[Prediction of Cadmium Uptake Factor in Wheat Based on Machine Learning].

Applying machine learning methods to resolve the cadmium (Cd) uptake characteristics of regional soil-wheat systems can contribute to the accuracy and rationality of risk decisions. Based on a regional survey, we constructed a Freundlich-type transfer equation, random forest (RF) model, and neural network (BPNN) model to predict wheat Cd enrichment factor (BCF-Cd); verified the prediction accuracy; and assessed the uncertainty of different models. The results showed that both RF (R2=0.583) and BPNN (R2=0.490) were better than the Freundlich transfer equation (R2=0.410). The RF and BPNN were further trained repeatedly, and the results showed that the mean absolute error (MAE) and root mean square error (RMSE) of RF and BPNN were close to each other. Additionally, the accuracy and stability of RF (R2=0.527-0.601) was higher than that of BPNN (R2=0.432-0.661). Feature importance analysis showed that multiple factors led to the heterogeneity of wheat BCF-Cd, in which soil phosphorus (P) and zinc (Zn) were the key variables affecting the change in wheat BCF-Cd. Parameter optimization can further improve the accuracy, stability, and generalization ability of the model.

[Effect of Zinc Fertilizer Application on Cadmium Accumulation in Wheat Grain and Its Application Risk].

The interaction of zinc (Zn) and cadmium (Cd) is an important research direction in the prevention and control of Cd pollution of wheat in recent years. In this study, a typical wheat field in North China was selected as the object to explore the control effect and application risk of Zn fertilizer on Cd pollution in a soil-wheat system through field experiments. The results showed that under the treatment of a low dosage of Zn, the Cd concentrations in wheat grains in Jiyuan City and Kaifeng City decreased by 33.4% and 25.3% compared with those in the control, respectively. By contrast, Cd concentrations in wheat grains treated with a high dosage of Zn increased by 22.4% and 34.2% compared with that of the low-dosage Zn treatment. After the application of Zn, the total amount and available Zn concentrations increased significantly, and Cd was partially activated in these two locations. Canonical correlation analysis (CCA) showed that when the Zn concentrations in the soils were less than 200 mg·kg-1, soil Zn was the main factor affecting Cd accumulation in the soil-wheat system, whereas when Zn concentrations in soils were greater than 200 mg·kg-1, the activation of soil Cd was the main factor affecting Cd accumulation in wheat grains. Regression analysis showed that when the soil Cd/Zn ratio decreased to 0.0089 (low dosage of Zn), Zn and Cd showed an antagonistic effect, whereas when the soil Cd/Zn ratio decreased to 0.0078 (high dosage of Zn), Zn and Cd showed a synergistic effect. According to the characteristics of regional Cd pollution, adjusting the amount of Zn fertilizer can improve the efficiency of pollution control and avoid aggravating the harm of Cd pollution.

Effect of Electroacupuncture on Gut Microbiota in Participants With Knee Osteoarthritis.

A close relationship between knee osteoarthritis (KOA) and gut microbiota has recently been described. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with KOA. We conducted a study of 60 participants with KOA and 30 matched healthy controls (HCs). Sixty participants were allocated to either EA group (n=30) or sham acupuncture (SA) group (n=30). Five obligatory acupoints and three adjunct acupoints were punctured in the EA group. Eight non-acupoints that were separated from conventional acupoints or meridians were used for the SA group. Participants in both groups received 24 sessions within eight weeks. Fecal microbial analyses by 16S ribosomal RNA gene sequencing were carried out after collecting stools at T0 and T8 weeks (Four samples with changed defecation habits were excluded). The results showed that both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (P=0.043) and NRS score (P=0.002) decreased more in EA group than those in SA group. Moreover, EA could reverse more KOA-related bacteria including Bacteroides, [Eubacterium]_hallii_group, Agathobacter and Streptococcus. The number of significantly different genera between KOA patients and HCs were less after EA treatment than that after SA treatment. This meant that EA modified the composition of the gut microbiome, making it closer to healthy people, while not significantly affecting the microbial diversity. Two genera including Agathobacter (P=0.0163), Lachnoclostridium (P=0.0144) were statistically increased than baseline in EA group (paired Wilcoxon rank sum test). After EA treatment, Bacteroides (P=0.0394) was more abundant and Streptococcus (P=0.0306) was significantly reduced in patients who demonstrated adequate response than in those with inadequate response (Wilcoxon rank-sum test). Spearman correlation test between gut microbe and KOA clinical outcomes indicated that Bacteroides and Agathobacter was negatively correlated with NRS score, WOMAC total score, and WOMAC pain, stiffness and pain scores (P<0.001 or 0.05 or 0.01), while Streptococcus was positively correlated with them (P<0.05 or 0.01). Our study suggests that EA contributes to the improvement of KOA and gut microbiota could be a potential therapeutic target.

