Effectiveness of high-dose third-generation EGFR-tyrosine kinase inhibitors in treating EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastasis.

BACKGROUND: Leptomeningeal metastasis (LM) is associated with an extremely poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-tyrosine kinase inhibitors (TKIs), currently the preferred drug of choice, have significantly improved treatment outcomes in these patients. However, the optimal dose of third-generation EGFR-TKIs for clinical use remains undetermined in NSCLC patients with LM. METHODS: We retrospectively analyzed the clinical characteristics and treatment outcomes of 105 patients with EGFR-mutated NSCLC and cytologically confirmed LM who had received third-generation EGFR-TKI treatment after LM diagnosis. Patients were stratified into high- and standard-dose groups based on the treatment dose of third-generation EGFR-TKI. Subsequent treatments for LM were collected, particularly the efficacy of different doses of third-generation EGFR-targeted drugs. RESULTS: The median follow-up period was 28.7 months (range 0.6-40.2) at the cut-off date of August 27, 2023. The 105 included patients who received third-generation EGFR-TKI treatment had a clinical response rate (CRR) of 54.3 % (57/105), and the median overall survival (OS) from LM diagnosis was 12.3 months (95 % confidence interval [CI] = 10.0-15.0). Among them, 46 (43.8 %) patients received a high-dose regimen, and the remaining 59 (56.2 %) patients were treated with standard-dose drugs. Patients treated with high-dose third-generation EGFR-TKIs showed a higher CRR and longer OS than those treated with standard-dose therapy (65.2 % vs. 45.8 %, p = 0.047; 15.0 vs. 10.2 months, p = 0.014). Importantly, high-dose third-generation EGFR-TKI showed superior OS than standard-dose treatment in all subgroups (prior first-/second-generation EGFR-TKI resistance group, 19.5 vs. 9.8 months, p = 0.047; third-generation EGFR-TKI resistance group, 10.0 vs. 4.3 months, p = 0.045; EGFR-TKI naive group, not reach vs. 15.6 months, p = 0.031). Multivariate analysis revealed that high-dose third-generation EGFR-TKIs, intrathecal chemotherapy, previous TKI treatment history, and Karnofsky Performance Status score were independent predictors of OS (all p < 0.05). CONCLUSIONS: High-dose third-generation EGFR-TKIs are effective treatments for NSCLC patients with EGFR mutations and LM, regardless of previous EGFR-TKI exposure.

Electroacupuncture for hot flashes in early postmenopause: A study protocol for a randomized sham-controlled trial.

Introduction: Many early postmenopausal women experience hot flashes (HFs). Electroacupuncture (EA) is a safe and effective therapy for menopause-related symptoms. However, there are few rigorous clinical trials on this topic. This randomized controlled trial is designed to explore the feasibility and efficacy of EA in the treatment of early postmenopausal HF. Methods: This study is a randomized, controlled trial involving 72 early postmenopausal patients. Patients will be randomized 1:1 to the EA or sham acupuncture (SA) group. The acupuncture points that will be used are Hegu (LI4), Fuliu (KI7), Taixi (KI3), Shenshu (BL23), Guanyuan (CV4), and Sanyinjiao (SP6). Participants in each group will receive 18 acupuncture sessions over 6 weeks (three times per week). The primary outcome is the hot-flash score at the end of the 6 week of intervention. Secondary outcome measures are the Pittsburgh Sleep Quality Index, Menopause-Specific Quality of Life, Menopause Rating Scale, Traditional Chinese Medicine Syndrome Score Scale, and estradiol, follicle-stimulating hormone, luteinizing hormone, and anti-Mullerian hormone levels. Safety will be assessed at every visit. Conclusion: This prospective trial will evaluate the efficacy of EA in the treatment of HFs among early postmenopausal women. Our results will provide additional knowledge for clinicians in the treatment of HFs.

Effect of Electroacupuncture Versus Cognitive Behavioral Therapy for Perimenopausal Insomnia: Protocol for a Noninferiority Randomized Controlled Trial.

