Effect of acupuncture timing on functional impairment at 6 months post-onset in patients with first-ever stroke: a prospective cohort study. / é’ˆåˆºæ—¶æœºå¯¹é¦–æ¬¡ä¸­é£Žæ‚£è€ å‘ç— åŽ6ä¸ªæœˆåŠŸèƒ½éšœç¢çš„å½±å“ï¼šå‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture intervention in the acute phase on functional impairment at 6 months post-onset in patients with first-ever stroke, and provide evidence for selecting optimal acupuncture timing in the real-world setting. METHODS: A total of 601 patients with first-ever stroke were divided into an acute intervention group (onset within 14 days, 256 cases) and a non-acute intervention group (onset between 15 and 90 days, 345 cases) based on whether they received acupuncture treatment in the acute phase. The assessments were conducted at baseline and 6 months post-onset, including modified Rankin scale (mRS) score, total number of acupuncture sessions, total number of combined therapies (moxibustion, cupping, tuina and rehabilitation treatment), recurrence, death events and disability. Logistic regression analysis was used to analyze the association between acupuncture timing and the risk of disability at 6 months post-onset. The mRS transition method was employed to assess the effect of acupuncture timing on functional improvement at 6 months post-onset. RESULTS: Without adjusting for confounding factors, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.434, 95%CI: 0.309-0.609, P=0.000). After adjusting for variables i.e. severity of illness, number of acupuncture sessions, and number of cupping sessions, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.588, 95%CI: 0.388-0.890, P=0.012). After adjusting for all confounding factors, including severity of illness, number of acupuncture sessions, number of cupping sessions, gender, smoking and drinking history, comorbidities, and diagnosis, compared with the non-acute intervention group, the patients in the acute intervention group continued to have a reduced risk of disability at 6 months post-onset (OR=0.629, 95%CI: 0.408-0.971, P=0.036). Both groups showed an overall shift towards lower mRS scores at 6 months post-onset compared to baseline, with a more significant shift towards lower scores in the acute intervention group than the non-acute intervention group. CONCLUSIONS: In the real-world setting, acupuncture intervention in the acute phase in patients with first-ever stroke, compared to acupuncture intervention after the acute phase, reduces the risk of disability at 6 months post-onset and improves functional status.

Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial.

Background: Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD. Methods: A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant's perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants' benefits, the data's credibility, and the results' validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy. Discussion: Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD. Trial registration number: https://www.chictr.org.cn/, identifier ChiCTR2200062786.

Retinoblastoma in Adults: Clinical Features, Gene Mutations and Treatment Outcomes: A Study of Six Cases.

Purpose: To report six Asian adult patients with retinoblastoma (RB). Design: Retrospective and observational small case series. Participants: Six patients with a white dome-shaped tumor of the retina were evaluated from May 10, 1995, to September 10, 2021. Main Outcome Measures: Initial tumor and associated fundus features, pathology, gene mutation, treatment, tumor course on follow-up, and salvage globe outcome. Results: The six affected Asian patients consisted of three men and three women. The mean age at the time of diagnosis was 36.5 years (median: 31 years, range: 20-55 years). All patients were unilateral. In all cases, the tumors were white, dome-shaped, with full-thickness retinal involvement, and mushroom-like protrusions into the vitreous cavity. The mean tumor thickness measured by ultrasonography was 4.5 mm (median: 3.2 mm, range: 3.2-6.8 mm). Associated characteristic symptoms included dilated retinal feeding artery and draining vein (100%), surrounding subretinal infiltration (83%), exudative retinal detachment (83%), and vitreous seeds (67%). Local tumor resection was performed in three patients, I-125 plaque brachytherapy combined with transpupillary thermotherapy (TTT) and intravitreous injection of melphalan (combination treatment) in one patient, I-125 plaque brachytherapy in two patients, and enucleation in one (20%) patient. RB1 gene testing was carried out on four patients and pathological diagnosis on five patients. Genetic analysis revealed that the RB1 mutation was a mosaic c.709dupG (p.Glu237GlyfsTer4) duplication in one patient, a mosaic c.763C>T(p.Arg255Ter) mutation in another patient, while the remaining two patients were RB1 negative. At the end of the follow-up, none of the patients had developed tumor-related metastasis or died. The findings were consistent in all patients who had an adequate follow-up. This study focused on this rare lesion to distinguish it from other intraocular white lesions in adults, including choroidal osteoma, vitreoretinal lymphoma, and retinal capillary hemangioma, all of which are different clinical entities. Conclusion: In adults, RB is typically a white, full-thickness retinal mass that is unilateral, often combining with retinal feeding vessels, subretinal infiltration, and vitreous seeds. Genetic studies on adult-onset RB are essential and still require elucidation. Despite RB being a malignant tumor, patient survival was minimally affected.