Dynamic Protective Effect of Chinese Herbal Prescription, Yiqi Jiedu Decoction, on Testis in Mice with Acute Radiation Injury.

OBJECTIVE: A Chinese herbal prescription, Yiqi Jiedu (YQJD) decoction, is used for injuries caused by radiotherapy. This study aimed to investigate the dynamic protective effects of YQJD decoction in mice on radiation damage at different time points of the testis. METHODS: The 200 male Balb/c mice were randomly divided into 5 groups (blank, model, Anduolin, low-dose YQJD, and high-dose YQJD groups). Blank and model groups were all given stomach deionized water. Anduolin group and high and low dose of Chinese herb groups were treated with Chinese material medical decoction compound for 2 weeks before being irradiated. Except for the blank group, other groups were given whole-body one-time irradiation of 5.5 Gy 60Co gamma rays. Histopathology examination of testes was conducted on the 1st, 7th, 21st, and 35th day after irradiation, respectively. Indexes of sperm motility rate, sperm count, serum levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured correspondingly. RESULT: Compared to 1 day and 7 days after irradiation, most of the indexes, including testis index, sperm motility, and count, were decreased on the 21st and 35th day in all irradiated groups. However, compared with the model group, the indexes to assess sperm quality and the morphological structures of testis in low-dose and high-dose YQJD groups were significantly recovered on the 21st and 35th days. Additionally, reproductive hormones, including testosterone and estradiol, were recovered more in low-dose and high-dose YQJD groups on the 21st and 35th days. CONCLUSION: The YQJD decoction is able to accelerate the recovery of sperm indexes, testosterone, and estradiol levels of sex hormones in mice after irradiation and demonstrated good protective effects on the testis.

Efficacy of Intensive Acupuncture Versus Sham Acupuncture in Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). METHODS: In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement. RESULTS: Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. CONCLUSION: Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up.

Effect of Electro-Acupuncture (EA) and Manual Acupuncture (MA) on Markers of Inflammation in Knee Osteoarthritis.

BACKGROUND: Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both electro-acupuncture (EA) and manual acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA. METHODS: Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, IL-18, IL-4, IL-10, IL-13, IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CC-chemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP)) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) at baseline and post-treatment. RESULTS: Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNFα, IL-1ß), and cartilage degradation biomarkers (MMP-3, MMP-13) significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p<0.05). Further, the reduction of TNF-α was more significant in EA when compared to MA (p=0.046). While there was no significant difference between groups in cytokines IL-1ß (p=0.102), MMP-3 (p=0.113), MMP-13 (p=0.623) or IL-13 (p=0.935). Moreover, in both EA and MA, the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups. CONCLUSION: Eight weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-α, IL-1ß and IL-13. TRIAL REGISTRATION: Controlled-Trials.com Identifier: NCT03274713.

Effect of Electroacupuncture versus Sham Electroacupuncture in Patients with Knee Osteoarthritis: A Pilot Randomized Controlled Trial.

