[Construction of a core outcome set in clinical research of acupuncture and moxibustion for treatment of adhesive capsulitis].

This study aims to construct the core outcome set for the clinical trials of adhesive capsulitis treated with acupuncture and moxibustion. Using systematic review, semi-structured interview, Delphi questionnaire survey, analytic hierarchy process and expert consensus meeting, the primary outcomes are obtained, i.e. local tenderness, pain degree during movement, range of motion, changes in range of motion, function score, and score of local symptoms of shoulder joint. The secondary outcomes are myofascial thickness, thickness of the inferior wall of the joint capsule, health status, activity of daily living, incidence of adverse events, laboratory indexes, vital signs, cost-effectiveness, total effective rate, and patient satisfaction. It is expected to provide a reference for the outcome selection in clinical trials and the generation of medical evidences in the treatment of adhesive capsulitis with acupuncture and moxibustion.

[Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm].

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives.

Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure-activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1ß, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.

Molecular Mechanism of Electroacupuncture Regulating Cerebral Arterial Contractile Protein in Rats with Cerebral Infarction Based on MLCK Pathway.

OBJECTIVE: To explore the effect of electroacupuncture (EA) intervention on the vasoconstriction of cerebral artery smooth muscle cells after cerebral infarction. METHODS: Male Wistar rats were randomly divided into 3 groups by a random number table: the model group (n=24), the EA group (n=24), and the normal group (n=6). The model and the EA groups were divided into different time subgroups at 0.5, 1, 3, and 6 h after middle cerebral artery occlusion (MCAO), with 6 rats in each subgroup. MCAO model was established using intraluminal suture occlusion method. The EA group was given EA treatment at acupoint Shuigou (GV 26) instantly after MCAO for 20 min. The contents of cerebrovascular smooth muscle MLCK, the 3 subunits of myosin light chain phosphatase (MLCP) MYPT1, PP1c-δ and M20, as well as myosin-ATPase activity were detected using immunohistochemistry and Western blotting. RESULTS: The overall expression level of the MYPT1 and PP1c-δ in the model group was significantly higher (P<0.01). After EA intervention, the 0.5 h group expression level was close to that of the normal group (P>0.05), and the other subgroups were still significantly higher than the normal group (P<0.01). After EA intervention, the expression level of each subgroup was significantly lower than the corresponding model group. There was a significant difference between the 0.5 and 1 h subgroups (P<0.01), while a difference was also observed between the 3 and 6 h subgroups (P<0.05). The dynamic change rule gradually increased with the prolongation of infarction time within 6 h after infarction. CONCLUSION: EA intervention can inhibit contraction of cerebral vascular smooth muscle cells and regulate smooth muscle relaxation by regulating MLCK pathway.

Assessment of reporting quality in randomized controlled trials of acupuncture for labor pain.

Objective: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for labor pain, and to explore relevant factors for facilitating reporting transparency and integrity for future RCTs. Method: Eight Chinese and English databases were systematically searched from their inception until August 31, 2021. General characteristics and methodological quality of the included reports were evaluated based on the CONSORT statement and the STRICTA guidelines. Descriptive statistical analysis was performed. Cohen's κ-statistics were calculated to assess the agreement of all items between two reviewers. Results: A total of 84 RCTs were included. Based on the CONSORT statement, a positive reporting rate (greater than 80%) was evident for the items "trial design" "participants" "intervention" "outcomes" "numbers analyzed" and "generalizability". The quality of reporting for the items "randomized in the title or abstract" "sample size" "allocation concealment" "implementation" "blinding" "recruitment" "ancillary analyses" "harms" "interpretation" "registration" and "protocol" was poor with positive rates less than 10%. Based on the STRICTA guidelines, the items "extent to which treatment varied" "number of needle insertions per subject per session" and "control or comparator interventions" had poor reporting quality with positive rates of less than 10%. Substantial agreement was observed for most items and excellent agreement for some items. Conclusion: The reporting quality of RCTs of acupuncture for labor pain is suboptimal generally. Rigorous adherence to the CONSORT statement and the STRICTA guidelines should be emphasized in future studies to improve the quality of acupuncture RCT reports.

