[Nomographic Model for Predicting Severe Foot Pain in Nurses from Tertiary Hospitals in China].

Objective: To investigate the prevalence and common sites of severe foot pain among nurses, to define the risk factors of severe foot pain in nurses in tertiary hospital in China, and to construct a nomograph model for predicting individuals' risks for severe foot pain. Methods: Between August 2019 and December 2019, a stratified global sampling method was used to select 10691 nurses from 351 tertiary hospitals in China to investigate the incidence of severe foot pain among them. The variables that may affect the occurrence of severe foot pain were analyzed by single factor analysis to identify the influencing factors of severe foot pain in nurses. Furthermore, the independent risk factors of severe foot pain were analyzed by stepwise logistic regression analysis. The statistically significant factors identified in the multivariate regression analysis were incorporated into the nomograph prediction model. The predictive performance of the nomograph was measured by the consistency index (C-index) and calibrated with 1000 Bootstrap samples. Results: A total of 3419 nurses out of the 10691 had foot pain, resulting in an incidence of 31.98%. The incidence of severe pain (VAS score 7-10) was 2.27% (243 of 10691). The locations of severe pain were more commonly found in the soles and heels of both feet. Six factors, including age, education, the material of the work shoes, comfortableness of the work shoes, number of complications, and foot injure history, were incorporated in the nomograph predicting model. The C-index value was 0.706 and the standard curve fitted well with the calibrated prediction curve. Conclusion: The risk prediction model constructed in this study showed sound performance in predicting the risk of severe foot pain in nurses, and all the indicators involved are simple and the relevant data are easily obtained. The model can provide reference for preventing severe foot pain in nurses.

[Effect of Tongdu Tiaoshen acupuncture on CREB/BDNF/TrkB signaling pathway of hippocampus in rats with post-stroke depression].

OBJECTIVE: To observe the regulative effect of Tongdu Tiaoshen acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD. METHODS: A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area. RESULTS: Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (P<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (P<0.05), MDA level in hippocampal CA1 area was increased in the model group (P<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (P<0.05), MDA level was decreased in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (P<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.

An Endo-Selective Epoxide-Opening Cascade for the Fast Assembly of the Polycyclic Core Structure of Marine Ladder Polyethers.

The rapid synthesis of marine ladder polyethers from polyepoxide precursors (in analogy with the biosynthetic pathway hypothesized by Nakanishi) is hampered by the fact that the exo-selective epoxide-opening cyclization cascade that gives THF-type polyethers is preferred over the endo-selective cascade that gives the desired products. We found that perfluoro-tert-butanol (PFTB) cooperating with 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM]BF4 ) can promote endo-selective epoxide-opening cyclization reactions of trisubstituted epoxy alcohols. Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all the endo-cyclization sites, we were able to construct polyethers up to five consecutive fused 6-, 7-, and/or 8-membered rings in one step. Notably, molecules with the 7/7/6/6 and 7/7/6/7/6 polyether frameworks of hemibrevetoxin B and brevenal, respectively, could be synthesized in 40 % and 17 % chemical yields.

[Effect of Tongdu Tiaoshen acupuncture on PI3K/Akt/mTOR signaling pathway and autophagy-related proteins of hippocampus in rats with post-stroke depression].

OBJECTIVE: To observe the improvement of Tongdu Tiaoshen acupuncture on depression-like behavior in rats with post-stroke depression (PSD), and to explore its possible mechanism. METHODS: A total of 48 SD rats were randomized into a sham-operation group, a model group, a Tongdu Tiaoshen group and a non-meridian-non-acupoint group, 12 rats in each group. In the the model group, the Tongdu Tiaoshen group and the non-meridian-non-acupoint group, PSD model was established by the compound method of cerebral medial arterial occlusion, chronic unpredictable mild stress and isolation. Acupuncture was applied at "Dazhui"(GV 14), "Shuigou"(GV 26), "Baihui"(GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, and at the bilateral dorsum hollows between 3rd and 4th metatarsal bones of the forelegs in the non-meridian-non-acupoint group, needles were retained for 40 min in the both groups, once a day, 6 times a week for 4 weeks. Before model establishment and after intervention, the ethology indice of Zea Longa neurological behavioral score, open-field test and sucrose preference test were evaluated in the 4 groups. The levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), Beclin1 and LC3B-Ⅱ/Ⅰin the CA1 region of hippocampus were detected by western blot. The expressions of Beclin1, LC3B-ⅡmRNA in the CA1 region of hippocampus were detected by real-time PCR. RESULTS: After model established, compared with the sham-operation group, the Zea Longa neurological behavioral scores were increased (P<0.05), the scores of horizontal and vertical motion of the open-field test and the consumption of sucrose solution were decreased in the model group, the Tongdu Tiaoshen group and the non-meridian-non-acupoint group (P<0.05). After intervention, compared with the sham-operation group, the Zea Longa neurological behavioral score, the expression of Beclin1, LC3B-Ⅱ/Ⅰ and LC3B-Ⅱin the CA1 region of hippocampus were increased (P<0.05), the scores of horizontal and vertical motion of the open-field test, the consumption of sucrose solution and the expression of PI3K, p-Akt and p-mTOR were decreased in the model group (P<0.05). After intervention, compared with the model group and the non-meridian-non-acupoint group, the Zea Longa neurological behavioral score, the expression of Beclin1, LC3B-Ⅱ/Ⅰ and LC3B-Ⅱin the CA1 region of hippocampus were decreased (P<0.05), the scores of horizontal and vertical motion of the open-field test, the consumption of sucrose solution and the expression of PI3K, p-Akt and p-mTOR were increased in the Tongdu Tiaoshen group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture can effectively improve the depression-like behavior in PSD rats, its mechanism may relate to the activation of PI3K/Akt/mTOR signaling pathway and the inhibition of hippocampal neuron autophagy.

