[Urine metabolomics study of intervention of Xihuang Pills in rats with hyperplasia of mammary gland].

This study aimed to investigate the mechanism of Xihuang Pills in improving hyperplasia of mammary gland(HMG) in rats based on urine metabolomics using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS). The HMG rat model was established by intramuscular injection of estradiol benzoate solution(0.5 mg·kg~(-1), 25 days) followed by progesterone injection(5 mg·kg~(-1), 5 days). UPLC-Q-Orbitrap-MS technology was used to establish the endogenous small-molecule metabolic profiles in urine samples of rats in the blank group, the HMG model group, and Xihuang Pills group. Multivariate statistical analysis was performed for pattern recognition, t test and variable importance in the projection(VIP) were used to screen potential biomarkers. The significantly changed differential metabolites were identified using the online database Human Metabolome Database(HMDB). Metabolic pathway enrichment analysis was conducted using the MetaboAnalyst 5.0 database. The results showed that 90 differential metabolites with significant changes(P<0.05) were identified between the blank group and the HMG model group using the HMDB. Among them, 48 metabolites significantly reverted(P<0.05) after administration of Xihuang Pills, which may be related to the regulatory effect of Xihuang Pills. Thirteen metabolic pathways significantly associated with HMG were identified when the differential metabolites were imported into the MetaboAnalyst 5.0 database, and Xihuang Pills could modulate seven of these pathways. These metabolic pathways mainly involved histidine metabolism, arginine and proline metabolism, ß-alanine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, pyrimidine metabolism, and amino sugar and nucleotide sugar metabolism. This study utilized UPLC-Q-Orbitrap-MS and urine metabolomics technology to analyze the mechanism of Xihuang Pills in improving HMG, laying the foundation for further in-depth research.

Characterization of changes in the intestinal microbiome following combination therapy with zinc preparation and conventional treatment for children with rotavirus enteritis.

Background: Rotavirus (RV) is one of the most common pathogens causing diarrhea in infants and young children worldwide. Routinely, antiviral therapy, intestinal mucosa protection, and fluid supplementation are used in clinic, however this is not efficacious in some severe cases. Zinc supplementation has previously been shown to improve resolution of symptoms from infectious diarrhea. Methods: In this study differences in response rate, duration of hyperthermia, vomiting, and diarrhea, and the persistence time of cough and lung rales in groups were compared. 16SrDNA gene sequencing technology was used to analyze and compare changes in the intestinal microflora of children with RV enteritis who received the conventional treatment with or without the zinc preparation. In addition, the correlations between the differential bacterial species and the related inflammatory factors were determined. Results: Conventional therapy combined with the zinc preparation significantly shortened the duration of hyperthermia, vomiting, and diarrhea compared with the conventional treatment alone. In addition, the time to symptom relief showed that the absorption time of cough and lung rales was significantly shorter in the combination treatment group than that in the conventional treatment group in the children with pneumonia. Further, compared with the conventional treatment, the combined treatment significantly increased the diversity and abundances of florae as compared with the conventional treatment. This combination therapy containing zinc preparation markedly increased the abundances of Faecalibacterium, Bacteroidales, Ruminoccoccoccus, and Lachnospiraceae at the genus level. The LEfSe analysis suggested that Clostridiumbolteae were most significantly altered after the combination therapy. In addition, a correlation analysis revealed significantly negative correlations between the inflammatory factors especially IL-6, TNF-a, CRP and some intestinal florae such as Bacteroides, Faecalibacterium, Blautia, Parabacteroides, Subdoligranulum, and Flavonifractor. Conclusion: Compared with the conventional therapy alone, the combined therapy with the zinc preparation significantly improves symptoms caused by RV. The combination therapy containing the zinc preparation significantly increases the diversity and abundances of some beneficial groups of bacteria. Further, The presence of these groups was further negatively correlated with relevant inflammatory factors. More importantly, this combination therapy containing the zinc preparation provides a reference for the clinical management of children with RV enteritis.