BACKGROUND: Perimenopausal insomnia (PMI) has a high global incidence, which is common in middle-aged women and is more severe than nonmenopausal insomnia. Effective treatments with fewer side effects and more consistent repeatable results are needed. Acupuncture, a therapy based on traditional Chinese medicine, is safe and may be effective for PMI. It is widely accepted in Western countries, and evidence supports the use of acupuncture as a main or supplementary therapy. Cognitive behavioral therapy is also used to improve sleep quality. It has structured sessions and has been recommended as a first-line treatment for insomnia (cognitive behavioral therapy for insomnia [CBT-I]) by the American Association of Physicians. However, few randomized controlled trials have been conducted to compare the effectiveness of these 2 therapies. This study will be performed in perimenopausal women with insomnia to determine the efficacy of electroacupuncture (EA) versus CBT-I. OBJECTIVE: This study aimed to compare the preliminary effectiveness and safety of EA and CBT-I for PMI through a randomized controlled noninferiority study design. METHODS: This study is designed as an assessor-blinded, noninferiority, randomized controlled trial. A total of 160 eligible participants with PMI will be randomly divided into 2 groups to receive either EA or CBT-I. Participants in the EA group will receive electroacupuncture for 8 weeks. The intervention will be delivered 3 times weekly for a total of 12 sessions and 2 times weekly for the next 4 weeks. Meanwhile, participants in the control group will undergo CBT-I (once a week) for 8 weeks. Treatment will use 7 main acupoints (GV20, DU24, EX-HN3, EX-HN18, EX-CA1, RN6, and RN4) and an extra 4 acupoints based on syndrome differentiation. The primary outcome is the Insomnia Severity Index. The secondary outcome measures are the Pittsburgh Sleep Quality Index; Menopause-Specific Quality of Life; Menopause Rating Scale; Hamilton Depression Scale; Hamilton Anxiety Scale; hot flash score; and the level of estradiol, follicle-stimulating hormone, and luteinizing hormone in serum. Sleep architecture will be assessed using polysomnograms. RESULTS: Participants are currently being recruited. The first participant was enrolled in January 2023, marking the initiation of the recruitment phase. The recruitment process is expected to continue until January 2025, at which point data collection will commence. CONCLUSIONS: This trial represents a pioneering effort to investigate the efficacy and safety of EA and CBT-I as interventions for PMI. It is noteworthy that this study is conducted solely within a single center and involves Chinese participants, which is a limitation. Nonetheless, the findings of this study are expected to contribute valuable insights for clinicians engaged in the management of PMI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070981; https://www.chictr.org.cn/showprojEN.html?proj=194561. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51767.

[Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency. METHODS: A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups. RESULTS: After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01). CONCLUSION: Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Effect of Acupuncture on Postoperative Pain in Patients after Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

Objective: To evaluate the efficacy and safety of acupuncture compared to that of parecoxib sodium on postoperative pain (POP), postoperative nausea and vomiting (PONV), and the Bruggemann Comfort Scale (BCS) in patients following laparoscopic cholecystectomy (LC). Methods: Eligible patients admitted to the hospital for LC were randomly allocated to either acupuncture or control groups in a 1 : 1 ratio. The subjects in the acupuncture group received acupuncture while those in the control group were injected by parecoxib sodium at their requests. The pain score, PONV score, and BCS were assessed at 0 h, 6 h, 9 h, and 12 h after operation. The primary outcome was the pain score. The secondary outcomes included the number of patients asking for parecoxib sodium from the two groups at 0-6 h and 6-12 h, PONV score, and BCS score. Results: The pain score of the acupuncture group were lower in acupuncture than that in the control group at 6 h and 9 h after operation (P=0.002, P=0.008). However, no difference was found at 12 h. Besides, the number of patients administered parecoxib sodium in acupuncture group was less than that in the control group both at 0-6 h and 6-12 h after operation (P=0.019, P < 0.001). Similarly, there were significantly lower levels of PONV score and higher levels of BCS at 6 h after operation in the acupuncture group than in the control group. However, no difference was found at 9 h and 12 h. Conclusion: Acupuncture can clinically improve the short-term treatment of postoperative pain after LC and reduce the request for extra analgesics; therefore, acupuncture might be a potential method as one of multimodal analgesia techniques to treat POP following LC. Trial Registrations. This trial is registered with ChiCTR2000036885 (Chinese Clinical Trial Registry).

Impact of Acupuncture on Sleep and Comorbid Symptoms for Chronic Insomnia: A Randomized Clinical Trial.

STUDY OBJECTIVES: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia. METHODS AND DESIGN: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures. RESULTS: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups. CONCLUSION: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia. CLINICAL TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.