Machine learning predicting wastewater properties of the aqueous phase derived from hydrothermal treatment of biomass.

Hydrothermal treatment (HTT) is a potential technology for producing biofuel from wet biomass. However, the aqueous phase (AP) is generated inevitably in the process of HTT, and studies are lacking on the detailed exploration of AP properties. Therefore, machine learning (ML) models were built for predicting the pH, total nitrogen (TN), total organic carbon (TOC), and total phosphorus (TP) of the AP based on biomass feedstock and HTT parameters. Results showed that the gradient boosting decision tree (average testing R2 0.85-0.96) can accurately predict the above wastewater properties for both single- and multi-target models. ML-based feature importance indicated that nitrogen content of biomass, solid content, and temperature were the top three critical features for pH, TN, and TP, while those for TOC were reaction time, lipid, and temperature. This ML approach provides new insights to understand the formation and properties of the HTT AP by ML rather than time-consuming experiments.

Auricular Acupressure for Hemodialysis Patients with Insomnia: A Multicenter Double-Blind Randomized Sham-Controlled Trial.

Background and objectives: The effect of auricular acupressure (AA) for maintenance hemodialysis (MHD) patients with insomnia has been controversial. This study assessed the efficacy and safety of AA for MHD patients with chronic insomnia. Design, setting, participants, and measurements: This was a multicenter, double-blind (participant and assessor), randomized sham-controlled trial. A total of 133 subjects were randomized to receive AA on active points (AA group, n = 64) or on sham auricular acupressure (SAA) points (SAA group, n = 69) for 8 weeks and followed up for 12 weeks. AA was provided by assigned qualified nurses who were not involved in assessment. The primary outcome was the clinical response rate, which was defined as the percentage of participants who reached a reduction of Pittsburgh Sleep Quality Index (PSQI) global score ≥3 in each group. Secondary outcomes included changes in PSQI scores over time, PSQI scores and hypnotics use at each visit, and changes in the weekly dose of hypnotics for drug-dependent subjects. Results: At week 8, the AA group yielded a higher clinical response rate than the SAA group (AA: 55% vs. SAA: 36%, odds ratio: 1.5, 95% confidence interval: 1.0-2.2, p = 0.033). Both groups showed a reduction in PSQI global scores during treatment and follow-up, compared with the baseline, respectively. A significant change of PSQI global score was observed over time (F = 28.387, p < 0.001). PSQI global score of the AA group was relatively lower than that of the SAA group at each visit (p < 0.05 at week 16 and 20). For those depending on hypnotics, AA reduced their consumption of hypnotics. The intervention was safe, and its adherence was satisfactory. Conclusion: AA could serve as a complementary or alternative therapy for MHD patients with insomnia by improving their sleep quality and reducing their use of hypnotics. Clinical trial registration: Clinicaltrials.gov, Identifier: NCT03015766.

Machine learning prediction and optimization of bio-oil production from hydrothermal liquefaction of algae.

Hydrothermal liquefaction (HTL) of algae is a promising biofuel production technology. However, it is always difficult and time-consuming to identify the best optimal conditions of HTL for different algae by the conventional experimental study. Therefore, machine learning (ML) algorithms were applied to predict and optimize bio-oil production with algae compositions and HTL conditions as inputs, and bio-oil yield (Yield_oil), and the contents of oxygen (O_oil) and nitrogen (N_oil) in bio-oil as outputs. Results indicated that gradient boosting regression (GBR, average test R2 âˆ¼ 0.90) exhibited better performance than random forest (RF) for both single and multi-target tasks prediction. Furthermore, the model-based interpretation suggested that the relative importance of operating conditions (temperature and residence time) was higher than algae characteristics for the three targets. Moreover, ML-based reverse and forward optimizations were implemented with experimental verifications. The verifications were acceptable, showing great potential of ML-aided HTL for producing desirable bio-oil.

Identification and characterization of murine adipose tissue-derived somatic stem cells of Shenque (CV8) acupoint.