NAC-Like Gene GIBBERELLIN SUPPRESSING FACTOR Regulates the Gibberellin Metabolic Pathway in Response to Cold and Drought Stresses in Arabidopsis.

To investigate the functions of NAC-like genes, we reported the characterization and functional analysis of one Arabidopsis NAC-like gene which showed a novel function in the regulation of gibberellin biosynthesis and named as GIBBERELLIN SUPPRESSING FACTOR (GSF). GSF acts as a transcriptional activator and has transactivation capacity based on yeast transcription activity assays. YFP + GSF-TM (lacking a transmembrane domain) fusion proteins accumulated in the nuclei, while the YFP + GSF fusion proteins only accumulated in the ER membrane and were absent from the nuclei. These results revealed that GSF requires processing and release from the ER and transportation into the nucleus to perform its function. The ectopic expression of GSF-TM caused a dwarfism phenotype, which was correlated with the upregulation of the gibberellin (GA) deactivation genes GA2-oxidases 2/6 (GA2ox2/6) and the downregulation of the GA biosynthetic genes GA20-oxidases 1-4 (GA20ox1-4). The external application of GA rescued the dwarfism in the 35 S::GSF-TM plants, indicating that GSF affects GA biosynthesis, rather than the GA signaling pathway. Further analysis indicated that the upregulation of GA2ox2/6 is a key factor for the GSF function to regulate the GA level, since 35 S::GA20ox1 could not rescue the dwarfism in the 35 S::GSF-TM plants. Cold treatment induced the processing of the YFP + GSF fusion proteins from the ER membrane and their entry into the nuclei, which is correlated with the cold-induced upregulation of GA2oxs. In addition, the expression of GA2oxs was induced by drought, and the 35 S::GSF-TM plants showed drought tolerance compared to the wild-type plants. Our data suggest a role for GSF in response to abiotic stresses, such as cold and drought, by suppressing the biosynthesis of GA in Arabidopsis.

[Protective effects on hippocampal neurons and the influence on hippocampal monoamine neurotransmitters with acupuncture for promoting the circulation of the governor vessel and regulating the mental state in rats with post-stroke depression].