[Clinical Significance of IgG4 Level in Predicting the Activity and Outcome of Phospholipase A2 Receptor-associated Membranous Nephropathy].

Objective To investigate the feasibility of IgG4 as a biomarker of the activity and outcome of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (PLA2R-MN). Methods Serum and urine samples were collected from 56 patients with PLA2R-MN,13 patients with secondary membranous nephropathy (SMN),and 10 patients with primary IgA nephropathy (IgAN) when kidney biopsy was performed in the Department of Nephrology,Hangzhou Hospital of Traditional Chinese Medicine from April 2017 to January 2018.Sandwich enzyme-linked immunosorbent assay was employed to measure the serum and urinary IgG4 levels. Results The PLA2R-MN group had higher median serum IgG4/IgG ratio than the SMN group (P=0.009) and the IgAN group (P<0.001) and higher median urinary IgG4/creatinine ratio than the SMN group (P=0.008).In the patients with PLA2R-MN,the median serum IgG4/IgG ratio and urinary IgG4/creatinine ratio were significantly higher in the renal insufficiency group than in the normal renal function group (P=0.049,P=0.015).Moreover,the median serum IgG4/IgG ratio was higher in those with a serum albumin level<30 g/L than in those with a serum albumin level ≥30 g/L (P=0.005).Fifty-three patients with PLA2R-MN were followed up for at least 1 year,and the serum IgG4/IgG ratios of the patients in remission were lower than those of the patients without remission (P=0.005).The median serum IgG4/IgG ratio of 23 patients in remission decreased from 5.82% (4.54%,10.20%)(at initial enrollment) to 2.91% (2.11%,5.37%)(after 1-year follow up) in remission patients (P<0.001).The receiver operating characteristic curve showed that the patients with a serum IgG4/IgG ratio<10.24% had a higher possibility of remission (P=0.005). Conclusion Serum and urinary IgG4 levels may be an indicator of the activity in PLA2R-MN patients and thus may be a predictive biomarker of the outcomes.

Outcomes in pediatric patients with documented delays between ileocolic intussusception diagnosis and therapeutic enema attempt: evaluation of reduction efficacy and complication rate.

BACKGROUND: Ileocolic intussusception is considered a pediatric emergency, with concerns for risk of significant morbidity in children with a prolonged intussusception state. Emergent therapy is standard of care, as prior studies have shown poor outcomes in patients with long delays (> 24 h) before intervention. Various factors can result in shorter delays, and there are limited studies evaluating outcomes in these patients. This study aimed to determine if there were differences in reduction success rates associated with short in-hospital time delays. OBJECTIVE: This study is to determine enema success rate and morbidity in patients with documented time delays between intussusception diagnosis and therapeutic enema. MATERIALS AND METHODS: A retrospective evaluation of pediatric patients with intussusception at a single children's hospital between 2007 and 2019 was performed. Patient's records were reviewed for time of symptom onset, radiologic diagnosis, and attempted enema. Ultrasounds and radiographs were reviewed for bowel obstruction, free peritoneal fluid, trapped fluid around the intussusceptum, and absent bowel wall perfusion. Patients were evaluated for efficacy of reduction attempt, requirement for surgical reduction, and complications including bowel resection and bowel perforation. RESULTS: There were 175 cases of ileocolic intussusception requiring enema reduction. Successful reduction occurred in 72.2% (13/18) of cases performed within 1 h of diagnosis; 74.3% (78/105) between 1 and3 h; 73.2% (30/41) between 3 and 6 h; and 81.2% (9/11) with greater than 6 h. Need for bowel resection was not associated with short delays between diagnosis and reduction attempts (p = .07). CONCLUSIONS: There was no difference in intussusception reduction efficacy or complication rate in patients with increasing time between imaging diagnosis of ileocolic intussusception and reduction attempt, including delay intervals up to 8 h.

