Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

Artificial blood is a type of liquid preparation with oxygen-loading capacity and can temporarily substitute some function of blood.The developed artificial blood can be divided into four categories:artificial synthetic hemo-globin,artificial red blood cells made from natural hemoglobin,perfluorocarbons,and stem cell-differentiated red blood cells.This review focuses on the domestic and foreign research progress of artificial blood in recent years,and discusses its clinical application value,development trend,and future research,in order to provide new ideas to the development the artificial blood products and promote clinical application.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Tandem occlusion of the anterior circulation is a specific acute large vessel occlusion, which is defined in most of the literature as a combination of intracranial large vessel occlusion and high degree of stenosis or occlusion of the ipsilateral extracranial internal carotid artery.Tandem occlusion is presented in approximately 15% patients with acute ischemic stroke in the anterior circulation who receive endovascular treatment. In patients with tandem occlusion, endovascular treatment is more effective than drug therapy; however, controversy still exists regarding the optimal management strategy of endovascular treatment. This article reviews the recent advance in endovascular treatment of tandem occlusion in the anterior circulation in recent years, to improve the overall care standard for acute ischemic stroke with tandem occlusion of the anterior circulation.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.
Humans ; Moxibustion ; Pressure Ulcer ; Acupuncture Therapy ; Acupuncture ; Apoptosis

Objective:To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial DNA 14453G>A (m.14453G>A) mutation.Methods:A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12, 2021 was reported. At the same time, the reported cases of MELAS and Leigh syndrome (LS) caused by the m.14453G>A mutation were reviewed. This enabled a comprehensive summarization, analysis, and comparison of these cases.Results:The patient was a female. She has suffered from the disease since 13-year old with seizures, accompanied by the disturbance of mood and the loss of memory. Brain magnetic resonance imaging findings consisted of lesions in frontal, parietal, occipital, temporal lobe and cerebellar. The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome. Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene, and the mutation rate was 17.0%, the patient eventually diagnosed with MELAS based on clinical manifestations, imaging examinations, and genetic testing results. Using "m.14453G>A" as the search term, the relevant literature in China and abroad was retrieved and those with complete clinical data were identified. A total of 11 cases of m.14453G>A mutation including this case were reported, of whom 5 patients were diagnosed as MELAS, and 6 patients were diagnosed as LS. Among the 11 patients, those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS; those being infant or young child and with lesions in basal ganglia, thalamus and brainstem could be LS. Conclusions:Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity, which can cause MELAS and LS. The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′ s location.

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
Animals ; Rats ; IgA Vasculitis/drug therapy* ; Network Pharmacology ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Metabolomics

Objective:To investigate the effects of Streptococcuspneumoniae (Spn) colonization and the change of upper airway microbiome on the clinical manifestations in children with respiratory syncytial virus (RSV) infection. Methods:A retrospective cohort included 508 RSV-infected children with pneumonia and hospitalized in Respiratory Department of Children′s Hospital of Chongqing Medical University from July 2009 to July 2018. A total of 508 cases of RSV-infected children (RSV non-sequencing group) were divided into 2 groups: children with Spn airway colonization (RSV+Spn group) and children without with Spn airway colonization (RSV group) according to the detection for virus and bacteria in nasopharyngeal aspirate, and these 2 groups were compared in terms of clinical manifestations by chi-square test in different age groups. In addition, in RSV pandemic season from November 2018 to February 2020, nasopharyngeal aspirates were collected from 20 children hospitalized in Respiratory Department of Children′s Hospital of Chongqing Medical University and infected with RSV but without any positive detection of bacteria (RSV 16 S-sequencing group) and from children undergoing surgery without any sign of respiratory infection (control group). The difference of microbiome detected by 16 S RNA sequencing was compared using rank sum test between RSV 16 S-sequencing group and control group, and also between children with severe and mild pneumonia in RSV 16 S-sequencing group.Results:A total of 508 RSV non-sequencing group included 346 males and 162 females, and the visiting age was 6 (2, 12) ?months. RSV group included 443 cases and RSV+Spn group included 65 cases. In the study 244 cases were aged <6 months and 264 cases were aged ≥6 months. In children aged ≥6 months of RSV non-sequencing group, the proportion of cases presenting fever over 38 ℃ and cases with severe pneumonia in RSV+Spn group were higher than those in RSV group (53.2% (25/47) vs. 34.6% (72/217), 38.3% (18/47) vs. 21.2% (46/217), χ2=5.70,6.15, both P<0.05). RSV 16 S-sequencing group included 16 males and 4 females and the visiting age was 3.0 (1.9, 8.0) months. Airway microbiome diversity in RSV 16 S-sequencing group was lower than that in control group (alpha index: 0.93 (0.42, 2.51) vs. 3.05 (2.88, 3.61), U=60.00, P=0.001). Conclusions:RSV infection is associated with the changes of the upper airway microbiome. When the balance of airway microbiome is broken and the presence of the dominant colonization of Spn follows, it may aggravate the severity of RSV infection in children aged ≥6 months.