Objective: To explore the clinical effect of percutaneous transforaminal endoscopic discectomy (PTED) combined with annulus fibrosus repair in the treatment of single-segment lumber disc herniation (LDH) in young and middle-aged patients. Methods: Ninty-six patients with single-segment LDH admitted to Baoding First Central Hospital from March 2021 to November 2022 were selected in the retrospective study. The patients were divided into endoscopic group and combined group according to different surgical methods. The surgical conditions, VAS score and ODI score the two groups of patients were compared, as well as the postoperative review results. Results: There were 50 patients in the endoscopic group the average operation time was 43.68 ± 10.77 minutes, the average intraoperative blood loss was 35.38 ± 10.02 ml, there were seven cases of surgical segment recurrence and 10 cases of postoperative intervertebral instability at the surgical segment. There were 46 patients in the combined group, the average operation time was 52.26 ± 8.39 minutes, the average intraoperative blood loss was 39.23 ± 9.02ml, there was one case of surgical segment recurrence and two cases of surgical segment intervertebral instability. The operation time (t=-4.328, P<0.01), postoperative recurrence cases (χ2=4.386, P<0.05) and intervertebral instability cases (χ2=5.366, P<0.05) of the two groups of patients). The difference was statistically significant. There was no significant difference in intraoperative blood loss between the two groups (t=-1.965, P>0.05). For six months after surgery, the differences in VAS and ODI scores between the two groups were statistically significant. In addition, there were statistically significant differences in the VAS scores and ODI scores of the two groups of patients at each time point after surgery compared with those before surgery (P<0.05). Conclusion: The clinical efficacy of PTED combined with annulus fibrosus repair showed better clinical efficacy than PTED alone, and it can reduce the occurrence of surgical segment recurrence and intervertebral instability, suggesting that PTED combined with annulus fibrosus repair may be worthy of promotion in clinical practice.
Drug-induced thrombocytopenia (DIT) deserves both clinical and research attention for the serious clinical consequences and high prevalence of the condition. The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with thrombocytopenia events. A disproportionality analysis of DIT was conducted using reports submitted to FARES from January 2004 to December 2022. Both the information component (IC) and reporting odds ratio (ROR) algorithms were applied to identify an association between target drugs and DIT events. A total of 15,940,383 cases were gathered in FAERS, 168,657 of which were related to DIT events. The top 50 drugs ranked by number of cases and ranked by signal strength were documented. The top 5 drugs ranked by number of cases were lenalidomide (10,601 cases), niraparib (3726 cases), ruxolitinib (3624 cases), eltrombopag (3483 cases), and heparin (3478 cases). The top 5 drugs ranked by signal strength were danaparoid (ROR 37.61, 95%CI 30.46-46.45), eptifibatide (ROR 34.75, 95%CI 30.65-39.4), inotersen (ROR 34.00, 95%CI 29.47-39.23), niraparib (ROR 30.53, 95%CI 29.42-31.69), and heparin (ROR 28.84, 95%CI 27.76-29.97). The top 3 involved drug groups were protein kinase inhibitors, antimetabolites, and monoclonal antibodies and antibody-drug conjugates. The current comprehensive pharmacovigilance study identified more drugs associated with thrombocytopenia. Although the mechanisms of DIT have been elucidated for some drugs, others still require further investigation.
Pharmacovigilance , Thrombocytopenia , United States , Humans , United States Food and Drug Administration , Antibodies, Monoclonal , Adverse Drug Reaction Reporting Systems , Heparin
OBJECTIVE: To assess whether earlier administration of antibiotic prophylaxis after prelabor rupture of membranes (PROM) at term would decrease the incidence of maternal and neonatal infections. METHODS: This is a retrospective cohort study comparing women with term PROM who were initiated antibiotic prophylaxis within or after 6 h, and within or after 12 h from PROM to delivery during January 2019 to December 2021. Women with term PROM receiving cephalosporin and without contraindications to vaginal delivery or confirmed or suspected infection were included in the study. The primary outcome was puerperal infection, which refers to the reproductive tract infection occurring within 42 days of delivery. The type of pharmacoeconomic evaluation was selected based on the results of compared effectiveness between the early group and the late group. Propensity-score matching (PSM) was used to adjust confounding. Subgroup and sensitivity analyses were used to verify the robustness of results. RESULTS: We enrolled 5353 women with term PROM, including 4331 initiated with antibiotic within 6 h, 1022 after 6 h, 5077 within 12 h, and 276 after 12 h. After PSM, no significant difference was observed in the baseline characteristics of the groups. There was no statistical difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in puerperal infection (4.6% vs. 4.3%, P = 0.826; 2.9% vs. 4.6%, P = 0.471, respectively), total maternal infection, neonatal sepsis, and total neonatal infection. Cost-minimization analysis showed there was no significant difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in direct medical costs. CONCLUSION: This study showed that there was no statistical difference in the efficacy and economy of antibiotic prophylaxis used within 6-12 h after rupture of membranes versus after 6-12 h in women with term PROM.
