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Objective To explore the efficacy of Krackow locking loop technique combined with the modified Kessler suture technique in the treatment of acute closed Achilles tendon rupture.Methods From January 2020 to January 2022,162 cases of acute closed Achilles tendon rupture were treated with Krackow locking loop technique combined with the modified Kessler suture technique.The patients were treated with the same postoperative rehabilitation plans.The American Orthopaedic Foot and Ankle Society(AOFAS)hindfoot score and Achilles Tendon Total Rupture Score(ATRS)were collected to evaluate the functions.Results The operation time was 24-40 min(mean,31.9±4.6 min).All incisions healed in one stage without infection or sural nerve injury.Complications occurred in 2 patients,including 1 case of deep venous thrombosis and 1 case of trauma-related re-rupture.The recovery time of ankle flexion and extension motion was4-12 weeks(mean,7.6±1.9 weeks),the recovery time of single-legged heel rise height on the affected side was 10-18 weeks(mean,13.3±1.8 weeks),and the recovery time of fast walking or jogging was 14-26 weeks(mean,19.1±1.8 weeks).The 162 patients was followed up for 14-25 months(mean,19.0 months).The AOFAS hindfoot score increased from(54.4±4.4)points preoperatively to(98.0±4.0)points at the last follow-up(t =-104.402,P =0.000).The ATRS score increased from(52.0±8.3)points preoperatively to(91.2±2.4)points at the last follow-up(t =-62.823,P = 0.000).Conclusions For young and middle-aged patients with acute closed Achilles tendon rupture,Krackow locking loop technique combined with the modified Kessler suture technique can achieve good clinical outcomes.Early functional exercise is required to return to work and life.
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AIM:Using bioinformatics analysis and experiment validation to explore the differential expres-sion genes related to abnormal lipid metabolism in hepatocellular carcinoma(HCC)and the molecular mechanism of pachymaran affecting pyroptosis through squalene epoxidase(SQLE)/nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)/gasdermin D(GSDMD)signaling pathway.METHODS:(1)The GEO,GSEA,DAVID,STRING and GEPIA databases were employed to screen abnormal lipid metabolism-related differentially expressed genes in HCC.(2)The tumor tissues from HCC patients(n=9)were collected to verify the differential expression of SQLE.(3)The inhibitory effect of pachymaran on the viability of human HCC cell line HepG2 was measured by CCK-8 assay.(4)The HepG2 cells were divided into control group and pachymaran(800 mg/L)group.The cell migration was analyzed by wound-healing assay,and RT-qPCR was used to measure SQLE mRNA expression.(5)The HepG2 cells with overexpres-sion of SQLE(OE-SQLE)were divided into 5 groups as follows:control group,overexpression negative control(OE-NC)group,OE-SQLE group,OE-NC+pachymaran group,and OE-SQLE+pachymaran group.The mRNA and protein expres-sion levels of SQLE and pyroptosis-related factors were determined by RT-qPCR and Western blot.Colorimetric method and ELISA were used to measure lactate dehydrogenase(LDH),interleukin-1β(IL-1β)and IL-18 levels.The necrosis of HepG2 cells was analyzed by flow cytometry.RESULTS:The SQLE gene was screened through bioinformatics analysis,and its mRNA expression was significantly increased in tumor tissues from HCC patients(P<0.01).In cell experiments,treatment with 800 mg/L pachymaran for 48 h had a significant inhibitory effect on HepG2 cell viability,and the expres-sion of SQLE mRNA was reduced(P<0.01).After overexpression of SQLE,the mRNA and protein levels of pyroptosis-re-lated factors,necrotic rate,and LDH,IL-1β and IL-18 levels were significantly decreased(P<0.05).After treatment with pachymaran,the above indicators were significantly increased(P<0.05).CONCLUSION:The SQLE is abnormal-ly highly expressed in HCC,and pachymaran can affect the growth of HCC cells by activating the NLRP3/GSDMD pyropto-sis pathway through SQLE.
