Ti2C3 MXene-based nanocomposite as an intelligent nanoplatform for efficient mild hyperthermia treatment.

Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti3C2@Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti3C2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti3C2@Qu nanocomposites were systematically investigated.

Real-Time Monitoring of Translocation, Dissipation, and Cumulative Risk of Maleic Hydrazide in Potato Plants and Tubers by Ion Exclusion Chromatography.

In this paper, a high-performance ion exclusion chromatographic (ICE) method was developed and applied for monitoring maleic hydrazide (MH) translocation in complex potato plant tissue and tuber matrices. After middle leaf uptake, most MH was trapped and dissipated in the middle leaf, and the rest was transported to other parts mainly through the phloem. Soil absorption significantly reduced the uptake efficiency of the root system, in which MH was partitioned to dissipate in root protoplasts or transfer through the xylem and persisted in the plant. Tuber uptake enabled MH to remain in the flesh and maintain stable levels under storage conditions, but during germination, MH was translocated from the flesh to the growing buds, where it dissipated through the short-day photoperiodic regime. The results demonstrated successful application of the ICE method and provided necessary insights for real-time monitoring of MH translocation behavior to effectively improve potato edible safety.

Zishen yutai pill as an adjuvant therapy in threatened Miscarriage:A meta-analysis of 23 randomized controlled trials.

Objective: The purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy. Methods: Randomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I2 statistics were used for heterogeneity test. Results: Twenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15-1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks. Conclusion: Zishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented. Systematic review registration: INPLASY202320039.

[Research progress on effective components and mechanisms of anti-depressive Chinese medicine].

Since the pathogenesis of depression is complicated, the therapeutic effects of western medicine are poor accompanied by severe side effects. Chinese medicine has unique advantages in the treatment based on syndrome differentiation and contains many effective components against depression, including flavonoids, terpenes, phenylpropanoids, quinones, and alkaloids. These chemical components can delay the course of the disease, improve the curative effect, and reduce side effects of western medicine by regulating the biochemical abnormalities of monoamine neurotransmitters, brain tissue protein content, and internal environment as well as energy metabolism to make the treatment of Chinese medicine highlighted and recognized. This study systematically reviewed the effective components and mechanisms of anti-depressive Chinese medicine to inspire the rational development and utilization of new Chinese medicines against depression.

Efficacy and safety of Yunkang oral liquid combined with conventional therapy for threatened miscarriage of first-trimester pregnancy a protocol for systematic review and meta-analysis.

INTRODUCTION: Threatened miscarriages is a common complication of first-trimester pregnancy. Due to the beneficial effects, there are increasing clinical studies on Yunkang oral liquid(YKOL). However, the efficacy and safety of YKOL are still unknown. The aim of this systematic review was to assess the efficacy and safety of YKOL in the treatment of threatened miscarriage during the first-trimester pregnancy (TMFP). METHODS: This protocol will be prepared according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will include all randomized controlled trials (RCTs) studies published until April 2021. Electronic sources including CNKI, WF, VIP, CBM, MEDLINE(PubMed), Embase, Cochrane Library, and Web of Science will be searched for potentially eligible studies. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched from their inception until April 1st, 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by two researchers independently. Statistical analysis will use RevMan 5.3.5 software. The strength of evidence from the studies will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. RESULTS: This study will provide evidence for YKOL combined with conventional therapy for TMFP. CONCLUSION: The efficacy and safety of YKOL combined with conventional therapy for TMFP will be assessed. SYSTEMATIC REVIEW REGISTRATION: INPLASY202140105 (https://www.doi.org/10.37766/inplasy2021.4.0105).

Metabolic Profile of C-Prenyl Coumarins Using Mass Spectrometry-Based Metabolomics.

