Observation of the Short-term Efficacy of Technetium-99 Conjugated with Methylene Diphosphonate Combined Therapy in the Treatment of Postmenopausal Osteoporosis.

OBJECTIVE: To investigate the short-term efficacy and safety of Yunke (technetium-99 conjugated methylene diphosphonate) combined with pulsed electromagnetic field (PEMF) and Gukang capsule in the treatment of postmenopausal osteoporosis (PMOP). METHODS: A total of 112 patients with PMOP who received treatment in the Department of Nuclear Medicine of the hospital from January 2019 to June 2020 were selected and randomly divided into 4 groups of 28 patients each. Group A received Yunke and PEMFs, group B received Gukang capsules and PEMFs, group C received Yunke and Gukang capsules and PEMFs, and group D received PEMFs. All groups were given adequate amounts of calcium and active vitamin D. Intervention 2 sessions of 3 months each. Outcome measures were bone mineral density (BMD) and pain improvement. RESULTS: Compared with 1 course of treatment, the symptoms of bone pain were relieved more significantly after 2 courses of treatment in group A (50.0% vs. 64.3%), group B (46.4% vs 64.3%), group C (78.6% vs 92.9%) and group D (21.4% vs 28.6%) (P < 0.05). After 2 courses of treatment, bone pain symptoms were less relieved in group A (96.4% vs. 64.3%), group B (96.4% vs 64.3%), and group D (96.4% vs 28.6%) compared with group C (P < 0.05). Compared with group C, BMD values of L4 vertebrae and femoral neck were significantly decreased in groups A, B, and D (P < 0.05). Compared with those before treatment, BMD of L4 vertebrae and femoral neck increased significantly in groups A, B, C, and D after 2 courses of treatment (P < 0.05). CONCLUSION: Yunke combined therapy can effectively relieve the pain symptoms, increase BMD, and reduce the risk of fracture in patients with PMOP in a short period, which is an effective method for the treatment of PMOP.

Natural soluble epoxide hydrolase inhibitors from Inula britanica and their potential interactions with soluble epoxide hydrolase: Insight from inhibition kinetics and molecular dynamics.

Soluble epoxide hydrolase (sEH) is a potential drug target to treat inflammation and neurodegenerative diseases. In this study, we found that the extract of Inula britanica exhibited significantly inhibitory effects against sEH, therefore, we investigated its phytochemical constituents to obtain seven new compounds together with sixteen known ones (1-20), including two pairs of novel enantiomers, (2S,3S)-britanicafanin A (1a), (2R,3R)-britanicafanin A (1b), (2R,3S)-britanicafanin B (2a), and (2S,3R)-britanicafanin B (2b), and three new lignans britanicafanins C-E (3-5). Their structures were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. All the isolates were evaluated for their inhibitory effects against sEH, compounds 1-3, 5-7, 9, 10, 13, 14, and 17-20 showed significant inhibitory effects against sEH with IC50 values from 3.56 µM to 26.93 µM. The inhibition kinetics results indicated that compounds 9, 10, 13, and 19 were all uncompetitive inhibitors, and their inhibition constants (Ki) values were 7.11, 1.99, 4.06, and 8.78 µM, respectively. Their potential interactions were analyzed by molecular docking and molecular dynamics (MD), which suggested that amino acid residues Asp335 and Asn359, especially Gln384, played an important role in the inhibition of compounds 10 and 13 on sEH, and compounds 10 and 13 could be considered as the potential candidates for the development of sEH inhibitors.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

Natural sesquiterpenoid oligomers: A chemical perspective.

Sesquiterpenoid oligomers, biogenetically assembled by at least two monomeric sesquiterpenoid units via diverse pathways, represent a unique class of natural products with distinct bioactivities. Herein, we provide a review covering the dimeric, trimeric, and tetrameric sesquiterpenoids categorized by reaction types in biosynthesis from a chemical perspective. Emphasis is focused on the biosynthetic oligomerization pathways of these interesting molecules and their related biological functions, which will supply inspiration for the total synthesis or biomimetic synthesis of more oligomeric sesquiterpenoids and further pharmacological investigations.

Effect of kai xin san on learning and memory in a rat model of paradoxical sleep deprivation.