Tanshinone IIA-Loaded Micelles Functionalized with Rosmarinic Acid: A Novel Synergistic Anti-Inflammatory Strategy for Treatment of Atherosclerosis.

Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis.

Reduning Injection versus Neuraminidase Inhibitors in the Treatment of Influenza: A Systematic Review and Meta-Analysis.

OBJECTIVE: To perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza. METHODS: The MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT. RESULTS: Twelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: -16.20 h, 95% CI: -19.40 to -12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: -4.09 h, 95% CI: -4.22 to -3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: -21.34 h, 95% CI: -41.56 to -1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: -31.83 h, 95% CI: -36.88 to -26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: -28.66 h, 95% CI: -32.23 to -25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe. CONCLUSIONS: This study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.

Effect of Electro-acupuncture on Vasomotor Symptoms in Rats with Acute Cerebral Infarction Based on Phosphatidylinositol System.

OBJECTIVE: To investigate the effect of electro-acupuncture (EA) on vasomotor symptoms in rats with acute cerebral infarction, by observing the changes in the expression of factors related to the phosphatidylinositol (PI) system. METHODS: Forty-two Wistar rats were randomly divided into 3 groups by a random number table: the control group (n=6), the model group (n=18) and the EA group (n=18). The EA group was given EA treatment at Shuigou (GV 26) instantly after modeling with middle cerebral artery occlusion (MCAO) method, while the model and control groups were not given any treatment. The degrees of neurological deficiency were evaluated using neurological severity scores (NSS) and the brain blood flow was evaluated by a laser scanning confocal microscope. Western blot analysis was conducted to detect the expression levels of G-protein subtype (Gq) and calmodulin (CaM). Competition for protein binding was conducted to detect the expression level of inositol triphosphate (IP3). Thin layer quantitative analysis was conducted to detect the expression level of diacylglycerol (DAG). The expression level of intracellular concentration of free calcium ion ([Ca2+]i) was detected by flow cytometry. RESULTS: The NSS of the model group was significantly higher than the control group at 3 and 6 h after MCAO (P<0.01), while the EA group was significantly lower than the model group at 6 h (P<0.01). The cerebral blood flow in the model group was significantly lower than the control group at 1, 3 and 6 h after MCAO (P<0.01), while for the EA group it was remarkably higher than the model group at the same time points (P<0.01). The expressions of Gq, CaM, IP3, DAG and [Ca2+]i in the model group were significantly higher than the control group (P<0.05 or P<0.01), and those in the EA group were significantly lower than the model group at the same time points (P<0.05 or P<0.01). CONCLUSION: EA treatment at GV 26 can effectively decrease the over-expression of related factors of PI system in rats with acute cerebral infarction, improve cerebral autonomy movement, and alleviate cerebral vascular spasm.

[Scalp acupuncture combined with suspension training for balance dysfunction in patients with stroke: a randomized controlled trial].

OBJECTIVE: To explore the effect of scalp acupuncture combined with suspension training on balance ability and motor function in stroke patients with balance dysfunction. METHODS: A total of 105 stroke patients with balance dysfunction were randomly divided into a combined group (35 cases, 2 cases dropped off), a scalp acupuncture group (35 cases, 3 cases dropped off) and a suspension training group (35 cases, 2 cases dropped off). The scalp acupuncture group was treated with scalp acupuncture at bilateral suboccipital lateral line, parietal midline, upper 1/5 line of anterior oblique line of parietal and temporal and line 1 of the parietal lateral line on the opposite side of hemiplegia. The suspension training group was treated with suspension training. The combined group was treated with suspension training at the same time of scalp acupuncture. All the treatment was given once a day, 30 min each time, 5 days a week, for a total of 6 weeks. The Berg balance scale (BBS) score, balance tester and Fugl-Meyer assessment (FMA) score were used to evaluate the motor function and balance ability before treatment, 3 and 6 weeks into treatment. The clinical efficacy was evaluated in the 3 groups. RESULTS: The scores of BBS and FMA in each group at 3 and 6 weeks into treatment were higher than those before treatment (P<0.05); the scores of BBS and FMA in the combined group were higher than those in the scalp acupuncture group and the suspension training group (P<0.05). At 3 and 6 weeks into treatment, the length and area of centroid locus of balance tester in each group were lower than those before treatment (P<0.05); the length and area of centroid locus of balance tester in the combined group were lower than those in the scalp acupuncture group and the suspension training group (P<0.05). The total effective rate of the combined group was 97.0% (32/33), which was higher than 87.5% (28/32) in the scalp acupuncture group and 90.9% (30/33) in the suspension training group (P<0.05). CONCLUSION: Scalp acupuncture combined with suspension training could improve the balance ability and motor function in stroke patients with balance dysfunction, and the curative effect is better than simple scalp acupuncture and simple suspension training.

