Comparative analysis and evaluation of wild and cultivated Radix Fici Simplicissimae using an UHPLC-Q-Orbitrap mass spectrometry-based metabolomics approach.

Radix Fici Simplicissimae (RFS) is widely studied, and is in demand for its value in medicines and food products, with increased scientific focus on its cultivation and breeding. We used ultra-high-performance liquid chromatography quadrupole-orbitrap mass spectrometry-based metabolomics to elucidate the similarities and differences in phytochemical compositions of wild Radix Fici Simplicissimae (WRFS) and cultivated Radix Fici Simplicissimae (CRFS). Untargeted metabolomic analysis was performed with multivariate statistical analysis and heat maps to identify the differences. Eighty one compounds were identified from WRFS and CRFS samples. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that mass spectrometry could effectively distinguish WRFS from CRFS. Among these, 17 potential biomarkers with high metabolic contents could distinguish between the two varieties, including seven phenylpropanoids, three flavonoids, one flavonol, one alkaloid, one glycoside, and four organic acids. Notably, psoralen, apigenin, and bergapten, essential metabolites that play a substantial pharmacological role in RFS, are upregulated in WRFS. WRFS and CRFS are rich in phytochemicals and are similar in terms of the compounds they contain. These findings highlight the effects of different growth environments and drug varieties on secondary metabolite compositions and provide support for targeted breeding for improved CRFS varieties.

Effect of acupuncture on arthritic pathological injury in rats with type â ¡ collagen-induced rheumatoid arthritis. / é’ˆåˆºæ”¹å–„â ¡åž‹èƒ¶åŽŸè›‹ç™½è¯±å¯¼æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ååº”çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type Ⅱ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA). METHODS: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 µL/rat) in the tail root region on the first day and repeat (100 µL/rat) once on the 9th day. Eighteen successful CIA rats were randomized into model, medication and acupuncture groups, with 6 rats in each group. Other 6 normal rats were used as the normal control group. For rats of the medication group, leflunomide (1.9 mg/kg) was administrated by gavage, once a day, and for rats of the acupuncture group, manual acupuncture stimulation was applied to bilateral GB34, ST36, GB39 for 30 min, once a day, for 12 weeks. The arthritis index (AI) score (0-4 points) was evaluated once every week. The contents of IL-6, IL-17 and TNF-α in the serum were determined by ELISA. Histopathological changes of the ankle joint were observed by H.E. staining. The protein and mRNA expression levels of mt-p53, NF-κB p65, and PPARγ in the knee joint synovial tissue were determined by Western blot and quantitative real time PCR, separately. RESULTS: Compared with the normal control group, the AI scores at different time-points after modeling, contents of serum TNF-α, IL-6 and IL-17, expression levels of mt-p53, NF-κB p65, PPARγ proteins and mRNAs were significantly increased in the model group (P<0.01, P<0.05). In comparison with the model group, the AI scores at the 10th week in the medication group and at the 3rd, 9th and 10th week in the acupuncture group, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins in both medication and acupuncture groups, as well as mt-p53 and NF-κB p65 mRNAs in the medication group were apparently decreased (P<0.01, P<0.05), while the expression levels of PPARγ protein in both medication and acupuncture group and PPARγ mRNA in the medication group were significantly up-regulated (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in down-regulating the AI score and serum TNF-α, IL-6 and IL-17 contents. The effect of acupuncture was weaker than that of medication in down-regulating the expression of mt-p53 and NF-κB p65 proteins and mRNAs and in up-regulating PPARγ mRNA (P<0.01). H.E. results showed ankle cartilage hyperplasia, reduced joint cavity, mild fibroproliferation and inflammatory cell infiltration in the surrounding soft tissue of the ankle joint in rats of the model group, which was milder in both medication and acupuncture groups. CONCLUSIONS: Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.

Relationship among Chinese herb polysaccharide (CHP), gut microbiota, and chronic diarrhea and impact of CHP on chronic diarrhea.

