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Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.
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Objective To investigate the influencing factors of peripheral infections of knee joint tumor prosthesis as well as the value of serum D-D and TLR2 in predicting the infection risks so as to provide a reference for early diagnosis of tumorous periprosthetic infection(PJI)of knee joint.Methods The patients who were treated and followed up in our department from January 2008 to June 2020 were selected.According to the inclusion and exclusion criteria,136 of the patients were selected.The data including age,gender,BMI,history of diabetes,smoking history,tumor location,stage of malignant tumor,operation time,osteotomy length,intraoperative bleed-ing,and the percentage of neutrophils,leukocytes,serum D-dimer,and serum TLR value 3 days after operation were collected.The risk factors of PJI and the diagnostic value of serum D-dimer and serum TLR were analyzed.Results The incidence of PJI was 11.76%.Postoperative chemotherapy and operation time≥180 min were the risk factors of PJI(P<0.05).The area under curve(AUC)of the combination of two indicators,serum D-dimer and serum TLR2 were 0.917,0.894 and 0.778,respectively.The AUC of TLR2 was lower than that of the combina-tion of two indicators(P<0.05);The sensitivity was 0.975,0.908 and 0.708,respectively,and the specificity was 0.75,0.75,and 0.812,respectively.Conclusion Postoperative chemotherapy and operation time≥180 min are the risk factors of PJI.The combination of D-dimer and TLR2 has good diagnostic value.
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A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.
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Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.
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@#Objective To provide reference for improving job satisfaction,ensuring service quality and promoting sustainable development of pre-hospital emergency care field,this paper investigated the current situation of job satisfaction of pre-hospital emergency staff in Beijing and analyzed it's differences and influencing factors.Methods SPSS 23.0 was used to input the data,and T-test,variance analysis,multiple linear regression and other processing were performed.Result Basic information of 714 pre-hospital emergency staff in Beijing in terms of subordinate unit,gender,age,education level,job post,title classification,title grade and working years;the proportion of job satisfaction of average and unsatisfactory reached 39.91%;the difference in job satisfaction among the seven categories was statistically significant;seven factors had statistically significant effects on job satisfaction;90.20%of pre-hospital emergency staff suggested improving their salary.Conclusion Prehospital emergency staff in Beijing are mainly young and middle-aged men,with a high proportion of college or university degree;job satisfaction is not good;pre-hospital emergency staff with different levels of education,jobs and working years have significant influence on job satisfaction;reinforcing the construction of talent team from the aspects of salary improvement and pre-hospital emergency technical training is important to improve the job satisfaction of pre-hospital emergency personnel.
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Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.
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Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.
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As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.
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【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.
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In recent years, with the development of ophthalmic therapeutic drugs, the vitreous body, as a channel for the treatment of ophthalmic diseases, especially fundus diseases, has opened up a new therapeutic approach for various choroidal neovascular diseases, macular edema, uveitis and other diseases associated with fundus diseases, which is represented by wet age-related macular degeneration (wAMD). The drugs administered through the vitreous body mainly include ocular anti-vascular endothelial growth factor (VEGF) injections, microplasmin and hormones. For this kind of ophthalmic products, there are no clear technical guidelines and norms for non-clinical research at home and abroad. This article combines review practices and cases of marketed products to sort out the research progress and considerations on non-clinical studies of ophthalmic drugs dosing through the ocular vitreous body, in order to provide references for the research and evaluation of such drugs.
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Systematic research on the quality evaluation methods of Chinese medicinal materials is an intrinsic requirement,which is beneficial to the clinical application of traditional Chinese medicine and the sound development of traditional Chinese medicinal industry.The intrinsic quality evaluation methods of Chinese medicinal materials have developed from chemical fingerprint to quality marker of Chinese medicinal materials,and it represents that the evaluation mode has developed from chemical component as research index to the combination of chemical component and pharmacodynamic components,chemical component and biological activity.The extrinsic character evaluation method of Chinese medicinal materials from"Quality Evaluation Through Morphological Identification"to the application of intelligent sensory technology make up for the accumulation of objective data.The trend of quality evaluation of the intrinsic quality and extrinsic traits of Chinese herbal medicines conform to the innovation strategy called integrated quality control of TCMs.This paper reviews the development and evolution of the research on the intrinsic quality and extrinsic traits of Chinese herbal medicines,systematically expounds the research status and development trend of"intrinsic and extrinsic combination",and facilitate the establishment of quality evaluation system of Chinese herbal medicines with standardization and informatization characteristics in accordance with the theory of traditional Chinese medicine.