[Electroacupuncture of "Shuigou"(GV26) improves neurological function by promoting angioge-nesis and Shh signaling in ischemic cerebral tissue of rats with cerebral infarction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Shuigou" (GV26) on the activities of sonic hedgehog(Shh) signaling molecules (Shh, Ptch, Smo，Gli and Gli2) in ischemic brain tissues in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of CI. METHODS: Male Wistar rats were randomly divided into blank control group(n=10), sham operation group (n=90), model group(n=90) and EA group (n=90). The CI model was established by occlusion of the right middle cerebral artery (MCAO). According to the postoperative time points of MCAO, the later three groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups, with 10 rats in each subgroup. EA (15 Hz, 2 mA) was applied to GV26 for 20 min. The 1 h to 24 h subgroups were treated immediately after modeling, the 3-12 d subgroups treated one time a day. The neurological severity score (NSS, 0 to 18 points) was used to evaluate the rats' neurological function, and TTC staining was employed to assess the cerebral ischemic volume (percentage of cerebral infarct volume, CIV). Western blot was employed to detect the expression of Shh, Ptch, Smo, Gli1 and Gli2 proteins in the ischemic cerebral tissue. RESULTS: Compared with the sham operation group, the NSS scores of the model group increased at all time points (P<0.01). The percentages of CIV of the model group from 3 h to 12 d were obviously higher than those of the sham operation group (P<0.01). The NSS scores at 3, 7 and 12 d and the percentages of CIV at 1, 3, 7 and 12 d after MCAO were significant lower in the EA group than in the model group (P<0.05). The protein expression levels of Shh from 12 h to 12 d (i.e. 12 h, 24 h, 3, 7 and 12 d), Ptch from 6 h to 12 d, Smo from 9 h to 12 d, Gli1 at 9 h, 12 h, and from 3 d to 12 d, Gli2 at 6, 9 and 12 h, and 3 d were significantly higher in the model group than in the sham operation group (P<0.05, P<0.01), while those of Shh at 3, 7 and 12 d, Ptch from 24 h to 7 d, Smo from 12 h to 7 d, Gli1 from 24 h to 7 d, Gli2 at 12 h, 3 and 7 d were significantly higher in the EA group than in the model group (P<0.05, P<0.01). No statistical significances were found between the sham operation and the blank control groups in all the indexes mentioned above (P>0.05). CONCLUSION: EA of GV26 can improve neurological function and reduce infarct volume in MCAO rats, which may be related to its function in up-regulating the activities of Shh signaling pathway in the ischemic cerebral tissues.