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AIM: To investigate the potential causal relationship between gut microbiota(GM)and primary open-angle glaucoma(POAG)based on a two-sample Mendelian randomization(MR)analysis.METHODS: The exposure data was derived from the Genome-Wide Association Studies(GWAS)of GM at the University of Bristol, while the outcome data for POAG was sourced from the MRC Integrative Epidemiology Unit(IEU)Open GWAS database. In this study, inverse variance weighted(IVW), MR Egger, weighted median(WM), Simple Mode, and Weighted Mode were analyzed to investigate the potential causal relationships between GM and POAG. IVW was used as the primary method for this study, and sensitivity analysis was conducted to assess the reliability of the MR analysis.RESULTS: The IVW analysis revealed that Butyrivibrio(OR=1.170, 95%CI: 1.057-1.295, P=0.002), Howardella(OR=1.188, 95%CI: 1.043-1.355, P=0.010), and LachnospiraceaeUCG001(OR=1.229, 95%CI: 1.016-1.485, P=0.033)were correlated with the risk of POAG. Conversely, Candidatus Soleaferrea(OR=0.810, 95%CI: 0.670-0.981, P=0.031), Ruminococcustorquesgroup(OR=0.656, 95%CI: 0.453-0.950, P=0.026), and RuminococcaceaeUCG013(OR=0.770, 95%CI: 0.598-0.990, P=0.041)were protective factors for POAG. Sensitivity analysis showed that there were no heterogeneity and pleiotropy among the instrumental variables.CONCLUSION: The MR study indicated a causal relationship between GM and POAG. Given the sight-threatening characteristic of POAG, early identification and intervention in the relative factors was significant for the prognosis of POAG.
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Cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinic acid to regulate cysteine accumulation in vivo. Elevated levels of cysteine have been shown to be cytotoxic and neurotoxic, and this is the first important step in the breakdown of cysteine metabolism in mammalian tissues. The human CDO1 gene is located on chromosome 5q23.2. Studies have shown that deletion or epigenetic silencing of this chromosomal region contributes to tumorigenesis. It is highly expressed in the liver and placenta, and weakly in the heart, brain and pancreas. CDO1 is a tumor suppressor gene (TSG) with a wide range of functions, which can be involved in various biological processes such as tumor cell proliferation, differentiation, apoptosis and iron death, thus affecting the tumor development. CDO1 is epigenetically regulated in human cancers, compared to normal tissues. The CDO1’s mRNA or protein expression levels were significantly down-regulated in tumor tissues, whereas promoter DNA methylation of the CDO1 gene usually accumulates with the progression of human cancers. Aberrant hypermethylation on the CDO1 promoter is a common event in tumor cells, which leads to transcriptional inactivation and silencing of the CDO1 gene. High frequency of methylation of CDO1 gene promoter methylation region in a variety of tumors including breast, oesophageal, lung, bladder, gastric and colorectal cancers. CDO1 gene promoter methylation levels reflect cancer progression and malignant tumorigenesis, which is a common molecular indicator explaining poor prognosis in human cancers. Treatment with 5-aza-2′-deoxycytidine (a drug that promotes demethylation) reactivated the CDO1 expression in most cancer cell lines, indicating that the transcriptional expression of CDO1 is closely correlated with its promoter methylation level, CDO1 gene promoter methylation and tumor progression have also received increasing attention from researchers. It was found that CDO1 gene promoter hypermethylation can be used as an early tumor marker for clinical aid diagnosis and helps to differentiate cancerous from benign diseases. It was also found that CDO1 promoter DNA methylation showed reliable tumor monitoring potential in human body fluids, and furthermore, the degree of CDO1 promoter methylation was strongly correlated with resistance to chemotherapy with tumor drugs, which would be helpful in evaluating the efficacy of chemotherapeutic drugs. Thus, CDO1, a common promoter methylation gene in human cancers, is closely associated with the development of a wide range of tumors and is one of the most promising candidate genes for assessing tumor-specific epigenetic changes. This article reviews the biological functions of CDO1 and its promoter DNA methylation in tumors, focusing on the mechanism of CDO1 DNA promoter methylation in tumors, with a view to providing theoretical guidance for the clinical diagnosis and treatment of tumors with CDO1 as a potential therapeutic target.
