Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy / 中国针灸

OBJECTIVE@#To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy.@*METHODS@#A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups.@*RESULTS@#The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01).@*CONCLUSION@#For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

Questionnaire survey and analysis of British People's cognition and attitude towards Traditional Chinese Medicine / 国际中医中药杂志

To understand the current British people's attitudes towards TCM and its influencing factors through a questionnaire survey; To provide data reference for the subsequent international dissemination of TCM. A sample of 200 British people (from Norwich and London) were selected randomly from June 5, 2021 to November 1, 2021 by snowball sampling method, and a questionnaire investigation was launched based on the design of demographic characteristics and Identity Scale of Chinese Medicine (CMIS) and etc. The average sores of CMIS were (71.53±0.76) points. 89.2% of British population showed no difference on attitudes towards TCM, and 10.8% of it showed more confidence in TCM. The single factor analysis showed that the age and education level mainly determine whether they accept TCM. The current attitudes towards TCM among British population are positive and optimistic. In the future, while maintaining the existing treatment advantages of TCM in the UK, it is necessary to conduct targeted promotions based on research of diseases for which TCM treatment has strengths in different age groups of local residents. Establishment of brands with TCM features is also a good way to increase the popularity of TCM. And multiple methods like new media, especially the coverage of local mainstream media, should be emphasized and used for the promotion of TCM and improvement of cognition level among British people.

Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke? / 대한뇌졸중학회지

Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.

Clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower extremity / 中华烧伤杂志

Objective: To observe the clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower limbs. Methods: A retrospective observational study was conducted. From December 2017 to December 2020, 8 patients with large skin and soft tissue defect caused by degloving injury in lower extremity were admitted to Ningbo No.6 Hospital, including 5 males and 3 females, aged from 39 to 75 years, with wound area of 25 cm×12 cm-61 cm×34 cm. The free latissimus dorsi myocutaneous flap with latissimus dorsi muscle in the width of 12-15 cm and flap area of 20 cm×8 cm-32 cm×8 cm was used to repair the skin and soft tissue defect of bone/tendon exposure site or functional area. The other defect was repaired with bilayer artificial dermis, and the flap donor site was sutured directly. After the artificial dermis was completely vascularized, the split-thickness skin graft from thigh was excised and extended at a ratio of 1∶2 to 1∶4 and then transplanted to repair the residual wound, and the donor site of skin graft was treated by dressing change. The survival of latissimus dorsi myocutaneous flap, artificial dermis, and split-thickness skin graft after operation was observed, the interval time between artificial dermis transplantation and split-thickness skin graft transplantation was recorded, and the healing of donor site was observed. The appearance and function of operative area were followed up. At the last outpatient follow-up, the sensory recovery of flap was evaluated by British Medical Research Council evaluation criteria, the flap function was evaluated by the comprehensive evaluation standard of flap in Operative Hand Surgery, the scar of lower limb skin graft area and thigh skin donor area was evaluated by Vancouver scar scale, and the patient's satisfaction with the curative effects was asked. Results: The latissimus dorsi myocutaneous flap survived in 6 patients, while the distal tip of latissimus dorsi myocutaneous flap was partially necrotic in 2 patient and was repaired by skin grafting after resection at split-thickness skin grafting. The artificial dermis survived in all 8 patients after transplantation. The split-thickness skin graft survived in 7 patients, while partial necrosis of the split-thickness skin graft occurred in one patient and was repaired by skin grafting again. The interval time between artificial dermis transplantation and split-thickness skin graft transplantation was 15-26 (20±5) d. The donor site of latissimus dorsi myocutaneous flap healed with linear scar after operation, and the thigh skin graft donor site healed with scar after operation. The patients were followed up for 6-18 (12.5±2.3) months. The color and elasticity of the flap were similar to those of the surrounding skin tissue, and the lower limb joint activity returned to normal. There was no increase in linear scar at the back donor site or obvious hypertrophic scar at the thigh donor site. At the last outpatient follow-up, the sensation of the flap recovered to grade S2 or S3; 3 cases were excellent, 4 cases were good, and 1 case was fair in flap function; the Vancouver scar scale score of lower limb skin graft area was 4-7 (5.2±0.9), and the Vancouver scar scale score of thigh skin donor area was 1-5 (3.4±0.8). The patients were fairly satisfied with the curative effects. Conclusions: In repairing the large skin and soft tissue defect from degloving injury in lower extremity, to cover the exposed bone/tendon or functional area with latissimus dorsi myocutaneous flap and the residual wound with artificial dermis and extended split-thickness skin graft is accompanied by harvest of small autologous flap and skin graft, good recovery effect of functional area after surgery, and good quality of healing in skin grafted area.