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Objective:To examine the renoprotective benefits of stroke volume variation(SVV)-guided fluid therapy in older patients under-going laparoscopic colorectal cancer resection with combined administration of epidural and general anesthesia.Methods:A total of 100 older patients underwent laparoscopic colorectal cancer resection with combined administration of epidural and general anesthesia at The Affiliated Hospital of Inner Mongolia Medical University.Participants were randomly allocated into the control(group C)and experimental groups(group S).Each group consisted of an equal distribution of 50 patients.Group C received routine rehydration,while group S under-went SVV-guided fluid rehydration.To compare the two groups,the levels of serum creatinine(Scr),blood urea nitrogen(BUN),neutrophil gelatinase-associated lipocalin protein(NGAL),and kidney injury molecule-1(KIM-1)were analyzed before and after surgery.Results:NGAL concentrations were significantly reduced in group S compared with those in group C at 2 and 24h after surgery(P=0.033,P=0.014).KIM-1 levels were significantly lower in group S than in group C 24h after surgery(P=0.012).Furthermore,Scr levels were significantly lower in group S than in group C 1 day after surgery(P=0.049).The incidence of postoperative acute kidney injury(AKI)was significantly higher in group C than in group S(P=0.027).Conclusions:In older patients undergoing laparoscopic radical resection of colorectal cancer,the imple-mentation of SVV-guided fluid therapy can improve postoperative plasma markers of renal injury and reduce the incidence of postoperative AKI,thereby protecting renal function.
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Objective:To investigate the effect of patellar replacement and patellar height on the therapeutic effect of total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted on 429 patients (92 males, 337 females; aged 66.81±7.05 years; left=226, right=203) with severe knee osteoarthritis who underwent TKA in the First Affiliated Hospital of Shandong First Medical University from July 2020 to December 2021, with the body mass index of 27.60±4.22 kg/m 2, Grade-III Kellgren-Lawrence, and Insall-Salvati (IS) ratio >0.8. Afterward, the patients were divided into 4 groups according to whether patellar replacement was performed or not and the preoperative IS ratio (IS of 0.8-1.2 for normal patellar and >1.2 for high patellar): the patellar replacement+normal height patellar group (263 cases), the patellar replacement+high height patellar group (66 cases), the patellar non-replacement+normal height patellar group (68 cases), and the patellar non-replacement+high height patellar group (32 cases). Moreover, postoperative intergroup IS ratio, Knee Society Score (KSS), Hospital for Special Surgery (HSS) knee score, Oxford Knee Score (OKS), knee range of motion, complications, and satisfaction were analyzed. Results:All patients were followed up, and the time was 1.15±0.16 years (range, 1-2 years). Postoperative symptoms such as knee pain, swelling, and limitation of movement were significantly improved compared with the preoperative period. Additionally, KSS pain score, knee range of motion, HSS score and OKS score were significantly different among the four groups ( F=9.49, P<0.001; F=11.09, P<0.001; F=6.74, P<0.001; F=3.24, P=0.022), but the difference in KSS functional scores was not statistically significant ( F=1.84, P=0.140). At the same time, the KSS pain score, HSS score, OKS score, and knee range of motion (41.84±5.25, 80.43±6.99, 14.27±5.39, and 122.33°±4.93°) in the patellar replacement+normal height patella group were all better than those in the patellar non-replacement +normal height patella group (38.31±7.31, 77.00±7.81, 16.05±5.81, 120.99°±4.90°) and patella non-replaced + high height patella group (37.97±7.28, 75.62±11.02, 16.63±6.67, 116.25°±13.08°), with statistically significant differences ( P<0.05). The patella replacement+ high height patella group only had better KSS pain scores than the patella non-replaced+normal height patella group and the patella non-replaced+high height patella group (41.74±6.35, 38.31±7.31, 37.97±7.28), with statistically significant differences ( P<0.05). Moreover, Knee mobility was better in the patellar replacement+high height patella group (121.68°±2.88°) and the patellar non-replacement+normal height patella group (120.99°±4.90°) than in the patellar non-replacement+high height patella group (116.25°±13.08°), and the differences were statistically significant ( P<0.05). There were statistically significant differences in the IS ratio before surgery, 1 day after surgery and 1 year after surgery among the four groups ( P<0.05), and the IS ratio at 1 day after surgery was lower than that before surgery with statistically significant differences ( P<0.05), but there was no statistically significant difference between