Chronic diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D), osmotic diarrhea, bile acid diarrhea, and antibiotic-associated diarrhea, is a common problem which is highly associated with disorders of the gut microbiota composition such as small intestinal bacterial overgrowth (SIBO) and so on. A growing number of studies have supported the view that Chinese herbal formula alleviates the symptoms of diarrhea by modulating the fecal microbiota. Chinese herbal polysaccharides (CHPs) are natural polymers composed of monosaccharides that are widely found in Chinese herbs and function as important active ingredients. Commensal gut microbiota has an extensive capacity to utilize CHPs and play a vital role in degrading polysaccharides into short-chain fatty acids (SCFAs). Many CHPs, as prebiotics, have an antidiarrheal role to promote the growth of beneficial bacteria and inhibit the colonization of pathogenic bacteria. This review systematically summarizes the relationship among gut microbiota, chronic diarrhea, and CHPs as well as recent progress on the impacts of CHPs on the gut microbiota and recent advances on the possible role of CHPs in chronic diarrhea.

Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Ginsenoside Rb1 Suppresses AOM/DSS-induced Colon Carcinogenesis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Current treatments, including surgery, radiotherapy, and chemotherapy, are limited by severe side effects and the development of resistance. OBJECTIVE: Therefore, it is important to find additional therapies to combat the problem. Ginsenoside Rb1 is the main active ingredient of ginseng, which is a well-known herb in traditional Chinese medicine. Ginsenoside is reported to play an important role in the prevention and treatment of cancer. METHODS: We established Azoxymethane (AOM)/Dextran sodium sulfate (DSS) colon cancer model based on inflammation, observed the beneficial effect of ginsenoside Rb1, and detected the changes in gut microbiota. RESULTS: Our experimental results showed that ginsenoside Rb1 significantly reduced the levels of TNF-α, IL-6, IL- 17A, IL-33, IL-1ß, and IL-22, increased the level of IL-10, and also changed the gut microbiota composition. These results suggested that ginsenoside Rb1 can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC by relieving chronic inflammation and restoring the gut microenvironment in the AOM/DSS-induced model of colitis-associated colorectal cancer in mice. CONCLUSION: Ginsenoside Rb1 significantly attenuated AOM/DSS-induced colon carcinogenesis.

Efficacy of Pretreatment with Lycium barbarum Polysaccharide in Various Doses in Influencing Splenic Immunity and Prognosis of Sepsis in Rats.

Objective: Sepsis, showing high mortality, is a lethal dysfunction of organs caused by an infection-induced disorder in the host response. It has complicated pathogenesis, which has not yet been elucidated completely. Recently, the principal factors causing pathogenesis and even death in sepsis patients are imbalance in inflammatory response and immunosuppression occurring when the host is challenged by infection. Previous studies found that Lycium barbarum polysaccharide (LBP) worked well in enhancing immunity. This study aims at exploring the efficacy of pretreatment with LPB in regulating splenic immunity during the pathogenesis of sepsis induced by cecum ligation perforation (CLP) in rats. Methods: This research established the cecum ligation perforation rat model. Using immunohistochemistry and flow cytometry, the effects of Lycium barbarum polysaccharide in various doses in influencing splenic immunity and prognosis of sepsis induced by cecum ligation perforation in rats were examined. Results: This study showed that LBP lowered the 72-hour mortality of sepsis rats induced by CLP, relieved systemic inflammation, improved the ratio of T-cell subgroups positive in CD3+, CD4+, or CD8+ and expression of HLA-DR protein, and repaired damage to splenic tissue, implying its efficacy in enhancing the immunity of sepsis rats induced by CLP. Conclusions: LBP may ameliorate clinical symptoms of rats with cecum ligation perforation, improve cellular immunity in the spleen, and treat sepsis so as to provide a theoretical basis for the pathogenesis and development of sepsis as well as its diagnosis and treatment, and offer scientific proof for the development and utilization of LBP applied to critical diseases.

Shen-Ling-Bai-Zhu-San (SL) and SL Derived-Polysaccharide (PL) Ameliorate the Severity of Diarrhea-Induced by High Lactose via Modification of Colonic Fermentation.

