Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer.

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. STATEMENT OF SIGNIFICANCE: Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron-hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Topology-regulated nanocatalysts for ferroptosis-mediated cancer phototherapy.

Ferroptosis-mediated tumor treatment is constrained by the absence of single-component, activatable multifunctional inducers. Given this, a topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi2O3:S) for tumor ferroptosis therapy. Photo-excited electrons can participate in the reduction reaction to produce harmful reactive oxygen species (ROS) when exposed to near-infrared light. Meanwhile, photo-excited holes can contribute to the oxidation reaction to utilize extra glutathione (GSH) in tumors. In the acidic tumor microenvironment, bismuth ions generated from Bi2O3:S may further cooperate with GSH to amplify oxidative stress damage and achieve biodegradation. Both promote ferroptosis by downregulating glutathione peroxidase 4 (GPX4) expression. Besides, sulfur doping optimizes its near-infrared light-induced photothermal conversion efficiency, benefiting its therapeutic effect. Thus, bismuth ions and holes synergistically drive photo-activable ferroptosis in this nanoplatform, opening up new avenues for tumor therapy.

The Efficacy and Safety of Xinjia Xuanbai Chengqi Granules in Acute Exacerbation of COPD: A Multicentre, Randomised, Double-Blind, Controlled Trial.

Purpose: The study aimed to explore the efficacy and safety of Xinjia Xuanbai Chengqi granules (XJXBCQ) combined with conventional medicine in the treatment of acute exacerbation of chronic pulmonary disease (AECOPD). Patients and Methods. This multicentre, double-blind, parallel, placebo-controlled, randomised clinical trial conducted in China from January 2019 to February 2021 recruited 330 participants who were allocated into three groups. All participants underwent conventional basic treatment with oxygen therapy, antibiotics, and a bronchodilator. Besides, group A received XJXBCQ granules and budesonide suspension for inhalation; group B received XJXBCQ granules and half dosage of budesonide suspension; and group C received budesonide suspension and a placebo. All therapies lasted for 5 days, and participants were followed up for 30 days after discharge. The primary outcomes were efficacy, traditional Chinese medicine (TCM) syndrome score, and clinical symptom score. Secondary outcomes included the blood gas analysis, serum inflammatory markers, adverse events, mortality, theoretical discharge time, actual hospitalisation time, proportion of patients requiring invasive mechanical ventilation, proportion of patients transferred to an intensive care unit (ICU), and readmission rate within 30 days after discharge. Results: XJXBCQ adjunct with conventional treatment could significantly improve the total efficacy (P < 0.05). Meanwhile, group A showed significantly better results than group C in the TCM syndrome score, phlegm score, and Wexner constipation score (P < 0.05). For modified British medical research council (mMRC), on day 3 (-0.17, 95% confidence interval [CI]: -0.33--0.01) and day 4 (-0.20, 95% CI: -0.39--0.02), group A performed statistically better than group C. No significant differences in other secondary outcomes were detected. Conclusion: XJXBCQ is beneficial and safe for AECOPD treatment and could be considered an adjunctive therapy for promoting the relief of clinical symptoms. This trial is registered with ChiCTR1800016915.

Exploration in the Mechanism of Zhisou San for the Treatment of Cough Variant Asthma Based on Network Pharmacology.

Background: Cough variant asthma (CVA) has no definitive diagnosis or pathogenic causes, and there is currently no effective and safe treatment. Methods: The network pharmacology was employed to investigate possible targets of Zhisou San (ZSS) in CVA treatment. The main chemical constituents of seven herbs in ZSS were collected based on the TCMSP. To explain the main mechanism, we sequentially screened the targets of each active ingredient and constructed the network of "herb-ingredient-target-disease." The core targets of ZSS were further confirmed by the molecular docking analysis. Furthermore, pulmonary function, histopathology, and biochemical assays in mice were used to investigate the effect of ZSS on the treatment of CVA. Results: A total of 137 active ingredients and 86 potential targets for the ZSS in the treatment of CVA were screened, which were connected with the regulation of inflammatory response and immune balance, such as IL-17 signaling pathway, Th17 cell differentiation, TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and other signaling pathways closely related to the pathogenesis of CVA. Thereinto, 29 core targets contained 8 of the highest scores and could evidently bind to components such as stigmasterol, quercetin, stemoninine B, luteolin, and ß-sitosterol predicted by molecular docking. Furthermore, experiments in vivo were conducted for further validation that ZSS had essential effects on lung function and histopathology as well as the inflammatory state in CVA mice, which was significantly related to regulating the Th17/Treg immune balance to reduce inflammation as the important pharmacological mechanism. Conclusion: This study revealed that ZSS has multicomponent and multipathway characteristics of ZSS in the treatment of CVA, which was primarily associated with inflammation and Th17/Treg immune balance. This study provides a scientific foundation for systematically elaborating the pharmacological activities and mechanism of ZSS, as well as explaining the reliability of the TCM compatibility theory.