The present study aimed to evaluate the effect of kai xin san (KXS, at doses of 500, 250, and 125 mg/kg body weight per day), a well-known traditional Chinese medicine, on learning and memory in paradoxical sleep deprivation (PSD)-induced cognition deficit rats. Two behavior tests (the Open Field test and the Morris water maze task) were used for testing the effects of KXS on a PSD-induced learning and memory deficit model. Furthermore, its effect on the glutamic acid (GLU) and γ-amino-butyric acid (GABA) levels in the brain tissue, brain-derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB), and phosphorylated-CREB (p-CREB) expression in the hippocampus was also tested. KXS exerted the greatest cognition against the 48 h PSD-induced cognitive deficit and these effects may be mediated by decreasing the GLU and GABA levels and increasing the levels of BDNF, CREB, and p-CREB. This study indicates that the effect of KXS on learning and memory in a rat model of PSD could be associated with the modulation of neurotransmitter levels and the expression of some genes in the brain that contribute to memory functions.

[Predictive value of corrected QT interval, corrected Tp-e interval and Tp-e/QT ratio on malignant arrhythmia events in acute ST-segment elevation myocardial infarction patients undergoing thrombolysis].

OBJECTIVE: The prognostic value of corrected QT interval (QTc), corrected Tp-e interval (Tp-ec) and Tp-e/QT ratio on occurrence of malignant arrhythmia events (MAE) in acute ST-segment elevation myocardial infarction (STEMI) patients underwent successful thrombolysis was explored and the potential association of these indices with MAE was analyzed. METHODS: Fifty-seven STEMI patients underwent successful thrombolytic therapy within 6 hours after admission and conservative medical treatment were included. QTc, Tp-ec, Tp-e/QT ratio were obtained and calculated in infarct-related electrocardiograph leads and non-infarct-related leads before thrombolysis, (7±1) days and (30±3) days after thrombolysis respectively, and incidence of MAE up to 30 days after thrombolysis was analyzed. Sixty age and gender matched normal subjects served as control group. RESULTS: (1) QTc, Tp-ec, Tp-e/QT in infarct-related and non-infarct-related leads in STEMI group before thrombolysis were significantly higher than those in control group (all P<0.05), and values from the infarct-related leads were significantly higher than those from non-infarct-related leads in STEMI group (all P<0.05). QTc, Tp-ec and Tp-e/QT all significantly and continuously reduced from 7 days and at 30 days post thrombolysis compared the before thrombolysis (P<0.05 vs. before thrombolysis). (2) Tp-ec≥100 ms and Tp-e/QT ratio≥0.25 before thrombolysis in infarct-related leads were linked with higher incidence of MAE within 30 days post thrombolysis in this patient cohort [28.1% (9/32) vs. 40% (1/25), 27.8% (10/36) vs.0, respectively, all P<0.05]. CONCLUSION: QTc, Tp-ec and Tp-e/QT values decreased post successful thrombolysis in STEMI patients and higher Tp-ec and Tp-e/QT values before thrombolysis in STEMI patients were related with higher MAE incidence up to 30 days post successful thrombolysis in this patient cohort.

[Effect and mechanism of dingzhixiao wan on scopolamine-induced learning-memory impairment in mice].

OBJECTIVE: To investigate the effect of Dingzhixiao Wan (DZXW), a classic traditional Chinese medicine formula consisting of Acorus tatarinowii, Polygala tenuifolia, Poria cocos and Panax ginseng in a proportion of 2: 2: 3: 3, on learning-memory impairment induced by scopolamine and its possible mechanisms. METHOD: The mice were randomly divided into six groups: the control group, the model group, the positive huperzine A (0.05 mg x kg(-1)) group, DZXW 700 mg x kg(-1), 350 mg x kg(-1) and 175 mg kg(-1) groups. DZXW extracts were orally administrated to the mice for 7 days. Scopolamine (1.5 mg x kg(-1), ip) was injected to establish the learning and memory impairment model in mice. Morris water maze (MWM) test was used to assess the learning and memory ability of each group. After the test, the activities of glutamic acid (Glu), gamma-amino-butyric acid (GABA), serotonin (5-HT), dopamine (DA), acetylcholine (Ach) and acetyl cholinesterase (AchE) in brain tissue were measured. RESULT: The praxiology test showed that DZXW significantly decreased the average latency of model mice in the place navigation test, and enhanced the frequency for passing through the platform in the spatial probe test, the percentage between target quadrant swimming distance and time. Moreover, DZXW could significantly increase the contents of Glu and 5-HT, DA and Ach, while reducing the levels of GABA and AchE in mice brain. CONCLUSION: DZXW could significantly ameliorate the scopolamine-induced learning-memory impairment in mice and improve their learning-memory capacity, which may be related to its effect on adjusting Glu/GABA system and increasing Ach and monoamine neurotransmitter contents in mice brain.

