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1.
Acta Pharmaceutica Sinica ; (12): 633-642, 2024.
Article in Chinese | WPRIM | ID: wpr-1016622

ABSTRACT

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

2.
Acta Pharmaceutica Sinica B ; (6): 635-652, 2024.
Article in English | WPRIM | ID: wpr-1011260

ABSTRACT

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

3.
Journal of Environmental and Occupational Medicine ; (12): 1307-1313, 2023.
Article in Chinese | WPRIM | ID: wpr-998756

ABSTRACT

Background Work-related musculoskeletal disorders (WMSDs) seriously affect work efficiency and quality of life of nurses. Currently, there are significant differences in the published studies on WMSDs in nurses. Objective To systematically evaluate the prevalence of WMSDs among nurses in the mainland of China and analyze its main influencing factors. Methods Eight databases (CNKI, Wanfang data, VIP, SinoMed, PubMed, Cochrane Library, Web of Science, and Embase) were selected for searching literature reporting prevalence and influencing factors of WMSDs among clinical nurses in China from inception to December 31, 2022. The literature was included according to a pre-set criteria of inclusion and exclusion. The quality of cross-sectional studies was assessed using the criteria recommended by the Agency for Healthcare Research and Quality (AHRQ), and the extracted data were analyzed by Stata 15.0 software. A random effect model or a fixed effect model was selected to calculate combined effects based on heterogeneity of included studies. Results A total of 19 studies were included in this meta-analysis, including 14 studies published in Chinese and 5 in English, involving 17852 nurses in total. The estimated prevalence rate of WMSDs since work among clinical nurses in China was 85.5% (95%CI: 79.8%, 91.1%), the estimated annual prevalence rate was 81.0% (95%CI: 75.2%, 86.8%), and the estimated weekly prevalence rate was 65.0% (95%CI: 48.5%, 81.5%). The results of subgroup analysis showed that the prevalence rate of WMSDs among nurses in specific departments of emergency, ICU, and midwifery was 88.6% (95%CI: 82.6%, 94.6%), higher than that among nurses in general departments [79.0% (95%CI: 72.5%, 85.5%)]. The reported prevalence of WMSDs from 2018 to 2022 was 82.2% (95%CI: 75.0%, 89.4%), which was higher than that from 2004 to 2017 [76.8% (95%CI: 67.2%, 86.4%)]. Age >40 years (OR=2.34, 95%CI: 1.69, 3.24), length of service >10 years (OR=2.12, 95%CI: 1.43, 3.15), obesity (OR=2.73, 95%CI: 1.56, 4.77), night shift (OR=2.03, 95%CI: 1.81, 2.28), lifting heavy objects (OR=3.80, 95%CI: 1.79, 8.07), rest during work (OR=0.49, 95%CI: 0.30, 0.83), and bending (OR=3.47, 95%CI: 2.37, 5.08) were influencing factors of WMSDs in nurses. Conclusion The prevalence rate of WMSDs among Chinese nurses is high, and it is increasing year by year. Nurses in specific departments such as emergency, ICU, and midwifery show higher prevalence rates than those in general departments. Age > 40 years, length of service >10 years, obesity, night shifts, lifting heavy objects, and bending are risk factors for WMSDs among nurses, while rest during work is a protective factor. Therefore, early prevention actions should be taken targeting the above factors, such as increasing auxiliary assistance facilities and improving work patterns, so as to reduce the risk of WMSDs.

4.
Intestinal Research ; : 235-243, 2023.
Article in English | WPRIM | ID: wpr-976810

ABSTRACT

Background/Aims@#The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. @*Methods@#Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. @*Results@#A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. @*Conclusions@#Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

