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Costly data movement in terms of time and energy in traditional von Neumann systems is exacerbated by emerging information technologies related to artificial intelligence. In-memory computing (IMC) architecture aims to address this problem. Although the IMC hardware prototype represented by a memristor is developed rapidly and performs well, the sneak path issue is a critical and unavoidable challenge prevalent in large-scale and high-density crossbar arrays, particularly in three-dimensional (3D) integration. As a perfect solution to the sneak-path issue, a self-rectifying memristor (SRM) is proposed for 3D integration because of its superior integration density. To date, SRMs have performed well in terms of power consumption (aJ level) and scalability (>102 Mbit). Moreover, SRM-configured 3D integration is considered an ideal hardware platform for 3D IMC. This review focuses on the progress in SRMs and their applications in 3D memory, IMC, neuromorphic computing, and hardware security. The advantages, disadvantages, and optimization strategies of SRMs in diverse application scenarios are illustrated. Challenges posed by physical mechanisms, fabrication processes, and peripheral circuits, as well as potential solutions at the device and system levels, are also discussed.
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BACKGROUND:Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury.3-Nitro-N-methylsalicylamide(3-NNMS)can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury,but there is no clear research and clinical application. OBJECTIVE:To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS:Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group,0,25 and 125 μg/mL 3-NNMS groups,with 10 rats in each group.Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups.3-NNMS was injected into the injury site 30 minutes before reperfusion.The animals were sacrificed 2 hours after reperfusion.Blood from the apical part of the heart,and the tissue of the rectus femoris muscle of the right lower limb were taken for testing.The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining.Serum levels of creatine kinase found in the skeletal muscle(CK-MM),lactate dehydrogenase,and myeloperoxidase were detected using ELISA;the levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde,reactive oxygen species,superoxide dismutase,catalase and glutathione peroxidase in the rectus femoris muscle were measured;and adenosine triphosphate(ATP)level,ATPase activity,and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION:Compared with the control group,the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase,increased levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle,and reduced ATPase activity and mitochondrial respiratory control rate.Moreover,cell morphology was irregular,inflammatory cell infiltration was obvious,and the cells were swollen in rats after ischemia-reperfusion injury.Compared with the 0 μg/mL group,the serum CK-MM and lactate dehydrogenase levels decreased,the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased,reactive oxygen species level decreased,and superoxide dismutase activity increased in the 25 μg/mL group;cell morphology was more regular,inflammatory cell infiltration was lighter,and cell swelling was alleviated.Compared with the 0 μg/mL group,the 125 μg/mL group had a reduction in the serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase and the levels of nuclear factor κB,tumor necrosis factor α,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle,and mitochondrial respiratory control rate.Moreover,the cells were arranged neatly,the outline was clear and complete,and the inflammatory cell infiltration was light.To conclude,3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion,and its mechanism of action may be through improving mitochondrial function,reducing reactive oxygen species production,decreasing oxidative stress and inflammatory response,and thus reducing tissue damage and repairing skeletal muscle function.
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Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.
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In August 2023, the European Society for Organ Transplantation (ESOT) published the ESOT Consensus Statement on Biomarkers in Liver Transplantation online. The consensus statement focuses on biomarkers in liver transplantation, clinical applicability, and future needs and explores the role of new biomarkers in predicting liver transplantation outcomes by reviewing the literature on primary disease recurrence, development of chronic kidney disease (CKD), and safe weaning of immunosuppression. This consensus statement conducts studies from the four aspects of recurrent liver disease after liver transplantation, recurrent hepatocellular carcinoma, weaning of immunosuppression, and CKD progression, emphasizes the importance of biomarkers in predicting or detecting disease recurrence, and proposes that large-scale prospective studies are still needed to improve the quality of evidence. The author’s team gives an excerpt of the consensus statement and systematically introduces the four aspects of the consensus statement and related discussions and conclusions, in order to provide more evidence-based medical evidence for identifying and exploring new biomarkers for liver transplantation.