OBJECTIVE: To observe the effects on hippocampal neuronal structure and hippocampal monoamine neurotransmitters such as norepinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) with acupuncture for promoting the circulation of the governor vessel and regulating the mental state (Tongdu Tiaoshen acupuncture) in rats with post-stroke depression and explore the underlying effect mechanism of Tongdu Tiaoshen acupuncture on post-stroke depression. METHODS: A total of 48 clean-grade SD rats were randomized into a sham-operation group, a model group, a Tongdu Tiaoshen acupuncture group and a non-meridian-non-acupoint group, 12 rats in each one. In the model group, the Tongdu Tiaoshen acupuncture group and the non-meridian-non-acupoint group, the compound method of cerebral medial arterial occlusion and the chronic unpredictable mild stress was adopted to prepare the model of post-stroke depression. In the sham-operation group, skin was opened and the fascia muscle was separated, after artery exposed, no ligation was operated and the incision was sutured directly. In the sham-operation group and the model group, no any intervention was performed. In the Tongdu Tiaoshen acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Shuigou" (GV 26), "Shenting" (CV 24) and "Dazhui" (GV 14) for 40 min in each treatment and the needles were manipulated at the acupoints once in 20 min. The treatment was given once a day, 6 times a week for 4 weeks consecutively. In the non-meridian-non-acupoint group, the depression between the 3rd and 4th metatarsal bones on the dorsum of the forelimb was selected in intervention and the needling technique was same as the Tongdu Tiaoshen acupuncture group. The behavioral changes were observed after intervention in each group. Using transmission electron microscopy, the ultrastructure of hippocampal CA 1 neurons was observed in the rats of each group. Using high performance liquid chromatography, the contents of NE, 5-HT and DA were determined. RESULTS: Compared with the sham-operation group, the Zea-longa neurobehavioral score was increased (P<0.01), the sucrose water consumption was reduced (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were reduced (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was aggravated and the contents of NE, 5-HT and DA were reduced in the model group (P<0.01). Compared with the model group, the Zea-Longa neurobehavioral score was reduced (P<0.01), the sucrose water consumption was increased (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (P<0.01, P<0.05). Compared with the non-meridian-non-acupoint group, the Zea-Longa neurobehavioral score was reduced (P<0.01), the sucrose water consumption was increased (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (P<0.01, P<0.05). CONCLUSION: The Tongdu Tiaoshen acupuncture improves the behavior of the model rats with post-stroke depression, repairs hippocampal neuronal damage, which is probably related to the contents of hippocampal monoamine neurotransmitters (NE, 5-HT and DA).

FOREVER YOUNG FLOWER Negatively Regulates Ethylene Response DNA-Binding Factors by Activating an Ethylene-Responsive Factor to Control Arabidopsis Floral Organ Senescence and Abscission.

In this study of Arabidopsis (Arabidopsis thaliana), we investigated the relationship between FOREVER YOUNG FLOWER (FYF) and Ethylene Response DNA-binding Factors (EDFs) and functionally analyzed a key FYF target, an Ethylene-Responsive Factor (ERF), that controls flower senescence/abscission. Ectopic expression of EDF1/2/3/4 caused promotion of flower senescence/abscission and the activation of the senescence-associated genes. The presence of a repressor domain in EDFs and the enhancement of the promotion of senescence/abscission in EDF1/2/3/4+SRDX (converting EDFs to strong repressors by fusion with the ERF-associated amphiphilic repression motif repression domain SRDX) transgenic plants suggested that EDFs act as repressors. The significant reduction of ß-glucuronidase (GUS) expression by 35S:FYF in EDF1/2/3/4:GUS plants indicates that EDF1/2/3/4 functions downstream of FYF in regulating flower senescence/abscission. In this study, we also characterized an ERF gene, FOREVER YOUNG FLOWER UP-REGULATING FACTOR1 (FUF1), which is up-regulated by FYF during flower development. Ectopic expression of FUF1 caused similar delayed flower senescence/abscission as seen in 35S:FYF plants. This phenotype was correlated with deficient abscission zone formation, ethylene insensitivity, and down-regulation of EDF1/2/3/4 and abscission-associated genes in 35S:FUF1 flowers. In contrast, significant promotion of flower senescence/abscission and up-regulation of EDF1/2/3/4 were observed in 35S:FUF1+SRDX transgenic dominant-negative plants, in which FUF1 is converted to a potent repressor by fusion to an SRDX-suppressing motif. Thus, FUF1 acts as an activator in suppressing EDF1/2/3/4 function and senescence/abscission of the flowers. Our results reveal that FYF regulates flower senescence/abscission by negatively regulating EDF1/2/3/4, which is the downstream gene in the ethylene response, by activating FUF1 in Arabidopsis.

Hot water-promoted cyclopropylcarbinyl rearrangement facilitates construction of homoallylic alcohols.

In refluxing 9 : 1 (v/v) H2O-1,4-dioxane and without an additional catalyst, the rearrangements of various types of cyclopropyl carbinols were attempted. It was found that the reactions generally gave homoallylic alcohols in good to very high chemical yields. Rearrangements of bicyclic or tricyclic cyclopropyl carbinols readily gave the desired ring-expanded cyclic homoallylic alcohols which are difficult to synthesize by other means.

1,n-Rearrangement of allylic alcohols promoted by hot water: application to the synthesis of navenone B, a polyene natural product.

It was reported for the first time that hot water as a mildly acidic catalyst efficiently promoted 1,n-rearrangement (n = 3, 5, 7, 9) of allylic alcohols. In some cases, the rearrangement reactions joined isolated C-C double or triple bonds to generate conjugated polyene or enyne structure motifs. We used the 1,3-rearrangement reaction of an allylic alcohol in hot water as part of an attractive new strategy for construction of the polyene natural product navenone B by iterative use of a Grignard reaction, a 1,3-rearrangement of the resulting allylic alcohol, and subsequent oxidation of the rearranged product.

