Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

亚治疗剂量低分子肝素作为机械瓣膜患者再次外科手术的桥接抗凝治疗效果

目的机械心脏瓣膜(MHV)患者接受再次手术时,需要中断华法林的抗凝治疗,往往需要桥接低分子肝素(LMWH)进行抗凝。本研究的目的是评估MHV患者再次接受择期手术(心脏手术和非心脏手术)桥接亚治疗剂量的LMWH是否是一种安全有效的方法。方法观察我院在2013年1月1日到2018年1月1日收治的需再次择期手术的机械瓣膜置换术后患者(瓣膜置换组,n = 47),瓣膜置换组纳入标准是围手术期桥接抗凝的机械瓣置换的患者,并经心外科医生制定桥接抗凝方案患者(机械瓣主动脉瓣置换术后患者14例,机械瓣二尖瓣/双瓣置换术后患者33例),以同期行相同手术的患者(未做过瓣膜置换术)为对照组(n = 47),主要观察指标是住院病死率、术中出血量、桥接后30 d内血栓栓塞事件或主要出血事件的发生率。结果瓣膜置换组术中出血量及术后第一个24 h出血量较对照显著增多(P < 0.05),瓣膜置换组1例死亡(2%),死亡原因为低心排,并出现1例(2%)出血事件,两组均未发生栓塞事件,但与对照组相比两组病死率、栓塞事件和出血事件发生率均无显著性差异。结论机械瓣膜置换术后患者在进行择期外科手术期间采用亚治疗剂量LMWH进行桥接抗凝术中出血量增多,但严重并发症发生率无显著增加,此结论尚需进一步验证。

Differences in clinical and genetic characteristics between early-and late-onset narcolepsy in a Han Chinese cohort

Early-and late-onset narcolepsy constitutes two distinct diagnostic subgroups.However,it is not clear whether symptomology and genetic risk factors differ between early-and late-onset narcoleptics.This study compared clinical data and single-nucleotide polymorphisms(SNPs)between early-and late-onset patients in a large cohort of 899 Han Chinese narcolepsy patients.Blood,cerebrospinal fluid,and clinical data were prospectively collected from patients,and patients were genotyped for 40 previously reported narcolepsy risk-conferring SNPs.Genetic risk scores(GRSs),associations of five different sets of SNPs(GRS1–GRS5)with early-and late-onset narcolepsy,were evaluated using logistic regression and receiver operating characteristic curves.Mean sleep latency was significantly shorter in early-onset cases than in late-onset cases.Symptom severity was greater among late-onset patients,with higher rates of sleep paralysis,hypnagogic hallucinations,health-related quality of life impairment,and concurrent presentation with four or more symptoms.Hypocretin levels did not differ significantly between early-and late-onset cases.Only rs3181077(CCR1/CCR3)and rs9274477(HLA-DQB1)were more prevalent among early-onset cases.Only GRS1(26 SNPs;OR=1.513,95%CI:0.893–2.585;P<0.05)and GRS5(6 SNPs;OR=1.893,95%CI:1.204–2.993;P<0.05)were associated with early-onset narcolepsy,with areas under the receiver operating characteristic curves of 0.731 and 0.732,respectively.Neither GRS1 nor GRS5 included SNPs in HLA regions.Our results indicate that symptomology and genetic risk factors differ between early-and late-onset narcolepsy.This protocol was approved by the Institutional Review Board(IRB)Panels on Medical Human Subjects at Peking University People’s Hospital,China(approval No.Yuanlunshenlinyi 86)in October 2011.

Beneficial for mental health,exercise more or less?

Regular physical activity may improve mental health during the pandemic by reducing inflammatory responses.However,overtraining or prolonged exercise training may adversely affect mental health.

Predictive correlation test of acute respiratory failure in children with hand foot mouth disease

Objective:To investigate the predictive correlation test of acute respiratory failure in children with hand foot mouth disease (HFMD).Methods: Selected from our hospital June 2014 to June 2017 HFMD incidence of acute respiratory failure in 31 cases as a observation group;Selected from our hospital same period HFMD patients without acute respiratory failure in 35 cases as the control group;the other is selected from healthy children 40 cases as normal group. There were collected three groups peripheral venous blood 2 mL, and serum was isolated. Enzyme linked immunosorbent assay was used for the determination of IL-6. The content of CRP was measured by Backman OLYMPUS AU640 automatic biochemical analyzer. The contents of creatine kinase (CK), creatine kinase isozyme (CK-MB) and lactate dehydrogenase (LDH) were determined by Backman OLYMPUS AU640 automatic biochemical analyzer. The content of troponin I (cTnI) was measured by Backman ACCESS2 chemiluminescence immunoanalyzer.Results:The serum levels of IL-6, CRP, CK, CK-MB, LDH and cTnI in the observation group were higher than those in the control group and the normal group. After treatment serum levels of IL-6, CRP, CK, CK-MB, LDH and cTnI were lower than those before treatment, and there were statistically significant differences.Conclusion: serum IL-6, CRP index and serum CK, CK-MB, LDH and cTnI indexes can be used as indicators for the prediction of acute respiratory failure in children with hand foot mouth disease, and have important clinical significance.

