordered order" in nature. From Year-1 spring to Year-3 autumn, general contents (%, w/w) of total flavonoids fluctuate up and down with a maximum value in Year-2 spring, and that of saccharides is relatively stable except for the attenuation from Year-2 autumn to Year-3 spring. From Year-1 autumn to Year-2 spring, flavonoid aglycones initially produced in Scutellaria baicalensis are extensively transformed to responding flavonoid glycosides. From Year-2 spring to Year-3 autumn, flavonoid glycosides are converted back to their corresponding aglycones. The best seasons for collecting Scutellaria baicalensis with a high content of flavonoid glycosides and aglycones would be Year-2 spring and Year-3 spring, respectively.

[Effect of platelet-rich plasma on cell proliferation and osteogenic activity of pulp stem cells].

OBJECTIVE: To evaluate the effects of different concentrations of platelet-rich plasma (PRP) on human dental pulp stem cells (hDPSC) proliferation and osteogenic differentiation activity so as to provide basis for future application of dental pulp stem cells and PRP in tissue engineering and bone repair therapy. METHODS: hDPSC were isolated and cultivated in vitro. Flow cytometric analysis was carried out to test the expression of STRO-1.hDPSC were cultured in various concentrations of PRP (1%, 5%, 10%, 20%). At the 2nd and 6th day 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was tested. Osteogenic differentiation of hDPSC was assessed using alkaline phosphatase (ALP) staining and Alizarin Red staining at the 7th and 14th day. RESULTS: Flow cytometric analysis demonstrated that 14.82% of hDPSC were STRO-1 positive. One percent to 20% PRP showed significant effect of promoting hDPSC proliferation. One percent to 10% PRP showed significant effect of promoting hDPSC osteogenic differentiation. CONCLUSIONS: Certain concentrations of PRP can promote hDPSC proliferate and osteogenic differentiate, and this finding suggests future application of dental pulp stem cells and PRP in bone tissue engineering.

[Physiological ecology responses of Scutellaria baicalensis to drought and rewatering].

To study the physiological ecology responses of Scutellaria baicalensis to drought and rewatering of short period, we tested and analyzed photosynthesis and chlorophyll fluorescence parameters of S. baicalensis leaves processed by different ways of water treatment in drought and rewatering period, characteristic indexes of physiology and biochemistry of root SOD, POD, PAL, C4H, etc. and accumulation dynamic change of root baicalin and baicalein. The result showed that along with the worsening drought, P(n), T(r), G(s) and F(v)/F(m) of S. baicalensis declined in different water supply, and F(o) increased. The response of SOD and POD's activity in S. baicalensis root to drought in I and II was earlier than it in III. The response time and increase range of baicalin accumulation existed differences in different water supply, and the indexes regained after rewatering. Therefore, photosynthesis of S. baicalensis changed and it destroyed the antioxidant metabolism balance when soil water content decreased resulting from drought. The synergistic effect of defence mechanism launched by S. baicalensis, SOD, POD, PAL, C4H, baicalin and baicalein reduced active oxygen's damage to the cell.

[The effect of umbilical cord mesenchymal stem cell transplantation on interstitial pneumonitis in MRL/lpr mice].

OBJECTIVE: To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSCs) transplantation on interstitial pneumonitis in MRL/lpr mice. METHODS: Twenty four 18-week-old MRL/lpr female mice were randomly divided into 3 groups: the single dose group received a single dose of UC-MSCs (1 x 10(6)) transfusion intravenously, the 3 dose group received 3 injections of UC-MSCs (1 x 10(6)) weekly for 3 weeks, and the control mice were treated with saline. Both the control and the treated mice were sacrificed at 29 weeks. The histopathology of the lungs were assessed by HE staining. RESULTS: In comparison to the control mice, UC-MSCs transplantation significantly attenuated interstitial pneumonitis in the MRL/lpr mice. The peribronchiolar lesion indices of the single dose treatment group (1.40 +/- 0.24) and the 3 dose treatment group (1.02 +/- 0.29) were significantly decreased as compared to the control group (1.95 +/- 0.35), q = 0.551, 0.937, all P < 0.01. The perivascular lesion index of the single dose treatment group (1.20 +/- 0.18) and the 3 dose treatment group (1.08 +/- 0.16) were also significantly reduced as compared to the control group (1.56 +/- 0.32), q = 0.360, 0.479, P < 0.05, P < 0.01. The inflammatory cell infiltration index of the control group (1.72 +/- 0.34) was significantly increased compared to the single dose treatment group (1.30 +/- 0.21) and the 3 dose treatment group (1.05 +/- 0.15), q = 0.417, 0.673, P < 0.05, P < 0.01. CONCLUSIONS: These findings indicate that UC-MSCs have a pleiotropic therapeutic effect on pneumonitis in MRL/lpr mice.