In our previous study, we demonstrated that Shen-ling-bai-zhu-san (SL), a classical Chinese herbal formula, could alleviate lactose-induced diarrhea. However, little is known about the mechanism underlying SL action or the efficacy of the polysaccharide (PL) derived from SL. In this study, we investigated the effect of SL and PL on improving the dysregulated luminal and mucosal microbiota in rats with high lactose diet using 16S rRNA analysis. The concentrations of lactose, lactic acid in cecum and short-chain fatty acids (SCFAs) in cecum and portal vein were measured, meanwhile the expression of ion transporters were ascertained. Our data suggest that the SL, PL and cecal microbiota transplantation (CMT) significantly decreased fecal water content and water intake. In the luminal microbiota there was a significant increase in Akkermansia, Bifidobacterium and Blautia and a lower abundance of Lactobacillus, Escherichia-Shigella, and Dubosiella, while the mucosal microbiota showed a significant increase in Bifidobacterium, Akkermansia, Albaculum, Bilophila, and Coriobacteriaceae_UCG-002 and a lower abundance of Enterococcus, Helicobacter, Dubosiella, and Collinsella. Furthermore, the treatments enhanced lactose fermentation and SCFA production, which may be related to the modulation of the luminal microbial community. A lower ratio of phosphorylation Na/H exchanger3/Na/H exchanger3 (pNHE3/NHE3) and a higher sodium monocarboxylate1 (sMCT1) expression were found in the treatment group than in the model group, which may be related to the changes in the mucosal microbial community. Also, the treatments may restore the impacted metabolic pathways of gut microbiota. These results provide an important foundation for mechanism of SL action and developing PL-based treatment for lactose-induced diarrhea.

[Spatial Distribution and Eco-stoichiometric Characteristics of Soil Nutrient Elements Under Different Vegetation Types in the Yellow River Delta Wetland].

To clarify the distribution characteristics and the ecological stoichiometric characteristics of nutrient elements in soils under different vegetation types, four typical natural wetlands, i.e., Phragmites australis wetland, Tamarix chinensis wetland, Suaeda salsa wetland, and Tidal flat wetland, as well as Gossypium spp. fields that were reclaimed from natural wetlands, were selected as study sites in the Yellow River Delta, and comparisons between the agricultural reclamation land and natural wetlands were conducted. The results showed that the soil total organic carbon (TOC) and total nitrogen (TN) contents in the natural wetlands were as follows:P. australis wetland and T. chinensis wetland>S. salsa wetland>Tidal flat, and the contents of TOC and TN were significantly negatively related to electrical conductivity (EC) and pH values (P<0.05). The contents of TOC, TN, and total phosphorus (TP) in Gossypium spp. fields were significantly higher than those in natural wetlands (P<0.05), especially the contents of nitrate nitrogen (NO3--N) in Gossypium spp. fields, which were 9.4-11.4 times that of natural wetlands. However, no significant correlations between TOC, TN, and TP and EC and pH values (P>0.05) were observed in Gossypium spp. fields. The results of correlation analysis showed that the C/N of natural wetlands were mainly controlled by the contents of TN (P<0.05), and the C/N of the Gossypium spp. fields were significantly lower than those of natural wetlands (P<0.05). The soil C/P and N/P of natural wetlands and Gossypium spp. fields in the Yellow River Delta were low, and the variation trends were consistent with those of soil TOC and TN. Comparative analysis revealed, on the whole, that there were significantly different soil nutrient element contents, C/N, C/P, and N/P in Gossypium spp. fields compared to those of natural wetlands (P<0.05). The process of reclamation could significantly change the spatial distribution of nutrient elements in wetlands. Our results should be of importance in revealing the biogeochemical process of soil nutrient elements in coastal wetland and the influence of agricultural reclamation activities on the differentiation of soil nutrient elements.

Prevalence of hyperhomocysteinemia (HHcy) and its major determinants among hypertensive patients over 35 years of age.

