Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

ObjectiveTo observe the clinical efficacy and mechanism of Tongnao Yizhi Formula （通脑益智方， TYF） in treating vascular cognitive impairment no dementia （VCIND） with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome. MethodsNinety-two VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome were randomly divided into control group （42 cases） and treatment group （52 cases）. Both groups received routine basic treatment. The control group was given donapezil hydrochloride capsules orally， 5 mg each time， once at night， while the treatment group was given TYF orally， 1 dose per day. Both groups were treated continuously for 3 months. The scores of Mini-Mental State Examination （MMSE）， Vascular Dementia Assessment Scale-Cognitive Subscale （VaDAS-Cog）， Activity of Daily Living Scale （ADL）， and TCM syndrome scores （the primary symptoms such as sluggish thinking， forgetfulness， temperament changes， and language confusion， and secondary symptoms such as weakness of waist and knees， dizziness and headache， occasional tinnitus， fatigue， heaviness of limbs， insomnia and irritability， poor appetite and abdominal distension， numbness of face） were observed before and after treatment in both groups. The changes in gut microflora diversity and flora abundance structure as well as fecal short-chain fatty acids （SCFAs） levels including acetic acid， propionic acid， butyric acid， isobutyric acid， isovaleric acid， valeric acid， and caproic acid were compared between groups. The feces of 20 healthy subjects in the same period were included as reference. Safety was evaluated during the study. ResultsAfter treatment， both groups exhibited significant increases in MMSE scores and decreases in VaDAS-cog scores （P＜0.05 or P＜0.01）， and ADL scores in the treatment group significantly increased （P＜0.05）. Scores of symptoms including sluggish thinking， forgetfulness， temperament change， language confusion， heaviness of limbs， insomnia， irritability， poor appetite， abdominal distension， and facial numbness as well as the total score significantly decreased in both groups after treatment （P＜0.05 or P＜0.01）. When compared between groups， the treatment group showed substantial reductions in scores of weakness of waist and knees， tinnitus， fatigue， heaviness of limbs， insomnia， irritability， loss of appetite and abdominal distension （P＜0.05 or P＜0.01）. The gut microflora diversity analysis showed that the Shannon index of the treatment group significantly increased after treatment （P＜0.05）.PCoA analysis and ANOSIM test indicated significant differences between groups， suggesting changes in microflora species （P＜0.01）. After treatment， the relative abundance of Bacteroidetes and Fusobacteria in the treatment group increased， while the relative abundance of Actinobacteria， Verrucomicrobia and Cyanobacteria decreased （P＜0.05）； the relative abundance of Faecalibacterium prausnitzii， Bifidobacterium， Lactobacillus， and Ruminococcus increased significantly （P＜0.05）. Compared to the the gut microflora species diversity of the healthy people， it is indicated that the gut microflora structure in the treatment group was close to that of the healthy people， while there was no such trend in the control group. In the treatment group， acetic acid， propionic acid， and butyric acid in the treatment group were all higher after treatment （P＜0.05 or P＜0.01）. ConclusionsTYF can improve the cognitive ability and quality of life of VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome， and this improvement may be related to regulating intestinal microecology.

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα_q/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gα_q/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gα_q/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
Humans ; Mice ; Animals ; Lipoylation ; NIH 3T3 Cells ; Uveal Neoplasms/genetics* ; Melanoma/genetics* ; Cell Proliferation ; Proto-Oncogene Proteins c-bcl-2 ; GTP-Binding Protein alpha Subunits, Gq-G11/genetics*

Objective:This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China.Methods:Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods.Results:A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes ( P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk ( OR=0.84, 95% CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA ( P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance ( P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion:The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