OBJECTIVE: To explore the feasibility of evaluating the effectiveness and safety of electroacupuncture versus sham electroacupuncture for patients with knee osteoarthritis (KOA). METHOD: A pilot randomized controlled trial was conducted at a teaching hospital in Beijing. A total of 30 patients with KOA (Kellgren grade II or III) were randomly allocated to an eight-week treatment of either electroacupuncture or sham electroacupuncture. Patients and outcome assessors were blinded to group allocation. The primary outcome was the proportion of responders achieving at least 1.14 seconds decrease in the Timed Up and Go Test (TUG) at week eight compared with baseline. The secondary outcomes included the knee range of motion, the knee extensor and flexor muscle strength, Lequesne index, 9-step stair-climb test (9-SCT), and TUG. RESULTS: Of 30 patients allocated to two groups, 27 (90%) completed the study. The proportion of responders was 53.3% (8 of 15) for electroacupuncture group and 26.7% (4 of 15) for sham electroacupuncture group by the intention-to-treat analysis (P = 0.264). There was no statistically significant difference in TUG between the two groups at eight weeks (P = 0.856). The compliance rate measured according to patients who conformed to the protocol and had received treatments ≥20 times was 93.3% (28 of 30). The dropout rate was 20% (3 of 15). Adverse effects were not reported in the study. CONCLUSION: Our research demonstrated that further evaluation of the effectiveness of electroacupuncture versus sham electroacupuncture was feasible and safe for patients with KOA. Whether or not the electroacupuncture can improve the physical functions of knee joint, expand the knee range of motion, and increase the extensor and flexor muscle strength more significantly than sham electroacupuncture, future studies can be designed with larger sample size, randomization design and less biases. This trial is registered with NCT03366363.

Qingxin Kaiqiao Fang Inhibits Aß 25-35-Induced Apoptosis in Primary Cultured Rat Hippocampal Neuronal Cells via the p38 MAPK Pathway: An Experimental Validation and Network Pharmacology Study.

Qingxin kaiqiao fang (QKF), a traditional Chinese medicine compound, has been applied to treat Alzheimer's disease (AD) for many years and has exhibited remarkable effects. However, the underlying mechanism is still not explicit. The current study aims to investigate whether QKF exerts an antiapoptotic role through the p38 MAPK pathway in the course of AD. Network pharmacology analysis was applied to study the effective components, possible therapeutic targets, and AD-related pathway of QKF. Further, the AD cell model was established using amyloid-beta (Aß)25-35 peptide and primary hippocampal neuronal cells extracted from newborn Sprague-Dawley rats. Microtubule-associated protein-2 (MAP-2) imaging was used to detect the morphology of hippocampal neurons. Western blot (WB) analysis was applied to detect the protein expression levels of p38 MAPK, p-p38 MAPK, Bcl-2, Bax, caspase-3, and cleaved caspase-3. Cell viability and apoptosis were determined using cell counting kit-8 (CCK-8) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. SB203580 and U46619 were used to detect changes in cell morphology, cell viability, and apoptosis upon inhibiting or activating p38 MAPK. Our present work showed that QKF protects hippocampal neuronal morphology, enhances cell viability, and reduces the number of TUNEL-positive cells. In addition, our results showed that QKF increased the expression levels of antiapoptotic proteins and decreased the expression of proapoptotic proteins. QKF at 25 mg·mL-1 best inhibited neuronal apoptosis among the three doses of QKF by suppressing p38 MAPK activity. Collectively, QKF plays an antiapoptotic role via the p38 MAPK pathway.

Pentamethylquercetin Inhibits Hepatocellular Carcinoma Progression and Adipocytes-induced PD-L1 Expression via IFN-γ Signaling.