5.
Chinese Journal of Preventive Medicine ; (12): 268-272, 2023.
Article in Chinese | WPRIM | ID: wpr-969877

ABSTRACT

Objective: To establish a rapid and specific quantitative real-time PCR (qPCR) method for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA (SgN) in patients with COVID-19 or environmental samples. Methods: The qPCR assay was established by designing specific primers and TaqMan probe based on the SARS-CoV-2 genomic sequence in Global Initiative of Sharing All Influenza Data (GISAID) database. The reaction conditions were optimized by using different annealing temperature, different primers and probe concentrations and the standard curve was established. Further, the specificity, sensitivity and repeatability were also assessed. The established SgN and genomic RNA (gRNA) qPCR assays were both applied to detect 21 environmental samples and 351 clinical samples containing 48 recovered patients. In the specimens with both positive gRNA and positive SgN, 25 specimens were inoculated on cells. Results: The primers and probes of SgN had good specificity for SARS-CoV-2. The minimum detection limit of the preliminarily established qPCR detection method for SgN was 1.5×102 copies/ml, with a coefficient of variation less than 1%. The positive rate of gRNA in 372 samples was 97.04% (361/372). The positive rates of SgN in positive environmental samples and positive clinical samples were 36.84% (7/19) and 49.42% (169/342), respectively. The positive rate and copy number of SgN in Wild strain were lower than those of SARS-CoV-2 Delta strain. Among the 25 SgN positive samples, 12 samples within 5 days of sampling time were all isolated with virus; 13 samples sampled for more than 12 days had no cytopathic effect. Conclusion: A qPCR method for the detection of SARS-CoV-2 SgN has been successfully established. The sensitivity, specificity and repeatability of this method are good.


Subject(s)
Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Subgenomic RNA , Real-Time Polymerase Chain Reaction/methods , RNA, Viral/genetics , Sensitivity and Specificity , Nucleocapsid/chemistry , COVID-19 Testing
6.
China Pharmacy ; (12): 837-843, 2023.
Article in Chinese | WPRIM | ID: wpr-969581

ABSTRACT

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial, a Markov model was constructed; the probabilities of risk events, health utility values, and costs of risk event management were obtained from relevant literature. The cycle length was 6 months, and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen (325 mg/d of CAPRIE trial dose), the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years, 20 years and 30 years were 4 284.06, 4 201.20 and 3 986.78 yuan/QALY, respectively, which were E-mail:liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay (WTP) threshold of one time 。 China’s per capita gross domestic product (GDP) in 2021. E-mail:scilwsjtu-wb@yahoo.com Compared with the aspirin regimen (clinically recommended dose in China, 100 mg/d), the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years, 20 years and 30 years were 58 238.27, 42 164.72 and 36 164.77 yuan/QALY, respectively, which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d, results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin, probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021, clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10, 20 or 30 years nor using different doses of aspirin (50, 100, 150, 200 or 250 mg/d) would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy, clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

7.
China Pharmacy ; (12): 391-396, 2023.
Article in Chinese | WPRIM | ID: wpr-962479

ABSTRACT

OBJECTIVE To evaluate the effectiveness, safety, economy, innovation, suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein (EC), and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin (TB-PPD) were analyzed by the method of systematic review. Cost minimization analysis, cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD, and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation, suitability and accessibility were determined by systematic review and improved Delphi expert consultation, and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness, safety, economy, innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent, while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight, the scores of effectiveness, safety, economy, innovation, suitability, accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD, EC performs better in all dimensions of effectiveness, safety, economy, innovation, suitability and accessibility. However, it is worth noting that EC should further improve its availability in the dimension of accessibility.

8.
Chinese Journal of Surgery ; (12): 791-797, 2023.
Article in Chinese | WPRIM | ID: wpr-985824

ABSTRACT

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

9.
Chinese Journal of Surgery ; (12): 753-760, 2023.
Article in Chinese | WPRIM | ID: wpr-985819

ABSTRACT

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18)years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033,P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3%(n=711), 89.0%(n=626) and 71.4%(n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

10.
Journal of Forensic Medicine ; (6): 373-381, 2023.
Article in English | WPRIM | ID: wpr-1009368

ABSTRACT

OBJECTIVES@#To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death.@*METHODS@#PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis.@*RESULTS@#Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine).@*CONCLUSIONS@#GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.