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BackgroundThe activity in precuneus within default mode network has been reported to be associated with antidepressant response, whereas the relationship between the functional network of precuneus and early response to antidepressant medications remains unclear. ObjectiveTo investigate the relationship between precuneus functional connectivity (FC) and early efficacy of antidepressant treatment in patients with major depressive disorder, so as to find a neurobiomarker to predict the early efficacy of antidepressants. MethodsA consecutive sample of 47 patients with major depressive disorder who attended the Mental Health Center, West China Hospital of Sichuan University from July 2017 to February 2019 and fulfilled the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited. Baseline resting-state functional magnetic resonance imaging scan findings and clinical assessments were recorded in participants. All patients treated with antidepressants for two weeks. Improvement was defined as 20% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptoms Self-Report Scale (QIDS-SR16) by treatment exit, and patients were then classified into early improved group (n=27) and non-improved group (n=20). FC values of precuneus and whole brain were calculated using bilateral precuneus as seed region, and baseline precuneus FC values were compared between two groups. Pearson correlation analysis was utilized to explore the correlation between FC values in brain regions with statistically significant differences and QIDS-SR16 total scores and reduction rates. ResultsFC values between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus in early improved group were both higher than those in non-improved group (GRF correction, P<0.01). The FC valves between the left precuneus and the left precentral gyrus and between the right precuneus and the right fusiform gyrus were positively correlated with QIDS-SR16 reduction rate (r=0.475, 0.297, P<0.05). ConclusionWeakened FC between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus are related to poor early efficacy to antidepressant treatment, and FC of precuneus may be a potential predictor of early response to antidepressants. [Funded by the National Key Research & Development Program of China (number, 2016YFC1307204); Key Development Project of the Sichuan Provincial Science and Technology Plan (number, 2018SZ0131)]
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The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
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Objective@#To explore the use of personal audio devices and hearing impairment among high school students, so as to provide reference for the development of adolescent hearing health work.@*Methods@#The simple random sampling method was used to collect research data relating to 1 768 high school students. The situation of personal audio players, headphone and hearing damage were investigated by using a self designed questionnaire, so as to identify the related factors of hearing impairment which were analyzed statistically by multivariate Logistic regression.@*Results@#The use rate of PAP and earphones was 98.64% and 94.12 %, respectively, and the use rate of female students(99.68%, 96.42%) was higher than that of male students(97.43%, 91.43 %)( χ 2=16.69, 19.79, P <0.01). Hearing impairment accounted for 13.35%. The Logistic regression analysis showed that PAP service years ( OR =1.59, P <0.05) were related to hearing impairment. Gender ( OR =0.60), in ear earphones ( OR =1.38), earplug earphones ( OR =1.37), and quiet use >1 h ( OR =1.50) were independently influenced with symptoms of hearing impairment during/after earphone use( P <0.05).@*Conclusion@#High usage rates of personal audio equipment among high school students lead to hearing impairment and related symptoms. Non essential use should be reduced.