[Involvement of Wnt/ß-catenin signaling in the osteogenesis of bone marrow mesenchymal stem cells induced by drynaria total flavonoids].

OBJECTIVE: To explore the effects of the expression of Wnt/ß-catenin signaling factor mRNA during drynaria total flavonoids on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: The BMSCs were isolated from SD rats by whole bone marrow culture method and purified by passage. And the P3 BMSCs were intervened with 100 µg/ml drynaria total flavonoids. At Day 21, mineralized staining was performed. At Days 7, 14, 21 and 28 post-intervention, the activity of alkaline phosphatase (ALP) was detected and polymerase chain reaction (PCR) used to detect the expressions of Wnt/ß-catenin signaling pathway related factors ß-catenin, LEF-1 and cycline D mRNA. RESULTS: At each time point post-intervention, comparing the ALP activity in cell supernatant between two group, the drynaria total flavonoids group was higher than the blank control group (7 d: 11.10 ± 0.08 vs 1.61 ± 0.14; 14 d: 24.62 ± 0.34 vs 1.64 ± 0.04; 21 d: 18.41 ± 0.06 vs 1.53 ± 0.04; 28 d: 14.9 ± 0.14 vs 1.52 ± 0.04; all P < 0.01). At Day 21, upon staining with alizarin red, the drynaria total flavonoids group was positive while the blank control group negative. At Day 14, the expression of ß-catenin mRNA was higher in the drynaria total flavonoids group higher than that in the blank control group (0.357 ± 0.063 vs 0.174 ± 0.013, P < 0.05). At Day 7, the expressions of LEF-1 and cycline D mRNA were higher in the drynaria total flavonoids group than those in the blank control group (LEF-1 0.0611 ± 0.0002 vs 0.0345 ± 0.0131; cycline D 0.1510 ± 0.0255 vs 0.0718 ± 0.0294, all P < 0.05). CONCLUSION: Drynaria total flavonoids induce BMSCs to differentiate into osteoblasts. And it is accompanied with the altered expression of Wnt/ß-catenin signaling pathway related factor mRNA.

Two concise enantioselective total syntheses of (-)-glabrescol implicate alternative biosynthetic pathways starting from squalene.

The C(2)-symmetric (-)-glabrescol was synthesized in two steps from (10S,11R)-dihydroxy-10,11-dihydrosqualene or squalene with 50% or 10% overall yields, respectively. These highly efficient and biomimetic syntheses employed a base-promoted middle-to-terminal double epoxide-opening cascade, which constructs the five tetrahydrofuran rings in glabrescol in one operation.

[Effect of soothing liver and invigorating spleen recipes on SREBP-1c mRNA and protein expression in hepatic tissues of rats with non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the effects of soothing liver and invigorating spleen recipes on expression levels of Sterol Regulatory Element-binding Protein-1c (SREBP-1c) mRNA and SREBP-1c protein in hepatic tissue of rats with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty-five SD rats were randomized into 5 groups: normal control group, model group, soothing liver group, invigorating spleen group and combination group. Except the normal group, the rats in model group and other treatment groups were fed with high-fat emulsion to induce NAFLD. The treatment groups were administered with respective traditional chinese medicine, the normal group and model group received correspondence volume distilled water. After treatment for 8 weeks, the rats were executed to obtain the liver for observing hepatic pathological changes. Expression levels of SREBP-1c mRNA and SREBP-1c protein in hepatic tissues were assayed using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. RESULTS: Compared with the normal group, the expression level of SREBP-1c mRNA and SREBP-1c protein in rat hepatic tissues of model group was significantly increased (P<0.01). Compared with the model group,the expression levels of SREBP-1c mRNA and SREBP-lc protein in the treated groups was decreased (P<0.01, P<0.05). Specially, expression levels of SREBP-1c mRNA were the lowest in soothing liver group and invigorating spleen group and hepatic fatty changes were the slightest. CONCLUSION: Soothing liver and invigorating spleen recipes can inhibit hepatic SREBP-1c expression. That may be one of their therapeutic mechanisms.

[Simple analysis on professor ZHANG Dao-Zong's academic thought of dredging the Governor Vessel and regulating mentality].

Introduce Professor Zhang Dao-zong's studies on the Governor Vessel and its academic thought of dredging the Governor Vessel and regulating mentality, and clinical experiences of dredging the Governor Vessel and regulating mentality therapy for apoplexy, epilepsy, vertigo, ankynosing spondylitis, traumatic paraplegia, child Tourette's disease, etc....