Fetal Membranes, Premature Rupture , Puerperal Infection , Pregnancy , Infant, Newborn , Female , Humans , Antibiotic Prophylaxis , Fetal Membranes, Premature Rupture/drug therapy , Retrospective Studies , Anti-Bacterial Agents/therapeutic use
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.
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.
Objective: To investigate the clinical efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of multi-segmental lumbar disc herniation (msLDH). Methods: From January 2021 to December 2021, 75 patients with msLDH admitted to Baoding No.1 Hospital of Traditional Chinese Medicine were selected and divided into PTED group (n=40) and posterior lumbar interbody fusion (PLIF) group (n=35) according to different surgical methods. The operative time, intraoperative blood loss, surgical complications, Oswestry disability index (ODI) and Japanese Orthopedic Association score (JOA) scores were compared between the two groups. Results: In the PTED group, the average operation time was 57.45±12.01minutes, and the average intraoperative blood loss was 50.57±16.69ml. There were three patients with surgical complications, including one case of hematoma, one case of aggravation of neurological symptoms and one case of new onset of neurological symptoms. In the PLIF group, there were 12 cases undergoing single-segment operation, 15 cases undergoing double-segment operation and 8 cases undergoing three-segment operation, the average operation time was 137.26±34.64minutes, and the average intraoperative blood loss was 456.06±33.06ml, there were four cases of wound fat liquefaction or delayed healing, two cases of hematoma, and three cases of exacerbation of original neurological symptoms or new neurological symptoms. At one month, six months, and one year of postoperative, the ODI and JOA scores of the two groups were significantly improved compared with those preoperative, and the ODI scores of the PTED group were better than those of the PLIF group (t=3.131, 2.263, 3.768, all P<0.05). Conclusion: The surgical effect of PTED in the treatment of LDH is similar to that of PLIF. However, PTED has the advantages of short operation time, less blood loss, fewer surgical complications, and high surgical safety. It is worthy of clinical promotion.
OBJECTIVE: This study aimed to explore the correlation between diabetes mellitus (DM) and gallbladder cancer (GBC) in an epidemiological setting. METHODS: The study summarized the clinical and laboratory data of 2210 GBC Chinese patients in the authors' hospital. A total of 17 influencing factors for GBC, including gender, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FINS), the homeostasis model assessment of insulin resistance (HOMA-IR), retinol-binding protein 4 (RBP4), and lipid indexes were analyzed using unconditional logistic regression analysis. RESULTS: Based on the results of univariate logistic regression, the risk of GBC was significantly and positively correlated with serum triglyceride, low-density lipoprotein, FINS, HOMA-IR, being female, BMI, DM, non-alcoholic fatty liver disease, and gallbladder stone disease (GSD), and significantly negatively correlated with high-density lipoprotein and FBG concentrations in serum, as well as hypertension. According to multivariate analysis, FINS was significantly positively associated with GBC risk, while DM showed an insignificant negative association; FBG was also not important. The most significant independent factor of GBC risk in patients with DM was HOMA-IR. Fasting blood glucose levels showed a significant negative relationship with GBC in patients with DM. In addition, this study indicated a significantly negative association between serum RBP levels and GBC. CONCLUSIONS: The findings of the current study revealed that the efficient treatment of insulin resistance is an important approach for decreasing GBC risk, as opposed to lowering blood sugar only, particularly in patients with DM. Interestingly, FBG may have had an inverse association with the development of GBC in patients with type 2 DM. Of note, the study found that a dramatic initial drop in RBP may help predict the occurrence of GBC.