BACKGROUND: Shenque (CV8) acupoint is located on the navel and has been therapeutically used for more than 2000 years in Traditional Chinese Medicine (TCM). However, clinical research on the underlying therapeutic molecular mechanisms of the CV8 acupoint lags far behind. This study aimed to study the mechanisms of umbilical acupoint therapy by using stem cells. METHODS: The morphological characteristics of CV8 acupoint were detected under a stereomicroscope using hematoxylin and eosin (H&E) staining. Oil Red, Masson, and immunohistochemical staining on multi-layered slices were used to identify the type of cells at the CV8 acupoint. Cell proliferation was measured by a cell counting kit-8 (CCK-8) method. Flow cytometry and immunohistochemistry were used for cell identification. Induced differentiation was used to compare the differentiation of cells derived from CV8 acupoint and non-acupoint somatic stem cells into other cell types, such as osteogenic, adipogenic, and neural stem cell-like cells. RESULTS: Morphological observations showed that adipose tissues at the linea alba of the CV8 acupoint in mice had a mass-like distribution. Immunohistochemical staining confirmed the distribution of stem cell antigen-1 (Sca-1) positive cells in the multi-layered slices of CV8 acupoint tissues. Cells isolated from adipose tissues at the CV8 acupoint exhibited high expression of Sca-1 and CD44 and low expression of CD31 and CD34, and these cells possessed osteogenic, adipogenic, and neurogenic stem cell-like cell differentiation ability. The cell proliferation (day 4: 0.5138 ±â€Š0.0111 vs. 0.4107 ±â€Š0.0180, t = 8.447, P = 0.0011; day 5: 0.6890 ±â€Š0.0070 vs. 0.5520 ±â€Š0.0118, t = 17.310, P < 0.0001; day 6: 0.7320 ±â€Š0.0090 vs. 0.6157 ±â€Š0.0123, t = 13.190, P = 0.0002; and day 7: 0.7550 ±â€Š0.0050 vs. 0.6313 ±â€Š0.0051, t = 42.560, P < 0.0001), adipogenic ([9.224 ±â€Š0.345]% vs. [3.933 ±â€Š1.800]%, t = 5.000, P = 0.0075), and neurogenic stem cell-like cell differentiation (diameter < 50 µm: 7.2000 ±â€Š1.3040 vs. 2.6000 ±â€Š0.5477, t = 7.273, P < 0.0001; diameter 50-100 µm: 2.6000 ±â€Š0.5477 vs. 1.0000 ±â€Š0.7071, t = 4.000, P = 0.0039; and diameter >100 µm: 2.6000 ±â€Š0.5477 vs. 0.8000 ±â€Š0.8367, t = 4.025, P = 0.0038) were significantly enhanced in somatic stem cells derived from the CV8 acupoint compared to somatic stem cells from the groin non-acupoint. However, cells possessed significantly weaker osteogenicity ([2.697 ±â€Š0.627]% vs. [7.254 ±â€Š0.958]%, t = 6.893, P = 0.0023) in the CV8 acupoint group. CONCLUSIONS: Our study showed that CV8 acupoint was rich with adipose tissues that contained abundant somatic stem cells. The biological examination of somatic stem cells derived from the CV8 acupoint provided novel insights for future research on the mechanisms of umbilical therapy.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Efficacy evaluation and mechanism study of electroacupuncture intervention in acute phase of IFP: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies had already reported the efficacy of electroacupuncture treatment for idiopathic facial nerve palsy (IFP) in a recovery phase; however, the initial use of electroacupuncture in the acute phase remains controversial. Hence, in the present study, we will add electroacupuncture intervention based on oral prednisone tablets in the acute phase of IFP and compare the clinical effects with simple oral prednisone tablets. Besides, the prognosis and safety will be evaluated. The present study aims to evaluate the clinical efficacy, prognosis, and safety of electroacupuncture combined with oral prednisone tablets in the acute phase of IFP, using surface electromyography (sEMG) to objectively observe the recovery of facial expression muscle function. In addition, the morphological changes of the facial nerve were observed dynamically by magnetic resonance imaging (MRI) in the acute phase to reveal the effect mechanism of this therapy. METHODS: Randomized controlled trials will be conducted in the first teaching hospital of Tianjin University of Traditional Chinese Medicine in China from September 2020 to April 2021. The treatment will be carried out in two phases, including the acute phase and the recovery phase. Eighty IFP patients will be recruited and randomized into two groups with a 1:1 ratio. Subjects in the acute phases of the control group will be given oral prednisone tablets, based on the control group, and subjects of the experimental group will be given electroacupuncture therapy simultaneously in the acute phase. Both groups will be stopped taking prednisone tablets and turn to electroacupuncture therapy in a recovery phase. Patients in the experimental group will receive treatment at least 6 times in the acute phase and both groups will receive treatment 9 times in the recovery phase, and there will be a follow-up period of 15 days after the treatment. The primary outcome is supposed to be related to the changes observed in the Sunnybrook (Toronto) Facial Grading System (SFGS) on the baseline and day 30 after the onset. Secondary outcome measures will include House-Brackmann Facial Nerve Grading System (H-B), measurement of Numerical Rating Scale (NRS), Facial Disability Index scale (FDI, including physical function subscore, FDIP, and social functioning and well-being subscore, FDIS), surface electromyogram (sEMG), and magnetic resonance imaging (MRI). Adverse events will be recorded for safety assessment. DISCUSSION: The results of this trial will allow the present study to compare the difference in efficacy and prognosis between the strategy of combined electroacupuncture in the acute phase and only oral prednisone tablets. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: CHICTR ChiCTR2000038472 . Registered on 23 September 2020.