the IS ratio at 1 year after surgery and that before surgery ( P>0.05).Furthermore, the preoperative differences in the incidence of anterior knee pain, patellar clicking and satisfaction rates in patients with different patellar heights were not statistically significant ( P>0.05). Finally, the patellar replacement group possessed a lower incidence of anterior knee pain (normal height patella: 7.6% vs. 16.2%, χ 2=4.68, P=0.031; high height patella: 9.1% vs. 25.0%, χ 2=4.46, P=0.035) and patellar clicking (normal height patella: 9.1% vs. 17.6%, χ 2=4.05, P=0.044; high patella: 13.6% vs. 31.2%, χ 2=4.28, P=0.039); there was no significant difference in satisfaction rate among the four groups after operation ( P>0.05). Conclusion:Postoperative outcomes were better in patients with patellar replacement during TKA than in patients with no patellar replacement, and knee range of motion was better in patients with normal-height patellas than in patients with high patellas preoperatively, with no effect of TKA on patellar height.
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Objective:To compare the clinical effecacy of artificial dermal regeneration matrix (as "artificial dermis" hereafter) and flap transfer in the treatment of soft tissue defects around interphalangeal joint.Methods:Through postoperative follow-up at outpatient clinic, a retrospective study was conducted on the clinical data of 60 patients who had soft tissue defects around the interphalangeal joints and received treatment in the Department of Hand Surgery, the Sixth Hospital of Ningbo from January 2018 to January 2022. According to applied surgical procedures, patients were divided into a flap transfer group (group A, n=30) and an artificial dermis group (group B, n=30). Group A included 19 males and 11 females aged 44.83 years ± 11.56 years including 5 patients with simple soft tissue defects, and 6 with soft tissue defects and fractures, 10 with soft tissue defects with tendon and (or) ligament injuries, 3 with soft tissue defects and vessel and (or) nerve injuries, and 6 with soft tissue defects and over 2 other types of compound injuries. The defect areas ranged from 2.5 cm×1.2 cm to 5.0 cm×1.6 cm. After emergency debridement and treatment for bone and tendon injuries, the patients in group A received transfers of free flap or transfers with adjacent digit flaps or island flaps. Postoperative functional exercise started from 1-6 weeks after surgery. Patients in group B included 17 males and 13 females, aged 44.70 years ± 11.20 years and there were 6 patients with simple soft tissue defects, 6 with soft tissue defects and fractures, 9 with soft tissue defects and tendon and (or) ligament injuries, 5 with soft tissue defects and vessel and (or) nerve injuries, and 4 with soft tissue defects and over 2 other types of compound injuries. The defect area ranged from 3.1 cm ×1.3 cm to 4.5 cm × 1.8 cm. Debridement and treatment of the bone and tendon injury in group B were the same as what in group A, but the patients in group B received artificial dermis coverage other than transfer of flap. After an artificial dermis had completely vascularised, a split-thickness skin graft was performed over the neo-dermis in the second phase surgery. Postoperative functional exercise started from 1-2 weeks after artificial dermis grafting surgery. The interval time of flap transfer or split-thickness skin grafting, survival rate of flap transfer or split-thickness skin grafting, Vancouver Scar Scale(VSS), TPD and total active movement(TAM) were compared between the 2 groups. The count data were analysed by Chi-square test. All measured data were analysed by independent sample t test or Mann-Whitney U test. P<0.05 indicates a statistically significant difference. Results:The interval time of flap transfer in group A and artificial dermis grafting in group B were 2.93 days ± 2.48 days and 19.87 days ± 3.35 days, respectively. There was a statistically significant difference between the 2 groups( P<0.05). All patients were entered in postoperative outpatient follow-up for 11-14 months(12.00 months ± 0.93 months). The appearance of flaps of some patients in group A was bloated with slightly limited digit movement. In group B, the digit movement was normal, without obvious scar hyperplasia in both of the recipient and donor sites. The survival rate of flap transfer or artificial dermis graft, TPD, VSS score and TAM score for group A and group B were 96.00% ± 9.32% and 98.17% ± 3.07%, respectively, 8.67 mm ± 2.01 mm and 9.50 mm ± 1.81 mm, 3.40 ± 1.07 and 3.17 ± 0.91 and 18.30 ± 1.97 and 18.93 ± 1.64, respectively. There were no significant differences between the 2 groups( P>0.05). Conclusion:In comparison with the transfer of flap, an artificial dermis is also effective and satisfactory in the treatment of soft tissue defects around the interphalangeal joint. Further large scale and multi-centre investigations are required.