Advances in mechanisms for inflammation-associated colon carcinogenesis and chemoprevention / 药学学报

Colorectal cancer is a common malignant tumor of digestive tract, and the risk of inflammatory bowel disease developing into colorectal cancer is significantly increased. Immune signaling pathways NF-κB, IL-6/STAT3, COX-2/PGE2, IL-23/Th17 and TLRs have been confirmed to promote the transformation from colitis to colorectal cancer. NOD2 and intestinal microbes also participate in the regulation of inflammation mediated carcinogenesis. Chronic inflammation is a potential risk for colorectal cancer, and anti-inflammatory drugs may play a chemical preventive role. In this review, we summarize the signaling pathways involved in inflammation-associated colon carcinogenesis and evaluate the chemoprophylaxis of colon cancer.

Effect of electroacupuncture at Neiguan (PC 6) on pulmonary function during one-lung ventilation in patients with lobectomy / 中国针灸

OBJECTIVE@#To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism.@*METHODS@#Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO@*RESULTS@#Compared with T@*CONCLUSION@#EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.

Technical and Clinical Aspects of Diagnostic Single-Balloon Enteroscopy in the First Decade of Use: A Systematic Review and Meta-analysis

Background/Aims@#Single-balloon enteroscopy (SBE) has been widely used in diagnosing small bowel disease. We conducted this study to systematically appraise its technical and clinical performance. @*Methods@#Studies on SBE published by September 2018 were systematically searched. Technical and clinical performance data were collected and analyzed with descriptive or meta-analysis methods. @*Results@#In total, 54 articles incorporating 4,592 patients (6,036 procedures) were included. Regarding technical parameters, the pooled insertion depths (IDs) for anterograde and retrograde SBE were 209.2 cm and 98.1 cm, respectively. The pooled retrograde ID in Asian countries was significantly greater than that in Western countries (129.0 cm vs 81.1 cm, p<0.001). The pooled anterograde and retrograde procedure times were 57.6 minutes and 65.1 minutes, respectively.The total enteroscopy rate was 21.9%, with no significant difference between Asian and Western countries. Clinically, the pooled diagnostic yield of SBE was 62.3%. Obscure gastrointestinal bleeding (OGIB) was the most common indication (50.0%), with a diagnostic yield of 59.5%. Vascular lesions were the most common findings in Western OGIB patients (76.9%) but not in Asian ones (31.0%). The rates of severe and mild adverse events were 0.5% and 2.5%, respectively. @*Conclusions@#SBE is technically efficient and is clinically effective and safe, but total enteroscopy is relatively difficult to achieve with this technique. Etiologies of OGIB in Asian countries differ from those in Western countries.

Analysis on tissue-related biomarkers in patients with acute aortic dissection / 中华心血管病杂志

Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ⅱb (ITGA2B), integrin α-M (ITGAM), integrin β-2 (ITGB2), integrin β-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.

Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α / 中国天然药物

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

Engineering progress in microbial production of polyhydroxyalkanoates / 生物工程学报

Polyhydroxyalkanoates (PHAs) are polymers obtained by esterification of hydroxy fatty acid monomers. Due to similar mechanical characteristics of traditional petroleum-based plastics, 100% biodegradability and biocompatibility, PHAs are considered to be one of the most potential green materials. However, the application and promotion of PHAs as a green and environmentally friendly material are difficult because of the high production costs. This article focuses on the current methods to reduce production cost of PHAs effectively, such as cell morphology regulation, metabolic pathway construction, economic carbon source utilization and open fermentation technology development. Despite most research results are still limited in laboratory, the research methods and directions provide theoretical guidance for the industrial production of economic PHAs.