ROS-mediated liposomal dexamethasone: a new FA-targeted nanoformulation to combat rheumatoid arthritis via inhibiting iRhom2/TNF-α/BAFF pathways.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide and its current management requires more successful therapeutic approaches. The combination of nanomedicines and pathophysiology into one system may provide an alternative strategy for precise RA treatment. In this work, a practical ROS-mediated liposome, abbreviated as Dex@FA-ROS-Lips that comprised synthetic dimeric thioether lipids (di-S-PC) and a surface functionalized with folic acid (FA), was proposed for dexamethasone (Dex) delivery. Incorporation with thioether lipids and a FA segment significantly improved the triggered release and improved the triggered release of cytotoxic Dex as well as the active targeting of RA, altering its overall pharmacokinetics and safety profiles in vivo. As proof, the designed Dex@FA-ROS-Lips demonstrated effective internalization by LPS-activated Raw264.7 macrophages with FA receptor overexpression and released Dex at the inflammatory site due to the ROS-triggered disassembly. Intravenous injection of this Dex@FA-ROS-Lips into adjuvant-induced arthritis (AIA) mice led to its incremental accumulation in inflamed joint tissues and significantly alleviated the cartilage destruction and joint swelling via suppression of proinflammatory cytokines (iRhom2, TNF-α and BAFF), as compared to the effect of commercial free Dex. Importantly, the Dex@FA-ROS-Lips nanoformulation showed better hemocompatibility with less adverse effects on the body weight and immune organ index of AIA mice. The anti-inflammatory mechanism of Dex@FA-ROS-Lips was further studied and it was found that it is possibly associated with the down-regulation of iRhom2 and the activation of the TNF-α/BAFF signaling pathway. Therefore, the integration of nanomedicines and the RA microenvironment using multifunctional Dex@FA-ROS-Lips shall be a novel RA treatment modality with full clinical potential, and based on the enhanced therapeutic effect, the signaling pathway of iRhom2/TNF-α/BAFF reasonably explained the mechanism of Dex@FA-ROS-Lips in anti-RA, which suggested a molecular target for RA therapy and other inflammatory diseases.

[Research progress on mechanisms of bidirectional regulation of acupuncture].

Bidirectional regulation is one of the key function of acupuncture. The stimulator, mediator and receptor are the basis while the specificity of acupoints and the multi-target regulation of receptors receiving stimulation signals are the essential link of the bidirectional regulation of acupuncture. The possible mechanisms of bidirectional regulation of acupuncture are discussed in 4 aspects, i.e. homeostasis mechanism, stress reaction, central adaptive regulation and autonomic nerve regulation. Knowing the limitations of bidirectional regulation and exploring suitable researchmethods are proposed to be the key points in future researches.

[Acupotomy combined with Xingnao Kaiqiao acupuncture therapy in treatment of sensory impairment in the recovery stage of cerebral infarction: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect on sensory impairment in the recovery stage of cerebral infarction between the combined treatment of acupotomy and Xingnao Kaiqiao acupuncture therapy (for regaining consciousness and opening the orifices) and the simple application of Xingnao Kaiqiao acupuncture therapy. METHODS: A total of 80 patients with cerebral infarction in the recovery stage were randomized into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 1 case dropped off). On the basis of the conventional treatment of internal medicine, in the control group, Xingnao Kaiqiao acupuncture therapy was adopted at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), etc., once daily, 6 times a week. In the observation group, on the base of the treatment as the control group, acupotomy was used at extraoccipital protuberance, posterior atlas nodules, cervical facet ligaments and posterior transverse nodules, once a week. The total treatment duration was 4 weeks. The scores of Fugl-Meyer assessment scale (FMA) and the visual analogue scale (VAS) were observed before and after treatment in the patients of the two groups. The clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, FMA scores were increased and VAS scores were decreased in the patients of the two groups (P<0.05). The increase range of FMA score and the decrease range of VAS score in the observation group were larger than those in the control group (P<0.05). The total effective rate was 89.5% (34/38) in the observation group, higher than 76.9% (30/39) in the control group (P<0.05). CONCLUSION: The combined treatment of acupotomy and Xingnao Kaiqiao acupuncture therapy relieves sensory impairment and pain symptoms in the patients with cerebral infarction in the recovery stage and its therapeutic effect is better than the simple use of Xingnao Kaiqiao acupuncture therapy.

Impact of a Pharmacist-Led Intensive Care Unit Sleep Improvement Protocol on Sleep Duration and Quality.