Antidepressant-like effect of the extracted of Kai Xin San, a traditional Chinese herbal prescription, is explained by modulation of the central monoaminergic neurotransmitter system in mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai Xin San (KXS) is a traditional Chinese herbal prescription for the treatment of depression-like disorders, anxiety, and impairment in learning and memory, however, there is very little scientific data concerning the efficacy of this. AIM OF THE STUDY: The present study aimed to investigate the antidepressant potential of Kai Xin San and its possible mechanisms. MATERIALS AND METHODS: Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of KXS. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis, akinesia and hypothermia and 5-HTP induced head-twitch response in mice. The contents of monoamine neurotransmitters including epinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) in mice brain were determined by Elisa. Spontaneous motor activities of mice and rotarod test were performed to find whether KXS has excitatory or inhibitory actions on the central nervous system. RESULTS: The results showed that intragastric administration of KXS at 175, 350, 700, 1400 mg/kg/day or fluoxetine at 28 mg/kg/day for 3 days significantly reduced the duration of immobility in TST and FST, while it showed no effect on the spontaneous motor activity and rotarod performance in mice. However, the effect was not dose-dependent. The pre-treatment with KXS or fluoxetine for 3 days could elevate the contents of NE, 5-HT and DA in mice brain significantly. When the mice were treated with KXS (350 mg/kg, p.o) or desipramine (30 mg/kg, p.o) for 7 days, both of them could antagonize reserpine-induced ptosis, akinesia and hypothermia. The KXS (350 mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 min when KXS at dosages of 175, 350, 700 and 1400 mg/kg/day were performed per os (p.o.) during a 1-day, 3-day or 7-day period. CONCLUSIONS: Our results suggested that KXS exerts antidepressant-like effect. A possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.

[The clinical epidemiology characteristics of HFMD in 2010 of Hangzhou].

OBJECTIVE: To analyze clinical epidemiology characteristics of HFMD in children from April 2010 to October in Hangzhou. METHODS: 1848 HFMD hospital patients are admitted to clinical epidemiological analysis. RESULTS: Onset ages of HFMD primarily under 3 years, boys more than girls, social above diasporas, rural above town. The highest peak in 5-7 months. Mostly clinical symptoms are mild, the prognosis is good. CONCLUSION: HFMD has obvious susceptible population and susceptibility season. Increase health interventions to susceptible regions and the crowd in popular season, early detection, active therapy, most prognosis is good.

Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines.

Recently, an interesting relationship between potassium channels and cancer has evolved. The aim of this study is to investigate expression of Eag1 potassium channel in gastric cancer and its role in cancer cells growth. The expression of Eag1 for gasric cancer patients and cell lines as well as gastric adenoma was investigated by immunohistochemistry and reverse transcription polymerase chain reaction. In addition, imipramine was used to identify the involvement of Eag1 in the growth of SGC-7901 and BGC-823 cells. Frequency of positive expression of Eag1 protein was 70.5% (67/95) and Eag1 mRNA was 68.2% (15/22) in gastric cancer primary tissues. Eag1 mRNA was positively expressed in two gastric cell lines. Eag1 protein and mRNA were negatively expressed in paired non-cancerous matched tissues and 5 cases of adenoma tissues. The expression level of Eag1 protein was associated with lymph node metastasis (P = 0.049) and stage (P = 0.039), but had no correlation with sex, age, differentiation grades, and other organs metastases. Imipramine significantly inhibited the proliferation of SGC-7901 and BGC-823 cells at 12 h and 24 h detected by cells number counting and MTT assay (P < 0.01). The study indicates Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells.

Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines.

AIM: To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relation-ship between their expression and clinico-pathological features. METHODS: The expression levels of Eag1 protein were determined in 76 cancer tissues with paired non-cancerous matched tissues as well as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was detected in 13 colorectal cancer tissues with paired non-cancerous matched tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell lines (LoVo and HT-29) by reverse transcription PCR. RESULTS: The frequency of positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9% (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was dependent on the tumor size, lymphatic node metastasis, other organ metastases and Dukes' stage (P < 0.05), while not dependent on age, sex, site and degree of differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue, and absolutely negative in colorectal adenomas except that one case was positively stained for Eag1 protein. CONCLUSION: Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. The high frequency of expression of Eag1 in tumors and the restriction of normal expression to the brain suggest the potential of this protein for diagnostic, prognostic and therapeutic purposes.