OBJECTIVE: Hyperhomocysteinemia (HHcy) and hypertension are associated with cardiovascular events. However, effects of Hcy-lowing interventions on cardiovascular outcome were conflicting. Serum folate level was proposed to be a possible determinant of efficacy of extra folate supplementation on cardiovascular outcome. The aims of the present study were to describe representative information on the levels of serum homocysteine and folate in hypertensive patients, and to explore the major determinants of HHcy. METHODS: 11,007 participants with hypertension were analyzed in this cross-sectional study. Blood pressure and serum levels of biochemical indicators were measured. Multivariate logistic regression model was used to assess the associated factors of HHcy. RESULTS: Geometric mean of serum total homocysteine was 14.1 (95% CI: 13.9, 14.4) µmol/L and prevalence of HHcy was 36.1 (95% CI: 34.0, 38.1) % in hypertensive patients. HHcy was strongly associated with factors including male sex, older age, elevated serum creatinine (SCr), lower serum folate and vitamin B12, and uncontrolled blood pressure in hypertensive patients. Elevated SCr attributed to HHcy with the etiologic fraction of 0.29. The change of the odds ratio of HHcy associated with folate was significantly higher in patients with elevated SCr compared with that of patients with normal SCr. CONCLUSION: The results suggested the protection of female sex and higher levels of folate and vitamin B12 from HHcy and attribution of older age and elevated SCr to HHcy. Restoring renal function deserved attention for hypertensive patients to benefit from Hcy-lowing measures.

[Effect of staging treatment of Tongyuan acupuncture on pregnancy outcome in patients with recurrent implantation failure of thin endometrium type].

OBJECTIVE: To compare the effect of Tongyuan acupuncture combined with medication and medication alone on pregnancy outcome in patients with recurrent implantation failure (RIF) of thin endometrium type. METHODS: A total of 74 patients with RIF of thin endometrium type undergoing freeze-thaw embryo transfer were randomly divided into an observation group (37 cases) and a control group (37 cases). The patients in the control group were treated with freeze-thaw embryo transfer in hormone replacement cycle, and the estradiol valerate tablets were taken orally from the fifth day of menstruation, 2 mg per day. On the basis of the control group, the observation group was additionally treated with Tongyuan acupuncture at Baihui (GV 20), Dazhui (GV 14), Qihai (CV 6), Guanyuan (CV 4), etc., combined with other acupoints based on syndrome differentiation and menstrual stage, once every other day. Both groups were treated for 3 menstrual cycles. The clinical pregnancy rate and embryo implantation rate of the two groups were observed after transplantation; the endometrial thickness and type, resistance index (RI) and pulsatility index (PI) of endometrial blood flow were measured before treatment and one day before transplantation, and adverse reactions was recorded. RESULTS: The clinical pregnancy rate was 37.8% (14/37) in the observation group, which was higher than 16.2% (6/37) in the control group (P<0.05). There was no significant difference in embryo implantation rate between the two groups (P>0.05). One day before transplantation, the endometrial thickness and the proportion of type A in endometrial classification in the two groups were increased compared with those before treatment (P<0.01), and those in the observation group were higher than the control group (P<0.01, P<0.05). The PI and RI of endometrial blood flow in the two groups were lower than those before treatment (P<0.01), and those in the observation group were lower than the control group (P<0.01, P<0.05). During the treatment, 6 patients in the control group had discomfort such as breast distending pain, stomach pain, dizziness and nausea, and there were no adverse reaction in the observation group. CONCLUSION: On the basis of conventional medication, Tongyuan acupuncture could increase the endometrial thickness, improve endometrial receptivity, improve pregnancy outcome and reduce adverse reactions in patients with RIF of thin endometrial type.

Stage- and Rearing-Dependent Metabolomics Profiling of Ophiocordyceps sinensis and Its Pipeline Products.