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This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
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Humans , SARS-CoV-2 , COVID-19 , Epidemics , IncidenceABSTRACT
ObjectiveThrough improving the potential of vascular endothelial growth factor receptor (VEGFR)-humanized mouse model (hKDR+/+) with C57BL/6N background to allow the growth of different mouse tumor cell lines, to establish novel tumor-bearing mouse models which can support in vivo tumorigenesis of different mouse tumor cell lines and be used to evaluate drugs targeting VEGFR.MethodsFirstly, a method to evaluate the in vivo activity of antibody targeting VEGFR based on the hKDR+/+ humanized mouse model was established. Recombinant activating gene 1 (Rag1) knockout mice (Rag1-/-) were established using CRISPR/Cas9 technology. Then these Rag1-/- mice were crossed with hKDR+/+ mice to get a double gene modified homozygous hKDR+/+/Rag1-/- mouse model by screening. Finally, tumor cell lines derived from different mouse strains were tested on the double gene-modified mouse model to compare the differences in tumor growth. ResultsAntibodies designed for VEGFR showed significant anti-tumor activity in hKDR+/+ mice, which significantly reduced tumor volume and weight compared with the PBS group (P<0.01, P<0.05). The number of B cells and T cells in the peripheral blood of Rag1-/- mice and hKDR+/+/Rag1-/- mice decreased (P<0.05, P<0.001). Tumors were observed in hKDR+/+/Rag1-/-, Rag1-/-, wild-type, and hKDR+/+ mice after 7 d of inoculation of MC38 cells derived from C57BL/6 mice. Tumors were only observed in groups of hKDR+/+/Rag1-/- and Rag1-/- mice, but not in the wild-type and hKDR+/+ mice after 10 d of inoculation with CT26 cells derived from BALB/c mice. After 3 weeks of inoculation, the tumor volume of hKDR+/+/Rag1-/- mice was significantly larger than that of Rag1-/- mice (P<0.01). ConclusionRag1 knockout mice were obtained and a novel hKDR+/+/Rag1-/- double genes modified mouse model was further screened. The tumor cell lines from different mouse strain origins were more prone to growth in mice with Rag1 gene deficiency. The results suggest that the reduced immune response of hKDR+/+ humanized mice will improve the capacity of supporting the growth of mouse tumor lines in the model. As a result, more tumor-bearing mouse models may be constructed for the evaluation of drugs targeting VEGFR in this way.
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OBJECTIVE@#To explore predictive value of Caprini score, Wells score and Autar score for lower extremity deep vein thrombosis (DVT) after hip fracture in elderly patients.@*METHODS@#A total of 310 elderly patients with hip fracture were selected from January 2018 to September 2022. According to the lower extremity color ultrasound examination results, 155 patients with DVT were divided into thrombosis group, included 42 males and 113 females, aged from 60 to 101 years old with an average of (80.58±8.84) years old; and 155 patients without DVT were divided into control group, included 58 males and 97 females, aged from 60 to 94 years old with an average of (79.01±8.99) years old. Caprini score, Wells score and Autar score immediately after admission were collected and compared between two groups. Receiver operating characteristic (ROC) curve was used to evaluate predictive value of three thrombus risk assessment tables for DVT after hip fracture in elderly patients.@*RESULTS@#Caprini score, Wells score and Autar score in thrombus group were significantly higher than those in control group (P<0.001). ROC curve analysis results showed that the best cut-off value of Caprini score was 8.5 points, the sensitivity was 46.5%, the specificity was 99.4%, and area under the curve(AUC) was 0.763. The best cut-off value of Wells score was 1.5, the sensitivity was 100%, the specificity was 99.4%, and AUC was 0.998. The best cut-off value of Autar score was 10.5 points, the sensitivity was 58.1%, the specificity was 84.5%, and AUC was 0.717.@*CONCLUSION@#Caprini scale, Wells scale and Autar scale all have good predictive efficacy for the risk of DVT in elderly patients with hip fracture, and could provide an important reference for clinical guidance for prevention, management and treatment of DVT after hip fracture in elderly patients, among which Wells scale has a higher predictive value.
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Male , Female , Humans , Aged , Middle Aged , Aged, 80 and over , Venous Thrombosis/etiology , Risk Assessment , Hip Fractures/complications , Ultrasonography , Lower Extremity , Risk Factors , Retrospective StudiesABSTRACT
Objective:This paper focused on the research of the appointment system in interdisciplinary research institutions of world-class universities in China and the United States. The positive effects of different employment and evaluation systems as well as existing problems were sorted out and analyzed, and some suggestions were put forward to optimize and innovate the teacher appointment system and promote the interdisciplinary construction of Chinese universities.Methods:This paper focused on the new teacher appointment system adopted by representative universities in China and the United States to promote the development of interdisciplinary research and used the methods of literature research, questionnaire survey, case analysis, and in-depth interview to sort out and analyze the different systems.Results:Based on the broad perspective of the ″new concept-(artificial) selection-stabilization″ system change, the implementation of an interdisciplinary joint appointment in our country has experienced a stage of ″new concept generation″ at present, but it is still in the stage of ″institution establishment and stabilization″. The personnel management system for teachers engaged in interdisciplinary research still needs to be improved, and there are still outstanding problems in the areas of evaluation and promotion pressure, financial resources guarantee, teachers′ sense of belonging, administrative costs, etc.Conclusions:Referring to the advanced experience at home and abroad, Chinese universities should focus on breaking the barriers of distributing the interests of results, improving interdisciplinary talent evaluation mechanisms, adopting a variety of flexible appointment systems depending on demands, and building a benign flow ecology of interdisciplinary human resources. Apart from these, urgent attention should be paid to improving the administrative work system and interdisciplinary cultural system construction.