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Objective:To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in brain abscesses.Methods:The data of patients with brain abscess in Tianjin Huanhu Hospital from January 2019 to December 2021 were retrospectively analyzed. All patients underwent stereotaxic abscess puncture and drainage. According to the different methods of pathogen detection, they were divided into bacterial culture group (bacterial culture only) and mNGS group (bacterial culture with mNGS). The clinical symptoms, abscess site, bacterial culture and mNGS results, antibiotic application protocol and prognosis of the patients were analyzed. The bacterial detection results of the two groups were analyzed, and the antibiotic application and prognosis were compared. χ 2 test, exact probability method and Mann Whitney test were used to compare the difference between the two groups. Results:A total of 43 patients with brain abscess were enrolled, including 21 cases in bacterial culture group and 22 cases in mNGS group. The positive rate of bacteria culture group was 42.9% (9/21), the positive rate of bacteria culture group was 45.5% (10/22), and the positive rate of mNGS detection was 100% (22/22). Only 3 cases in the bacterial culture group could have a clear bacterial source, while 17 cases in the mNGS group could have a clear bacterial source according to the bacterial results, showing a significant statistical difference between the two groups (χ 2=19.69, P<0.001). The return time of bacterial culture was 7.0 (4.0,7.0) days, and the average return time of mNGS was 1.5 (1.5,1.5) days, the difference of bacterial return time between the two groups was statistically significant ( Z=0.00, P<0.001). The cost of antibiotic use in bacterial culture group was 24.00 (5.60,31.00) thousands yuan, and the cost of antibiotic use in mNGS group was 12.00 (2.10, 20.00) thousands yuan, and there was significant statistical difference between them ( Z=5.22, P=0.026). Conclusions:MNGS can quickly and accurately identify the types and sources of brain abscess pathogens, guide the clinical application of antibiotics more targeted, reduce the cost of antibiotic use, and is an effective method for the detection of brain abscess pathogenic bacteria.
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Objective:To investigate the clinical manifestations, pathogenesis,diagnosis and treatment of negative pressure hydrocephalus (NPH).Methods:A retrospective analysis was performed on the 5 patients with NPH admitted to the Department of Neurosurgery, Tianjin Huanhu Hospital from January 2019 to December 2021. All of the patients underwent lumbar puncture and ventricular puncture to test the pressure. Three patients underwent endoscopic third ventriculostomy (ETV), the outcome of the patients was observed.Results:The pressure of subarachnoid was not equal to intraventricular, and the pressure of intraventricular was negative. Cisternography showed cerebrospinal fluid circulation obstruction in all 5 cases. The symptoms of 1 patient were improved after external negative pressure drainage, 3 patients were improved after further ETV and 1 patient had pulmonary infection without further surgical treatment.Conclusion:With the obstruction of cerebrospinal fluid circulation, the pressure of lateral ventricle and subarachnoid is different, when the pressure of brain or subarachnoid drop, the ventricular expansion under the effect of pressure gradient, intraventricular pressure drop even for the negative pressure. CT cisternography provides strong evidence for the diagnosis of this disease. External ventricular drainage with negative pressure and ETV are effective treatment methods.