Aikeqing, a kidney- and spleen-tonifying compound Chinese medicine granule, prevented ovariectomy-induced bone loss in rats via the suppression of osteoclastogenesis.

Postmenopausal women are prone to osteoporosis due to increased osteoclast activation and bone resorption caused by oestrogen deficiency. In Traditional Chinese Medicine theory, medicines with spleen- and kidney-nourishing effects are commonly used in postmenopausal osteoporosis (PMOP) treatment. Aikeqing (AKQ) is a compound Chinese medicinal granule with spleen- and kidney-nourishing effects. Herein, we investigate the in vitro and in vivo anti-osteoporotic effects of AKQ, its underlying mechanisms and pharmacodynamic basis. In vitro antiosteoporotic effects of AKQ were assessed by its ability to promote osteoblastogenesis in MC3T3-E1 and/or inhibit RANKL-induced osteoclastogenesis in murine bone marrow monocytes (BMMs). The protective effect of AKQ on bone loss induced by oestrogen deficiency was evaluated in ovariectomized rats. The underlying mechanisms were studied in BMMs by detecting the effects of AKQ on the RANKL-induced expression of genes and proteins involved in the regulation of osteoclastogenesis. The main chemical constituents of AKQ in the granule were analyzed by UPLC-QTOF-MS. Our findings show that AKQ did not affect osteoblastogenesis, but it inhibited RANKL-induced osteoclastogenesis. In the ovariectomized rats, oral administration of AKQ (4 g/kg/d) for 90 d effectively prevented oestrogen deficiency-induced bone loss. Mechanistic studies in BMMs revealed that AKQ inhibited RNAKL-induced activation of NF-κB (p65) and MAPKs (p38 and JNK) via blocking the RANK-TRAF6 interaction, subsequently suppressing the translocation and expression of NFATc1 and c-Fos. UPLC-QTOF-MS analysis quantified the 123 main components of AKQ. Taken together, AKQ was demonstrated for the first time as a novel alternative therapy for osteoclast-associated bone diseases.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

BACKGROUND: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. OBJECTIVE: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. METHOD: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameter ≤10µm (PM10), sulfur dioxide (SO2), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. RESULTS: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of PM2.5, PM10, SO2 and CO were the 21th to 24th weeks of pregnancy. Every 10-µg/m3 increase in PM2.5 and PM10, 5-µg/m3 increase in SO2, and 0.1-mg/m3 increase in CO was associated with low maternal hemoglobin levels [-0.94g/L (95% confidence interval (CI): -1.15, -0.73), -1.31g/L (95% CI: -1.55, -1.07), -2.96g/L (95% CI: -3.32, -2.61), and -1.11g/L (95% CI: -1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. CONCLUSIONS: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

[Mechanism of blood-activating and mass-dissipating Chinese patent medicine against hyperplasia of mammary glands and use with other medicine: a review].

Caused by endocrine disorder, hyperplasia of mammary glands(HMG) tends to occur in the young with increasing incidence, putting patients at the risk of cancer and threatening the health of women. Therefore, the prevention and treatment of HMG is attracting more and more attention. Amid the modernization of traditional Chinese medicine(TCM), many scholars have found that Chinese patent medicine has unique advantages and huge potential in treatment of endocrine disorder. Particularly, Chinese patent medicine with the function of blood-activating and mass-dissipating, such as Xiaojin Pills and Xiaozheng Pills, has been commonly used in clinical treatment of HMG, which features multiple targets, obvious efficacy, small side effect, and ease of taking and carrying around. Clinical studies have found that the combination of Chinese patent medicine with other medicine can not only improve the efficacy and relieve symptoms such as hyperplasia and pain but also reduce the toxic and side effects of western medicine. Therefore, based on precious pharmacological research and clinical research, this study reviewed the mechanisms of blood-activating mass-dissipating Chinese patent medicine alone and in combination with other medicine, such as regulating levels of in vivo hormones and receptors, promoting apoptosis, inhibiting angiogenesis, improving hemorheology indexes, enhancing immunity, and boosting antioxidant ability. In addition, limitations and problems were summarized. Thereby, this study is expected to lay a theoretical basis for the further study and clinical application of blood-activating mass-dissipating Chinese patent medicine alone or in combination with other medicine against HMG.

[Mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering component based on UPLC-Q-TOF-MS and network pharmacology].

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.

Antibiotic-impregnated calcium sulfate for the treatment of pediatric hematogenous osteomyelitis.

BACKGROUND: Antibiotic-impregnated calcium sulfate has excellent curative efficacy in chronic osteomyelitis. However, its curative efficacy in pediatric hematogenous osteomyelitis has not been sufficiently studied. The purpose of this study was to evaluate the curative effects of antibiotic-impregnated calcium sulfate in the treatment of pediatric hematogenous osteomyelitis. METHODS: Overall, twenty-one pediatric patients with hematogenous osteomyelitis treated at our hospital between 2013 and 2018 were included for assessment. The clinical history, clinical manifestation, infection recurrence rate, sinus leakage, incision leakage, pathological fractures, bone growth and surgical procedures were analyzed. RESULTS: The infection recurrence rate was 0% (0/21) at a minimum of 31 months (range 31 to 91 months) of follow-up. Postoperative incision leakage was found in one pediatric patient. Osteolysis was found in one pediatric patient. Acceleration of bone growth occurred in one pediatric patient. Retardation of bone growth occurred in one pediatric patient. Genu valgus deformity occurred in one pediatric patient. CONCLUSIONS: Although noninfectious complications occurred, the curative effect of antibiotic-impregnated calcium sulfate in pediatric hematogenous osteomyelitis was satisfactory.

Development of precocious puberty in children: Surmised medicinal plant treatment.

Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious puberty has significantly increased globally. Precocious puberty negatively affects the physical and mental health of children and may increase the risk of hypertension, diabetes, obesity and infertility in adulthood. Therefore, the initiating factors of adolescence have become core issues in the study of sexual development in children. Owing to developments in molecular genetics, many studies have been able to show that precocious puberty is mostly resulted in autosomal inheritance. For instance, makorin ring finger protein 3 gene (MKRN3) may be implicated in familial CPP. Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard for treatment, but its safety still requires long-term evaluation and management. Traditional medicinal plants have been used in clinical treatments and in exploring novel treatment methods. From the collected datas, in Asia, traditional Chinese medicine treatment is based on the principles of nourishing Yin, lowering fire and draining fire from the liver to help precocious children and alleviate or delay the onset of precocious puberty by medicinal plants such as Anemarrhena asphodeloides Bge., Phellodendron amurense Rupr., Rehmannia glutinosa and Poria cocos Wolf. They play an important role in exploring the pharmacological mechanisms of precocious puberty treatment effects and drug development. Therefore, by elucidating the occurrence and development of precocious puberty, this review provides novel and valuable insights of paediatric endocrine therapy accessing the published researches on the effectiveness of traditional herbal medicine in the treatment of precocious puberty and its therapeutic mechanisms.

Effectiveness of Aromatherapy Yoga in Stress Reduction and Sleep Quality Improvement among Chinese Female College Students: A Quasi-Experimental Study.

College students, particularly female students, often suffer from severe stress and poor sleep. Aromatherapy yoga has become a popular exercise in recent years and may help reduce stress and improve sleep quality, although empirical evidence is limited. We investigated the effectiveness of aromatherapy yoga intervention in reducing stress and improving sleep quality among Chinese female college students. A total of 89 participants-44 in the experimental group (aromatherapy yoga) and 45 in the control group (yoga)-with an average age of 19.88 ± 1.13 years, were enrolled in this quasi-experimental study. Interventions were performed in the respective groups once a week for 12 weeks, for 90 min each time. The Wilcoxon signed-rank test and Mann-Whitney U test (including effect size) were used to test the differences in stress reduction and sleep quality before and after the intervention. From the findings of the current research, both therapies did not help female students' stress levels or sleep hygiene significantly. However, aromatherapy yoga has the potential to improve sleep disturbances experienced by female college students. Additionally, there was no difference in the amount of stress or the quality of sleep between the aromatherapy yoga groups and the regular yoga groups before and after therapy.