BACKGROUND: Sleep improvement protocols are recommended for use in the intensive care unit (ICU) despite questions regarding which interventions to include, whether sleep quality or duration will improve, and the role of pharmacists in their development and implementation. OBJECTIVE: To characterize the impact of a pharmacist-led, ICU sleep improvement protocol on sleep duration and quality as evaluated by a commercially available activity tracker and patient perception. METHODS: Critical care pharmacists from a 40-bed, mixed ICU at a large community hospital led the development and implementation of an interprofessional sleep improvement protocol. It included daily pharmacist medication review to reduce use of medications known to disrupt sleep or increase delirium and guideline-based recommendations on both environmental and nonpharmacological sleep-focused interventions. Sleep duration and quality were compared before (December 2018 to December 2019) and after (January to June 2019) protocol implementation in non-mechanically ventilated adults using both objective (total nocturnal sleep time [TST] measured by an activity tracker (Fitbit Charge 2) and subjective (patient-perceived sleep quality using the Richards-Campbell Sleep Questionnaire [RCSQ]) measures. RESULTS: Groups before (n = 48) and after (n = 29) sleep protocol implementation were well matched. After protocol implementation, patients had a longer TST (389 ± 123 vs 310 ± 147 minutes; P = 0.02) and better RCSQ-perceived sleep quality (63 ± 18 vs 42 ± 24 mm; P = 0.0003) compared with before implementation. CONCLUSION AND RELEVANCE: A sleep protocol that incorporated novel elements led to objective and subjective improvements in ICU sleep duration and quality. Application of this study may result in increased utilization of sleep protocols and pharmacist involvement.

Stuck-moving needle acupuncture myofascial trigger point to treat idiopathic frozen shoulder: study protocol for a randomized controlled trial.

BACKGROUND: There are evidence for the efficacy of acupuncture treatment for chronic shoulder pain, however, it remains unclear the best acupuncture modes for effective treatment. We compared the effect of the myofascial trigger point (MTrp) stuck-moving needle acupuncture with that of common acupuncture treatments. Further, we evaluated the efficacy and safety of stuck-moving needle acupuncture for the MTrp in improving pain and range of motions in patients with idiopathic frozen shoulder. The aim of present study is to select an effective therapy for patients with idiopathic frozen shoulder. METHODS: Randomized controlled trial will be conducted in the three clinical centers of Qingyang Traditional Chinese Medicine Hospital, Qingyang Xifeng district People's Hospital, and Qingyang Second People's Hospital in China from February 2020 to January 2021. One hundred and eight frozen shoulder patients will be recruited and randomized into one of three groups in a 1:1:1 ratio of the stuck-moving needle acupuncture group, common acupuncture control group, and physical exercise control group. This trial will include a 1-week baseline period, a 3-week treatment period, and a 12-week follow-up period. During the 3 weeks of the treatment period, patients will receive nine sessions of acupuncture. The primary outcome will be related to change in the Visual Analogue Scale (VAS) and measurement of range of joint motion (ROM) from the baseline period to the 12-week follow-up period. Secondary outcome measures will include measurement of pressure pain threshold (PPT), pressure pain tolerance (PTT), Oxford Shoulder Score (OSS), 36-item short form survey, and patient satisfaction evaluation. Adverse events also will be recorded for safety assessment. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between stuck-moving needle acupuncture MTrP with that of common acupuncture treatments. The findings from this trial will be published in the peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry (ChiMCTR1900002862) and Chinese Clinical Trial Registry (ChiCTR1900028452). Registered on 22 December 2019. http://www.chictr.org.cn/showproj.aspx?proj=47354.

Chromosome Level Genome Assembly of Andrographis paniculata.