Cordyceps, a parasitic complex of the fungus Ophiocordyceps sinensis (Berk.) (Hypocreales: Ophiocordycipitaceae) and the ghost moth Thitarodes (Lepidoptera: Hepialidae), is a historical ethnopharmacological commodity in China. Recently, artificial cultivation of Chinese cordyceps has been established to supplement the dwindling natural resources. However, much is unknown between the natural and cultivated products in terms of nutritional aspect, which may provide essential information for quality evaluation. The current study aims to determine the metabolic profiles of 17 treatments from 3 sample groups including O. sinensis fungus, Thitarodes insect and cordyceps complex, using Gas Chromatography - Quadrupole Time-of-Flight Mass Spectrometry. A total of 98 metabolites were detected, with 90 of them varying in concentrations among groups. The tested groups could be separated, except that fungal fruiting body was clustered into the same group as Chinese cordyceps. The main distinguishing factors for the groups studied were the 24 metabolites involved in numerous different metabolic pathways. In conclusion, metabolomics of O. sinensis and its related products were determined mainly by the fruiting bodies other than culture methods. Our results suggest that artificially cultured fruiting bodies and cordyceps may share indistinguishable metabolic functions as the natural ones.

Regulatory Effect of Modified Banxia Xiexintang on Insulin Resistance of Patients with Nonalcoholic Fatty Liver / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Banxia Xiexintang on nonalcoholic fatty liver （NAFLD） and the regulatory effect on insulin resistance （IR）. Method:One hundred and forty patients were randomly divided into control group and observation group. A total of 63 patients in control group completed the therapy （4 patients fell off or were lost to follow-up， 3 were eliminated）， while 65 patients in observation group completed the therapy （5 patients fell off or were lost to follow-up， none was eliminated）. Both groups' patients got lifestyle intervention， liver protection and lipid regulation. Patients in control group got Huazhi Rougan granule， 1 pack/time， 3 times/day. Patients in observation group got modified Banxia Xiexintang， 1 dose/day. And the course of treatment for the two groups was 12 weeks， and a 12 week follow-up was recorded. Before and after treatment and during the follow-up， fat content of liver was recorded by instantaneous elastic recorder， fasting blood glucose （FBG） and fasting insulin （FINS） were detected， and insulin sensitivity index （ISI）， insulin resistance index （HOMA-IR） and islet <italic>β</italic> cell function index （HOMA-<italic>β</italic>） were detected. After treatment， B-mode ultrasonography and ratio of liver/spleen CT were detected. And levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， adiponectin， leptin， serine protease inhibitor （Vaspin）， tumor necrosis factor （TNF）-<italic>α</italic> and interleukin-6 （IL-6） were detected. And the safety was evaluated. Result:CAP and HOMA-IR in observation group were lower than those in control group after treatment and during the follow-up （<italic>P</italic><0.01）， and ISI and HOMA-<italic>β</italic> were higher than those in control group （<italic>P</italic><0.01）. Amelioration of indexes of blood lipid was better than those in control group （<italic>P</italic><0.01）. Levels of ALT， AST， FBG and FINS were lower than those in control group （<italic>P</italic><0.01）. Scores of traditional Chinese medicine （TCM） syndromes were lower than those in control group （<italic>P</italic><0.01）， ratio of liver/spleen CT and adiponectin was higher than that in control group （<italic>P</italic><0.01）. Levels of TNF-<italic>α</italic>， IL-6， vaspin and leptin were lower than those in control group （<italic>P</italic><0.01）. B-ultrasound efficacy and fat content of liver were superior to those of control group （<italic>P</italic><0.05）. There were no serious adverse events and drug-related adverse reactions. Conclusion:Modified Banxia Xiexintang can regulate glucose and lipid metabolism， improve insulin sensitivity and HOMA-<italic>β</italic> cell function， improve IR， regulate adipocytokines and inflammatory factors， relieve clinical symptoms and liver fat content， and improve CT ratio of liver/spleen， with a better clinical efficacy and safety.

Study on association between shear wave elastography parameters and clinicopathological characteristics in breast cancer: A protocol for systematic review.