Mechanisms of Xiong-Pi-Fang in treating coronary heart disease associated with depression: A systematic pharmacology strategy and in vivo pharmacological validation.

BACKGROUND: Coronary heart disease (CHD) and depression are very common and often co-existing disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating CHD associated with depression. However, its mechanism of action is still unknown. PURPOSE: To employ a systematic pharmacology approach for identifying the action mechanisms of XPF in treating CHD associated with depression. METHODS: We used a systematic pharmacology approach to identify the potential active mechanisms of XPF in treating CHD with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. RESULTS: Network pharmacology predicted 42 key targets and 20 signaling pathways involved in XPF-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic-pituitary-adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing CHD within the depression model in rats. In addition, XPF intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, XPF exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression. CONCLUSIONS: Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of XPF against CHD with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for CHD therapy with depression.

Combination of Ligustri Lucidi Fructus with Ecliptae Herba and their phytoestrogen or phytoandrogen like active pharmaceutical ingredients alleviate oestrogen/testosterone-induced benign prostatic hyperplasia through regulating steroid 5-α-reductase.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a urinary system disease with high prevalence among the middle and elder men. In BPH, proliferation of prostate cells and the imbanlance between androgen and estrogen are both important inducers. Previous studies have demonstrated that compounds from Ligustri Lucidi Fructus (LLF) and Ecliptae Herba (EH) are of phytoestrogenic or phytoandrogenic activities. The combination of LLF with EH at the ratio of 1:1 on crude drugs quantity is called Erzhi formula (EZF), which is used for in vivo research of our study. PURPOSE: This study aimed to investigate potential mechanisms of EZF and its active pharmaceutical ingredients on BPH in vitro and in vivo. METHODS: Therapeutic effects of EZF was evaluated in E2/testosterone (1:100) induced BPH rats model. The pathological changes of prostate, concentrations of testosterone, DHT, E2, PSA in rats' plasma and prostate were detected. The expressions of PCNA, AR, ERα, ERß, SRD5A1, SRD5A2 were measured in BPH rat prostates and E2-stimulated human benign prostatic epithelial cells (BPH-1). RESULTS: EZF treatment significantly attenuated rat prostate enlargement, alleviated BPH pathological features, and decreased the expression of PCNA. The up-regulation of AR, ERα, SRD5A1/2 expressions, and down-regulation of ERß expression at prostate of rat BPH model were significantly blocked by EZF administration. The expression levels of testosterone, DHT, E2, PSA were strongly inhibited by EZF treatment. At the cellular level, ligustrosidic acid and echinocystic acid inhibited E2-induced BPH-1 cell proliferation and PCNA expressions, which were consistent with the results in vivo. And these two ingredients also down-regulated the expressions of AR, ERα, SRD5A1/2 and up-regulated the expression of ERß in BPH-1 cells. CONCLUSION: EZF, ligustrosidic acid from LLF and echinocystic acid from EH showed inhibitive effects on BPH via down-regulating prostatic AR, ERα, SRD5A1/2 expressions and up-regulating ERß expression.

Mechanisms of Lian-Gui-Ning-Xin-Tang in the treatment of arrhythmia: Integrated pharmacology and in vivo pharmacological assessment.