Subject(s)
Rats , Animals , Metabolomics/methods , Brain Injuries , Biomarkers/metabolism , Brain Stem/metabolism
11.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 79-87, 2023.
Article in Chinese | WPRIM | ID: wpr-996813

ABSTRACT

ObjectiveTo explore the hub genes of acute-on-chronic liver failure (ACLF) using bioinformatics methods, predict the potential traditional Chinese medicines (TCMs) against ACLF, and verify the treatment mechanism based on experiments. MethodPerl and R were used to analyze the GSE142255 dataset to obtain the differentially expressed genes (DEGs), from which the hub genes in the protein-protein interaction of DEGs were identified by five algorithms of the CytoHubba plug-in. The receiver operating characteristic (ROC) curve and GSE168048 dataset were then used to verify the hub genes. Coremine Medical was employed to map the TCMs corresponding to the hub genes and then the natures, tastes, and meridian tropism of the TCMs were analyzed. The TCM systems pharmacology database and analysis platform (TCMSP) and DEGs were used to obtain the common targets shared by high-frequency TCMs and ACLF, and Cytoscape was used to establish the "hub gene-high-frequency TCM-active ingredient-common target" network. Furthermore, gene ontology (GO) annotation, Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and in vitro experiments were performed. ResultA total of 388 DEGs were obtained, in which the 7 hub genes encoded CD4 integrin subunit alpha M (ITGAM), CD2, lymphocyte-specific protein tyrosine kinase (LCK) proto-oncogene, C-C motif chemokine ligand 5 (CCL5), matrix metallopeptidase-9 (MMP-9), and Fc epsilon receptor IG (FCER1G). The TCM candidates for treating ACLF were mainly cold, bitter, and had tropism to the liver meridian, among which the high-frequency TCMs (Hedyotis Diffusae Herba, Ganoderma, and Astragali Radix) and the active ingredients (quercetin, kaempferol, and beta-sitosterol) had significant therapeutic potential. The enrichment analysis results showed that TCMs acted on multiple targets and pathways such as autophagy, oxidative stress, and inflammatory cytokines in addition to regulating hub genes. L02 cell experiments showed that the quercetin group had lower levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), lower protein levels of ubiquitin-binding protein p62 and MMP-9, and higher levels of superoxide dismutase (SOD), glutathione (GSH), and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ (LC3 Ⅱ/Ⅰ) than the D-galactosamine (D-GaLN) group (P<0.05, P<0.01). In addition, the pretreatment with 3-methyladenine (3-MA) inhibited the activating effect of quercetin on the autophagy of L02 cells. ConclusionThe potential TCMs and active ingredients predicted based on the hub genes of ACLF have a great research value. Quercetin has the potential to treat ACLF by inhibiting the D-GaLN-induced oxidative stress and inflammatory response in L02 cells and regulating the expression of MMP-9, which may be associated with the activation of autophagy.

12.
Chinese Journal of Ocular Fundus Diseases ; (6): 223-226, 2023.
Article in Chinese | WPRIM | ID: wpr-995617

ABSTRACT

Objective:To observe the clinical and multimodal imaging characteristics of eyes with acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective clinical study. From December 18 to 26, 2022, 16 eyes of 8 patients with AMN associated with COVID-19 were included in the study. There were 4 males and 4 females; all cases were bilateral. The age was (31.5±9.6) years old. The time from fever to decreased vision was (3.75±1.04) days. The best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundus microscopy, fundus color photography, and optical coherence tomography (OCT) were performed in all patients. Infrared fundus photography (IR), OCT angiography (OCTA) and fluorescein fundus angiography (FFA) were performed in 14, 6 and 4 eyes respectively. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for statistics. The clinical data, IR, OCT and OCTA imaging features of the patients were retrospectively analyzed.Results:The logMAR BCVA of AMN eyes was 4.21±0.74, intraocular pressure was (14.87±1.50) mm Hg (1 mm Hg=0.133 kPa). Fundus color photography showed that multiple gray-white petal-shaped lesions were arranged around the macular fovea in 2 eyes; no obvious abnormality was found in the macular area in 14 eyes. Of the 14 eyes examined by IR, 6 eyes had irregular weak reflective lesions around the macular fovea. OCT showed strong reflex in the outer nuclear layer and outer plexiform layer of all eyes, including 15 eyes with elliptical zone injury. In 6 eyes examined by OCTA, the blood flow density of the superficial and deep capillary plexus (DCP) of retina decreased, and the blood flow density of DCP decreased significantly. The en-face image of DCP showed the wedge-shaped strong reflective lesion area with the tip pointing to the central fovea in 2 eyes. No abnormal fluorescence was observed in FFA.Conclusions:The characteristic manifestation of AMN associated with COVID-19 is weak reflex focus in IR; OCT shows strong reflection in outer core layer and outer plexiform layer; OCTA showed that retinal DCP blood flow density decreased.