Discussions on real-world acupuncture treatments for chroni clow-back pain in older adults

Chronic low-back pain(CLBP) is one of the most common pain conditions. Current clinical guidelines for low-back pain recommend acupuncture for CLBP. However, there are very few high-quality acupuncture studies on CLBP in older adults. Clinical acupuncture experts in the American Traditional Chinese Medicine Association(ATCMA) were interested in the recent grant on CLBP research announced by the National Center for Complementary and Integrative Health. The ATCMA experts held an online discussion on the subject of real-world acupuncture treatments for CLBP in older adults. Seven participants, each with more than 20 years of acupuncture practice, discussed their own unique clinical experience while another participant talked about the potential mechanism of acupuncture in pain management. As a result of the discussion, a picture of a similar treatment strategy emerged across the participants for CLBP in older adults. This discussion shows that acupuncture may have complicated mechanisms in pain management, yet it is effective for the treatment of chronic pain involving maladaptive neuroplasticity;therefore, it should be effective for CLBP in older adults.

Discrimination of toxic ingredient between raw and processed Pinellia ternata by UPLC/Q-TOF-MS/MS with principal component analysis and T-test

Objective: To investigate the toxicity difference between raw and processed Pinelliae Rhizoma(Banxia in Chinese, BX), the rhizoma of Pinellia ternata, from the view of chemical composition.Methods: Sixteen samples of raw and processed BX were prepared and analyzed by UPLC/Q-TOF-MS/MS.The discrimination(chemical marker) between the two group was investigated by principal component analysis(PCA) and T-test analysis. According to the accurate charge-to-mass ratio, MS/MS fragments, and comparison of corresponding data with the reference or database, the chemical markers were identified preliminarily.Results: Liquiritin, liquiritigenin, and lysophosphatidylcholine(LPC) were identified as the characteristic markers. The reducing of LPC in processed BX was one of the main reasons for detoxification because LPC could induce the inflammatory response;Liquiritin and liquiritigenin showed the anti-inflammatory effect and reduced liver injury, therefore the appearance of them in processed BX was an another reason for detoxification.Conclusion: An approach to explain the mechanisms of reducing the toxicity in medicinal plants by processing was proposed. Moreover, the chemical markers of toxicity could be used to differentiate the raw material from processed herbs for the quality control and safety application in clinical practice.

Revealing the Distribution of Aggregation-Induced Emission Nanoparticles via Dual-Modality Imaging with Fluorescence and Mass Spectrometry

Aggregation-induced emission nanoparticles(AIE NPs)are widely used in the biomedical field.However,understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth.Herein,we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging(LDI MSI)to map and quantify the biodistribution of AIE NPs(TPAFN-F127 NPs)by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule.We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen,and most gradually excreted from the body after 5 days.The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model.As a proof of concept,the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI,and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone.The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure.This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.

Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1

Background:Recent genome-wide association studies have identified an important role of T-cell receptor α(TRA) gene in the development of narcolepsy type 1.However,the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear.This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy.Methods:Totally,903 patients with narcolepsy type 1 were included in the study.Patients were divided into different groups according to their symptoms.First,13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy.We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy.Further,we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model.Results:According to the results of the logistic regression,TRA haplotypes TG and CT were significantly associated with auditory hallucination,with odds ratios of 1.235 (95% confidence interval [CI],1.012-1.507) and 1.236 (95% CI,1.012-1.511),respectively (P < 0.05).Contusions:The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1.However,further studies are needed to confirm our results and explore the underlying mechanisms.