Effects of Electroacupuncture on Sleep via the Dopamine System of the HPA Axis in Rats after Cage Change.

BACKGROUND: Insomnia is often related to stressful events. The hypothalamus-pituitary-adrenal (HPA) axis is related to stress, and dopamine (DA) and DA receptors are involved in the regulation of HPA axis. Electroacupuncture (EA) can improve sleep in individuals with insomnia, but the mechanism is unclear. We demonstrated that EA can improve sleep in rats after cage change through DA and the DA receptors in the HPA axis. METHODS: A rat model of insomnia was established by cage change to a dirty cage. The rats in treatment groups were intervened by EA and D1R (or D2R) antagonists. Electroencephalography (EEG) and electromyogram (EMG) were recorded to compare the changes in sleep. The DA, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the plasma and hypothalamus were measured by ELISAs, and the D1R and D2R levels were measured by RT-PCR and immunohistochemistry. RESULTS: The dirty group showed a significant increase in the amount of wakefulness and decrease in the amount of NREM sleep, with decreased numbers of long NREM sleep bouts and REM sleep bouts and increased mean duration of wakefulness during the light period. EA and D1R (or D2R) antagonists intervention could improve sleep disturbance by decreasing wakefulness in the light period after cage change, EA and D1R (or D2R) antagonists could increase the hypothalamus DA, CRH, ACTH, CORT level, and the D1R and D2R mRNA levels in the HPA axis, and the effect of EA plus D1R (or D2R) antagonist was not superior to that of EA or D1R (or D2R) antagonists alone. CONCLUSIONS: EA can improve the sleep of rats after cage change, and the mechanism may be related to the regulation of DA and D1R or D2R in the HPA axis.

Cigarette smoke exposure impairs lipid metabolism by decreasing low-density lipoprotein receptor expression in hepatocytes.

BACKGROUND: Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear. METHODS: In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%. RESULTS: The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 µM melatonin. CONCLUSIONS: In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers.

Acupuncture for insomnia with short sleep duration: protocol for a randomised controlled trial.

INTRODUCTION: Insomnia with short sleep duration has a more serious negative impact on patient health. The existing literature suggests that medication therapy is more effective for this phenotype of insomnia compared with cognitive-behavioural therapy. However, the potential side effects of hypnotic medications hinder their clinical application. Acupuncture has been widely used in the treatment of insomnia, but it remains unclear whether it has therapeutic efficacy for insomnia with short sleep duration. The purpose of this trial is to evaluate the efficacy and safety of acupuncture for insomnia with short sleep duration. METHODS AND ANALYSIS: This study is designed as a randomised, single-centre, single-blinded, placebo acupuncture controlled trial involving 152 participants. Eligible patients will be divided into two groups according to the objective total sleep time: insomnia with normal sleep duration group and insomnia with short sleep duration group. Then, patients in each group will be randomly assigned to two subgroups, the treatment group (acupuncture) and the control group (placebo acupuncture), in a 1:1 ratio with 38 subjects in each subgroup. The primary outcome is the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. Secondary outcomes are actigraphy, the Beck Anxiety Inventory, the Beck Depression Inventory and the Fatigue Severity Scale. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, post treatment, as well as at 1-week and 1-month follow-up. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (no. 2019-17). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications. TRIAL REGISTRATION NUMBER: ChiCTR1900023473; Pre-results.

[Electroacupuncture at "Zusanli"(ST36) and "Xuanzhong"(GB39) improves inflammatory reactions and reduces levels of serum MMP-3 and MMP-9 in adjuvant arthritis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Xuanzhong" (GB39) on joint inflammatory reactions and serum matrix metalloproteinase-3 (MMP-3) and MMP-9 contents in rats with adjuvant arthritis (AA), so as to explore its mechanism underlying improvement of AA. METHODS: Forty male SD rats were randomly divided into control, model, acupoint and non-acupoint groups (n=10 in each group). The arthritis model was established by hypodermic injection of complete Freund's adjuvant (0.1 mL) into the bilateral footpads. EA (2 Hz, 3 V) was applied to bilateral ST36 and GB39 or two non-acupoints (5 mm left to ST36 and GB39) for 15 min, once every other day for a total of 8 times. The arthritis index score was evaluated according to the severity of local erythema and swelling of the ankle joint, plantar joint, toe joint and foot metacarpal joint (0-4 points). The inflammatory conditions of the ankle joint were observed by H.E. staining, and the contents of serum MMP-3 and MMP-9 were assayed by ELISA. RESULTS: The arthritis index score and serum concentrations of MMP-3 and MMP-9 were significantly increased in the model group relevant to the control group (P<0.01), and obviously decreased after EA intervention on the 18th day (P<0.01). The therapeutic effect of acupoint EA was notably superior to non-acupoint EA in down-regulating the arthritis index score and serum MMP-3 and MMP-9 concentrations (P<0.01). Under light microscope, marked proliferation of the synovial cells, inflammatory cell infiltration and increase of newly blood vessels were observed in the ankle joint of the model group, which was relatively milder in the acupoint group. CONCLUSION: acupoint EA intervention can significantly alleviate the inflammatory reaction of AA rats, which may be related to its effects in reducing the levels of serum MMP-3 and MMP-9.