C-prenyl coumarins (C-PYCs) are compounds with similar structures and various bioactivities, which are widely distributed in medicinal plants. Until now, the metabolic characterizations of C-PYCs and the relationship between metabolism and bioactivities remain unclear. In this study, ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics (UPLC-ESI-QTOF-MS) was firstly used to determine the metabolic characterizations of three C-PYCs, including meranzin hydrate (MH), isomeranzin (ISM), and meranzin (MER). In total, 52 metabolites were identified, and all of them were found to be novel metabolites. Among these metabolites, 10 were from MH, 22 were from ISM, and 20 were from MER. The major metabolic pathways of these C-PYCs were hydroxylation, dehydrogenation, demethylation, and conjugation with cysteine, N-acetylcysteine, and glucuronide. The metabolic rate of MH was much lower than ISM and MER, which was only 27.1% in MLM and 8.7% in HLM, respectively. Additionally, recombinant cytochrome P450 (CYP) screening showed that CYP1A1, 2B6, 3A4, and 3A5 were the major metabolic enzymes involved in the formation of metabolites. Further bioactivity assays indicated that all of these three C-PYCs exhibited anti-inflammatory activity, but the effects of ISM and MER were slightly higher than MH, accompanied by a significant decrease in inflammatory cytokines transcription induced by lipopolysaccharide (LPS) in macrophages RAW 264.7. Taken together, the metabolic characterizations of the three C-PYCs suggested that the side chain of the prenyl group may impact the metabolism and biological activity of C-PYCs.

Comparative Analysis of the Effect of Low-Frequency Repeated Transcranial Magnetic Stimulation and Extracorporeal Shock Wave on Improving the Spasm of Flexor after Stroke.

Poststroke spasticity (PSS) patients with muscle spasticity are effectively relieved by low-frequency repetitive transcranial magnetic stimulation (rTMS) or extracorporeal shock wave treatment (ESWT). However, there are relatively few reports about the difference in the efficacy of rTMS and ESWT for PSS. In this study, we examined and recorded the levels of UE motor section of the Fugl-Meyer Motor Assessment Scale (FMA-UE), myoelectric signal time-domain range integral values (iEMG), Modified Ashworth Scale (MAS), and Modified Barthel Index (MBI) before and after treatment to observe the differences in treatment effects between rTMS and ESWT in patients with PSS. 66 patients with PSS were enrolled in the study and signed an informed consent form, and the study was approved by the Ethics Committee of the First Hospital of Soochow University (2019008). The patients were divided into rTMS group, ESWT group, and regular group according to the random number table method, and there were 22 patients in each group. The rTMS group and ESWT group were treated with rTMS and ESWT on the basis of conventional treatment in the regular group, 5 times a week, and the total treatment time was 4 weeks. The results of the study showed that iEMG, MAS, FMA-UE, and MBI scores in the rTMS, ESWT, and regular groups were significantly ameliorated after treatment compared with those before treatment. The efficacy of the ESWT group was significantly better than in the regular group and slightly better than in the rTMS group, as shown by the iEMG, MAS, FMA-UE, and MBI scores, and the iEMG score of the ESWT group was significantly better than the rTMS group, while there were no significant differences in other indexes. The FMA-UE and MBI scores in the rTMS group were significantly better than those in the regular group after treatment in the rTMS group; however, the comparison between iEMG and MAS scores was not statistically significant. It can be seen that both rTMS and ESWT can alleviate upper limb flexor spasm, improve upper limb motor function, and improve activities of daily living in patients with PSS. Among them, ESWT has better antispasmodic effect and better short-term treatment effect.

Discovery of quality markers in Rubus Chingii Hu using UPLC-ESI-QTOF-MS.

Raspberry, the fruit of Rubus Chingii Hu, has been used as a traditional Chinese medicine (TCM) to nourish kidney and strengthen Yang-qi. In order to determine the quality of raspberry, the quality markers (Q-markers) of raspberry that can improve renal function were investigated using UPLC-ESI-QTOF-MS in this study. The results of serum pharmacochemistry indicated that six components rutin, ellagic acid, kaempferol-3-rutinoside, astragalin, tiliroside, and goshonoside F5 in raspberry were absorbed into rat blood. The HEK293 cells treated with cisplatin were used to evaluate the kidney-protecting activity of these absorbed components. All these components could markedly inhibit cell damage induced by cisplatin and restore the levels of malondialdehyde (MDA) and catalase (CAT) in the cells, suggesting that these components may be the Q-markers of raspberry. More importantly, except for ellagic acid, other five Q-markers in raspberries from Dexing of Jiangxi province were higher than those from most of other areas. It is well known that Dexing raspberry is the Dao-di herbs raspberry used in the clinic of Chinese Medicine, demonstrating that these components could be used as Q-markers of raspberry. This study provides a reliable and valuable method for quality evaluation of raspberry.