BACKGROUND: Lian-Gui-Ning-Xin-Tang (LGNXT), a classical traditional Chinese medicine (TCM) formula, has been widely used in clinical practice and has shown satisfactory efficacy in the treatment of arrhythmias. However, its mechanism of action in the treatment of arrhythmias is still unknown. Moreover, the complex chemical composition and therapeutic targets of LGNXT pose a challenge in pharmacological research. PURPOSE: To analyze the active compounds and action mechanisms of LGNXT for the treatment of arrhythmias. METHODS: Here, we used an integrated pharmacology approach to identify the potential active compounds and mechanisms of action of LGNXT in treating arrhythmias. Potential active compounds in LGNXT were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and the potential related targets of these compounds were predicted using an integrated in silico approach. The obtained targets were mapped onto relevant databases to identify their corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. RESULTS: Eighty-three components were identified in herbal materials and in animal plasma using UPLC-Q-TOF/MS and were considered the potential active components of LGNXT. Thirty key targets and 57 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified as possible targets and pathways involved in LGNXT-mediated treatment using network pharmacology, with the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/Ca2+ system pathway being the most significantly affected. This finding was validated using an adrenaline (Adr)-induced rat model of arrhythmias. Pretreatment with LGNXT delayed the occurrence, shortened the duration, and reduced the severity of arrhythmias. LGNXT exerted antiarrhythmic effects by inhibiting cAMP, PKA, CACNA1C, and RyR2. CONCLUSIONS: The findings of this study revealed that preventing intracellular Ca2+ overload and maintaining intracellular Ca2+ homeostasis may be the primary mechanisms of LGNXT in alleviating arrhythmias. Thus, we suggest that the ß-adrenergic receptor (AR)/cAMP/PKA/Ca2+ system signaling hub may constitute a promising molecular target for the development of novel antiarrhythmic therapeutic interventions. Additionally, we believe that the approach of investigation of the biological effects of a multi-herbal formula by the combination of metabolomics and network pharmacology, as used in this study, could serve as a systematic model for TCM research.

The role of parathyroid hormone during pregnancy on the relationship between maternal vitamin D deficiency and fetal growth restriction: a prospective birth cohort study.

Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted ß = -49·4 g, 95 % CI -91·1, -7·8, P < 0·05; for severe VDD: adjusted ß = -79·8 g, 95 % CI -127·2, -32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted ß = -44·5 g, 95 % CI -82·6, -6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted ß = -124·7 g, 95 % CI -194·6, -54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.

Extensive eggshell-like debridement technique plus antibiotic-loaded calcium sulphate for one-stage treatment of chronic calcaneal osteomyelitis.

BACKGROUND: Management of chronic calcaneal osteomyelitis is challenging. At present, there is still no widely accepted, simple, and effective surgical method to eradicate the infection and prevent osteomyelitis recurrence. The objective of this study was to assess the outcomes of one-stage treatment of chronic calcaneal osteomyelitis with a shape-preserving debridement technique combined with antibiotic-loaded calcium sulphate. METHODS: Between 2012 and 2018, 33 patients (33 limbs) with chronic calcaneal osteomyelitis were treated with a novel debridement technique, named "eggshell-like debridement", plus antibiotic-impregnated calcium sulphate. The infection remission rate, recurrence rate, and amputation rate were analyzed. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to assess postoperative hindfoot function. RESULTS: 26 patients (81.8%) achieved infection remission without recurrence. In the patients with osteomyelitis remission, pain, limitation of movement, sinus tracts, and typical redness and swelling were generally eliminated. Most of the patients could tolerate full weight-bearing without pain. The average AOFAS ankle and hindfoot score was 88 points (range, 67-100 points), implying the foot function was mostly restored. 6 patients (18.2%) had osteomyelitis recurrence but no amputation was required to elimilate the infection. CONCLUSIONS: Eggshell-like debridement combined with antibiotic-loaded calcium sulphate is an effective method for one-stage management of chronic calcaneal osteomyelitis. With the application of this technique, secondary autogenous bone or muscle flap grafts are unnecessary. The surgical procedure can be simplified whlie the hindfoot function is well preserved.