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Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
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Brucelose , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , Relatos de Casos como AssuntoRESUMO
Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
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OBJECTIVE@#Current clinical evidence on the effects of home blood pressure telemonitoring (HBPT) on improving blood pressure control comes entirely from developed countries. Thus, we performed this randomized controlled trial to evaluate whether HBPT plus support (patient education and clinician remote hypertension management) improves blood pressure control more than usual care (UC) in the Chinese population.@*METHODS@#This single-center, randomized controlled study was conducted in Beijing, China. Patients aged 30-75 years were eligible for enrolment if they had blood pressure [systolic (SBP) ≥ 140 mmHg and/or diastolic (DBP) ≥ 90 mmHg; or SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg with diabetes]. We recruited 190 patients randomized to either the HBPT or the UC groups for 12 weeks. The primary endpoints were blood pressure reduction and the proportion of patients achieving the target blood pressure.@*RESULTS@#Totally, 172 patients completed the study, the HBPT plus support group ( n = 84), and the UC group ( n = 88). Patients in the plus support group showed a greater reduction in mean ambulatory blood pressure than those in the UC group. The plus support group had a significantly higher proportion of patients who achieved the target blood pressure and maintained a dipper blood pressure pattern at the 12th week of follow-up. Additionally, the patients in the plus support group showed lower blood pressure variability and higher drug adherence than those in the UC group.@*CONCLUSION@#HBPT plus additional support results in greater blood pressure reduction, better blood pressure control, a higher proportion of dipper blood pressure patterns, lower blood pressure variability, and higher drug adherence than UC. The development of telemedicine may be the cornerstone of hypertension management in primary care.
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Humanos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Hipertensão/terapia , Telemedicina/métodos , HipotensãoRESUMO
OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Brucelose , COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , Relatos de Casos como AssuntoRESUMO
Background: The optimal treatment for elderly patients with severe heart failure depends on the accurate assessment of their hemodynamic status. Due to its less invasive nature, the safety and efficacy of invasive pulse-induced contour cardiac output (PiCCO)-based hemodynamic monitoring remains uncertain. Methods: This was a prospective observational study. Between January 2016 and July 2020, 190 elderly patients with severe heart failure were consecutively enrolled. The PiCCO group (89 patients) and non-invasive hemodynamic monitoring group (101 patients) were observed. Hospital stays results were evaluated. Results: No significant difference in clinical data (P > 0.05) or the incidence of 1-month mortality (16.0 vs. 35.0%, P = 0.141) were observed between groups. The coronary care unit (CCU) stay was shorter in the PiCCO group than in the non-invasive group (40.0 vs. 43.0%, P = 0.049). Indicators such as low Extravascular Lung Water Index (EVLWI), high Body Mass Index (BMI), low Pulmonary Artery Pressure (PAP), and high Left Ventricular Ejection Time (LVET), were associated with favorable clinical results. Conclusion: Early invasive PiCCO monitoring is safe in critically ill elderly patients with severe heart failure. The hospital stay was reduced using PiCCO monitoring. These encouraging PiCCO results favor its use in elderly patients with severe heart failure at CCUs.
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The occurrence of pellicle on the surface of paocai brine is a common undesirable phenomenon during the multi-rounds of paocai fermentation, which is mainly caused by the growth of microorganisms related to pellicle formation. But the detailed information on these microorganisms and volatile components produced by them, as well as the changes of the microorganisms during the process of paocai recovery, are still rare in the literature. Therefore, the purpose of this study was (1) to analyze the pellicle formation related microorganisms by comparing the differential microorganisms in initial brine and the brine when pellicle occurred through metagenomic sequencing technology, (2) to explore the changes of microorganisms in the fermentation system after addition Baijiu and/or salt, and (3) to further detect the VOCs in paocai samples by gas chromatography-mass spectrometry (GC-MS). The relationship between VOCs and the selected marker microorganisms was also determined. The results showed that the diversity of fungi was increased when pellicle formed, the pellicle formation related microorganisms mainly belonged to six genus, including Kazachstania, Lactobacillus, Pichia, Candida, Lachancea, and Saccharomyces. Apart from the unknown function and basic life activities of microorganisms, the metabolic activities of these pellicle formation related microorganisms were mainly carbohydrate transport and metabolism, and amino acid transport and metabolism. The growth of pellicle formation related microorganisms could be inhibited by adding Baijiu (1.5% v/v), but the addition of salt (7% salt (w/v) did not promote this inhibitory effect. Through PCA analysis, it was found that the VOCs of paocai were significantly affected by adding Baijiu and Baijiu and salt. The undesirable smell at the beginning of pellicle formation may be related to Propanoic acid, hexyl ester, 1,3-Dimethyl-1-cyclohexene, Oxime-, methoxy-phenyl- and Phenylethyl Alcohol.