BACKGROUND: Obesity is a significant risk factor for the development of types of cancer. Programmed death 1 and its ligand programmed death-ligand 1 (PD-L1) play a crucial role in tumor immune escape. Although, the role of PD-L1 in obesity-associated hepatocellular carcinoma (HCC) remains unknown. We previously showed that the natural flavonoid pentamethylquercetin (PMQ) possesses anti-obesity properties. OBJECTIVE: This study was designed to investigate the effects of PMQ on the development of HCC in obese mice and whether PMQ regulates PD-L1 and expression in HCC. METHODS: Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells. Tumor volumes and weights were measured. In vitro, 3T3-L1 preadipocytes were differentiated and lipid accumulation was measured by oil-red staining, and IFN-γ level was detected by Elisa. Hepatoma HepG2 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Western blotting was applied to detect PD-L1 protein levels in tumor tissue and HepG2 cells. RESULTS: Compared with control mice, H22 tumors grew faster and exhibited higher PD-L1 protein levels in obese mice. PMQ inhibited H22 tumor growth and reduced PD-L1 expression in tumor tissues. PD-L1 protein level was elevated in adi-CM-treated HepG2 cells. IFN-γ was detectable in adi-CM and exogenous IFN-γ induced PD-L1 expression in HepG2 cells. PMQ affected the differentiation of 3T3-L1 preadipocytes, decreased the level of IFN-γ secreted by adipocytes and downregulated adi-CM-induced PD-L1 expression in HepG2 cells. CONCLUSION: PMQ could inhibit HCC progression in obese mice at least in part through down-regulating adipocytes-induced PD-L1 expression via IFN-γ signaling.

Qingxin Kaiqiao Recipe Improves Cognitive Performance, Inhibits Apoptosis, and Reduces Pathological Deposits in APP/PS1 Double Transgenic Mice via the PI3K/Akt Pathway.

The traditional Chinese medicine of Qingxin Kaiqiao Recipe (QKR) is effective in the treatment of Alzheimer's disease (AD). This study aims to investigate whether QKR improves the cognitive ability and takes neuroprotective effect on APP/PS1 double transgenic mice via the PI3K/Akt pathway. APP/PS1 double transgenic mice were randomly divided into a model, donepezil-treated, or QKR-treated group (L-QKR: 4.75 mg/kg/d, M-QKR: 9.5 mg/kg/d, and H-QKR: 19 mg/kg/d, respectively). Wild-type C57/BL6J mice were used as the control group. Morris water maze (MWM) was used to test the ability of spatial navigation and memorization; terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay was applied to test the apoptosis; amyloid protein granule deposition was detected via Methenamine silver staining; Western blot (WB) analysis, immunohistochemistry, and RT-PCR were applied to measure the expression of Aß and corresponding indicators of the PI3K/Akt pathway. Compared with the model group, QKR significantly relieved the cognitive impairment, reduced the deposition of senile plaques, decreased the expression of GSK-3α and Aß, and increased the expression of p-PI3K, p-Akt, and IDE. In addition, the number of TUNEL-positive cells decreased after treatment using QKR. The current study proved that QKR, especially at the high dose tested, exerted a protective effect on improving learning and memory, inhibiting apoptosis, and reducing the process of pathological degeneration in the hippocampus of AD mice.

Electroacupuncture versus manual acupuncture for knee osteoarthritis: a randomized controlled pilot trial.

OBJECTIVE: We aimed to explore the feasibility of evaluating the comparative effectiveness and safety of electroacupuncture (EA) relative to manual acupuncture (MA) for the treatment of knee osteoarthritis (KOA). METHODS: A multicenter randomized controlled clinical trial was conducted in Beijing from September 2017 to January 2018. A total of 60 participants with KOA were randomly allocated to either EA (n = 30) or MA (n = 30) groups. Participants in the EA group were treated with EA at six to seven local traditional acupuncture points or ah shi points, and two to three distal points. Participants in the MA group had the same schedule as the EA group except that the electrical apparatus featured a working power indicator without actual current output, constituting a sham EA procedure, in order to blind participants. Both groups received 24 sessions over 8 weeks. The primary outcome was response rate, defined as a change of ⩾50% from baseline in the total scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after 8 weeks. Secondary outcomes included pain, stiffness, function, quality of life, and acupuncture-related adverse events (AEs) at 4 and 8 weeks. RESULTS: Of 60 participants randomized, 53 (88%) completed the study. Response rates were 43% for the EA group and 30% for the MA group by the intention-to-treat analysis. Although significant differences were observed in WOMAC pain, stiffness, and function scores within both groups, between-group differences at 8 weeks did not reach statistical significance (odds ratio = 1.75 (95% confidence interval = 0.593-5.162)). Rates of AEs were low and similarly distributed between groups. CONCLUSION: Both EA and MA interventions in KOA were feasible and appeared safe. Whether or not EA may have a stronger impact on pain and function requires further evaluation through larger, adequately powered, randomized controlled trials. TRIAL REGISTRATION NUMBER: NCT03274713.