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.

Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report.

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.

Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.

HINT1 (Histidine Triad Nucleotide-Binding Protein 1) Attenuates Cardiac Hypertrophy Via Suppressing HOXA5 (Homeobox A5) Expression.

BACKGROUND: Cardiac hypertrophy is an important prepathology of, and will ultimately lead to, heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. This study aims to elucidate the effects and mechanisms of HINT1 (histidine triad nucleotide-binding protein 1) in cardiac hypertrophy and heart failure. METHODS: HINT1 was downregulated in human hypertrophic heart samples compared with nonhypertrophic samples by mass spectrometry analysis. Hint1 knockout mice were challenged with transverse aortic constriction surgery. Cardiac-specific overexpression of HINT1 mice by intravenous injection of adeno-associated virus 9 (AAV9)-encoding Hint1 under the cTnT (cardiac troponin T) promoter were subjected to transverse aortic construction. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against Hoxa5 (homeobox A5) was administrated to investigate whether the effects of HINT1 on cardiac hypertrophy were HOXA5-dependent. RNA sequencing analysis was performed to recapitulate possible changes in transcriptome profile.Coimmunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. RESULTS: The reduction of HINT1 expression was observed in the hearts of hypertrophic patients and pressure overloaded-induced hypertrophic mice, respectively. In Hint1-deficient mice, cardiac hypertrophy deteriorated after transverse aortic construction. Conversely, cardiac-specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler polymerase chain reaction array showed HOXA5 is 1 target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown in vivo. Hoxa5 was identified to affect hypertrophy through the TGF-ß (transforming growth factor ß) signal pathway. Mechanically, HINT1 inhibited PKCß1 (protein kinase C ß type 1) membrane translocation and phosphorylation via direct interaction, attenuating the MEK/ERK/YY1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/yin yang 1) signal pathway, downregulating HOXA5 expression, and eventually attenuating cardiac hypertrophy. CONCLUSIONS: HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.

AB4 inhibits Notch signaling and promotes cancer cell apoptosis in liver cancer.

The etiology for liver cancer has been clearly defined. Unfortunately, therapeutic approaches for liver cancer are rather limited, and liver cancer is insensitive to chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) has become a promising strategy for cancer treatment as TCM elicits broad spectrum anticancer activity. In the present study, we evaluated the anticancer efficacy of AB4, an extract from the medical herb Pulsatilla chinensis (Bunge) Regel, in liver cancer in vitro and in vivo. We found that AB4 readily dose­ and time­dependently inhibited liver cancer HepG2 and Huh­7 cell proliferation and colony formation. Western blot and flow cytometry analyses suggested that AB4 treatment induced liver cancer cell apoptosis. Moreover, these findings could be readily recaptured in vivo, in which the AB4 regimen resulted in tumor suppression and cancer cell apoptosis in xenograft tumor­bearing nude mice. Importantly, we noted that treatment with a Notch signaling inhibitor DAPT produced very similar anticancer efficacy in both HepG2 and Huh­7 cell lines, and administration of DAPT also efficiently suppressed HepG2 xenograft outgrowth. To this end, we anticipated that AB4 and DAPT may act on the same signaling pathway, probably through inhibition of the Notch pathway. Indeed, we found decreased expression of Notch1 protein, as well as downstream targets Hes1 and Hey1, after AB4 treatment. Immunohistochemistry analysis further confirmed the suppression of Notch signaling in HepG2 xenograft­bearing mice. Taken together, our study highlighted the anticancer efficacy of AB4 in liver cancer. We also provided preliminary data showing Notch as a therapeutic target of AB4. It would be interesting to investigate the anticancer efficacy of AB4 in other types of cancer with elevated Notch activity.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial.

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

Antiatherosclerosis Properties of Total Saponins of Garlic in Rats.