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Lactobacillus , Saccharomycetales , Fermentação , Lactobacillus/metabolismo , Metagenoma , Metagenômica , PichiaRESUMO
Background/purpose: The restoration of endodontically treated teeth (ETT) with cervical defects has been a challenge for dentists. The purpose of this study was to evaluate the effect of restorative treatment on the fracture resistance of ETT with cervical defects. Materials and methods: One hundred and twenty freshly extracted human intact straight-single-root maxillary premolars were randomly divided into 6 groups. Group 1 remained untreated. Cervical defects of 4 mm-depth and 3 mm-height were created in groups 2-6. Group 3-6: root canal treatment. Group 4: direct composite resin restoration. Group 5: 2-mm full-cusp-coverage composite resin restoration. Group 6: fiber-post-supported composite resin restoration. A static fracture test was used to determine the fracture resistance of teeth under axial (n = 10) and palatal (30°) (n = 10) loading. Fracture modes were categorized as restorable and unrestorable. Results: Compared with intact teeth, the axial fracture resistance of teeth with cervical defects decreased by approximately 39%, and endodontic procedures resulted in 10% more reduction. When ETT with cervical defects were restored using direct composite resin filling, the axial fracture resistance recovered to 72% of that of intact teeth, but no significant change occurred under oblique loading. After full-cusp-coverage or fiber-post-supported restoration, fracture resistance showed complete recovery to the value of intact teeth (P > 0.05). Sixty percent of fractures were unrestorable for fiber-post-supported teeth, while in the full-cusp-coverage restoration group, 80-90% of fractures were restorable. Conclusion: Full-cusp-coverage restoration or fiber-post-supported restoration could improve the fracture resistance of ETT with cervical defects, whereas unrestorable fractures easily occurred in fiber-post-supported restorations.
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Various S-bonding configurations existing in sulfur-doped reduced graphene oxide (S-rGO) show different electronic structures and physiochemical properties. Thus, understanding the properties of unique S-bonding configurations requires the construction of S-rGO with only single configuration. Here, we synthesized S-rGO with a pure thiophene-sulfur configuration through a simple and low-cost hydrothermal method by simply controlling the oxidation degree of the graphene oxide (GO) precursor. Through the use of a GO precursor with a high content of C-O groups, pure doping of the thiophene-sulfur configuration in the rGO can be achieved. Further electrochemical characterization reveals an increased electrocatalytic activity of the pure thiophene-sulfur-doped S-rGO in the oxygen reduction reaction, indicating the important role of thiophene-sulfur. The present work deepens the understanding of the functions of doped nonmetal elements in carbon materials in electrocatalysis and helps in the design of high performance electrocatalysts.
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Liver transplantation is the most effective way to treat end-stage liver disease, but biliary stenosis after liver transplantation, and tumor recurrence after liver transplantation impairs patients’ life quality and long-term survival. This article discussed the current status of treatment of biliary stenosis after liver transplantation and tumor recurrence after liver transplantation which based on the latest domestic and international researches and the authors’ clinical experience.