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Moody and colleagues discovered the presence of venous collagenosis (VC) in periventricular of human brains by pathological study obtained at autopsy in 1995, which was described as a noninflammatory collagenous thickening of venous walls resulting in severe periventricular venous stenosis or occlusion. Due to the lack of specific markers and staining methods, there are few studies of cerebral venous disease, and the pathological features and pathogenesis are still unclear. However, studies have reported that VC is associated with cerebral small vessel disease (CSVD) and Alzheimer′s disease (AD), suggesting that VC may play an important role in exploring and elucidating pathogenesis. The article aims to provide a review of researches on VC pathological features, possible pathogenesis and correlation with CSVD and AD.
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Objective:To compare percutaneous cannulated screw (PCS) fixation and plating via a minimally invasive longitudinal approach (MILA) after closed reduction for the treatment of intra-articular tongue-type calcaneal fractures.Methods:A retrospective analysis was conducted of the 67 patients with intra-articular tongue-type calcaneal fracture who had been treated at Department of Orthopedics, The Third Hospital of Peking University from May 2017 to May 2020. They were 56 males and 11 females, 19 to 58 years of age (average, 34.5 years). Of them, 32 were treated by the PCS fixation after closed reduction (PCS group) and 35 by the MILA plating after closed reduction (MILA group). The operation time, preoperative time, post-operative hospital stay, blood loss and postoperative complications were recorded and compared between the 2 groups. The calcaneal length, width and height, Gissane angle, B?hler angle, varus angle, valgus angle and visual analog scale (VAS) were compared between the 2 groups at preoperation, immediate postoperation, 3 months postoperation, and the last follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score was used at 3 months postoperation and the last follow-up to evaluate the function of the injured hindfoot.Results:There was no significant difference in the preoperative general data between the PCS group and the MILA group, showing they were comparable ( P>0.05). All patients were followed up for an average of 18.5 months (from 15 to 25 months). For the PCS group and the MILA group, respectively, the operation time was 60.5 (51.5, 68.0) min and 86.0 (78.0, 96.0) min, the blood loss 10 (5.0, 20.0) mL and 20 (15, 25) mL, the postoperative hospital stay 1 (1.0, 1.8) d and 2 (2, 3) d, the calcaneal width at immediate postoperation (43.8±4.4) mm and (40.6±2.8) mm, the calcaneal width at 3 months postoperation 43.8 (39.6, 48.3) mm and 41.5 (38.8, 44.5) mm, the calcaneal width at the last follow-up 44.2 (40.2, 48.0) mm and 41.3 (39.0, 44.3) mm, the VAS at the last follow-up 5.0 (5.0, 5.0) and 6.0 (5.0, 6.0). The comparisons of the above items showed significant differences between the 2 groups (all P<0.05). No significant differences were observed between the 2 groups in the calcaneal length or height, Gissane or B?hler angle, AOFAS hindfoot score, or complication rate (all P>0.05). Conclusions:In the treatment of tongue-type calcaneal fractures, after closed reduction, the PCS fixation can shorten operation time and postoperative hospital stay, and reduce intraoperative blood loss and postoperative pain, but the MILA plating is more advantageous in restoring the calcaneal width.
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Objective To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. Methods The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. Results A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. Conclusions Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.
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This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.