A boronic acid modified binary matrix consisting of boron nitride and α-cyano-4-hydroxycinnamic acid for determination of cis-diols by MALDI-TOF MS.

A MALDI-TOF mass spectrometric method is described for the determination of small molecule compounds with cis-diol. It is based on the use of a binary matrix consisting of boron nitride (BN) and α-cyano-4-hydroxycinnamic acid that was modified with the derivatization reagent of (3-(acridin-9-ylamino)phenyl)boronic acid which can recognize cis-diols. The binary matrix is used for desorption/ionization (DI) in the positive ion mode. The mechanism leading to DI enhancement was investigated. The results imply that BN is beneficial for the DI because it induces an enhancement in the positive ion mode. The boronic acid-functionalized binary matrix was successfully applied to capture the glucose, shikimic acid and quinic acid. The method was applied to the determination of 3-chloro-1,2-propanediol in plant oil. Graphical abstract Schematic representation of a method for detecting the cis-diol compounds on matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) using the binary matrix of boron nitride (BN)/α-cyano-4-hydroxycinnamic acid (CHCA) that was modified with (3-(acridin-9-ylamino)phenyl) boronic acid (AYPBA).

Acupuncture of different treatment frequency in knee osteoarthritis: a protocol for a pilot randomized clinical trial.

BACKGROUND: This study aims to determine whether 3 sessions per week of acupuncture treatment is superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. METHODS/DESIGN: This is a two parallel-group, assessor-blinded, randomized controlled trial. Sixty patients with knee osteoarthritis (Kellgren-Lawrence grade II or III) will be recruited and randomly allocated to receive 24 or 8 sessions (group M or group L) of acupuncture treatment in a 1:1 ratio. Patients in group M will receive 3 sessions per week of acupuncture for 8 weeks. Patients in group L will receive acupuncture once per week for 8 weeks. The primary outcome is the response rate-the percentage of patients achieving a decrease ≥ 2 points on a numerical rating pain scale and a decrease ≥ 6 points in the Western Ontario and McMaster Universities Osteoarthritis Index function score at 8 weeks compared with baseline. Secondary outcomes include pain, function, overall effect, quality of life, and treatment credibility and expectancy. DISCUSSION: Three sessions per week of acupuncture treatment may be superior to 1 session per week of acupuncture treatment for symptomatic outcomes in knee osteoarthritis. Results of the study will be of great importance for the guidelines of clinical therapy. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03359603 . Registered on 1 December 2017.

[Researches status on time-effect of acupuncture].

OBJECTIVE: To summarize the research status and influencing factors of the time-effect of acupuncture and to explain and analyze the optimal effect timing of acupuncture, and provide reference for obtaining the best clinical therapeutic effect. METHODS: Literature regarding the studies of the time-effect of acupuncture published from January 2000 to August 2018 was searched, concluded and analyzed in CNKI, WANFANG, VIP and PubMed databases. RESULTS: A total of 43 papers were included. The time-effect relationship of acupuncture was studied from various aspects: immediate effect, post-effect and total time-effect. The influencing factors of time-effect of acupuncture included needle retention time, acupoint types, number of acupoints and frequency of acupuncture treatment. CONCLUSION: Even though preliminary achievements have been made in the study of the time-effect of acupuncture, there are many limitations and deficiency. These studies are mostly isolated and unsystematic, and the observation time of needle retention time and post-effect is not long enough to observe the exact best induction period, half-life period and residual effect period of acupuncture.In the future, we should combine the existing research experience and achievements to formulate a more reasonable research plan and observe the entire period of acupuncture in a longitudinal direction.

A retrospective study of acupuncture as an adjunctive therapy to topical ibuprofen for chronic knee pain due to osteoarthritis.