13.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 528-533, 2023.
Article in Chinese | WPRIM | ID: wpr-991780

ABSTRACT

Objective:To investigate the cost-effectiveness of long-acting versus short-acting recombinant human granulocyte stimulating factor in the treatment of III° and IV° bone marrow suppression after chemotherapy. Methods:The data of patients who presented with III and IV° bone marrow suppression after chemotherapy and received treatment with recombinant human granulocyte stimulating factor from January 2018 to December 2019 were collected. These patients were divided into the short-acting recombinant human granulocyte stimulating factor group (rhG-CSF group) and the long-acting recombinant human granulocyte stimulating factor group (PEG-rhG-CSF group) group. Clinical efficacy, the incidence of adverse reactions, and cost-effectiveness were compared between the two groups.Results:There were 88 patients, aged (63.97 ± 11.64) years, in the rhG-CSF group. There were 80 patients, aged (63.26 ± 9.09) years in the PEG-rhG-CSF group. There was no significant difference in baseline data between the two groups ( P > 0.05). Total response rate was 72.72% (64/88) in the rhG-CSF group and 78.75% (63/80) in the PEG-rhG-CSF group ( χ2 = 0.82, P = 0.360). The incidence of related adverse reactions was 7.95% (7/88) and 7.5% (6/80) in the rhG-CSF and PEG-rhG-CSF groups respectively ( χ2 = 0.01, P = 0.910). The average cost was (124.88 ± 113.07) yuan and (3 159.04 ± 505.05) yuan in the rhG-CSF and PEG-rhG-CSF groups respectively ( t = 51.68, P < 0.01). The cost-effectiveness ratio was 1.55 and 40.11 in the rhG-CSF and PEG-rhG-CSF groups respectively. Taking the rhG-CSF group as a reference, the incremental cost-effectiveness ratio in the PEG-rhG-CSF group was 505.13. Conclusion:Long-acting and short-acting recombinant human granulocyte stimulating factors have similar curative effects and related adverse reactions in the treatment of III° and IV°bone marrow suppression after chemotherapy. The cost-effectiveness ratio of the rhG-CSF group is lower than that of the PEG-rhG-CSF group. Appropriate treatment schemes for increasing white blood cell levels should be selected based on the individual situation of the patient.