Objective:To explore the association between maternal passive smoking during perinatal period and congenital heart disease (CHD) in their offspring.Methods:A case-control study was designed. Data being used was based on a case-control study of congenital heart disease collected in Shaanxi province from January 2014 to December 2016. Cases under this study were perinatal infants diagnosed as CHD from 28 weeks of gestation to 7 days after birth, and fetus less than 28 weeks of gestation but diagnosed as CHD by ultrasonography. The controls would include newborn infants without any birth defects, born at the same period of the cases. Logistic regression model with confounding factors adjusted was established to analyze the association between maternal passive smoking status during perinatal period and CHD in their offspring. Subgroup analysis was carried out to explore its stability.Results:A total of 2 259 subjects, consisting 695 cases and 1 564 controls were included in this study. Passive smokers accounted for 26.76 % in the case group while only 6.01 % in the control group. After adjusting for related confounding factors, the risk of CHD in the offspring of passive smokers was 3.32 times higher than that of the non-passive smokers ( OR=3.32, 95 %CI: 2.41-4.56), during the perinatal period. Results also showed that related risk accumulated with the increase of exposure frequency to passive smoking. For mothers who smoked passively for 1-3 days per week, the risk of CHD in their offspring was 2.75 times higher than that of those non-passive smokers ( OR=2.75, 95 %CI: 1.62-4.66). For mothers who smoked passively for more than 3 days per week, the risk was 3.62 times higher than the non-passive smokers ( OR=3.62, 95 %CI: 2.48-5.29). Data from the subgroup analysis showed that the association between maternal passive smoking during perinatal period and CHD in their offspring appeared stable. Conclusions:Maternal passive smoking during perinatal period seemed a risk factor for congenital heart disease related to their offspring. Pregnant women should avoid exposure to second-hand smoke as much as possible, so as to prevent the harm from passive smoking.

Objectives:To analyze the epidemiological characteristics and levels of vitamin B 12 and folate as well as their relationship in women awaiting delivery, in Shaanxi province. Methods:Data were collected from healthy pregnant women who gave birth at six top hospitals in Shaanxi, from January 2014 to December 2016. Blood samples were taken prenatally to determine the levels of vitamin B 12 and folate. Quantile regression model was used to analyze the relationship between the levels of vitamin B 12 and folates in women awaiting delivery. Results:A total of 1 277 women awaiting delivery were included in this study. Among them, the median level of serum vitamin B 12 was 164.7 pg/ml, in women at late pregnancy, with the deficiency rate as 69.6%, while the median level of serum folate was 7.6 ng/ml, with the deficiency rate as 12.1%. 58.4% of these women presented simple vitamin B 12 deficiency and 0.9% with simple folate deficiency. Women living in rural areas showed lower levels of both vitamin B 12 and folate than the women from the urban areas. Both the levels of vitamin B 12 and folate increased with age but were significantly lower in women under the age of 25. Among those with or without folate deficiency, the average difference in the levels of vitamin B 12 was 37.62 pg/ml. Quantile regression models showed that the vitamin B 12 levels in women with folate deficiency were significantly lower than those without, despite the different levels of vitamin B 12. This difference appeared increasing along with the increase of the vitamin B 12 levels. Conclusions:Our data showed that both vitamin B 12 and folate were deficient in women awaiting delivery, in Shaanxi. We suggest that vitamin B 12 should also be added into the folic acid supplementation program, together with the reinforcement on health education program to improve the awareness of nutrient supplementation in rural and young women. Hopefully, these strategies could increase the levels of both vitamin B 12 and folate, in the province.

BACKGROUND: Three-dimensional printing technology is a new technology which can quickly and accurately transform the virtual computer-aided design into the three-dimensional physical prototypes. Three-dimensional printing physical model method can replace the method of traditional preoperative planning and repair surgical simulation, with the characteristic of repeatable, which has been deepened day after day in clinical application of spine surgery. OBJECTIVE: To summarize the application status of three-dimensional printing technology in spine surgery and look forward to its future development directions. METHODS: The articles regarding the application of three-dimensional printing technology on clinical applications in spine surgery were retrieved from PubMed databases, Google Scholar, China National Knowledge Infrastructure and Wanfang Database from January 2000 to July 2015. The key words were 3D printing technology, rapid prototyping technology, spine, vertebra, department of orthopedics, fracture, joint, hand and foot, bone tumor, trauma, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, sacral vertebrae, pedicle of vertebral arch, vertebral body, intervertebral disc, and clinical application. A total of 50 articles with a good representation were selected and discussed after repetitive studies and reviews were excluded. RESULTS AND CONCLUSION: The three-dimensional printing technique has been applied in preoperative diagnosis, individualized orthosis customerization, the communication between doctors and patients, teaching, the formulation of individualized and high-accurate repairing plan, intraoperative navigation and individualized implant customization. These results suggest that with the rapid development of medical imaging, digital medicine and technologies of the cel and tissue culture and new materials, three-dimensional printing technology wil have a wide range of applications in spine surgery.

Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth.Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C.albicans growth were first investigated and compared by microcalorimetry coupled with multiple analytical methods.The quantitative thermo-kinetic parameters obtained from these curves were analyzed to show difference of the actions.Results By analyzing the main parameters screened from principal component analysis together with 50％ inhibiting concentration values,it was demonstrated that both CUR and DMC showed good antifungal activities and CUR was stronger.It was further concluded from structure-activity relationship that the existence of methoxy group might enhance lipophilicity of the mother nucleus,which made it easier for the molecular to enter into the cell membrane of fungi to inhibit its growth.Conclusion This study provides a new method for screening new antifungal agents with high efficacy and low toxicity.Meanwhile,it contributes to the application of curcuminoids as food additive,colorant,and drug.Microcalorimetry is real-time,online,and dynamic,and it could be used to characterize the subtle difference among the effects of synthetic and natural products on the vital process of fungi.

ObjectiveTo evaluate the safety and efficacy of 30 mg pioglitazone hydrochloride combined with sulphonyurea in the treatment of type 2 diabetic patients.MethodsA randomized, double blind, placebo-controlled, parallel group, multicenter study was performed.A total of 236 patients, who had fasting plasma glucose(FPG) 7.5-13.0 mmol/L and glycosylated hemoglobin A1c(HbA1 c) 7.0％ -12.0％,treated with stable dosage of a sulphonyurea for at least 30 days previously, were randomized to receive placebo or pioglitazone 30 mg once daily for 16 weeks.The sulphonyurea and dosage remained unchanged.ResultsThe patients who had been treated with pioglitazone 30 mg showed significant decrease than that in the placebo group on the average from baseline in FPG [(1.48 ±2.08) mmol/L vs (-0.17 ± 1.92)mmol/L, P＜0.05], and in HbAlc [(0.92 ±0.10)％ vs (0.28 ±0.11)％, P＜0.05].Since fasting plasma insulin (Flns) levels decreased (0.24 ±0.04) mU/L and (0.09 ±0.04) mU/L in the two groups.The homeostatic model assessment insulin resistant (HOMA-IR) decreased 1.42 ± 2.90 and 0.46 ± 3.53 in two groups.The triglyceride level was decreased 0.36 mmol/L and 0.14 mmol/L, and the HDL-C level increased 0.17 mmol/L and 0.05 mmol/L in two groups.There were significant differences in two groups (all P ＜ 0.05).ConclusionsThe 16-week clinical study demonstrated that pioglitazone hydrochloride with a dosage of 30mg daily, could significantly improve the blood glucose control and enhance the insulin sensitivity, lower triglyceride and raise HDL-C level as an additional therapy to a stable-dose sulphonyurea in Chinese type 2 diabetic patients previously poorly controlled by single sulphonyurea therapy, and furthermore had good safety and compliance.

Bioassay, which construct the characteristics consistents with Chinese medical science, is the core mode and methods for the quality control of Chinese materia medica. Taking the bioassay of Radix Isatidis as an example, the contribution, status and application of bioassay in the quality control of Chinese materia medica were introduced in this article, and two key issue (the selection of reference and measurement methods) in the process of establishing bioassay were also explained. This article expects to provide a reference for the development and improvement of the bioassay of Chinese materia medica in a practical manipulation level.
Aconitum ; Materia Medica ; Medicine, Chinese Traditional ; utilization ; Quality Control