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Chromatography, High Pressure Liquid/methods , Cistanche , Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Tandem Mass Spectrometry/methodsABSTRACT
Objective:To investigate the effects of polyethylene glycol 400 (PEG400) on the pharmacokinetics and anti-inflammatory effect of baicalin, and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucuronide (B6G) by molecular docking. Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix, and rats were administrated the equal dose of baicalin aqueous solution (baicalin+water group) and baicalin PEG400 solution (baicalin+PEG400 group). After the plasma samples were processed at different time periods, the concentrations of baicalin and B6G in rat plasma were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group (normal saline, 20 mL·kg<sup>-1</sup>), aspirin group (dose of 0.2 g·kg<sup>-1</sup>), baicalin/baicalin+PEG400 high and low dose (3.0, 1.5 g·kg<sup>-1</sup>) groups, after continuous administration for 7 days, the mouse ear swelling and foot swelling models were established, and the swelling degree and swelling inhibition rate were calculated. Result:The pharmacokinetic study showed that compared with baicalin+water group, the plasma concentrations of baicalin and B6G increased after administration of baicalin PEG400 solution, and the area under the curve (AUC<sub>0-</sub><italic><sub>t</sub></italic>) increased by 2.36, 1.97 times, and the peak concentration (<italic>C</italic><sub>max</sub>) increased by 2.12, 1.65 times, respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition, molecular docking results showed that baicalin and B6G could site bind to multiple target proteins [tumor necrosis factor (TNF)-<italic>α</italic>, interleukin (IL)-6, IL-1<italic>β</italic>, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and nuclear transcription factor-<italic>κ</italic>B (NF-<italic>κ</italic>B)] with higher affinity, which was superior to the positive drug aspirin. Conclusion:PEG400 can increase the plasma concentration of baicalin and its main metabolite B6G, and enhance the anti-inflammatory effect. Baicalin and B6G can form strong hydrogen bonds with various inflammatory factors and of nuclear transcription factors, it is speculated that baicalin and B6G jointly play an anti-inflammatory role.
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Objective:To systematically study the chemical components of Qianyang Yuyin granules and explore its main pharmacodynamic substances and mechanism in the prevention and treatment of hypertensive renal damage. Method:Liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was employed to comprehensively analyze the chemical components of Qianyang Yuyin granules. Agilent Poroshell 120 SB-C<sub>18</sub> column (3.0 mm×100 mm, 2.7 μm) was used, flow rate was 0.4 mL·min<sup>-1</sup>, electrospray ionization (ESI) was applied and operated in positive and negative ion modes, the acquisition range was <italic>m</italic>/<italic>z</italic> 25-1 000. Mobile phase in positive ion mode consisted of water+10 mmol·L<sup>-1</sup> ammonium formate+0.125% formic acid+0.1% methanol (A)-[acetonitrile-water (9∶1)+10 mmol·L<sup>-1</sup> ammonium formate+0.125% formic acid] (B), and in negative ion mode consisted of water+10 mmol·L<sup>-1</sup> ammonium formate+0.1% methanol (A)-[acetonitrile-water (9∶1)+10 mmol·L<sup>-1</sup> ammonium formate] (B) with the gradient elution (0-3.5 min, 5%B; 3.5-4 min, 5%-10%B; 4-9 min, 10%-25%B; 9-18 min, 25%-30%B; 18-25 min, 30%-50%B; 25-27 min, 50%-90%B; 27-32 min, 90%B; 32-33 min, 90%-5%B; 33-39 min, 5%B). According to the information of the accurate mass, the multistage fragment ions, the mass spectrometric data of the standard substances and the relative reference literature, the structures of the chemical components in Qianyang Yuyin granules were identified. Based on the identified components, network pharmacology study, including target prediction and functional enrichment was applied to screen out the main active substances against hypertensive renal damage, and explore the potential mechanism. Result:A total of 99 chemical components were identified, from which 43 active substances and 48 key targets were screened out. The key components contained kaempferol, quercetin, ferulic acid, luteolin, caffeic acid methyl ester, cinnamic acid, aloe-emodin, emodin, gallic acid, <italic>N</italic>-<italic>trans</italic>-feruloyltyramine, isoorientin, 8-<italic>O</italic>-feruloylharpagide, ethyl caffeate, isookanin, cyasterone, 2,3,5,4'-tetrahydroxystilbene-2-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucopyranoside, loganin, alisol B-23-acetate and harpagide. The key targets included vascular endothelial growth factor A (VEGFA), serine/threonine protein kinase 1 (AKT1), Jun proto-oncogene (JUN), etc. Conclusion:Qianyang Yuyin granules mainly exert the effects of removing heat from the liver, tonifying the kidney and removing blood stasis via modulation of vascular endothelium, angiogenesis, inflammatory reaction, oxidative stress, immune response and so on.