Effect of electroacupuncture at the ST36 and GB39 acupoints on apoptosis by regulating the p53 signaling pathway in adjuvant arthritis rats.

p53 and mouse double minute 2 homolog (MDM2) serve key regulatory roles in the apoptosis of synovial cells. The present study aimed to investigate the effects of electroacupuncture (EA) at the 'Zusanli' (ST36) and 'Xuanzhong' (GB39) acupoints on apoptosis in an adjuvant arthritis (AA) rat model. A total of 40 male Sprague­Dawley rats were randomly divided into Control, AA, AA + EA and AA + sham EA groups (n=10 rats in each group). Rats in all the groups, with the exception of the control group, were injected with Complete™ Freund's adjuvant into the bilateral hindlimb footpad to establish the AA model. Rats in the AA + EA group were treated with EA at the ST36 and GB39 acupoints. Rats in the AA + sham EA group were treated with percutaneous electrical stimulation at a position of 5 mm away from the ST36 and GB39 acupoints. The arthritis index scores and hindlimb paw volumes of the rats in each group were recorded. Subsequently, pathological changes in the synovial tissue were evaluated by hematoxylin and eosin (H&E) staining, and the apoptotic rate of the synovial cells was detected by TUNEL staining. In addition, the expression levels of the apoptosis­associated proteins, Bax, phorbol­12­myristate­13­acetate­induced protein 1 (Noxa) and p53 upregulated modulator of apoptosis (PUMA), were determined by western blot analysis. The expression of both the gene and protein of p53 and MDM2 in synovial tissue was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis, respectively. The results indicated that the arthritis index scores and hindlimb paw volumes upon EA stimulation were significantly decreased compared with those of the AA group (P<0.05). H&E staining revealed that the synovial inflammation of EA stimulation was significantly decreased compared with the AA group (P<0.05). The TUNEL assay results indicated that the apoptotic rate of synovial cells in the AA + EA group was significantly increased compared with that in the AA group (P<0.05). Furthermore, an increased expression of proapoptotic proteins was confirmed by the increased expression levels of Bax, Noxa and PUMA in the AA + EA group. The results of RT­qPCR and western blot analysis demonstrated that, compared with the AA group, EA stimulation led to a marked increase in p53 (P<0.05) and a significant decrease in MDM2 (P<0.05) gene and protein expression. Taken together, these results demonstrated that EA performed on the ST36 and GB39 acupoints led to a significant amelioration in AA injury of model rats, by regulating the p53 signaling pathway and inducing apoptosis.

[Regularity of Acupoint Selection in Treatment of Insomnia by Catgut Embedding Therapy].

