Prevention of new-onset atrial fibrillation in elderly patients undergoing anatomic pulmonary resection by infusion of magnesium sulfate: protocol for a randomized controlled trial.

Atrial fibrillation (AF) is the most commonly sustained arrhythmia after pulmonary resection, which has been shown to predict higher hospital morbidity and mortality. The lack of strong evidence-based medical evidence makes doctors have very few options for medications to prevent new-onset AF following thoracic surgery. Magnesium can prevent perioperative AF in patients undergoing cardiac surgery. However, this has not yet been fully studied in patients undergoing non-cardiac thoracic surgery, which is the aim of this study. This is a single-center, prospective, double-blind, randomized controlled trial. In total, 838 eligible patients were randomly assigned to one of two study groups, namely, the control group or the magnesium group. The patients in the magnesium group preoperatively received 80 mg magnesium sulfate/kg ideal weight in 100 ml normal saline 30 min. The control group received the same volumes of normal saline simultaneously. The primary outcome is the incidence of new-onset AF intra-operative and on the first, second, and third postoperative days. The secondary outcomes are bradycardia, hypertension, hypotension, and flushing. The occurrence of stroke or any other type of arrhythmia is also recorded. Postoperative respiratory suppression and gastrointestinal discomfort, intensive care unit stays and total duration of hospital stays, in-hospital mortality, and 3-month all-cause mortality are also recorded as important outcomes. This study aims to prospectively evaluate the prophylactic effects of magnesium sulfate against AF compared with a placebo control group during and following anatomic pulmonary resection. The results may provide reliable evidence for the prophylactic value of magnesium against AF in patients with lung cancer. The trial was approved by the Clinical Research Ethics Committee of Shanghai Pulmonary Hospital and has been registered at Chinese Clinical Trial Registry: www.chictr.org.cn, identifier: ChiCTR2300068046.

Novel role for epalrestat: protecting against NLRP3 inflammasome-driven NASH by targeting aldose reductase.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive and inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocellular injury, inflammation, and fibrosis in various stages. More than 20% of patients with NASH will progress to cirrhosis. Currently, there is a lack of clinically effective drugs for treating NASH, as improving liver histology in NASH is difficult to achieve and maintain through weight loss alone. Hence, the present study aimed to investigate potential therapeutic drugs for NASH. METHODS: BMDMs and THP1 cells were used to construct an inflammasome activation model, and then we evaluated the effect of epalrestat on the NLRP3 inflammasome activation. Western blot, real-time qPCR, flow cytometry, and ELISA were used to evaluate the mechanism of epalrestat on NLRP3 inflammasome activation. Next, MCD-induced NASH models were used to evaluate the therapeutic effects of epalrestat in vivo. In addition, to evaluate the safety of epalrestat in vivo, mice were gavaged with epalrestat daily for 14 days. RESULTS: Epalrestat, a clinically effective and safe drug, inhibits NLRP3 inflammasome activation by acting upstream of caspase-1 and inducing ASC oligomerization. Importantly, epalrestat exerts its inhibitory effect on NLRP3 inflammasome activation by inhibiting the activation of aldose reductase. Further investigation revealed that the administration of epalrestat inhibited NLRP3 inflammasome activation in vivo, alleviating liver inflammation and improving NASH pathology. CONCLUSIONS: Our study indicated that epalrestat, an aldose reductase inhibitor, effectively suppressed NLRP3 inflammasome activation in vivo and in vitro and might be a new therapeutic approach for NASH.

Optimal transplantation strategy using human induced pluripotent stem cell-derived cardiomyocytes for acute myocardial infarction in nonhuman primates.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have the potential to be a therapeutic option for myocardium restoration. However, hiPSC-CMs of varying maturation and transplantation routes exhibit different reactivity and therapeutic effects. We previously demonstrated that the saponin+ compound induces more mature hiPSC-CMs. The safety and efficacy of multi-route transplantation of saponin+ compound-induced hiPSC-CMs in a nonhuman primate with myocardial infarction will be investigated for the first time in this study. Our findings indicate that optimized hiPSC-CMs transplanted via intramyocardial and intravenous routes may affect myocardial functions by homing or mitochondrial transfer to the damaged myocardium to play a direct therapeutic role as well as indirect beneficial roles via anti-apoptotic and pro-angiogenesis mechanisms mediated by different paracrine growth factors. Due to significant mural thrombosis, higher mortality, and unilateral renal shrinkage, intracoronary transplantation of hiPSC-CMs requires closer attention to anticoagulation and caution in clinical use. Collectively, our data strongly indicated that intramyocardial transplantation of hiPSC-CMs is the ideal technique for clinical application; multiple cell transfers are recommended to achieve steady and protracted efficacy because intravenous transplantation's potency fluctuates. Thus, our study offers a rationale for choosing a therapeutic cell therapy and the best transplantation strategy for optimally induced hiPSC-CMs.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Bergapten inhibits NLRP3 inflammasome activation and pyroptosis via promoting mitophagy.

Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 µM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1ß release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1ß, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.

Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis.

To explore the serum levels of IL-39, CXCL14, and IL-19 in patients with tuberculosis (TB) along with their clinical significances and their concentration changes in macrophages after Bacille Calmette-Guérin vaccine (BCG) or Mycobacterium tuberculosis (M. tb) H37Rv stimulation in vitro. The serum levels of IL-39, CXCL14, and IL-19 of 38 TB patients, and 20 healthy staff members were measured by enzyme-linked immunosorbent assay. Moreover, the levels of IL-19, CXCL14, and IL-39 in cultured THP-1 macrophages were detected at 12, 24, and 48 h after stimulation with BCG or M. tb H37Rv strains. It was found the serum level of IL-39 was significantly reduced and CXCL14 was remarkably elevated in TB patients. In vitro, at 48 h after stimulation, IL-39 level of cultured THP-1 macrophages in the H37Rv group was significantly lower than that in the BCG and control groups, and the CXCL14 level of cultured THP-1 macrophages in the H37Rv stimulation group was remarkably higher than that in the control group. Therefore, IL-39 and CXCL14 may be involved the pathogenesis of TB, and serum IL-39 and CXCL14 could potentially serve as a new biomarker of TB.

Single cell landscape of parietal epithelial cells in healthy and diseased states.

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.

[Characteristics of Benthic Diatom Community Structure and Water Ecological Health Evaluation in the Lalin River Basin].

With the improvement of public requirements for the health status of aquatic ecosystems, there have been innovative assessment methods developed for aquatic ecosystems. In this study, benthic algae assemblages and water quality variables were analyzed to develop a benthic diatom-based index of biotic integrity (D-IBI) for the assessment of the aquatic environment in the Lalin River. In addition, using redundancy analysis (RDA) based on dominant species and physicochemical indexes, the ecological distribution characteristics of the benthic diatom community were revealed, and the key influencing factors were identified. The results showed that the benthic diatom community structure in the Lalin River basin had obvious spatial differences. The application of the index revealed that the water quality could be described as excellent condition in the upper reaches of the Lalin River, good to common condition in the middle of the sites, and moderate to poor condition in the downstream. The assessment further revealed that the main reason for the degradation of the Lalin River ecosystem was nutrient enrichment through agricultural land use.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Hypoxia-inducible factor 1-alpha is a driving mechanism linking chronic obstructive pulmonary disease to lung cancer.

Patients with chronic obstructive pulmonary disease (COPD), irrespective of their smoking history, are more likely to develop lung cancer than the general population. This is mainly because COPD is characterized by chronic persistent inflammation and hypoxia, which are the risk factors for lung cancer. However, the mechanisms underlying this observation are still unknown. Hypoxia-inducible factor 1-alpha (HIF-1α) plays an important role in the crosstalk that exists between inflammation and hypoxia. Furthermore, HIF-1α is the main regulator of somatic adaptation to hypoxia and is highly expressed in hypoxic environments. In this review, we discuss the molecular aspects of the crosstalk between hypoxia and inflammation, showing that HIF-1α is an important signaling pathway that drives COPD progression to lung cancer. Here, we also provide an overview of HIF-1α and its principal regulatory mechanisms, briefly describe HIF-1α-targeted therapy in lung cancer, and summarize substances that may be used to target HIF-1α at the level of COPD-induced inflammation.

An automatic drug injection device with spatial micro-force perception guided by an microscopic image for robot-assisted ophthalmic surgery.

Retinal vein injection guided by microscopic image is an innovative procedure for treating retinal vein occlusion. However, the retina organization is complex, fine, and weak, and the operation scale and force are small. Surgeons' limited operation and force-sensing accuracy make it difficult to perform precise and stable drug injection operations on the retina in a magnified field of image vision. In this paper, a 3-DOF automatic drug injection mechanism was designed for microscopic image guiding robot-assisted needle delivery and automatic drug injection. Additionally, the robot-assisted real-time three-dimensional micro-force-sensing method for retinal vein injection was proposed. Based on the layout of three FBG sensors on the hollow outer wall of the nested needle tube in a circular array of nickel-titanium alloys, the real-time sensing of the contact force between the intraoperative instrument and the blood vessel was realized. The experimental data of 15 groups of porcine eyeball retinal veins with diameters of 100-200 µm showed that the piercing force of surgical instruments and blood vessels is 5.95∼12.97 mN, with an average value of 9.98 mN. Furthermore, 20 groups of experimental measurements on chicken embryo blood vessels with diameters of 150-500 µm showed that the piercing force was 4.02∼23.4 mN, with an average value of 12.05 mN.

Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis.

BACKGROUND: Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China. METHODS: We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock. RESULTS: Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%-32.8%, I2 = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I2 = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%-46.0%, I2 = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed. CONCLUSIONS: Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).

Early renal impairment is associated with in-hospital death of patients with COVID-19.

INTRODUCTION: Renal impairment is a common complication in coronavirus disease 2019 (COVID-19), although its prognostic significance remains unknown. OBJECTIVES: This study determines the impact of early renal impairment on the clinical outcome of COVID-19. METHODS: Patients diagnosed with COVID-19 and hospitalized in Xiaogan Central Hospital from 20 January to 29 February 2020 were retrospectively included and grouped into two cohorts (cohort with normal renal function and cohort with renal insufficiency) based on the renal function detected on admission. Records of clinical manifestation, laboratory findings and clinical outcome were collected and compared between these two cohorts. RESULTS: A total 543 COVID-19 patients were included. Among these patients, 70 patients developed early renal impairment, with an incidence of 12.89%. A significantly higher white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine (Cr), blood urine nitrogen (BUN) and brain natriuretic peptide (BNP) and a significantly lower blood platelet (PLT), lymphocyte count, prealbumin and albumin (ALB) were detected in the cohort with renal insufficiency (P < 0.05). Patients with early renal impairment were also associated with higher incidences of haematuria/proteinuria, higher incidences of mortality and prolonged hospitalization duration. The independent risk factors for in-hospital death included age >65 years old, complication of diabetes, renal impairment on admission (Cr > 73 µmol/L and eGFR < 60 ml/min 1.73 m2 ), WBC > 9.5 × 109 /L and ALB < 35 g/L. CONCLUSION: Early renal impairment is associated with higher risk of in-hospital death for patients with COVID-19. Risk stratification according to renal function can better guide the clinical management of COVID-19.

Can eastern wisdom resolve western epidemics? Traditional Chinese medicine therapies and the opioid crisis.

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

LMR-101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ-aminobutyric acid type A receptors.

OBJECTIVE: LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic. METHODS: Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties. RESULTS: In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR-101 also suppressed seizure behaviors evoked by (+)-bicuculline in mice in a dose-dependent manner. In the pilocarpine-induced SE model, LMR-101 significantly decreased the maximum seizure score and seizure duration in a dose-dependent manner. The median effective dose for LMR-101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR-101 primarily inhibited tert-[35 S] butylbicyclophosphorothionate binding to γ-aminobutyric acid type A (GABAA ) receptors (half-maximal inhibitory concentration = 2.06 µmol·L-1 ), but it did not affect [3 H] flunitrazepam or [3 H] muscimol binding. SIGNIFICANCE: It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABAA receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABAA receptors.

Thyroid hormone disorders: a predictor of mortality in patients with septic shock defined by Sepsis-3?

Decreased serum thyroid hormone levels and their prediction of mortality in septic patients are still controversial, especially with the evolution of the definition of sepsis. This study aimed to assess the ability of thyroid hormone disorders to predict the early mortality of patients with septic shock defined by Sepsis-3. Sixty-three adult patients with septic shock admitted to a university hospital emergency intensive care unit (EICU) were studied. Serum free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), C-reactive protein (CRP), procalcitonin (PCT), and lactate levels were determined and compared with survival status and organ dysfunction. Among the 63 patients studied, lower serum FT3 and FT4 levels were significantly associated with higher sequential organ failure assessment (SOFA) scores. Patients with septic shock with lower levels of FT3 (≤ 1.70 pmol/L) and FT4 (≤ 9.99 pmol/L) had significantly increased 28-day mortality. There was no significant difference in the serum TSH level between the survivor and nonsurvivor groups. The areas under the receiver operating characteristic curves for FT3 and FT4 levels were associated with 28-day mortality (0.92 and 0.89, respectively) and were higher than that for SOFA (0.82), CRP (0.65) and lactate (0.59). The decrease in serum levels of FT3 and FT4 in patients with septic shock is associated with the severity of organ dysfunction and 28-day mortality. Early detection of serum FT3 and FT4 levels could help clinicians to identify patients at high risk of clinical deterioration.