Toujie Quwen granule used with conventional western therapy for coronavirus disease 2019: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an epidemic infectious disease resulted from 2019 novel coronavirus (2019-nCoV). Up till now, COVID-19 has swept globally. Currently, due to many high-profiled benefits, clinical studies on Toujie Quwen granule (TJQW) have been increasing. The aim of the study is to assess the efficacy and safety of TJQW used with conventional western therapy for COVID-19. METHODS: Relevant randomized controlled trials (RCTs) were searched in Chinese and English databases, and the search time is January 2020 to May 2021. English databases include PubMed, Embase, Web of Science, and the Cochrane Library. Chinese databases include CNKI, WF, VIP, and CBM. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched by us from January 2020 to May 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by 2 researchers independently. Statistical analysis will be conducted using the RevMan 5.3.5 software. After screening the literature based on the inclusion and exclusion criteria, The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality of each result. RESULTS: This study will provide the evidence for TJQW to be used with conventional western therapy for COVID-19. CONCLUSION: The efficacy and safety of TJQW used with conventional western therapy for COVID-19 will be assessed. INPLASY REGISTRATION NUMBER: INPLASY202150038.

Yiqi Fumai Injection as an Adjuvant Therapy in Treating Chronic Heart Failure: A Meta-Analysis of 33 Randomized Controlled Trials.

BACKGROUND: Yiqi Fumai injection (YQFM) is a traditional Chinese medicine widely used for cardiovascular diseases in China. This systematic review aimed to evaluate whether YQFM could be an effective and safe complementary therapy for chronic heart failure (CHF). METHODS: Eight electronic literature databases were searched up to March 31, 2020. Randomized controlled trials (RCTs) comparing YQFM + conventional treatment with conventional treatment alone for CHF were included. The primary outcome was response to treatment, which was graded by improvements in heart function based on the New York Heart Association (NYHA) criteria, while the secondary outcomes included the left ventricular ejection fraction (LVEF), cardiac output, left ventricular end-systolic diameter (LVESD), amino-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test performance (6MWT), quality of life (QoL) as assessed by the Minnesota Living with Heart Failure questionnaire, and adverse reactions. Data from individual RCTs were pooled by a random-effects meta-analysis with effect measures of proportional odds ratios (pORs) and 95% confidence intervals (95% CIs) for the ordinal outcomes and the mean difference (MD) and 95% CI for the continuous outcomes. RESULTS: In total, 33 RCTs involving 3070 patients with an overall moderate-to-high risk of bias were selected. The meta-analysis showed that compared with conventional treatment alone, YQFM plus conventional treatment had a significantly higher likelihood of improving the response to treatment (pOR 1.88, 95% CI 1.47 to 2.42, I 2 = 0%). YQFM also significantly improved the LVEF (MD 5.53%, 95% CI 4.73 to 6.33, I 2 = 82%), cardiac output (MD 0.32 L/min, 95% CI 0.19 to 0.45, I 2 = 47%), and LVESD (MD -3.73 mm, 95% CI -5.51 to -1.95, I 2 = 22%), reduced the NT-proBNP levels (MD -341.83 pg/mL, 95% CI -417.89 to -265.77, I 2 = 88%), and improved the 6MWT (MD 61.86 m, 95% CI 45.05 to 78.67, I 2 = 64%) and QoL (MD -9.82, 95% CI -14.17 to -5.46, I 2 = 81%). No serious adverse events related to YQFM were reported. CONCLUSION: Although limited by a moderate-to-high risk of bias, the current evidence suggests that YQFM as a complementary treatment significantly improves heart function and related indicators in patients with CHF. The clinical use of YQFM needs careful safety monitoring. Well-designed studies are still required to further evaluate the efficacy and safety of YQFM for CHF.