This retrospective study investigated the effectiveness and safety of acupuncture as an adjunctive therapy to topical ibuprofen (TIP) for patients with chronic knee pain (CKP) due to osteoarthritis.This retrospective study analyzed medical records of 84 patients with CKP due to osteoarthritis. These patients were divided into a treatment group (n = 42) and a control group (n = 42). The patients in the treatment group were treated with acupuncture plus TIP, while the subjects in the control group received TIP monotherapy. The primary effectiveness endpoint was assessed by Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The secondary effectiveness endpoints were evaluated by the numeric rating scale (NRS), 12-item Short FormHealth Survey (SF-12, mainly including mental component summary [MCS], and physical component summary [PCS]), and adverse events. All patients received an 8-week treatment. All endpoints were measured pre-treatment and posttreatment.The patients who received acupuncture plus TIP showed better effectiveness in both primary endpoint of WOMAC scale (pain, P < .01; function, P < .01; and stiffness, P < .01) and secondary endpoints of NRS (P < .01), and SF-12 (MCS, P < .01; and PCS, P < .01), than patients who received TIP monotherapy. In addition, both groups had similar safety profile.The results of this study showed that the effectiveness of acupuncture plus TIP may be better than TIP monotherapy for patients with CKP due to osteoarthritis.

Correction to: Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: study protocol for a randomised controlled trial.

After publication of the original article [1], the authors have notified us that the Trial registration number NCT03274713 should be replaced by NCT03366363 in the Abstract section of the paper.

Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: study protocol for a randomised controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. METHODS/DESIGN: This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. DISCUSSION: This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.

Effectiveness and feasibility of acupuncture for knee osteoarthritis: a pilot randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. DESIGN:: Pilot randomized controlled trial. SETTING:: Three teaching hospitals in China. SUBJECTS:: Patients with knee osteoarthritis (Kellgren grade II or III). INTERVENTIONS:: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. MAIN MEASURES:: The primary outcome was response rate-the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. RESULTS:: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. CONCLUSION:: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

Routine Surveillance of Chemotherapy Toxicities in Cancer Patients Using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

INTRODUCTION: Systematic documentation of chemotoxicities in outpatient clinics is challenging. Incorporating patient-reported outcome (PRO) measures in clinical workflows can be an efficient strategy to strengthen the assessment of symptomatic treatment toxicities in oncology clinical practice. We compared the adequateness, feasibility, and acceptability of toxicity documentation using systematic, prospective, application of the PRO Common Toxicity Criteria for Adverse Events (PRO-CTCAE) tool. METHODS: At a comprehensive cancer center, data abstraction of electronic health record reviews elucidated current methods and degree of chemotoxicity documentation. Web-based 32-item PRO-CTCAE questionnaires, administered in ambulatory clinics of patients receiving chemotherapy, captured chemotoxicities and respective severities. Patient telephone surveys assessed whether healthcare providers had addressed chemotoxicities to the patients' satisfaction. RESULTS: Over a broad demographic of 497 patients receiving chemotherapy, 90% (95% CI 84-96%) with significant chemotoxicities (n = 107) reported that their providers had discussed toxicities with them; of these, 70% received a therapy management change, while among the rest, 17% desired a change in management. Of patients surveyed, 91% (95% CI 82-99%) were satisfied with their current chemotoxicity management. Clinician chart documentation varied greatly; descriptors rather than numerical grading scales were typically used. Although 93% of patients were willing to complete the PRO survey, only 50% thought that it would be acceptable to complete this survey at routine clinic visits. CONCLUSION: Use of PRO-CTCAE in routine clinical practice promotes systematic evaluation of symptomatic toxicities and improves the clarity, consistency, and efficiency of clinician documentation; however, methods to improve patient willingness to complete this tool routinely are needed.

Discovery of pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives as a new class of histone lysine demethylase 4D (KDM4D) inhibitors.

Herein we report the discovery of a series of new small molecule inhibitors of histone lysine demethylase 4D (KDM4D). Molecular docking was first performed to screen for new KDM4D inhibitors from various chemical databases. Two hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the more selective one, compound 2, which led to the discovery of several new KDM4D inhibitors. Among them, compound 10r is the most potent one with an IC50 value of 0.41±0.03µM against KDM4D. Overall, compound 10r could be taken as a good lead compound for further studies.