Can eastern wisdom resolve western epidemics? Traditional Chinese medicine therapies and the opioid crisis / 中西医结合学报

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

Recombinant human ulinastatin improves immune dysfunction of dendritic cells in septic mice by inhibiting endoplasmic reticulum stress-related apoptosis.

Urinary trypsin inhibitor (UTI), also known as ulinastatin, has been reported to protect multiple organs against inflammation- and/or injury-induced dysfunction. In the present study, we aimed to investigate the immunomodulation effects of a recombinant human ulinastatin (urinary trypsin inhibitor, UTI) (rhUTI) on splenic dendritic cells (DCs) in cecal ligation and puncture (CLP)-induced septic mice. CLP mice were treated with rhUTI intramuscularly at 0, 12, and 24 h after procedure. Splenic CD11c+ DCs were isolated and accessed with flow cytometry for apoptotic or phenotypic analysis. Protein markers and cytokines were determined with Western blotting or ELISA. Treatment with rhUTI could markedly upregulate levels of costimulatory molecules (CD80, CD86) and MHC-II on surface of the splenic DC in CLP mice. The apoptotic rate of splenic DCs was decreased in CLP mice after rhUTI treatment. The survival rate of septic mice was increased after treatment with rhUTI. In addition, protein level of markers in endoplasmic reticulum stress (ERS)-related apoptotic pathways (including GRP78, caspase-12, and CHOP) were obviously down-regulated in the rhUTI-treated group when compared with the CLP group. These results indicate that rhUTI protects CLP-induced sepsis in mice by improving immune response of splenic DCs and inhibiting the excessive ERS-mediated apoptosis.

In vitro screening and toxic mechanism exploring of leading components with potential hepatotoxicity of Herba Epimedii extracts.

Herba Epimedii is a famous Chinese edible herb, and due to its potential hepatotoxic effects, the safety associated with this herb has attracted a great deal of attention. In this study, the components of four types of the Herba Epimedii extracts were identified by HPLC-MS/MS. Among these components, 11 components that were present in all four extracts and could be obtained as reference substances were evaluated for their ability of cytotoxicity in HL-7702 and HepG2 cells, resulting in the identification of icarisid I and sagittatoside A as the most relevant with respect to the toxicity of the extracts. The targeted toxicological effects were further investigated using a series of correlated biological indicators to elucidate potentially hepatotoxic mechanisms. The results showed that the extracts and the selected compounds had varying degrees of influence on the leakage of ALT, AST and LDH; the activity of SOD, GSH and MDA; the increase in intercellular ROS; and the decrease in MMP. Among the tested substances, the ethanol extracts exhibited stronger hepatotoxicity, with icarisid I and sagittatoside A correlating with this toxic effect, and the hepatoxic mechanisms of which may be associated with damaged cell structure, increased oxidative stress and induction of apoptosis.

Combining the wisdoms of traditional medicine with cutting-edge science and technology at the forefront of medical sciences.

BACKGROUND: A central topic is to bring traditional medicine to a new horizon by integrating the latest advances in genomic, metabolomic, and system biological approaches, in order to re-examine the wisdom and knowledge of traditional Chinese medicine (TCM) and other traditional medicines. PURPOSE: A new consortium has been formed at a conference of the Harvard Medical School, Boston, on October 29-30, 2018. The main goal was to build a collaborative platform for the scientific investigation of traditional medicine with cutting edge sciences and technologies at the forefront of biomedicine. RESULTS: Traditional medicines are largely experience-based, but the scientific basis is largely non-satisfactory. Therefore, the transformation from experience-based to evidence-based medicine would be an important step forward. The consortium covers three main fields: TCM diagnostics, acupuncture and TCM pharmacology. Diseases occur because of regulatory imbalances of holistic physiological display and genetic information/expression related to systems biology and energy consumption/release (e.g. cold and hot) within body. As organs are interconnected by meridians, affecting the meridians by acupuncture and medicinal herbs restores healthy organ function and body balance. There are two concepts in herbal medicine: The traditional way is based on complex herbal mixtures. The second concept is related to Western pharmacological drug development including the isolation of bioactive phytochemicals, which are subjected to preclinical and clinical investigations. CONCLUSION: Development of collaborative scientific project to integrate the best of both worlds - Western and Eastern medicine into a "One World Integrative Medicine" for the sake of patients worldwide.