Efficacy and Safety of Shengmai Injection for Chronic Heart Failure: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Shengmai injection (SMI) is made from purified ginseng, Radix Ophiopogonis, and Schisandra chinensis. It has cardiotonic effects and is clinically used for the adjuvant treatment of chronic heart failure (CHF). However, its efficacy and safety are uncertain. The purpose of this study was to systematically evaluate the existing efficacy and safety evidence in randomized controlled trials (RCTs) that studied SMI for the treatment of CHF. METHODS: PubMed, Embase, Cochrane Library, clinicaltrials.gov, CNKI, Wanfang, VIP, and CBM databases were searched up to September 10, 2019. RCTs that compared basic Western medicine treatment with SMI + basic Western medicine were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the risk of bias in the RCTs. The meta-analysis used the random effects model; the mean difference (MD) and 95% confidence intervals (CIs) were combined using the inverse variance method, and the Mantel-Haenszel method was used to combine the relative risk (RR) and 95% CIs. Heterogeneity was assessed using I2 and Q tests, and the source of heterogeneity was explored by analyzing three preset subgroup hypotheses. RESULTS: A total of 20 RCTs were included (n = 1562), with a moderate-to-high risk of bias. The meta-analysis showed that, compared with Western medicine alone, SMI adjuvant therapy significantly improved cardiac function indicators, including left ventricular ejection fraction (MD 6.8%, 95% CI 4.68 to 8.91), stroke volume (MD 9.81 ml, 95% CI 5.67 to 13.96), cardiac output (MD 0.96 L/min, 95% CI 0.66 to 1.25), and cardiac index (MD 0.53 L/min, 95% CI 0.36 to 0.70); heterogeneity was generally high among these outcomes. Compared with the controls, patients receiving SMI adjuvant therapy also had a higher response to treatment (RR 2.89, 95% CI 2.10 to 3.99; I2 = 0%), a greater decrease in brain natriuretic peptide levels (MD -284.66 ng/l, 95% CI -353.73 to -215.59, I2 = 0%), and a greater increase in six-minute walk test performance (MD 70.67 m, 95% CI 22.92 to 118.42; I2 = 84%). Nine studies reported mild adverse events, such as gastrointestinal reactions, and no serious adverse events were reported. CONCLUSION: Currently, available evidence indicates that SMI, as an adjuvant for basic Western medicine treatment, can improve the cardiac function of patients with CHF with good safety outcomes. Because of the high risk of bias among the included RCTs and the large heterogeneity of partial outcomes, the findings of this study must be verified by high-quality studies with large sample sizes.

Acupuncture and related techniques for obesity and cardiovascular risk factors: a systematic review and meta-regression analysis.

OBJECTIVE: To assess how acupuncture and related techniques affect weight-related indicators and cardiovascular risk factors compared with non-acupuncture interventions in overweight and obese patients. METHODS: We searched PubMed, Embase and CENTRAL up to 19 April 2018 and included relevant randomised controlled trials (RCTs). Weighted mean differences (WMDs) and 95% confidence intervals (CI) were pooled using the inverse variance method with random-effects model. Prespecified hypotheses were tested in meta-regression to investigate the source of heterogeneity. Statistical software packages used were RevMan 5.3.5 and Stata 14.0. RESULTS: Thirty-three RCTs were included (n=2503 patients). Compared with non-acupuncture interventions, acupuncture produced a greater reduction in body weight (WMD -1.76 kg, 95% CI -2.22 to -1.30, I2=77%; moderate quality), body mass index (WMD -1.13 kg/m2, 95% CI -1.38 to -0.88, I2=85%; low quality) and waist circumference (WMD -2.42 cm, 95% CI -3.22 to -1.62, I2=75%; moderate quality). Acupuncture plus lifestyle intervention resulted in a greater reduction in body weight than acupuncture alone (MD -1.94 kg, 95% CI -3.17 to -0.70). Acupuncture also led to a greater reduction in total cholesterol (WMD -12.87 mg/dL, 95% CI -22.17 to -3.57, I2=87%; very low quality) and low-density lipoprotein cholesterol (WMD -13.52 mg/dL, 95% CI -21.47 to -5.58, I2=74%; low quality). The differences were not statistically significant for blood glucose or blood pressure. CONCLUSION: In the short term, acupuncture and related techniques may produce a small but statistically significant degree of weight loss based on moderate- to low-quality evidence, and improve serum lipid parameters based on low- to very-low-quality evidence. Their effects on blood glucose and blood pressure remain uncertain.

Efficacy and safety of Hou Gu Mi Xi for peptic ulcer diseases: Study protocol for a randomized controlled trial.