14.
Chinese Journal of Digestive Surgery ; (12): 742-747, 2023.
Article in Chinese | WPRIM | ID: wpr-990697

ABSTRACT

Objective:To investigate the incidence and influencing factors of anastomotic leakage after laparoscopic anterior resection for rectal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 804 patients with rectal cancer who were admitted to Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from January 2017 to December 2019 were collected. There were 521 male and 283 female, aged 63(range, 27-94)years. All 804 patients underwent laparoscopic anterior resection for rectal cancer. Observation indicators: (1) surgical situations; (2) incidence of postoperative anastomotic leakage; (3) follow-up; (4) influencing factors of postoperative anastomotic leakage; (5) subgroup analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribu-tion were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Univariate analysis was conducted using the chi-square test or independent sample t test. Factors with P≤0.2 in univariate analysis were included in multivariate Logistic regression analysis. Results:(1) Surgical situations. All 804 patients underwent laparoscopic radical resection of upper and middle rectal cancer successfully, with the operation time and volume of intraoperative blood loss as 135(range, 118-256)minutes and 30(range, 5-350)mL. All 804 patients completed end-to-end colon rectal anastomosis, including 287 patients with reinforced sutures at the anastomotic site, and 517 patients with routine anastomosis. (2) Incidence of postoperative anastomotic leakage. Of the 804 patients, 40 patients had postoperative anastomotic leakage, with the incidence rate as 4.98%(40/804). (3) Follow-up. All 804 patients were followed up for 32(range, 6-49)months. None of patient died during the perioperative period. (4) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that unreinforced suture at the anastomotic site was an independent risk factor for postoperative anastomotic leakage ( odds ratio=2.78, 95% confidence interval as 1.21-6.37, P<0.05). (5) Subgroup analysis. Of the 804 patients, 202 patients received neoadjuvant therapy and 602 patients did not receive neoadjuvant therapy. Of the 602 patients who did not receive neo-adjuvant therapy, cases with postoperative anastomotic leakage was 6 in the 253 patients with reinforced sutures, versus 21 in the 349 patients with routine sutures, showing a significant difference between them ( χ2=4.56, P<0.05). Conclusion:Unreinforced anastomosis at the anasto-motic site is an independent risk factor for anastomotic leakage after laparoscopic anterior rectal resection, especially for rectal cancer patients without neoadjuvant radiochemotherapy.

15.
Chinese Journal of Emergency Medicine ; (12): 210-214, 2023.
Article in Chinese | WPRIM | ID: wpr-989802

ABSTRACT

Objective:To explore the clinical characteristics of patients with colchicine poisoning, and analyze the risk factors affecting the prognosis of colchicine poisoning and its value in the prognostic assessment.Methods:Patients with colchicine poisoning admitted to the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to October 2022 were retrospectively included and divided into the survival group and death group according to the 14-d outcome. The general conditions of the two groups of patients were compared, and the clinical characteristics of patients with colchicine poisoning were analyzed. The differences of laboratory indexes, electrocardiogram, cardiac ultrasound and other clinical indexes during the first admission of patients between the two groups were compared, and their value in the prognosis evaluation of patients with colchicine poisoning was explored.Results:There were 41 patients with colchicine poisoning, aged 15-85 years, including 35 males and 6 females. There were 27 patients (65.9%) in the survival group and 14 patients (34.1%) in the death group, including accumulative poisoning (58.7%) and suicide poisoning (41.3%). The main clinical manifestations of patients with colchicine poisoning were gastrointestinal symptoms (82.93%), multiple organ dysfunction (78.05%), infectious fever (73.17%), myocardial damage (48.78%), coagulation dysfunction (46.34%), and bone marrow suppression (41.46%). Intestinal obstruction (19.51%) and rhabdomyolysis (2.44%) occurred in some patients. Multivariate Logistic regression analysis showed that the increase in absolute value of QTc interval ( OR=1.028, 95% CI: 1.000~1.056, P<0.05), lactic acid ( OR=1.599, 95% CI: 1.088~2.350, P<0.05), prothrombin time ( OR=1.205, 95% CI: 1.002~1.450, P<0.05), D-dimer ( OR=1.242, 95% CI: 1.089~1.417, P<0.05), and alkaline phosphatase ( OR=1.013, 95% CI: 1.002~1.024, P<0.05) were the risk factors for the prognosis of patients with colchicine poisoning. The decrease in the absolute value of ADL score ( OR=0.947, 95% CI: 0.909~0.988, P<0.05) and indirect bilirubin ( OR=0.756, 95% CI: 0.572~0.999, P<0.05) were the protective factors for the prognosis of patients with colchicine poisoning. D-dimer (AUC=0.913), lactic acid (AUC= 0.875) and alkaline phosphatase (AUC=0.770) had predictive value for the prognosis of patients with colchicine poisoning, and their cut-off values were 8.965 mg/L, 4.05 mmol/L and 230.5 U/L, respectively. Conclusions:The patients with colchicine poisoning have multiple organ dysfunction on admission, and are in a critical condition. The early levels of D-dimer, lactic acid and alkaline phosphatase could effectively predict the prognosis of patients with colchicine poisoning.