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Objective:To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury (IRI) and the potential mechanisms.Methods:Eighteen male specific pathogen free SD rats (7-8 weeks, about 250g) were randomly divided into three groups: Sham group (Sham), hepatic ischemia reperfusion (IRI) and IL-22 preconditioning group (IL-22+ IRI), respectively. The liver IRI model of 70% rats was established. The IL-22+ IRI group was intraperitoneally injected with rcIL-22 (50 mg/kg) 1 hour before surgery, and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery. After 1 h ischemia and 6 h reperfusion, blood was collected from the abdominal aorta, then liver tissue, serum aspartate transaminase (AST) and alanine aminotransfease (ALT) levels were measured. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The expression of signal transducer and activator of transcription 3 (STAT3), p-STAT3, nuclear factor erythorid-2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blot. Results:Compared with Sham group, serum AST [(1 923.50±92.63) U/L, (1 004.25±65.05) U/L)] and ALT [(1 172.51±180.31) U/L, (583.50±164.75) U/L] levels were increased in IRI group and IL-22+ IRI group (AST: F=293.62; ALT: F=30.33, P<0.05). The levels of MDA in IRI group and IL-22+ IRI group [(1.72±0.12) μmol/mg, (0.98±0.05) μmol/mg] in liver tissue were higher than those in Sham group (0.58±0.14) μmol/mg protein ( F=186.73, P<0.05), and the expression of p-STAT3, Nrf2 and HO-1 was increased. SOD level in IRI group (28.51±3.85) U/mg was lower than that in Sham group (70.25±5.64) U/mg protein ( F=203.41, P<0.05). Compared with IRI group, serum AST and ALT levels in IL-22+ IRI group were decreased, SOD activity in liver tissue was increased, MDA level was decreased, and p-STAT3, Nrf2 and HO-1 expression was increased (all P<0.05). Conclusion:IL-22 could alleviate liver IRI in rats, and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.
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In recent years, chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy, as a new idea of tumor immunotherapy, has been proved to be effective in hematological diseases. More and more studies have been focusing on this field. At present, some progress have been made in the treatment of hepatocellular carcinoma with CAR-T, but some problems such as solid tumor inherent barrier, tumor microenvironment, immune escape and specific tumor associated antigens still need to be further figure out. Nevertheless, CAR-T immunotherapy will provide a more cutting-edge treatment for hepatocellular carcinoma immunotherapy. In addition, the combination of CAR-T and other methods may also be the direction to be explored in the next step.
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Objective: To investigate the clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns. Methods: A retrospective observational study was used. From June 2017 to June 2019, 33 patients (24 males and 9 females, aged 8-50 years) who met the inclusion criteria with hypertrophic scars in non-functional sites outside the face after burns were treated in General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients underwent scalp transplantation after perforation of retained split scar matrix in situ (with scar thinning area of 90-500 cm2), and then the vacuum sealing drainage was performed. The hematoma and infection of wounds were observed on the 7th day after operation. At the same time, the survival rate of skin grafting was observed and calculated. The flatness and thickness of the scar in the operative area were observed in 12 months after operation, and the itching and pain of the patients were recorded. Vancouver Scar Scale was used to score the scar of patients before operation and at 3, 6 and 12 months after operation. The healing time and hair growth of donor site were observed. Data were statistically analyzed with repeated analysis of variance, paired sample t test and bonferroni correction. Results: On the 7th day after operation, local subcutaneous hematoma appeared in the wound of 2 patients, which healed after dressing change; no infection occurred. On the 7th day after operation, the survival rate of skin grafting of patients was 94.6%-99.0%(96.8±1.2)%. Scar flatness was well, the thickness of scar was not significantly higher than that of normal skin in 12 months after operation, and the symptoms of itching pain of patients disappeared or significantly relieved. Vancouver Scar Scale scores of patients before operation and at 3, 6, and 12 months after operation were 12.1±2.8, 8.5±1.5, 7.6±1.6, 6.7±1.3, respectively, and the scores of 3, 6, and 12 months after operation were all significantly lower than that before operation (with t values of 4.48, 4.06, and 3.97, respectively, P<0.01). All the donor sites of the head healed well in 4-7 days after operation. By 3-6 months after operation, all patients had good hair growth in the donor site and achieved no scar healing. Conclusions: The treatment of hypertrophic scar in non-functional sites outside the face after burns by in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage can effectively improve the appearance of hypertrophic scar in non-functional areas after burn and reduce its degree of hyperplasia, with scar-free donor site healing.