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Objective:To explore the depression of patients with systemic lupus erythematosus (SLE) during the coronavirus disease 2019 (COVID-19) pandemic.Methods:Patients with SLE and healthy subjects(control group) from August 16, 2020 to September 2, 2020 in Urumqi, Xinjiang were collected. The depression and sleep quality were assessed by Self rating Depression Scale (SDS) and Pittsburgh sleep quality index (PSQI). The nonparametric data were represented by median (quartile spacing), and the rank sum test was used to compare the continuous variables between the two groups. Pearson correlation test was used for continuous variables, and Spearman correlation test was used for rank variables or classified variables. Statistical product and service solutions.Results:The prevalence rate of depression in the SLE group (41.9%) was significantly higher than that in healthy control group (32.1%). The difference was statistically significant ( χ2= 10.312, P<0.01). The prevalence rate of poor sleep in the SLE group (31.8%) was significantly higher than that in healthy control group (21.6%). The difference was statistically significant( χ2=3.885, P=0.049). The total score of VAS ( OR=1.366, P<0.01) , PSQI( OR=1.198, P<0.01) were the risk factor of depression in patients with SLE. Conclusion:SLE patients have a higher prevalence of depression during pandemic quarantinee-period, pain and poor sleep quality are risk factors. We need to pay attention to the psychological status of SLE patients.
ABSTRACT
The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.
ABSTRACT
OBJECTIVE@#To describe and assess the repair technique and perioperative management for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture via extradural anterior skull base approach.@*METHODS@#This was a retrospective review conducted at the Department of Neurosurgery of the Shanghai Tenth People's Hospital from January 2015 to April 2020. Patients with traumatic CSF rhinorrhea resulting from extensive anterior skull base fracture treated surgically via extended extradural anterior skull base approach were included in this study. The data of medical and radiological records, surgical approaches, repair techniques, peritoperative management, surgical outcome and postoperative follow-up were analyzed. Surgical repair techniques were tailored to the condition of associated injuries of the scalp, bony and dura injuries and associated intracranial lesions. Patients were followed up for the outcome of CSF leak and surgical complications. Data were presented as frequency and percent.@*RESULTS@#Thirty-five patients were included in this series. The patients' mean age was 33 years (range 11-71 years). Eight patients were treated surgically within 2 weeks; while the other 27 patients, with prolonged or recurrent CSF rhinorrhea, received the repair surgery at 17 days to 10 years after the initial trauma. The mean overall length of follow-up was 23 months (range 3-65 months). All the patients suffered from frontobasal multiple fractures. The basic repair tenet was to achieve watertight seal of the dura. The frontal pericranial flap alone was used in 20 patients, combined with temporalis muscle and/or its facia in 10 patients. Free fascia lata graft was used instead in the rest 5 patients. No CSF leak was found in all the patients at discharge. There was no surgical mortality in this series. Bilateral anosmia was the most common complication. At follow-up, no recurrent CSF leak or meningitis occurred. No patients developed mucoceles, epidural abscess or osteomyelitis. One patient ultimately required ventriculoperitoneal shunt because of progressive hydrocephalus.@*CONCLUSION@#Traumatic CSF rhinorrhea associated with extensive anterior skull base fractures often requires aggressive treatment via extended intracranial extradural approach. Vascularized tissue flaps are ideal grafts for cranial base reconstruction, either alone or in combination with temporalis muscle and its fascia---fascia lata sometimes can be opted as free autologous graft. The approach is usually reserved for patients with traumatic CSF rhinorrhea in complex frontobasal injuries.