OBJECTIVE: To analyze the regularity of acupoint selection in the treatment of insomnia by using catgut embedding so as to provide reference and evidence for clinical application. METHODS: Sixty-six studies about acupoint catgut embedding treatment of insomnia published from 1996 to 2017 were finally selected from the databases of China National Knowledge Infrastructure (CNKI), Chinese Journal of Science and Technology of VIP (VIP), and WanFang Database. The Excel 2016 software was used for data processing and analysis, SPSS 21.0 was employed for descriptive and cluster analyses, and the Clementine 12.0 software was employed to analyze the association regularities of the most frequently used acupoints or acupoint recipes. RESULTS: The most frequently selected main acupoints for insomnia by using catgut embedment are Xinshu (BL 15), Shenshu (BL 23), Sanyinjiao (SP 6), Pishu (BL 20), Ganshu (BL 18), combined with adjuvant acupoints Danshu (BL 19) and Fenglong (ST 40). The most frequently selected channels are the Bladder and Stomach Meridians, and the most frequently involved body positions are the back and lower limbs. Effective clusterings are BL 20-SP 6, Shenmen (HT 7)-Anmian, ST 40-Shenting (GV 24), Qihai (CV 6)-Jueyinshu (BL 14). Descriptive analysis indicated: ①The stronger correlation acupoint groups between back-shu points are BL 18-BL 23; BL 18，BL 15-BL 23; BL 18，BL 20，BL 15-BL 23. ②The stronger correlation acupoint groups between common acupoints are Neiguan (PC 6)，Zusanli (ST 36) -SP 6; PC 6, HT 7 - SP 6.③The stronger correlation acupoint groups between common acupoints and back-shu points are BL 18, SP 6-BL 23; PC 6, BL 23 - SP 6; ST 36, PC 6, BL 15 - SP 6; BL 18，BL 15，SP 6 - BL 23. CONCLUSION: Acupoint catgut embedding therapy is effective in the treatment of insomnia, being worthy of further popularization in clinical practice.

Acupuncture Improves Peri-menopausal Insomnia: A Randomized Controlled Trial.

Study Objectives: To evaluate the short-term efficacy of acupuncture for the treatment of peri-menopausal insomnia (PMI). Methods: Design: A randomized, participant-blind, placebo-controlled trial consisted of the acupuncture group (n = 38) and placebo-acupuncture group (n = 38). Setting: A tertiary teaching and general hospital. Participants: 76 peri-menopausal women with insomnia disorder based on the International Classification of Sleep Disorders, Third Edition. Interventions: A 10-session of acupuncture at bilateral Shenshu (BL 23) and Ganshu (BL 18) with unilateral Qimen (LR 14) and Jingmen (GB 25) or Streitberger needles at the same acupoints was performed for over 3 weeks. Measurements: Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with over-night polysomnography (PSG) exam were completed at baseline and post-treatment. Results: After the treatments, the decrease from baseline in PSQI score was 8.03 points in acupuncture group and 1.29 points in placebo-acupuncture group. The change from baseline in ISI score was 11.35 points in acupuncture group and 2.87 points in placebo-acupuncture group. In PSG data, acupuncture significantly improved the sleep efficiency and total sleep time, associated with less wake after sleep onset and lower percent stage 1 after the treatment. No significant differences from baseline to post-treatment were found in placebo-acupuncture group. Conclusions: Acupuncture can contribute to a clinically relevant improvement in the short-term treatment of PMI, both subjectively and objectively. Clinical Trial Registration: Acupuncture for peri-menopause insomnia: a randomized controlled trial, http://www.chictr.org.cn/showproj.aspx?proj=12118 ChiCTR-IPR-15007199, China.

[Effects of Electroacupuncture on Joint Function in Rheumatoid Arthritis Patients of Liver- and Kidney-Yin Deficiency Type].

OBJECTIVE: To compare the effects between electroacupuncture (EA) plus western medicine and simple western medicine in improving clinical symptoms and local joint function of rheumatoid arthritis (RA) patients with yin deficiency of Liver and Kidney. METHODS: A total of 68 RA patients of yin deficiency of Liver and Kidney were equally randomized into EA+medication group and medication group (n=34 in each group). Both groups were given once-a-week methotrexate (7.5 mg/time) and once-a-day leflunomide (10 mg/time), while EA+medication group was additionally treated by EA at bilateral Ganshu (BL 18), Shenshu (BL 23), Xuanzhong (GB 39), Zusanli (ST 36), Taichong (LR 3), Hegu (LI 4) 3 times/week. The treatment lasted for 12 weeks. The visual analogue scale (VAS, for assessing rest pain), swollen joint count (SJC), tender joint count (TJC), patient's global assessment (PGA), physician's global assessment (PhGA), traditional Chinese medicine (TCM) symptom scoring, 28 joints activity index (disease activity score, DAS 28), American College of Rheumatology 20 (ACR 20, i.e. 20% of clinical improving rate), and health assessment questionnaire (HAQ) were assessed and erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) levels were examined for comparison. RESULTS: Statistical differences were observed in before-after-treatment comparisons in both groups in reducing rest pain, SJC, TJC, serum CRP content, PGA and PhGA, HAQ scoring and DAS 28 (P<0.05, P<0.01). The ESR in the medication group and TCM symptom scoring of the EA+medication group were also significantly decreased after the treatment (P<0.05).The effects of the EA+medication group were superior to those of the medication group in reducing rest pain, SJC, TJC, TCM symptom and HAQ score, and the total effetive rate (P<0.05,90.9% vs 66.67%). Adverse reactions as pharyngeal obstruction sensation, anorexia, abdominal distension, etc. can be reduced by EA therapy coordinated with western medicine. CONCLUSIONS: EA is effective in relieving symptom and joint function in RA patients with yin deficiency of Liver and Kidney.