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Real-World Effects of Chinese Herbal Medicine for Idiopathic Membranous Nephropathy (REACH-MN): Protocol of a Registry-Based Cohort Study.

Introduction: Some encouraging findings of Chinese herbal medicine (CHM) in management of idiopathic membranous nephropathy (IMN) obtained in the setting of clinical trials are hard to validate in the daily clinical practice due to a complicated treatment scenario of CHM in practice. The primary objective of this registry is to provide a description of treatment patterns used in management of IMN and assess clinical remission in daily practice in a Chinese population sample with IMN. Methods and analysis: This is a prospective, multicenter cohort which will comprise 2000 adults with IMN regardless of urinary protein levels that will be recruited from 11 nephrology centers across China. The participants will be followed for up to at least 2 years. Primary outcome is composite remission (either complete remission or partial remission) 24 months after enrolment. The secondary outcomes are complete remission, partial remission, time to remission, no response, relapse, proteinuria, annual change of glomerular filtration rate, antibodies against PLA2R, and composite endpoint of 40% reduction of glomerular filtration rate, doubling of serum creatinine, end-stage renal disease, and death. Propensity score analysis will be used for matching and adjustment. Ethics and dissemination: This study has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2020-094-01). Results of the study will be published in both national and international peer-reviewed journals, and presented at scientific conferences. Investigators will inform the participants as well as other IMN patients of the findings via health education. Study registration: ChiCTR2000033680 (prospectively registered).

Protocol of the Development of a Core Outcome Set for Ischemic Stroke in Clinical Trials of Chinese Medicine.

Background. Ischemic stroke (IS) seriously impacts the quality of life of survivors. Chinese medicine (CM) has been developed for more than 2000 years and plays a key role in the treatment of ischemic stroke. Many Chinese medicine clinical trials have been conducted; however, the heterogeneity of outcome measurements and reporting limits implications of the findings in clinical practice and health policy development. Therefore, it is important to develop a core outcome set (COS) that should be used and reported in trials for ischemic stroke treated by Chinese medicine. This protocol describes the process of developing the IS-CM-COS. Methods and Analysis. The development of the COS will involve the following four steps: (1) A list of outcomes reported in the registered and published Chinese medicine trials of ischemic stroke will be extracted by conducting a systematic literature review. (2) An additional outcome list will be collected by semistructured interview to patients with ischemic stroke. (3) A two-round Delphi survey will be performed to prioritize and condense the outcomes. (4) In the consensus meeting, a final recommended COS will be developed. Discussion. The COS could improve the reliability and consistency of outcome reporting. We hope that this IS-CM-COS will be used in the future Chinese medicine trials for the treatment of ischemic stroke and improve research quality. Trial Registration. This study was registered with the Core Outcome Measures in Effectiveness Trials Initiative (http://www.comet-initiative.org/studies/details/1282).