Garlic has been proven effective in the prevention and treatment of atherosclerosis (AS), which is widely used as a food and medicine by people in daily life. Garlic saponins are the main active nonsulfur compounds of garlic, which have a variety of pharmacological activities against cardiovascular diseases. In this study, the antiatherosclerosis properties and mechanism of total saponins of garlic (TSG) in rats were explored. The AS animal model was established by a combination of high-fat feeding, intraperitoneal injection of vitamin D3, and ovalbumin-induced inflammation in SD rats. Then, the atherosclerotic rats were gavaged daily by TSG for 4 weeks. Administration of TSG markedly decreased atherosclerotic lesions in the aorta of atherosclerotic rats. TSG restored the serum lipid profile by significantly decreasing the lipid levels and had effective antioxidation by inhibiting the content of malondialdehyde (MDA) and restoring the reduced activity of superoxide dismutase (SOD). Additionally, the ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α ) could be maintained in a relatively stable dynamic balance after administration of TSG to maintain the vascular homeostasis. In summary, TSG had therapeutic effects on AS, which are promising as functional foods or nutraceuticals for the prevention and treatment of AS.

Adult loss of Cacna1a in mice recapitulates childhood absence epilepsy by distinct thalamic bursting mechanisms.

Inborn errors of CACNA1A-encoded P/Q-type calcium channels impair synaptic transmission, producing early and lifelong neurological deficits, including childhood absence epilepsy, ataxia and dystonia. Whether these impairments owe their pathologies to defective channel function during the critical period for thalamic network stabilization in immature brain remains unclear. Here we show that mice with tamoxifen-induced adult-onset ablation of P/Q channel alpha subunit (iKOp/q) display identical patterns of dysfunction, replicating the inborn loss-of-function phenotypes and, therefore demonstrate that these neurological defects do not rely upon developmental abnormality. Unexpectedly, unlike the inborn model, the adult-onset pattern of excitability changes believed to be pathogenic within the thalamic network is non-canonical. Specifically, adult ablation of P/Q channels does not promote Cacna1g-mediated burst firing or T-type calcium current (IT) in the thalamocortical relay neurons; however, burst firing in thalamocortical relay neurons remains essential as iKOp/q mice generated on a Cacna1g deleted background show substantially diminished seizure generation. Moreover, in thalamic reticular nucleus neurons, burst firing is impaired accompanied by attenuated IT. Interestingly, inborn deletion of thalamic reticular nucleus-enriched, human childhood absence epilepsy-linked gene Cacna1h in iKOp/q mice reduces thalamic reticular nucleus burst firing and promotes rather than reduces seizure, indicating an epileptogenic role for loss-of-function Cacna1h gene variants reported in human childhood absence epilepsy cases. Together, our results demonstrate that P/Q channels remain critical for maintaining normal thalamocortical oscillations and motor control in the adult brain, and suggest that the developmental plasticity of membrane currents regulating pathological rhythmicity is both degenerate and age-dependent.

Mechanism of Traditional Chinese Medicine in Treating Drug-resistant Bacterial Infection / 中国实验方剂学杂志

The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.

[Technical specification of expert consensus statement in developing clinical practice guidelines of traditional Chinese medicine].

The formation of expert consensus statement is an indispensable part in the process of developing clinical practice guidelines. The Guidelines International Network believes that experts make group decisions for different stages and issues,and the process of gathering expert opinions is the process of reaching the consensus. GRADE system also requires that recommendations should be formed based on expert consensus in consideration of the risk and bias,patients' preferences and values,resources and other factors. At present,the main method for reaching consensus is the formal consensus method. According to the published clinical guidelines,most of them failed to report the specific methods and process of reaching expert consensus. Therefore,it is impossible to obtain an objective evaluation. This phenomenon is more common in the field of clinical practice guidelines of traditional Chinese medicine( TCM). There are two main reasons for this phenomenon. For one thing,the developers of the guidelines neglect the importance of transparency and objectivity in the implementation of expert consensus. For another,they know little about the methods and technical specifications for the formation of expert consensus. To solve them,based on the internationally recognized consensus-building methods,as well as the specific stages in the process of developing clinical practice guidelines of traditional Chinese medicine,it is of great significance to put forward the technical norms for TCM researchers to develop the expert consensus. This guide will provide detailed guidance for forming the expert consensus for TCM clinical practice guideline. This guideline has been approved and published by the Chinese Association of Traditional Chinese Medicine( No. T/CACM 1049-2017).

[Expert consensus statement on Pudilan Xiaoyan Oral Liquid in clinical practice].

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.

[Expert consensus statement on Xiyanping Injection for respiratory system infectious diseases in clinical practice(adults)].

Xiyanping Injection is widely used in the treatment of respiratory infectious diseases. However,its package insert is still less instructive for physicians in understanding the specific clinical application of Xiyanping Injection. To discover potential clinical advantages of Xiyanping Injection,the team invited clinical experts of traditional Chinese medicine and western medicine from the field of respiratory diseases,pharmacists and methodologists of evidence-based medicine to compile the consensus. The consensus was based on a combination of clinical research evidence and expert experience,involving recommendations for clinical problems supported by clini-cal evidence as well as consensus suggestions for clinical problems with no clinical evidence. The consensus recommended the indication,timing of intervention,usage,dosage,course of treatment,combined medication of Xiyanping Injection used for adults,and introduced the safety and precautions of its clinical application. It is suitable for guiding clinical medical workers to rationally use Xiyanping Injection in the treatment of adult's respiratory infectious diseases.