Electroacupuncture attenuates collagen-induced arthritis in rats through vasoactive intestinal peptide signalling-dependent re-establishment of the regulatory T cell/T-helper 17 cell balance.

OBJECTIVE: Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance. MATERIALS AND METHODS: A collagen-induced arthritis (CIA) model was induced in Sprague-Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined. RESULTS: EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4(+)FOXP3(+) Treg cell frequency and a reduction in CD4(+)IL17(+) Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells. CONCLUSIONS: EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance.

[Sesquiterpenoids of Coniogramme maxima].

OBJECTIVE: To study sesquiterpenoids of Coniogramme maxima. METHOD: Chemical constituents were separated by chromatography and their structures were identified according to physicochemical property and spectrum data. RESULT: Fifteen compounds were separated by chromatography technique. Their structures were determined by spectral data, including 10 sesquiterpenoids as (3S)-pteroside D (1), epi-pterosin L (2), pterosin D (3), onitin (4), pterosin Z (5), onitisin (6), onitisin-glucopyranoside (7), onitin-15-O-beta-D-glucopyranoside (8), (2S,3R)-pterosin-L-2'-O-beta-D-glucopyranoside (9) and (3R)-peterosin D-3-O-beta-D-glucopyranoside (10). The other compounds were uracil (11), 3,4-dihydroxybenzaldehyde (12), 5-hydroxymethyl-2-furancarboxaldehyde (13), beta-sitosterol (14) and daucosterol (15). CONCLUSION: The above 15 compounds are separated from C. maxima for the first time, including 9 compounds being first separated from genus Coniogramme.

Preparation and application of attapulgite/iron oxide magnetic composites for the removal of U(VI) from aqueous solution.

Recently, magnetic sorbents have received considerable attention because of their excellent segregative features and sorption capacities. Herein, attapulgite/iron oxide magnetic (ATP/IOM) composites were prepared and characterized. The sorption results indicated that ATP/IOM composites were superior to ATP and iron oxides individually for the removal of U(VI) from aqueous solution. Based on X-ray photoelectron spectroscopy (XPS) analysis and surface complexation model, the main sorption species of U(VI) on ATP were==X(2)UO(2)(0) below pH 4.0 and==S(s)OUO(2)(+), ==S(w)OUO(2)CO(3)(-), and==S(w)OUO(2)(CO(3))(2)(3-) above pH 5.0. However the prevalent species on ATP/IOM composites were==S(s)OUO(2)(+) and==S(w)OUO(2)(CO(3))(2)(3-) over the observed pH range. ATP/IOM composites are a promising candidate for pre-concentration and immobilization of radionuclides from large volumes of aqueous solutions, as required for remediation purposes.

Enhancement of artemisinin content in tetraploid Artemisia annua plants by modulating the expression of genes in artemisinin biosynthetic pathway.

Tetraploid Artemisia annua plants were successfully inducted by using colchicine, and their ploidy was confirmed by flow cytometry. Higher stomatal length but lower frequency in tetraploids were revealed and could be considered as indicators of polyploidy. The average level of artemisinin in tetraploids was increased from 39% to 56% than that of the diploids during vegetation period, as detected by high-performance liquid chromatography-evaporative light scattering detector. Gene expressions of 10 key enzymes related to artemisinin biosynthetic pathway in different ploidy level were analyzed by semiquantitative polymerase chain reaction and significant upregulation of FPS, HMGR, and artemisinin metabolite-specific Aldh1 genes were revealed in tetraploids. Slight increased expression of ADS was also detected. Our results suggest that higher artemisinin content in tetraploid A. annua may result from the upregulated expression of some key enzyme genes related to artemisinin biosynthetic pathway.