BACKGROUND: Peptic ulcer disease (PUD) is a major burden worldwide. Several challenges remain with standard Western treatment of PUD, such as persistent weakness, fatigue, and relapse. A dietary traditional Chinese medicine (TCM) formula, Hou Gu Mi Xi (HGMX), has been developed as a complementary treatment for PUD. AIMS: This multicenter, double-blind, randomized controlled trial will assess efficacy and safety of HGMX in patients with PUD. METHODS: Three hundred sixty eligible patients will be assigned to receive HGMX, placebo, HGMX + rabeprazole or placebo + rabeprazole for 4 weeks after 2 weeks of standard Western treatment. This first step, with a 2 × 2 factorial design, will focus on assessing the main and interaction effects of HGMX and rabeprazole on ulcer healing. Then, rabeprazole will be stopped, and HGMX will be continued for up to 1 year. The second step, with a placebo-controlled design, will compare the long-term effects of HGMX and placebo. Extended follow-up with no treatment will continue for up to 2 years. Independent and paired t tests, Pearson χ test and the rank-sum test will be used to compare between-group differences. The P value will be adjusted using the O'Brien & Fleming method for multiple comparisons. EXPECTED OUTCOMES: The primary outcomes are total efficacy rate of PUD treatment, quality of ulcer healing, and changes in spleen qi deficiency symptoms. The secondary outcomes include ulcer area, PUD recurrence, Helicobacter pylori eradication rate, gastric function, body weight, and body mass index. Adverse events (AEs), severe AEs, treatment-related AEs, and withdrawal owing to AEs will be recorded to assess treatment safety. DISCUSSION: The trial results will provide high-quality evidence for HGMX, as a complementary therapy, for the long-term management of PUD and will be valuable for the development of related guidelines and regulations. TRIAL REGISTRATION: The protocol of this trial was approved in all research hospitals and was registered in ClinicalTrials.gov at October 25, 2017(No. NCT03320538).

Efficacy and safety of Hou Gu Mi Xi in patients with spleen qi deficiency syndrome who underwent radical gastrectomy for gastric cancer: protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Spleen qi deficiency (SQD), a syndrome based on traditional Chinese medicine (TCM) theory, is common in patients after radical gastrectomy. SQD manifests with chronic gastrointestinal disorders and systemic symptoms and is challenging to manage. Hou Gu Mi Xi (HGMX) is a dietary TCM formula for SQD. This study aims to evaluate the efficacy and safety of HGMX in patients with SQD who have undergone radical gastrectomy for gastric cancer. METHODS AND DESIGN: This study is a multicenter, randomized, double-blind, placebo-controlled trial. One hundred thirty patients with SQD who have undergone radical gastrectomy for gastric cancer will be assigned to receive either HGMX or placebo for 2 years. The main outcome will be changes in SQD symptoms assessed by the Spleen Qi Deficiency Symptoms Grading and Quantifying Scale. The secondary outcomes will be changes in quality of life assessed by the Short Form 36 scale, performance status as assessed by the Eastern Cooperative Oncology Group Performance Status scale, body weight, and body mass index. Progression-free survival will also be assessed as a secondary outcome. Adverse events (AEs), severe AEs, and study withdrawal due to AEs will be recorded to evaluate the safety of HGMX. DISCUSSION: The results of this trial will provide initial evidence for the use of HGMX as an alternative and complementary intervention to manage chronic postoperative complications in patients who have undergone radical gastrectomy for gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03025152 . Registered on 17 January 2017.