BACKGROUND: This study aims to explore the association between shear wave elastography parameters (SWEPs) and clinicopathological characteristics (CPCs) in breast cancer (BC). METHODS: The electronic databases of Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, WANGFANG, VIP, and China National Knowledge Infrastructure will be used to search for studies dated from database inception to the present. No limitations of language and publication status will be applied in this study. Only case-controlled study and randomized controlled trials investigating the association between SWEP and CPC in BC will be included. Cochrane risk of bias will be used to assess study quality for each included study. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide accurate data to appraise the association between SWEP and CPC in BC. CONCLUSION: This study will summarize the most recent evidence to improve our understanding of the association between SWEP and CPC in BC. OSF REGISTRATION NUMBER:: osf.io/vmkwu.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Effectiveness and Safety of Acupuncture for the Treatment of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Background: The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture for the treatment of AD. Methods: PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data were searched to identify relevant randomized controlled trials from inception to January 19, 2019. Data were extracted and evaluated by two authors independently. The data analysis was conducted using R (version 3.6.0) and RStudio (version 1.2.1335) software. Results: Thirty trials involving 2,045 patients were included. Acupuncture plus drug therapy may have been more beneficial for general cognitive function in AD patients than drug therapy alone (short-term treatment: MD, mean difference = 1.94, 95% CI: 1.11, 2.77; p < 0.01; medium-term treatment: MD = 4.41, 95% CI: 1.83, 7.00; p < 0.01). People who received acupuncture plus drug therapy attained higher ADL (Activities of Daily Living) scores than patients who received drug therapy alone for medium-term treatment duration (MD = -2.14; 95% CI: -3.69, -0.59; p < 0.01). However, there is no statistically significant difference in subgroup effect on MMSE (Mini-mental Status Examination) and ADLs (p > 0.05) when comparing acupuncture treatment with drug therapy (such as Donepezil hydrochloride, Nimodipine, or Yizhijiannao), or acupuncture plus drug therapy (such as Donepezil hydrochloride, Dangguishaoyaosan, or Jiannaosan) with drug therapy alone. There was also no significant difference in general cognitive function, ADLs, or incidence of adverse events between acupuncture treatment and drug therapy (p > 0.05). Conclusions: This review indicates that acupuncture plus drug therapy may have a more beneficial effect for AD patients than drug therapy alone on general cognitive function in the short and medium term and on ADLs in the medium term. Acupuncture alone may not have superior effects compared with drug therapy on global cognitive function, ADLs, and incidence of adverse events. Duration of treatment may not modify the effect of acupuncture in comparison with drug therapy. Additional large-scale and high-quality clinical trials are needed.

Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high-fat feed-induced hyperlipidemia in rats.

In this study, we focused on studying the changes in urine metabolites in hyperlipidemic rats using ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS) and metabolomics, as well as the effect of Citri Reticulatae Chachiensis Pericarpium (CRCP) on hyperlipidemia. These urine samples were examined by UPLC-Q-TOF/MS to obtain MS data. The MS data were analyzed by principal component analysis and partial least squares-discriminant analysis to identify the differential metabolites. CRCP reduced the body weight and levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol and abnormally decreased high-density lipoprotein cholesterol in hyperlipidemic rats, which were significantly raised by a high-fat diet. Twenty-seven potential biomarkers were identified within the complex sample matrix of urine. Fourteen biomarkers increased in the hyperlipidemia rats compared with normal rats. Meanwhile, 13 biomarkers decreased. CRCP reversed abnormal changes in biomarkers, including 5-l-glutamyl-taurine, 5-aminopentanoic acid, cis-4-octenedioic acid and 2-octenedioic acid. These biomarkers show that hyperlipidemia is related to the metabolic pathways of taurine and hypotaurine metabolism, fatty acid biosynthesis, and arginine and proline metabolism. CRCP mainly prevents hyperlipidemia by intervening in these metabolic pathways.

Phospholipase D-derived phosphatidic acid promotes root hair development under phosphorus deficiency by suppressing vacuolar degradation of PIN-FORMED2.