The association of vitamin D status and supplementation during pregnancy with gestational diabetes mellitus: a Chinese prospective birth cohort study.

BACKGROUND: Previous studies have shown conflicting findings regarding the relation of vitamin D status and supplementation during pregnancy with gestational diabetes mellitus (GDM). Most of these studies hypothesized that 25-hydroxyvitamin D [25(OH)D] concentrations were associated with GDM risk and glucose metabolism based on linear association models. OBJECTIVES: We aimed to estimate the associations of 25(OH)D concentrations and vitamin D supplementation with GDM risk and glucose metabolism and determine the threshold concentrations of 25(OH)D that could significantly affect glucose metabolism and GDM risk. METHODS: In a prospective birth cohort study, we collected information about sociodemographic characteristics, health status, and lifestyle from 4984 pregnant women. Vitamin D supplementation and 25(OH)D concentrations were assessed in the second trimester. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. RESULTS: A total of 922 (18.5%) women were diagnosed with GDM. Compared with women with 25(OH)D concentrations <25 nmol/L, the GDM risk was significantly lower in women with 25(OH)D concentrations ranging from 50 to 75 nmol/L (RR: 0.74; 95% CI: 0.58, 0.95) and >75 nmol/L (RR: 0.40; 95% CI: 0.22, 0.70). The curve-fitting models suggested a significant large reduction in GDM risk, fasting plasma glucose, and area under the curve of glucose with increasing 25(OH)D concentrations only for concentrations >50 nmol/L. Consistently, GDM risk was significantly reduced only in women who took 400-600 IU vitamin D/d (RR: 0.83; 95% CI: 0.70, 0.97) with a mean 25(OH)D concentration of 50 nmol/L but not in women taking vitamin D sometimes with a mean 25(OH)D concentration of 40 nmol/L. CONCLUSIONS: GDM risk was significantly reduced only in pregnant women with 25(OH)D concentrations >50 nmol/L. Pregnant women taking 400-600 IU vitamin D/d with mean 25(OH)D concentrations of 50 nmol/L had a lower risk of GDM.

Infected bone resection plus adjuvant antibiotic-impregnated calcium sulfate versus infected bone resection alone in the treatment of diabetic forefoot osteomyelitis.

BACKGROUND: Managing with diabetic foot osteomyelitis (DFO) is challenging. Even after infective bone resection and thorough debridement, DFO is still difficult to cure and has a high recurrence rate. This retrospective study aims to compare the outcomes of two treatment methods, infected bone resection combined with adjuvant antibiotic-impregnated calcium sulfate and infected bone resection alone, for the treatment of diabetic foot osteomyelitis. METHODS: Between 2015 to 2017, 48 limbs (46 patients) with DFO met the criteria were included for assessment. 20 limbs (18 patients) were included in the calcium sulfate group (the CS group) in which vancomycin and/or gentamicin-impregnated calcium sulfate was used as an adjuvant after infected bone resection while 28 limbs (28 patients) as the control group were undergone infected bone resection only. Systemic antibiotics, postoperative wound care and offloading were continued to be applied following surgery in both groups. The time to healing, healing rate, recurrence rate and amputation rate were compared between the two groups. RESULTS: In total, 90% (18/20) limbs in the CS group as compared to 78.6% (22/28) infected limbs in the control group went to heal (P = 0.513). The Mean time to healing was 13.3 weeks in the CS group and 11.2 weeks in control group (P = 0.132). Osteomyelitis recurrence rate was 0% (0/18) in the CS group and 36.4% (8/22) in the control group (P = 0.014). Postoperative leakage in calcium sulfate group was 30.0% (6/20) with a mean duration of 8.5 weeks. Amputation rate in the control group was 7.1% (2/28) compared to 0% (0/20) in the CS group (P = 0.153). CONCLUSIONS: Antibiotic-impregnated calcium sulfate as an adjuvant prevents the recurrence of DFO but cannot improve the healing rate, reduce the postoperative amputation rate or shorten the time to healing. Prolonged postoperative leakage as the most common complication can be managed with regular dressing. LEVEL OF EVIDENCE: III, Retrospective Comparative Study.