Acupuncture price in forty-one metropolitan regions in the United States: An out-of-pocket cost analysis based on Ok Copay.com

Few studies have focused on the cost of acupuncture treatments although acupuncture has become popular in the United States(U.S.). The purpose of the current study was to examine the out-of-pocket costs incurred from acupuncture services based on an online website, Ok Copay.com. We examined descriptive statistics(range, median and 20% intervals) for the cost of acupuncture "first-time visits"and "follow-up visits" in 41 metropolitan regions in the U.S. The acupuncture prices of 723 clinics throughout 39 metropolitan regions were included, except for Birmingham, Alabama and Detroit, Michigan as there was no online data available at the time of the study for these two regions. The cost range for a first-time acupuncture visit was $15–400;the highest median was $150 in Charleston, South Carolina,while the lowest was $45 in St. Louis, Missouri. The top 10 cities for the highest median were:Baltimore, Washington, D.C., New York, San Francisco, San Jose, Boston, Atlanta, Seattle, Portland and Indianapolis, with the median $120, while the median for all 723 clinics was $112. For the follow-up visits,the cost range was $15–300;the highest median was $108 in Charleston, South Carolina, and the lowest$40 in Miami, Florida. The 10 cities with highest median follow-up acupuncture visit costs were: New York, Baltimore, New Orleans, Washington, D.C., Philadelphia, San Francisco, San Jose, Seattle, Boston and Atlanta, with the median $85, while for all 723 clinics the median price was $80. The estimation of the average gross annual income of each acupuncturist from the regions studied was $95,760, while the total annual cost of patients seeking acupuncture services in the U.S. was about $3.5 billion in 2018.

Influence of soy protein isolate on the gel properties of walnut protein isolate-κ-carrageenan treated with NaCl

The demand for plant protein is increasing significantly due to the shortage of protein resources.Walnut protein,the main by-product of preparing walnut oil,has limited application in the food industry due to its poor solubility.It was found that the soy protein isolate(SPI)concentration had significant effects on the gel properties of the walnut protein isolate(WNPI)-κ-Carrageenan(KC)composite system treated with 15 mmol/L NaCl.The results showed that the gel strength of the composite system increased first and then decreased with the increased concentration of SPI from 0 to 2.5%.The best rheological properties,texture properties,water holding capacity((92.03±1.05)%),swelling ratio((2.04±0.19)%),freeze-thaw stability and thermal stability(85.53°C)of the composite gel were found at an SPI concentration of 1%.In the meantime,the secondary structure of protein had the least α-helix content of 10.17% and the highest β-sheet content of 39.64%,the fluorescence intensity and free sulfhydryl content reached the highest value.1% SPI could also act as a filler for WNPI to enhance the intermolecular forces such as hydrophobic interaction between the two substances,thus forming a stable gel network structure.This study can provide technical support for improving the gel properties of walnut protein and producing new plant protein gel products.

Effectiveness of two different acupuncture strategies in patients with vulvodynia Study protocol for a pilot pragmatic controlled trial

Background： Vulvodynia, or vulvar pain, is a common condition in women; however, there are few evidence-based clinical trials evaluating nonpharmacological therapies for this condition. Acupuncture is one complementary and integrative medicine therapy used by some patients with vulvodynia. This study evaluates two different acupuncture strategies for the treatment of vulvodynia and aims to evalu- ate whether either of the acupuncture protocols reduces vulvar pain, pain duration or pain with inter- course. The study also examines how long the effect of acupuncture lasts in women with vulvodynia. Methods/design： The study is designed as a randomized controlled trial, focused on two acupuncture protocols. Fifty-one patients who have had vulvodynia for more than 3 months will be recruited. Among them, 34 patients will be randomized into Groups la and 1b; those who are unwilling to receive acupuncture will be recruited into the standard care group （Group 2）. Patients in Group la will have acupuncture focused on the points in the pudendal nerve distribution area, while patients in Group lb will receive acupuncture focused on traditional （distal） meridian points. Patients in Group 2 will receive routine conventional treatments, such as using pain medications, local injections and physical therapies or other nonsurgical procedures. Acupuncture will last 45 min per session, once or twice a week for 6 weeks. The primary outcome measurement will be objective pain intensity, using the cotton swab test. The secondary outcome measurement will be subjective patient self-reported pain intensity, which will be conducted before cotton swab test. Pain intensities will be measured by an 11-point Numeric Pain Rating Scale. Pain duration and pain score during intercourse are recorded. Local muscle tension, tender- ness and trigger points （Ashi points） are also recorded. All measurements will be recorded at baseline （before the treatment）, at the end of each week during treatment and at the end of the 6weeks. Follow-up will be done 6 weeks following the last treatment. Discussion： Results of this trial will provide preliminary data on whether acupuncture provides better outcomes than nonacupuncture treatments, i.e., standard care, and whether acupuncture focused on the points in pudendal nerve distribution, near the pain area, has better results than traditional acupunc- ture focused on distal meridian points for vulvodynia.