Root hair development is crucial for phosphate absorption, but how phosphorus deficiency affects root hair initiation and elongation remains unclear. We demonstrated the roles of auxin efflux carrier PIN-FORMED2 (PIN2) and phospholipase D (PLD)-derived phosphatidic acid (PA), a key signaling molecule, in promoting root hair development in Arabidopsis thaliana under a low phosphate (LP) condition. Root hair elongation under LP conditions was greatly suppressed in pin2 mutant or under treatment with a PLDζ2-specific inhibitor, revealing that PIN2 and polar auxin transport and PLDζ2-PA are crucial in LP responses. PIN2 was accumulated and degraded in the vacuole under a normal phosphate (NP) condition, whereas its vacuolar accumulation was suppressed under the LP or NP plus PA conditions. Vacuolar accumulation of PIN2 was increased in pldζ2 mutants under LP conditions. Increased or decreased PIN2 vacuolar accumulation is not observed in sorting nexin1 (snx1) mutant, indicating that vacuolar accumulation of PIN2 is mediated by SNX1 and the relevant trafficking process. PA binds to SNX1 and promotes its accumulation at the plasma membrane, especially under LP conditions, and hence promotes root hair development by suppressing the vacuolar degradation of PIN2. We uncovered a link between PLD-derived PA and SNX1-dependent vacuolar degradation of PIN2 in regulating root hair development under phosphorus deficiency.

Effects of photoelectric therapy on proliferation and apoptosis of scar cells by regulating the expression of microRNA-206 and its related mechanisms.

Human skin fibroblast (HSF) cells were irradiated with different energy lasers to detect cell proliferation, apoptosis, and expression of microRNA-206 and protein, and to further summarise the therapeutic effect of laser on scar cells. Human scar cell line HSF cells were cultured in three groups. The control group was not irradiated by laser, the low-energy group was irradiated by 10 J/cm2 laser, and the high-energy group was irradiated by 20 J/cm2 laser. After irradiation, HSF cells were cultured for 20 hours. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. Transwell migration assay was used to detect cell migratory ability. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect miR-206 and mTOR gene levels. The levels of MMP-9, Bax, Bcl-2, cyclin D1, and mTOR signalling pathway proteins were detected by Western blotting assays. The results showed that after laser irradiation, the proliferation of cells decreased, and the difference between the control group and the experimental group was significant (P < .05). The higher the energy was, the greater the upregulation of apoptosis was. Apoptosis and cell migration increased (P < .05). The expressions of microRNA-206, MMP-9, and Bax were upregulated, while the expressions of mTOR, Bcl-2, and cyclin D1 were downregulated. To sum up, laser irradiation can significantly inhibit the proliferation of HSF cells, affect cell cycle, and increase cell apoptosis and migratory ability.

Discrimination of Citrus reticulata Blanco and Citrus reticulata 'Chachi' as well as the Citrus reticulata 'Chachi' within different storage years using ultra high performance liquid chromatography quadrupole/time-of-flight mass spectrometry based metabolomics approach.

Using ultra high performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UPLC-QTOFMS) based metabolomics, we focused on developing a method for the comprehensive distinction between Citri Reticulatae Blanco Pericarpium(CRBP) and Citri Reticulatae Chachi Pericarpium (CRCP), as well as the CRCP within different storage years in this study. Through this, we hope to enhance Citri Reticulatae Pericarpium (CRP) Quality Control system. Using UNIFI software and an online database identified chemical components in the 3-30 years CRCP(40 batches) and CRBP (10 batches)samples, and multivariate statistical analysis methods and heat-map were applied to distinguish between CRCP and CRBP and CRCP in different storage years. The results showed that a total of 92 compounds were identified from CRCP and CRBP samples, most of which were flavonoids. Principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) indicated that it can effectively distinguish between CRBP and CRCP and various storage years CRCP, and 19 metabolites were identified as potential markers for distinguishing between CRBP and CRCP, and 15 potential markers showed a higher level of CRCP than CRBP. At the same time, 31 metabolites were identified to distinguish CRCP in different storage years, metabolite levels increased in 3-10 years and decreased after 15-30 years. Therefore, this approach can effectively distinguish between CRCP and CRBP and CRCP with different storage years, and may also provide a feasible strategy for the certification of Chinese herbal medicines from different species and storage years.

CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway.

Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl4. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl4-treated rats. Compared to rats treated with CCl4 alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.