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{L-End}Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) of live-electric line workers in the power supply enterprises. {L-End}Methods A total of 1 479 live-electric frontline workers in the power supply bureaus under China Southern Power Grid Co., LTD in Guangxi Zhuang Autonomous Region, Guangdong Province and Yunnan Province were selected as the research subjects using the cluster sampling method. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs and their influencing factors in the past year. {L-End}Results The prevalence of WMSDs was 61.4%. The prevalence of WMSDs in nine body sites ranged from 11.3% to 45.1%, with the highest prevalence being on three sites of neck, shoulder and lower back with a prevalence of 45.1%, 36.0% and 30.8%, respectively. The results of multivariate logistic regression analysis showed that the influencing factors of WMSDs in the neck, shoulder, and lower back were different, but all related to individual factors, poor ergonomics factors, and unreasonable work organization factors. The influencing factors simultaneously affecting these three sites included length of service, educational level, working in a sitting posture for a long time, working in uncomfortable postures, adequate rest time, starting to work after rest, deciding when to start and finish by oneself, and shortage of staff in the department or group. The factors affecting both neck and shoulder WMSDs were gender and back bending slightly for a long time. The factors affecting both neck and lower back were age and back bending significantly for a long time. {L-End}Conclusion The prevalence of WMSDs in the live-electric line workers in power supply enterprises is high, mainly occurring in the neck, shoulders, and lower back. The influencing factors are individual factors, poor ergonomics factors, and unreasonable work organization.
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Aim This study aimed to assess the therapeutic potential of ACT001, a micheliolide derivative, in the treatment of acute lung injury ( ALI) induced by sepsis and investigate its pharmacological mechanisms. Methods At the animal level, an ALI model was established in mice through intraperitoneal injection of li-popolysaccharide (LPS). Subsequently, ACT001 was administered to the ALI-afflicted mice. The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate, lung inflammation, and pulmonary edema. At the cellular level, RAW264. 7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001. The study examined inflammatory response and oxidative stress levels, and proteomics analysis was conducted to investigate the underlying molecular mechanisms. Results At the animal level, ACT001 can improve the survival of mice with ALI, reduce lung inflammation, and reduce the levels of inflammatory cytokines in serum. At the cellular level, ACT001 promotes the polarization of RAW264. 7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-II related pathways, inhibiting the production of NO and related inflammatory cytokines while increasing SOD content and scavenging ROS. Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity, mainly by inhibiting the STAT1/ CIITA/ MHC-II pathway. ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.
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Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis, which have potential to serve as "autotrophic cell factories". However, the synthesis of biofuels and chemicals using cyanobacteria as chassis are suffered from poor stress tolerance and low yield, resulting in low economic feasibility for industrial production. Thus, it's urgent to construct new cyanobacterial chassis by means of synthetic biology. In recent years, adaptive laboratory evolution (ALE) has made great achievements in chassis engineering, including optimizing growth rate, increasing tolerance, enhancing substrate utilization and increasing product yield. ALE has also made some progress in improving the tolerance of cyanobacteria to high light intensity, heavy metal ions, high concentrations of salt and organic solvents. However, the engineering efficiency of ALE strategy in cyanobacteria is generally low, and the molecular mechanisms underpinning the tolerance to various stresses have not been fully elucidated. To this end, this review summarizes the ALE-associated technical strategies and their applications in cyanobacteria chassis engineering, following by discussing how to construct larger ALE mutation library, increase mutation frequency of strains and shorten evolution time. Moreover, exploration of the construction principles and strategies for constructing multi-stress tolerant cyanobacteria, and efficient analysis the mutant libraries of evolved strains as well as construction of strains with high yield and strong robustness are discussed, with the aim to facilitate the engineering of cyanobacteria chassis and the application of engineered cyanobacteria in the future.
Sujet(s)
Technologie , Photosynthèse/génétique , Cyanobactéries/génétique , Lumière , BiocarburantsRÉSUMÉ
This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.