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Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Queimaduras/cirurgia , Cicatriz Hipertrófica/cirurgia , Tratamento de Ferimentos com Pressão Negativa , Couro Cabeludo/cirurgia , Transplante de PeleRESUMO
The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-ß(TGF-ß) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 µmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1ß and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
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Lesão Pulmonar Aguda , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Lipopolissacarídeos , NF-kappa B/genética , NF-kappa B/metabolismo , Rizoma , Transdução de SinaisRESUMO
Background: Recently, Chinese patent medicines (CPMs) have been widely used to treat children with influenza in China, with curative effects. Therefore, the efficacy and safety of such treatment require further evaluation. The present meta-analysis integrated data from several independent studies to determine overall treatment trends in children with influenza. Methods: The following databases were searched for randomized controlled trials (RCTs) published from their inception to December 12, 2020: CNKI, Wanfang, SinoMed, PubMed, Cochrane library, and Embase. Two researchers independently extracted the data, assessed the methodological quality of the studies, and conducted a meta-analysis of the results using Review Manager 5.2. The results were assessed using forest plots, and publication bias was evaluated using a funnel plot. Results: A total of 21 RCTs involving 2960 cases were included. Compared to oseltamivir alone, CPMs combined with oseltamivir reduced the duration of symptoms, including that of fever (mean difference [MD] = -0.64, 95% confidence interval [CI]: -0.86 to -0.41, P < 0.00001), cough (MD = -0.82, 95% CI: -1.02 to -0.62, P < 0.00001), nasal obstruction (MD = -0.88, 95% CI: -1.15 to -0.61, P < 0.00001), and sore throat (MD = -0.92, 95% CI: -1.26 to -0.57, P < 0.00001). Combined therapy also reduced the time of viral shedding (MD = -0.53, 95% CI: -0.70 to -0.36, P < 0.00001) and the occurrence of adverse drug reactions (ADRs) (RR=0.53, 95% CI: 0.34 to 0.83, P = 0.005). Conclusions: CPMs combined with oseltamivir reduced the duration of symptoms, shortened the time of viral shedding, and reduced the number of ADRs. However, these results should be considered with caution because there was marked heterogeneity and publication bias in the research data. More rigorous RCTs should be designed to verify the effect of CPMs in children with influenza.
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OBJECTIVE: Early triage of patients with coronavirus disease 2019 (COVID-19) is pivotal in managing the disease. However, studies on the clinical risk score system of the risk factors for the development of severe disease are limited. Hence, we conducted a clinical risk score system for severe illness, which might optimize appropriate treatment strategies. METHODS: We conducted a retrospective, single-center study at the JinYinTan Hospital from January 24, 2020 to March 31, 2020. We evaluated the demographic, clinical, and laboratory data and performed a 10-fold cross-validation to split the data into a training set and validation set. We then screened the prognostic factors for severe illness using the least absolute shrinkage and selection operator (LASSO) and logistic regression, and finally conducted a risk score to estimate the probability of severe illness in the training set. Data from the validation set were used to validate the score. RESULTS: A total of 295 patients were included. From 49 potential risk factors, 3 variables were measured as the risk score: neutrophil to lymphocyte ratio ( OR, 1.27; 95% CI, 1.15-1.39), albumin ( OR, 0.76; 95% CI, 0.70-0.83), and chest computed tomography abnormalities ( OR, 2.01; 95% CI, 1.41-2.86) and the AUC of the validation cohort was 0.822 (95% CI, 0.7667-0.8776). CONCLUSION: This report may help define the potential of developing severe illness in patients with COVID-19 at an early stage, which might be related to the neutrophil to lymphocyte ratio, albumin, and chest computed tomography abnormalities.
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COVID-19/diagnóstico , Medição de Risco , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Objective@#Early triage of patients with coronavirus disease 2019 (COVID-19) is pivotal in managing the disease. However, studies on the clinical risk score system of the risk factors for the development of severe disease are limited. Hence, we conducted a clinical risk score system for severe illness, which might optimize appropriate treatment strategies.@*Methods@#We conducted a retrospective, single-center study at the JinYinTan Hospital from January 24, 2020 to March 31, 2020. We evaluated the demographic, clinical, and laboratory data and performed a 10-fold cross-validation to split the data into a training set and validation set. We then screened the prognostic factors for severe illness using the least absolute shrinkage and selection operator (LASSO) and logistic regression, and finally conducted a risk score to estimate the probability of severe illness in the training set. Data from the validation set were used to validate the score.@*Results@#A total of 295 patients were included. From 49 potential risk factors, 3 variables were measured as the risk score: neutrophil to lymphocyte ratio ( @*Conclusion@#This report may help define the potential of developing severe illness in patients with COVID-19 at an early stage, which might be related to the neutrophil to lymphocyte ratio, albumin, and chest computed tomography abnormalities.