Cynomorium songaricum Rupr demonstrates phytoestrogenic or phytoandrogenic like activities that attenuates benign prostatic hyperplasia via regulating steroid 5-α-reductase.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynomorium songaricum Rupr. (CS) belongs to the genus of parasitic perennial flowering plants, mostly used in Chinese traditional medicine for benign prostatic hyperplasia (BPH) treatment. BPH is a chronic disease in men that both androgen and estrogen play a crucial role in promoting its development via their receptors. Previously we have showed that compounds from CS have the phytoestrogenic and/or phytoandrogenic activities that may have the potential suppressive effects on BPH, while the mechanism remains unclear. AIM OF THE STUDY: In this study, we aim to investigate the effect of CS and its derived compounds: luteolin (LUT), gallic acid (GA), protocatechuic acid (PA) and protocatechualdehyde (Pra) on inhibition of rat BPH and proliferation of BPH-1 cell line respectively, and further uncover whether it is related with the phytoestrogenic and / or phytoandrogenic activities. MATERIALS AND METHODS: Estradiol/testosterone (1:100) was subcutaneous injected to induce BPH in a castrated rat model, and CS was orally administrated for 45 days. Then the weights of the body and prostate were recorded, the pathogenesis changes of prostate were analyzed by Hematoxylin and eosin (H&E) and immunohistochemical (IHC). The levels of 17ß-estradiol (E2), testosterone, and dihydrotestosterone (DHT) from rats' serum were measured by enzyme-linked immunosorbent assay (ELISA). In vitro, human benign prostatic epithelial cell BPH-1 was cultured and treated with or without different CS compounds and DHT or E2. MTT and CCK-8 assays were performed to detect the regulatory effects on cell proliferation. The expressions of PCNA, AR, ERα, ERß, and steroid 5-α-reductases (SRD5A1 and SRD5A2) were further analyzed by western blotting upon treatment. RESULTS: Treatment with CS significantly inhibited rat prostate enlargement, improved the pathological feature and reduced the thickness of smooth muscle layer. The up-regulated AR and ERα expressions and down-regulated ERß in BPH rat prostate were significantly blocked after CS administration. Moreover, the enhanced values of E2/testosterone and the level of DHT in serum were also strongly inhibited in CS group compared with those in BPH groups. In cellular level, LUT, GA, PA, or Pra significantly inhibited DHT- or E2- induced BPH-1 cell proliferation and PCNA expressions. Consistently with the data in vivo, compounds from CS interfered the DHT or E2-regulated AR, ERα and ERß expressions in BPH-1 cells as well. Importantly, the dramatic increased SRD5A1 and SRD5A2 expressions were observed in BPH rat prostates and DHT or E2-stimulated BPH-1 cells. However, treatment with CS in rat or with compounds isolated from CS in BPH-1 cells significantly blocked the induction of SRD5A1 and SRD5A2. CONCLUSIONS: CS suppressed BPH development through interfering with prostatic AR, ERα/ß, and SRD5A1/2 expressions, which provided evidence of CS for BPH treatment.

Bakuchiol exhibits anti-metastasis activity through NF-κB cross-talk signaling with AR and ERß in androgen-independent prostate cancer cells PC-3.