Acupuncture combined with speech rehabilitation training for post-stroke dysarthria: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The evidence of Acupuncture combined with speech rehabilitation training for post-stroke dysarthria is insufficient and there is no consensus on its efficacy. METHODS: We searched seven Chinese and English medicine databases for randomized controlled trials (RCTs) from their inception to November 2019. The primary outcome measure was the clinical response rate, assessed with the Frenchay Dysarthria Assessment (FDA) tool. We assessed risk of bias using the Cochrane risk-of-bias tool. We used GRADE to assess the certainty of evidence (CoE). RESULTS: Thirty studies were included in this systematic review, 23 of which were pooled in meta-analysis. Acupuncture combined with speech rehabilitation training is likely beneficial for was response rate (n = 1685; RR = 1.37; 95% CI [1.29, 1.46], P < 0.01, I 2 = 34%; 17 studies, low CoE) compared to speech rehabilitation treatment alone. CONCLUSION: The combination of acupuncture and speech rehabilitation training may improve total response rate of stroke patients with dysarthria. However, more RCTs with rigorous study design and validated outcome measures are needed to confirm the evidence.

Mechanism of Huang-lian-Jie-du decoction and its effective fraction in alleviating acute ulcerative colitis in mice: Regulating arachidonic acid metabolism and glycerophospholipid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-lian-Jie-du decoction (HLJDD) is a traditional Chinese medicine prescription for clearing away heat, purging fire and detoxifying, which can be used to treat sepsis, stroke, Alzheimer's disease and gastrointestinal diseases. Our previous studies have shown that HLJDD can effectively alleviate acute ulcerative colitis (UC) in mice, and its n-butanol fraction (HLJDD-NBA) is the effective fraction. The aim of this study is to further investigate the mechanism of HLJDD and HLJDD-NBA in relieving UC in mice from a holistic perspective. METHODS: The acute UC model of BABL/c mice was induced by 3.5% (w/v) dextran sodium sulfate drinking water. At the same time of modeling, HLJDD and HLJDD-NBA were given orally for treatment respectively. During the experiment, the clinical symptoms of mice were recorded and the physiological and biochemical indexes of mice were detected after the experiment. In addition, the plasma metabolites of mice in each group were detected and analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry and multivariate statistical analysis method. Then, the potential target metabolic pathway of drug intervention was screened through the enrichment analysis of differential metabolites. Finally, we use molecular simulation docking technology to further explore the molecular regulatory mechanism of HLJDD and HLJDD-NBA on potential target metabolic pathways. RESULTS: HLJDD and HLJDD-NBA intervention can significantly reduce the disease activity index of UC mice, inhibit colon length shortening and pathological damage, and relieve the abnormal changes of physiological and biochemical parameters of UC mice. Moreover, HLJDD and HLJDD-NBA can significantly inhibit the metabolic dysfunction of UC mice by reversing the abnormal changes of 24 metabolites in UC mice, and the arachidonic acid metabolic pathway and glycerophospholipid metabolic pathway are the target metabolic pathways regulated by them. Further literature review and molecular simulation docking analysis showed that HLJDD and HLJDD-NBA may inhibit the disorder of arachidonic acid metabolism pathway and glycerophospholipid metabolism pathway by inhibiting COX-2 protein expression and PLA2, 5-LOX activity. CONCLUSIONS: Our experiments revealed that HLJDD and HLJDD-NBA can alleviate UC of mice by regulating arachidonic acid metabolism and glycerophospholipid metabolism, which points out the direction for further research and development of HLJDD as a new anti-ulcer drug.

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: -2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: -4.03,-0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

Therapeutic effect of n-butanol fraction of Huang-lian-Jie-du Decoction on ulcerative colitis and its regulation on intestinal flora in colitis mice.

Huang-lian-Jie-du Decoction (HLJDD) is a classical prescription for clearing away heat and detoxification. In order to screen the effective fraction of HLJDD in the treatment of ulcerative colitis (UC) in mice and explore its effects on intestinal flora in UC mice, we prepared different polar fractions of HLJDD by system solvent extraction method. Subsequently, the contents of 13 active compounds in different polar fractions of HLJDD were determined by HPLC. Further, the UC model induced by dextran sodium sulfate was used to evaluate the therapeutic effects of different polar fractions of HLJDD. Finally, cecal contents were used for sequencing and analysis of bacterial 16S rRNA genes. The results showed that the yield of HLJDD-n-butanol (HLJDD-NBA) fraction was the highest, and the content or proportion of 13 active compounds in HLJDD-NBA fraction were the most similar to HLJDD. In addition, in vivo pharmacodynamic experiments showed that HLJDD-NBA intervention not only significantly alleviated the clinical symptoms of UC mice and ameliorated the pathological damage of colon tissue, but also showed significant anti-inflammatory and antioxidative effects (p < 0.05), which were comparable to HLJDD (p > 0.05). Moreover, both HLDD and HLJDD-NBA treatments can restore the intestinal flora homeostasis of UC mice by inhibiting the growth of intestinal pathogens and preventing the decrease of beneficial bacteria. Meanwhile, they can also significantly correct the dysfunction of intestinal flora in UC mice. In conclusion, we proved that HLJDD-NBA fraction is an effective fraction of HLJDD in treating UC in mice, and it can maintain the intestinal flora homeostasis of UC mice, which increases our understanding of the mechanism of HLJDD in treating UC and lays a foundation for the development of new anti-ulcer drugs.

Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice via Regulating NF-κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function.

Evidence shows that intestinal inflammation, oxidative stress, and injury of mucosal barrier are closely related to the pathogenesis of ulcerative colitis (UC). Huang-lian-Jie-du Decoction (HLJDD) is a well-known prescription of traditional Chinese medicine with anti-inflammatory and antioxidative activities, which may be used to treat UC. However, its therapeutic effect and mechanism are still unclear. In this study, the UC model of BABL/c mice were established by DSS [3.5% (w/v)], and HLJDD was given orally for treatment at the same time. During the experiment, the clinical symptoms of mice were scored by disease activity index (DAI). Besides, the effects of HLJDD on immune function, oxidative stress, colon NF-κB and Nrf2 signaling pathway, and intestinal mucosal barrier function in UC mice were also investigated. The results showed that HLJDD could alleviate body weight loss and DAI score of UC mice, inhibit colonic shortening and relieve colonic pathological damage, and reduce plasma and colon MPO levels. In addition, HLJDD treatment significantly up-regulated plasma IL-10, down-regulated TNF-α and IL-1ß levels, and inhibited the expression of NF-κB p65, p-IκKα/ß, and p-IκBα proteins in the colon. Moreover, NO and MDA levels in colon tissues were significantly reduced after HLJDD treatment, while GSH, SOD levels and Nrf2, Keap1 protein expression levels were remarkably elevated. Additionally, HLJDD also protected intestinal mucosa by increasing the secretion of mucin and the expression of ZO-1 and occludin in colonic mucosa. These results indicate that HLJDD could effectively alleviate DSS-induced mice UC by suppressing NF-κB signaling pathway, activating Nrf2 signaling pathway, and enhancing intestinal barrier function.

Pueraria lobata for Diabetes Mellitus: Past, Present and Future.

Gegen (Radix Puerariae Lobatae), the root of Pueraria lobata, is an edible and medicinal herb which has been used in treating diabetic symptoms in the orient for thousands of years. We present an evidence map of the efficacy and safety of Gegen and Gegen formulas (GGFs) that use Gegen as an essential herb for diabetes, and also its mechanism of actions. We comprehensively searched the ancient medical records to identify empirical evidence; conducted a systematic review (SR) based on moderate- to high-quality randomized controlled trials (RCTs) to synthesize the clinical evidence; and reviewed the possible mechanisms of its antidiabetic effects. Empirical application of Gegen in treating diabetic symptoms dated back to more than 2000 years ago. Common herbs used in RCTs that accompany with Gegen included Radix et Rhizoma Glycyrrhizae, Radix et Rhizoma Ginseng, Rhizoma Dioscoreae, Poria, and Radix Ophiopogonis. The combinations used today are consistent with their usage in ancient times. Results of the SR showed that GGFs could benefit patients with type 2 diabetes for blood glucose control. When in combination with hypoglycemic agents or insulin, GGFs enhanced the glucose-lowering effect as well as the lipid-lowering effects. Also, the incidence and the risk of adverse events (AE), especially the hypoglycemic episodes, were lower in the combination group. No serious or life-threatening AE was reported. The experimental evidence presented that Gegen and GGFs might exert and enhance the anti-diabetic effects through activation of multiple mechanisms, such as reducing insulin resistance, increasing insulin release, inhibiting glucose absorption and reabsorption, and improving insulin sensitivity, glucose uptake, and metabolism.

Xinmailong Modulates Platelet Function and Inhibits Thrombus Formation via the Platelet αIIbß3-Mediated Signaling Pathway.

Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects. Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bß3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3ß, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model. Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3ß, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model. Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.