Progress of effects of 14-3-3 protein on gastric cancer and its mechanism / 解放军医学杂志

14-3-3 proteins are a highly conserved family of cellular proteins, and widely expressed in all eukaryotes. Because they can bind to a variety of functional signal proteins, so be regarded as "bridge proteins" in protein interaction. Studies have shown that the expression level of 14-3-3 protein family in malignant tumors is closely related to tumor size, depth of invasion and metastasis. Some other studies have shown that 14-3-3 protein plays a pivotal role in cell signal transduction, control of cell cycle process and regulation of apoptosis, and plays an important role in the development of gastric cancer, proliferation, invasion, prognosis and drug resistance, so is expected to become a novel therapeutic target for gastric cancer. The present paper aims to expound the role and relevant mechanisms of 14-3-3 protein in gastric cancer.

Professor 's clinical experience in treatment of infertility of ovulation disturbance with acupuncture-moxibustion therapy / 中国针灸

The characteristics of syndrome differentiation and the experience of professor were briefly introduced for the treatment of infertility of ovulation disturbance, including three aspects, named the thought of diagnosis and treatment, the therapeutic method and the acupoint prescription, as well as the clinical case report. Academically, professor is deeply influenced by professor , the acupuncture master of Xin'an school and Lingnan school. Regarding the treatment of gynecological diseases, the academic thought of professor - and - is contributed. Professor attaches the importance to the syndrome differentiation based on meridian and collateral, supplemented by the syndrome differentiation of , , and blood, cold and heat, as well as the deficiency and excess. In clinical treatment, the acupoints are selected specially from the conception vessel, the governor vessel, the thoroughfare vessel and the belt vessel. The extra meridians are equally important as the regular ones in the treatment, especially the belt vessel. Additionally, the treatment focuses on communicating the congenital with the acquired one, regulating the liver and benefiting the kidney, as well as adjusting the heart, the spleen and the stomach to ease the uterus. Simultaneously, the great consideration is paid to the menstruation regulation so as to promote pregnancy.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Research progress in polyhydroxyalkanoates (PHA) and their blend fibers / 生物工程学报

Polyhydroxyalkanoate (PHA) is a representative biodegradable polymer with more than 150 varieties and various properties. This article reviews the research status and potential applications of PHA, and introduces the properties of four-generation commercial PHA and its research progress in blend fibers with other biodegradable materials.

Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients / 中华心血管病杂志

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Outcomes of chronic total occlusions in coronary arteries according to three therapeutic strategies: a meta-analysis with 6985 patients from 8 published observational studies

Abstract Objective: To perform a systematic review and meta-analysis of studies comparing coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical treatment (MT) in patients with chronic total occlusions (CTOs). Methods: We identified eligible observational studies published in the China National Knowledge Infrastructure database, PubMed, Excerpta Medica database, Google Scholar, Cochrane Library, Web of Science, and "Clinical trials" registration from 1999 to October 2018. Main outcome measures were all-cause mortality, cardiac death, major adverse cardiac events (MACEs), and myocardial infarction (MI). Results: There were eight observational studies including 6985 patients. Patients' mean age was 64.4 years. Mean follow-up time was 4.3 years. Comparing with MT (2958 patients), PCI (3157 patients) presented decreased all-cause mortality (odd ratio [OR]: 0.46, 95% confidence interval [CI]: 0.36-0.60; P<0.001), cardiac death (OR: 0.40, 95% CI: 0.31-0.52; P<0.001), MACE (OR: 0.55, 95% CI: 0.43-0.71; P<0.001), and MI (OR: 0.40, 95% CI: 0.26-0.62; P<0.001). Comparing with MT, CABG (613 patients) presented lower all-cause mortality (OR: 0.50, 95% CI: 0.36-0.69; P<0.001) and MACE (OR: 0.50, 95% CI: 0.26-0.96; P=0.04), but not lower MI (OR: 0.23, 95% CI: 0.03-1.54; P=0.13) and cardiac death (OR: 0.83, 95% CI: 0.51-1.35). Comparing with CABG, PCI did not present decreased risk for those outcomes. Conclusions: PCI or CABG was associated with better clinical outcome in patients with CTO than MT. PCI is not better than CABG in decreasing mortality, MI, cardiac death, and MACE in coronary CTO patients.

A minimally invasive alternative for the treatment of nutcracker syndrome using individualized three-dimensional printed extravascular titanium stents / 中华医学杂志(英文版)

Background@#This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.@*Method@#The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV’s primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.@*Results@#The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.@*Conclusion@#The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.