Androgen-independent prostate cancer (PCa) is a developed tumor derived from the local androgen dependent PCa, which often affects elderly men. Psoralea corylifolia L, a traditional Chinese medicine, has been widely used for PCa treatment as an important part of a common prescription, while the mechanism remains unclear. Our study was aimed to investigate the tumor-inhibitory effect of its main component bakuchiol in androgen-independent PCa cell line PC-3 cells. Bakuchiol significantly suppressed PC-3 cell proliferation and migration; the expressions of PCNA and MMP-9 were consistently down regulated as well. Meanwhile, both the constitutive and LPS-induced NF-κB activation were significantly inhibited by bakuchiol. The inhibitory effects of bakuchiol on cell proliferation, migration and invasion were recovered when LPS were added together with bakuchiol. SiRNA against androgen receptor (AR) or estrogen receptor ß (ERß) were transfected and the regulation of bakuchiol-suppressed proliferation, invasion, NF-κB signaling and MMP-9 secretion in response to LPS were blocked. Taken together, our data demonstrated that bakuchiol inactivated NF-κB signaling via AR and ERß, which contributes to inhibition of PC-3 cell proliferation and migration, indicating that bakuchiol is one of the key component from P. corylifolia L for PCa treatment and has a potential as anti-prostate cancer drug candidates.

Effect of temperature and dispersant (COREXIT® EC 9500A) on aerobic biodegradation of benzene in a coastal salt marsh sediment.

The coastal ecosystem in the northern Gulf of Mexico (GoM) has been seriously impacted by the 2010 BP oil spill. Two experiments were conducted to study the effect of temperature and addition of the dispersant on biodegradation of benzene, as a representative of petroleum hydrocarbon, in a coastal salt marsh sediment under aerobic conditions. The results show that benzene biodegradation was approximately 6 time faster under aerobic conditions (Eh > +300 mV) than under anaerobic iron-reduction conditions (+14 mV < Eh < +162 mV). Benzene biodegradation in response to temperature was in an order of 20 °C > 10 °C > 30 °C as expected in a saline environment. Application of the dispersant caused initial fluctuations of benzene vapor pressure during the incubation due to its hydrophobic and hydrophilic nature of the molecules. Presence of the dispersant shows an inhibitory effect on benzene biodegradation, and the inhibition increased with concentration of the dispersant. The Gulf coast sediment seems in a favorable scenario to recover from the BP oil spill with an average temperature around 20 °C in spring and fall season. Application of the dispersant may be necessary for the oil spill rescue operation, but its side effects may deserve further investigations.

Current Recommended Vitamin D Prenatal Supplementation and Fetal Growth: Results From the China-Anhui Birth Cohort Study.

Context: Maternal vitamin D insufficiency has been associated with fetal growth restriction. However, the effect of maternal vitamin D supplementation on fetal growth has not been confirmed. Objective: To assess the effect of maternal vitamin D supplementation recommended by the Institute of Medicine (IOM) during pregnancy on the neonatal vitamin D status and the risk of small for gestational age (SGA). Design and Participants: As part of the China-Anhui Birth Cohort study, maternal sociodemographic characteristics, food intake, lifestyle, information on vitamin D supplementation, and birth outcomes were prospectively collected. For participants, 600 IU/d of vitamin D3 was routinely advised to take during pregnancy. Cord blood levels of 25-hydroxyvitamin D [25(OH)D], calcium, and phosphorus were measured in 1491 neonates who were divided into three groups based on the duration of maternal vitamin D supplementation during pregnancy. Results: Mean cord blood concentrations of 25(OH)D were 3.5 nmol/L higher [95% confidence interval (CI), 0.8, 6.2] in neonates (median, 37.9 nmol/L) whose mother took vitamin D supplementation for >2 months during pregnancy compared with those (median, 34.3 nmol/L) whose mother did not take any supplement. These significant differences on cord blood concentrations of 25(OH)D occurred regardless of the season of birth. The adjusted risk of SGA in pregnant women with vitamin D supplementation for >2 months was significantly decreased than that in women without any vitamin D supplementation (11.8% vs 6.9%; adjusted odds ratio = 0.53; 95% CI, 0.32, 0.87). Conclusions: The findings from China suggest that maternal vitamin D supplementation recommended by the IOM results in a slight but significantly higher fetal level of 25(OH)D and improves fetal growth.