16.
Chinese Journal of Emergency Medicine ; (12): 203-209, 2023.
Article in Chinese | WPRIM | ID: wpr-989801

ABSTRACT

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.

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Journal of Sun Yat-sen University(Medical Sciences) ; (6): 758-767, 2023.
Article in Chinese | WPRIM | ID: wpr-988721

ABSTRACT

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K, 5 K or 25 K medium containing ATM-specific inhibitors (Ku55933, 10 µmol/L; Ku60019, 15 µmol/L) for Hoechst stain and apoptosis analysis, or cultured for different lengths of time (2, 4, 8 h) to detect the protein expression levels of ATM, caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs, and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h, Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h, transcriptome sequencing, differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h, then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K, CGNs nuclear pyknosis rate, cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control, CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group; 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group; 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups, while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway, NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control, mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K, while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

18.
Chinese Journal of Emergency Medicine ; (12): 344-348, 2022.
Article in Chinese | WPRIM | ID: wpr-930231

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Objective:To evaluate the effect of gabapentin on myocardial ischemia-reperfusion injury and its mechanism.Methods:Sixty male clean SD rats, aged 10 weeks and weighing 250 g~300 g, were divided into 5 groups ( n=12) with 12 rats in each group by random number table method: Sham group, myocardial ischemia reperfusion group (group I/R), gabapentin group (group Gap), LY294002 group (group LY) and gabapentin +LY294002 group (group Gap +LY). The model of myocardial ischemia reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min. Heart rate (HR), mean arterial pressure (MAP) and the rate pressure product (RPP) were recorded at baseline before ischemia (T 0) for 30 min (T 1) and reperfusion for 120 min (T 2) to evaluate hemodynamic changes during ischemia and reperfusion; The frequency of PVCs and VT/VF were recorded to evaluate the occurrence of arrhythmias during ischemia/reperfusion. TTC staining was used to detect myocardial infarction area. And the protein expression levels of PI3K and Akt in myocardial tissue were detected by Western blotting. Results:Compared with group I/R, the myocardial infarction area, PVCs and VT/VF times, and the protein expression levels of PI3K and p-Akt were significantly increased in group Gap ( P<0.05). Compared with group Gap, the area of myocardial infarction, the number of PVCs and VT/VF, and the protein expression of PI3K and p-Akt were significantly decreased in the group Gap +LY ( P<0.05). Conclusions:Gabapentin can alleviate myocardial ischemia-reperfusion injury, and its mechanism is related to the activation of PI3K-AKT signaling pathway.

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International Journal of Surgery ; (12): 279-283, 2022.
Article in Chinese | WPRIM | ID: wpr-930009

ABSTRACT

Microribonucleic acid (miRNAs) is a widely existing endogenous single-stranded non-coding small RNA, which is stably expressed in tissues and body fluids. By complementing messenger RNA(mRNA) sequences, miRNAs degrade target mRNA and block the expression of protein-coding genes, playing a key role in post-transcriptional regulation and different biological processes. In recent years, more and more studies have shown that miRNAs are closely related to the occurrence and development of tumors. Among them, as a member of the miRNAs family, microribonucleic acid-196 (miR-196) is abnormally expressed in the serum, tissues and cells of patients with non-small cell lung cancer, participating in the occurrence and development of non-small cell lung cancer and playing an important regulatory role in various biological processes such as proliferation, invasion and metastasis, providing diagnostic evidence for early screening of non-small cell lung cancer.This paper reviews the progress of miR-196 in the development and diagnosis of non-small cell lung cancer.

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Chinese Journal of Gastrointestinal Surgery ; (12): 522-530, 2022.
Article in Chinese | WPRIM | ID: wpr-943029

ABSTRACT

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.


Subject(s)
Humans , Anastomotic Leak/etiology , Laparoscopy/methods , Postoperative Complications/epidemiology , Prognosis , Prospective Studies , Rectal Neoplasms/pathology , Rectum/surgery , Retrospective Studies , Transanal Endoscopic Surgery/methods , Treatment Outcome
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