Diabetes Mellitus, Type 2 , Gallbladder Neoplasms , Insulin Resistance , Humans , Female , Male , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Case-Control Studies , Gallbladder Neoplasms/epidemiology , Fasting , Retinol-Binding Proteins, Plasma/metabolism
Bovine mammary epithelial cells (bMECs) are involved in the early defense against the invasion of intramammary pathogens and are essential for the health of bovine mammary gland. MicroRNA (MiRNA) is a key factor that regulates cell state and physiological function. In the present study, the transcriptome profiles of miR-223 inhibitor transfection group (miR-223_Inhibitor) and negative control inhibitor transfection group (NC_Inhibitor) within bMECs were detected via the RNA sequencing (RNA-seq) platform. Based on these experiments, the differentially expressed mRNAs (DE-mRNAs) of the miR-223_Inhibitor transfection group were screened, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses of DE-mRNAs were performed. The results revealed that compared with the NC_Inhibitor, 224 differentially expressed genes (DEGs) were identified in the miR-223_Inhibitor, including 184 upregulated and 40 downregulated genes. The functional annotation of the above DEGs indicated that some of these genes are involved in the immune response generated by extracellular substance stimulation, regulation of the activity of cytokines and chemokines, and the immune signaling pathways of NF-κB and TNF. Meanwhile, miR-223_inhibitor upregulated the immune key genes IRF1 and NFκBIA, cytokines IL-6 and IL-24, as well as chemokines CXCL3, CXCL5, and CCR6, triggering a signaling cascade response that exacerbated inflammation in bMECs. These results suggested that miR-223 plays an important role in inhibiting the inflammatory response and maintaining the stability of bMECs, and is a potential target for treating mastitis in dairy cows.
Cattle Diseases , MicroRNAs , Female , Cattle , Animals , RNA-Seq/veterinary , Mammary Glands, Animal/metabolism , Inflammation/genetics , Inflammation/veterinary , Inflammation/metabolism , Sequence Analysis, RNA/veterinary , Epithelial Cells/metabolism , Cytokines/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Cattle Diseases/metabolism
BACKGROUND: Myzus persicae (Hemiptera: Aphididae) is one of the most notorious pests of many crops worldwide. Most Cry toxins produced by Bacillus thuringiensis show very low toxicity to M. persicae; however, a study showed that Cry41-related toxin had moderate toxic activity against M. persicae. In our previous work, potential Cry41-related toxin-binding proteins in M. persicae were identified, including cathepsin B, calcium-transporting ATPase, and Buchnera-derived ATP-dependent 6-phosphofructokinase (PFKA). Buchnera is an endosymbiont present in almost all aphids and it provides necessary nutrients for aphid growth. This study investigated the role of Buchnera-derived PFKA in Cry41-related toxicity against M. persicae. RESULTS: In this study, recombinant PFKA was expressed and purified, and in vitro assays revealed that PFKA bound to Cry41-related toxin, and Cry41-related toxin at 25 µg ml-1 significantly inhibited the activity of PFKA. In addition, when M. persicae was treated with 30 µg ml-1 of Cry41-related toxin for 24 h, the expression of dnak, a single-copy gene in Buchnera, was significantly decreased, indicating a decrease in the number of Buchnera. CONCLUSION: Our results suggest that Cry41-related toxin interacts with Buchnera-derived PFKA to inhibit its enzymatic activity and likely impair cell viability, resulting in a decrease in the number of Buchnera, and finally leading to M. persicae death. These findings open up new perspectives in our understanding of the mode of action of Cry toxins and are useful in helping improve Cry toxicity for aphid control. © 2023 Society of Chemical Industry.
Aphids , Buchnera , Animals , Phosphofructokinases/metabolism , Phosphofructokinase-1/metabolism , Adenosine Triphosphate/metabolism
INTRODUCTION: Diabetic nephropathy (DN) is one of the most common and lethal diabetic complications worldwide and is associated with a high risk of mortality. However, the exact mechanism behind its development is unknown. The mesangial cells (MCs) and non-coding RNAs are critical for DN, but it is unknown whether a MEG3/miR-21/ORAI1 regulatory axis exists in MCs. Hence, in this study, we aimed to understand whether the MEG3/miR-21/ORAI1 regulatory axis has a role in the pathophysiology of DN. RESULTS: We demonstrated that high-glucose stimuli downregulated MEG3 and ORAI1 expression while enhancing miR-21 expression. Exogenous miR-21 mimics inhibited ORAI1 expression, which was partially salvaged or reversed by MEG3 overexpression. Furthermore, RIP assay demonstrated that the beads labeled with AGO2 antibody could enrich more miR-21 and MEG3 than those labeled with control IgG antibody; both of them formed the RNA-induced silencing complex. Further, the biochemical indicators of db/db mice significantly improved, and renal fibrinoid necrosis was ameliorated using a miR-21 inhibitor. CONCLUSION: The MEG3/miR-21/ORAI1 axis regulates the manifestation of DN in diabetic mice and MCs, and the miR-21 inhibitor can be a potential therapeutic strategy to alleviate DN, once the presence of such an axis is found in humans.
Diabetes Mellitus, Experimental , Diabetic Nephropathies , MicroRNAs , RNA, Long Noncoding , Animals , Humans , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Necrosis , ORAI1 Protein , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
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.
Rats , Animals , Metabolomics/methods , Brain Injuries , Biomarkers/metabolism , Brain Stem/metabolism
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.
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.
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.
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.
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.
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.
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.
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.
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.