Cardioprotection via the skin: nociceptor-induced conditioning against cardiac MI in the NIC of time.

Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9-T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.

Mechanism of Chinese Material Medica in Treatment of Diabetes Mellitus Cerebral Infarction / 中国实验方剂学杂志

Diabetes mellitus complicated with cerebral infarction is the commonest and most serious vascular complication of diabetes mellitus. With a high disability and mortality rate, it seriously threatens human health. Because the pathogenesis is still unclear, more and more scholars have focused on the research of diabetic cerebral infarction at home and abroad. Traditional Chinese medicine(TCM) compounds have a remarkable curative effect in the treatment of diabetic cerebral infarction. Its mechanisms of action mainly include anti-hypertension, reduction of blood sugar and lipid, promotion of vascular regeneration and vascular endothelial function, anticoagulation, anti-thrombosis, improvement of nerve function defect, reduction of infarct volume, improvement of hemorheological, inhibition of inflammation and platelet aggregation, and promotion of collateral circulation. Through literature search, this paper summarizes the research progress of the mechanisms of TCM compounds in treating diabetic cerebral infarction in recent five years at home and abroad, in order to provide reference for clinical treatment.

[Clinical characteristics of five traditional Chinese medicine injections in treating heart failure based on Meta-analysis literature].

In this article, we analyze the clinical characteristics of five kinds of traditional Chinese medicine injections in treating heart failure based on Meta-analysis. A total of 24 Meta-analysis papers were included, which involved Shenfu Injection, Shenmai Injection, Shengmai Injection, Danhong Injection and Huangqi Injection. The numbers of literatures of Shenfu Injection, Shenmai Injection and Shengmai Injection are high than the other two injections. The efficiencies of these injections combined with Western medicine are higher than the Western medicine used alone. They can improve 6 minute walk test result, ejection fraction, the level of brain peptide sodium and so on. Shenfu Injection can also improve the living quality of patients' life, heart rate and other indicators. Shenfu Injection can be used for patients with Yin deficiency, while Shenmai Injection can be used for patients with Yin deficiency and Shengmai Injection can be used for patients with Qi and Yin deficiency. From this information, we can see that Western medicine combined with traditional Chinese medicine injections can significantly improve the clinical efficiency. These injections need to be used according to patients' symptom. In the present, as the quality of clinical research literature of traditional Chinese medicine injections is low, the efficiency and safety evaluation of Chinese medicine injections still requires higher level of clinical evidence.

Therapeutic effects of Saussurea involucrata injection against severe acute pancreatitis- induced brain injury in rats.

OBJECTIVES: To observe the therapeutic effects of Saussurea involucrata (Sau) injection against severe acute pancreatitis (SAP)-induced brain injury. METHODS: Sodium taurocholate-induced SAP-modeled rats were equally randomized into an SAP model group (SAP group) and a Sau treated group (Sau  +  S group). Healthy rats were equally randomized into a Sau treated group (Sau  +  H group) and a sham operation group (SO group). Serum amylase levels, endothelin-1 (ET-1) and nitric oxide (NO) contents were determined by optical turbidimetry, ELISA and nitrate reductase method respectively. Western blot was used to detect protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), ET-1, inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) while mRNA levels of these biomarkers in brain tissue were measured by quantitative real-time PCR. Furthermore, pathological changes, as well as all above indexes of pancreas and brain, were observed at 6, 24 and 48 h after administration. RESULTS: There was a significant difference in mortality between SAP and Sau  +  S groups (P  <  0.05). Serum amylase levels, ET-1 and NO contents, ET-1/NO ratio, relative expression levels of ET-1 and iNOS protein/mRNA of brain tissue in Sau + S group were lower than those in SAP group at 24 and 48 h post-operation (P  <  0.05 or 0.01), meanwhile, pancreas and brain pathological scores showed similar tendency (P  <  0.01). However, both protein and mRNA levels of PI3K, Akt and eNOS of brain tissue in Sau + S group were higher than those in SAP group (P  <  0.05 or P  <  0.01). There were no significant differences in all indexes between Sau + H and SO groups at all designated time points (P  >  0.05). CONCLUSIONS: Sau injection has therapeutic effects on SAP-induced brain injury in rats.