Acupuncture and related techniques for type 2 diabetes mellitus: A systematic review protocol.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health problem. As a complementary treatment, acupuncture and related techniques are widely used to treat metabolic and endocrine diseases, but their efficacy and safety for T2DM are yet to be established. This systematic review will qualitatively and quantitatively summarize the current randomized controlled trial (RCT) evidence regarding the efficacy and safety of acupuncture and related techniques in patients with T2DM. METHODS: Comprehensive literature searches will be performed on PubMed, Embase, Cochrane Central Register of Controlled Trials, and a trial registry "ClinicalTrials.gov" from inception to December 3, 2018. We will include RCTs for patients with T2DM that compared acupuncture with placebo, antidiabetic drugs, lifestyle interventions, or the combination. Primary outcomes are fasting blood glucose and hemoglobin A1c. Secondary outcomes include 2-hour blood glucose, fasting insulin, homeostatic model assessment for insulin resistance, incidence of diabetic complications, and acupuncture-related adverse events. The risk of bias of the RCTs included in the review will be examined using a revised Cochrane handbook tool. Heterogeneity will be detected using Cochran Q test and I statistics. With the use of random effects model, we will perform meta-analyses to pool results of RCTs. The effect measures will be weighted or standardized mean difference with 95% confidence intervals (CIs) for the continuous outcomes and risk ratio with 95% CIs for the dichotomous outcomes. Subgroup analyses and meta-regression with predefined effect modifiers will be performed to explore the sources of heterogeneity. Where appropriate, we will assess the possibility of reporting bias based on funnel plots and quantitative detection. We will appraise the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation system for each outcome. RESULTS: This study will provide accurate results and balanced inferences on the efficacy and safety of acupuncture and related techniques on T2DM. CONCLUSION: This well-designed systematic review will establish high-quality evidence of the efficacy and safety of acupuncture and related techniques for T2DM to facilitate the clinical practice and guideline development. PROSPERO REGISTRATION NUMBER: CRD42018115639.

Effects of Gua Sha therapy on perimenopausal syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: In East Asia, Gua Sha therapy is widely used in patients with perimenopausal syndrome. The goal of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of Gua Sha therapy for the treatment of patients with perimenopausal syndrome. METHODS: Databases searched from inception until June 2017 included: PubMed, Embase, the Cochrane Central Register of Controlled Trials and four Chinese databases [WanFang Med Database, Chinese BioMedical Database, Chinese WeiPu Database, and the China National Knowledge Infrastructure (CNKI)]. Only the RCTs related to the effects of Gua Sha therapy on perimenopausal syndrome were included in this systematic review. A quantitative analysis of RCTs was employed using RevMan 5.3 software. Study selection, data extraction, and validation were performed by two independent reviewers. Cochrane criteria for risk-of-bias were used to evaluate the methodological quality of the trials. RESULTS: A total of 6 RCTs met the inclusion criteria, and most were of low methodological quality. When compared with Western medicine therapy alone, meta-analysis of 5 RCTs indicated favorable statistically significant effects of Gua Sha therapy plus Western medicine on the Kupperman Menopausal Index (KMI) Score [mean difference (MD) = -4.57, 95% confidence interval (CI) (-5.37, -3.77), p < 0.01; heterogeneity: Chi2 = 29.57 p < 0.01, I2 = 86%]. Moreover, study participants who received Gua Sha therapy plus Western medicine therapy showed significantly greater improvements in serum levels of follicle-stimulating hormone (FSH) [MD = -5.00, 95% CI (-9.60, -0.40), p = 0.03], luteinizing hormone (LH) [MD = -4.00, 95% CI (-7.67, -0.33), p = 0.03], and E2 [MD = -6.60, 95% CI (-12.32, -0.88), p = 0.02] compared to participants in the Western medicine therapy group, with a low heterogeneity (Chi2 = 0.12, p = 0.94, I2 = 0% in FSH; Chi2 = 0.19 p = 0.91, I2 = 0% in LH; Chi2 = 0.93, p = 0.63, I2 = 0% in E2). In addition, the pooled results displayed favorable significant effects of Gua Sha therapy plus the Western medicine therapy on the MENQOL scale when compared with the Western medicine therapy alone [MD = -5.13, 95% CI (-7.45, -2.81), p < 0.01] with low heterogeneity (Chi2 = 0.66, p = 0.42, I2 = 0%). CONCLUSION: Preliminary evidence supported the hypothesis that Gua Sha therapy effectively improved the treatment efficacy in patients with perimenopausal syndrome. Additional studies will be required to elucidate optimal frequency and dosage of Gua Sha.

Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy.

Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of programmed cell death and has been proved to involve in protecting against oxidative stimuli. Confronted by this challenge, we propose and validate here a novel upconversion photosensitizing nanoplatform which enables significant reduction of cancer resistance and improve PDT efficacy. The upconversion nanophotosensitizer contains the photosensitizing molecules - Zinc phthalocyanine (ZnPc) and Bcl-2 inhibitor - ABT737 small molecules, denoted as ABT737@ZnPc-UCNPs. ABT737 molecules were encapsulated, in a pH sensitive way, into the nanoplatform through Poly (ethylene glycol)-Poly (l-histidine) diblock copolymers (PEG-b-PHis). This nanosystem exhibits the superiority of sensitizing tumor cells for PDT through adjuvant intervention strategy. Upon reaching to lysosomes, the acidic environment changes the solubility of PEG-b-PHis, resulting in the burst-release of ABT737 molecules which deplete the Bcl-2 level in tumor cells and leave the tumor cells out from the protection of anti-apoptotic survival pathway in advance. Owing to the sensitization effect of ABT737@ZnPc-UCNPs, the PDT therapeutic efficiency of cancer cells can be significantly potentiated in vitro and in vivo.

Homology modeling and docking studies of ENPP4: a BCG activated tumoricidal macrophage protein.

BACKGROUND: The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette-Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells. RESULTS: Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand-enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells. CONCLUSIONS: These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained.

Mechanisms of improvement of intestinal transport of baicalin and puerarin by extracts of Radix Angelicae Dahuricae.

Radix Angelicae Dahuricae is the dried root of Angelicae Dahurica (Fisch.ex Hoffm.)Benth.et Hook.f. var.formosana (Boiss.) Shan et Yuan (Fam.Umbelliferae). The total coumarins (Cou) and volatile oil (VO) were main active components that drived from Radix Angelicae Dahuricae. Our previous studies have shown that Cou and VO could increase intestinal absorption for transmucosal drug delivery with unknown mechanism. The aim of this study was to investigate the molecular mechanism of Radix Angelicae Dahuricae for improving drug intestinal transport. Caco-2 cell model was used to study the effect of Radix Angelicae Dahurica on transepithelial electrical resistance. Western blot was used to study its effect on the expression of the actin and ZO-1, tight junction proteins. The effect of Radix Angelicae Dahurica on the expression of P-gp protein was investigated using flow cytometry. VO (0.036-2.88 µL/mL) and Cou (0.027-0.54 mg/mL) caused a reversible, time- and dose-dependent decrease in transepithelial electrical resistance. VO and/or Cou could inhibit the expression of the tight junction protein, ZO-1 and actin. VO and/or Cou also could inhibit the expression of P-gp. These data suggested that Radix Angelicae Dahurica increased cell permeability by affecting the expression of actin, ZO-1 or P-gp, opening the tight junction or inhibiting the efflux induced by P-gp.

A UPLC-MS/MS method for in vivo and in vitro pharmacokinetic studies of psoralenoside, isopsoralenoside, psoralen and isopsoralen from Psoralea corylifolia extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruit of Psoralea corylifolia L. has been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been reported to show estrogen-like activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. The first aim of this study is to develop a rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneous determination of PO, IPO, P and IP in rat plasma and samples collected from in vitro incubation experiments. The second aim is to investigate the pharmacokinetic properties of PO, IPO, P and IP after oral administration of Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. MATERIALS AND METHODS: A UPLC-MS/MS method with a C18 column and a mobile phase of methanol-0.1% aqueous formic acid was validated according to the criteria in FDA guidelines about bioanalytical method, which was developed to investigate the pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways of PO to P or IPO to IP. RESULTS: The criteria for establishment of a new UPLC-MS/MS method including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect and stability were validated. This method was successfully applied to the quantitative determination of PO, IPO, P and IP in biological samples collected from both in vitro incubations and in vivo rat experiments. After oral administration of PCE to rat, pharmacokinetic parameters of these four compounds indicated that in vivo biotransformation may occur between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF), containing only PO and IPO, was orally administered to rats to further confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. An in vitro incubation study elucidated that PO and IPO were metabolized to P and IP by intestinal microflora through de-glucosylation. CONCLUSIONS: This paper developed a rapid, sensitive and selective UPLC-MS/MS method for simultaneous determination of PO, IPO, P and IP from PCE in biological samples, and investigated on their comprehensive in vivo and in vitro pharmacokinetic studies. These obtained results showed that the metabolism by intestinal bacteria plays an important role in pharmacological effects of orally administered PCE.