Andrographis paniculata (Chinese name: Chuanxinlian) is an annual dicotyledonous medicinal plant widely grown in China and Southeast Asia. The dried plant has a highly acclaimed usage in the traditional Chinese medicine for its antipyretic, anti-inflammatory, and analgesic effects. In order to help delineate the biosynthetic pathways of various secondary metabolites, we report in this study a high-quality reference genome for A. paniculata. With the help of both PacBio single molecule real time sequencing and Illumina sequencing reads for error correction, the A. paniculata genome was assembled into a total size of 284 Mb with a contig N50 size of 5.14 Mb. The contigs were further assembled into 24 pseudo-chromosomes by the Hi-C technique. We also analyzed the gene families (e.g., KSL, and CYP450) whose protein products are essential for synthesizing bioactive compounds in A. paniculata. In conclusion, the high-quality A. paniculata genome assembly builds the foundation for decoding the biosynthetic pathways of various medicinal compounds.

Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis.

Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-α)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-α-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1ß secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-κB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-κB-NLRP3 axis to alleviate RA symptoms. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Gentiopicroside (PubChem CID: 88708).

[Effect of electroacupuncture on neurological function and Wnt signaling pathway in ischemic brain tissue of cerebral infarction rats].

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) underlying improvement of cerebral infarction (CI) by investigating its influence on expression of cerebral Wnt7a, lymphoid enhancer factor-1 (LEF1), glycogen synthase kinase 3ß(GSK-3ß) and Dickkopf-1(DKK1) mRNA and proteins in CI rats. METHODS: A total of 280 male Wistar rats were randomly divided into blank control (n＝10), sham-operation, model and EA groups，and 90 rats of the last 3 groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups with 10 rats in each subgroup. The CI model was established by occlusion of the middle cerebral artery (MCAO). The sham-operation group received the same surgical operation but without thread embolus insertion. EA (2 Hz/15 Hz, 2 mA) was applied to "Shuigou" (GV26) for 20 min, once a day for 1, 3, 7 and 12 d, respectively. The neurological deficit was evaluated by using Neurological Severity Scores (NSS). The expression levels of Wnt7a，LEF1, GSK-3ß and DKK1 mRNAs and proteins in the right ischemic brain tissues were detected by Quantative real-time PCR and Western blot, respectively. RESULTS: After MCAO, the NSS score was significantly increased in the model and EA groups relevant to the blank control and sham-operation groups (P<0.01) and gradually decreased with the prolongation of ischemia time. After EA, the NSS scores were notably decreased on day 3, 7 and 12 in the EA group compared with the model group (P<0.05, P<0.01). After modeling, the expression levels of Wnt7a and LEF1 mRNAs from 3 h to 12 d, Wnt7a and LEF1 proteins from 6 h to 12 d were considerably increased (P<0.01, P<0.05), while those of GSK-3ß mRNA at 9, 12 and 24 h, GSK-3ß protein at 24 h and 3 d, and DKK1 mRNA at 24 h and 3 d and DKK1 protein at 3 d were obviously decreased in the model group relevant to the sham-operation group (P<0.05, P<0.01). After the intervention, the expression levels of Wnt7a mRNA at 12 h to 3 d, Wnt7α protein from 24 h to 12 d, LEF1 mRNA from 24 h to 12 d, and LEF1 protein from 3 d to 12 d were further apparently up-regulated (P<0.01, P<0.05), while those of GSK-3ß mRNA at 9 h, 3，7 and 12 d, and GSK-3ß protein at 12 h, 7 d and 12 d, and DKK1 mRNA at 12 h, 24 h and 3 d, and DKK1 protein at 24 h to 12 d were obviously down-regulated in the EA group relevant to the model group (P<0.01, P<0.05). No significant difference was found between the blank and sham-operation groups in the NSS scores and expression levels of Wnt7a, LEF1, GSK-3ß and DKK1 mRNAs and proteins at all the time points (P>0.05). CONCLUSION: EA of GV26 can significantly improve the neurological deficit symptoms in MCAO rats, which may be associated with its effects in up-regulating the expression of Wnt7a and LEF1 mRNAs and proteins, and in down-regulating the expression of GSK-3ß and DKK1 mRNAs and proteins.