Thyroid-associated ophthalmopathy(TAO)is a progressive eye disease characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue.TAO tends to have complex and diverse symptoms and signs,with the features of diversity and concealment,which seriously affect the quality of life of patients.The pathogenesis of TAO is closely associated with thyroid autoimmunity.This article reviews the pathogenesis,clinical features,and treatment of TAO.

Objective:To analyze the drug-resistance pattern and molecular epidemiological characteristics of Enterobacteriales carrying the blaNDM gene in Lishui, aiming to guide clinical anti-infection treatment. Methods:Non-duplicate blaNDM-carrying Enterobacteriales, isolated from Lishui Central Hospital, were collected and identified by VITEK MS. The minimal inhibitory concentrations (MICs) were detected by the broth microdilution method. The ST types of the strains were determined by multilocus sequence typing (MLST). Plasmid types were identified by transformation or conjugation experiments and replication initiator amplification experiments. The transposon structures were detected by PCR amplification. Finally, the epidemic regularity of blaNDM gene in Lishui was analyzed from three levels: clonal group, plasmid, and mobile genetic elements. Results:A total of 109 blaNDM-positive strains were collected. Among them, 60 strains carried the blaNDM-1 gene and 49 strains carried the blaNDM-5 gene. The 109 strains showed 100% resistance to ceftazidime and cefotaxime. The resistance rates to peracillin-tazobactam and imipenem were higher than 80%. Strains carrying the blaNDM-5 gene were more resistant to meropenem than those carrying blaNDM-1 gene( P<0.05). A total of 68 STs were detected from 109 strains, and IncX3, IncFⅡγ, IncA/C and IncT/R plasmids were detected, and 90.83% of the blaNDM genes were located in the IncX3 plasmid. Twelve types of blaNDM gene surrounding structures existed, and they all carried the highly conserved blaNDM- bleMBL- trpF gene sequence. Conclusions:The blaNDM gene has diverse transmission modes in Lishui. The IncX3 plasmid is the main factor mediating its transfer, and all strains carry highly conserved blaNDM- bleMBL- trpF gene sequence.

Objective To investigate the anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective:To analyze the drug-resistance pattern and molecular epidemiological characteristics of Enterobacteriales carrying the blaNDM gene in Lishui, aiming to guide clinical anti-infection treatment. Methods:Non-duplicate blaNDM-carrying Enterobacteriales, isolated from Lishui Central Hospital, were collected and identified by VITEK MS. The minimal inhibitory concentrations (MICs) were detected by the broth microdilution method. The ST types of the strains were determined by multilocus sequence typing (MLST). Plasmid types were identified by transformation or conjugation experiments and replication initiator amplification experiments. The transposon structures were detected by PCR amplification. Finally, the epidemic regularity of blaNDM gene in Lishui was analyzed from three levels: clonal group, plasmid, and mobile genetic elements. Results:A total of 109 blaNDM-positive strains were collected. Among them, 60 strains carried the blaNDM-1 gene and 49 strains carried the blaNDM-5 gene. The 109 strains showed 100% resistance to ceftazidime and cefotaxime. The resistance rates to peracillin-tazobactam and imipenem were higher than 80%. Strains carrying the blaNDM-5 gene were more resistant to meropenem than those carrying blaNDM-1 gene( P<0.05). A total of 68 STs were detected from 109 strains, and IncX3, IncFⅡγ, IncA/C and IncT/R plasmids were detected, and 90.83% of the blaNDM genes were located in the IncX3 plasmid. Twelve types of blaNDM gene surrounding structures existed, and they all carried the highly conserved blaNDM- bleMBL- trpF gene sequence. Conclusions:The blaNDM gene has diverse transmission modes in Lishui. The IncX3 plasmid is the main factor mediating its transfer, and all strains carry highly conserved blaNDM- bleMBL- trpF gene sequence.

Objective To investigate the anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To evaluate the risk factors of acute kidney injury (AKI) in patients with multiple wasp stings.Methods:Patients with multiple wasp stings were retrospectively enrolled in Hanzhong Central Hospital from September 2010 to November 2020. Based on whether the patients developed AKI, the patients were divided into AKI group and non-AKI group. The general characteristics and laboratory examinations between the two groups were compared. The logistic regression model was used to analyze the risk factors of AKI.Results:A total of 356 patients with multiple wasp stings were recruited in this study, with 196 males (55.1%). The age was 56.0(45.0, 64.0) years old. There were 59 patients (16.6%) with hypertension and 13 patients (3.6%) with diabetes. There were 51 patients (14.3%) in the AKI group and 305 patients (85.7%) in the non-AKI group. Baseline data and biochemical examinations indicated that the two groups showed significant differences in gender, age, sting sites (systemic or local), sting needles, proportions of gross hematuria, leukocyte count, hemoglobin, creatine kinase, alanine transaminase, aspartate aminotransferase, total bilirubin, proportions of urinary protein, and proportions of urine occult blood (all P<0.05). The multivariate logistic regression analysis results showed that the increasing number of sting needles (every 10 needles increase, OR=1.866, 95% CI 1.289-2.071, P=0.001), gross hematuria ( OR=9.770, 95% CI 2.586-36.910, P=0.001), decreasing hemoglobin (every 1 g/L increase, OR=0.016, 95% CI 0.001-0.355, P=0.009), increasing aspartate aminotransferase (every 100 U/L increase, OR=1.311, 95% CI 1.144-1.502, P<0.001), and increasing total bilirubin (every 10 μmol/L increase, OR=1.200, 95% CI 1.008-1.430, P=0.041) were independent influencing factors of AKI. Conclusions:The increasing number of sting needles, gross hematuria, decreasing hemoglobin, increasing aspartate aminotransferase, and increasing total bilirubin are independent risk factors of AKI in patients with multiple wasp stings.

Objective:To investigate the sedative effect after congenital heart disease surgery in children under the bi-spectral index monitoring(BIS).Methods:A prospective cohort study was performed, we selected 264 children with congenital heart disease who were admitted to the cardiac intensive care unit at Shanghai Children′s Medical Center from September 2018 to August 2019, 126 cases in the intervention group, and 138 cases in the control group.The control group used Ramsay sedation score to evaluate the sedative effect, meanwhile the intervention group was evaluated by Ramsay sedation score and BIS.The incidence of adverse events related to extubation performed within 8 hours after congenital heart disease surgery, and the length of stay in ICU between two groups were compared.The average mechanical ventilation time of the patients whose mechanical ventilation time was more than 8 hours in two groups was compared.The use of sedative drugs midazolam and morphine in children with mechanical ventilation time for more than 24 hours and liver damage, and the incidence of respiratory depression during ventilator withdrawal were analyzed.Results:In children with early extubation, there were 62 cases in the intervention group and 70 cases in the control group.Compared with the control group, the intervention group had a low incidence of extubation-related adverse events (including unplanned extubation, dysphoria after sputum aspiration, and inhalation inhibition after extubation). The average mechanical ventilation time in the intervention group[(8.18±1.95)h] was less than that in the control group[(9.53±1.37)h, P<0.05] of the patients whose mechanical ventilation time was more than 8 hours but less than 24 hours.In children with mechanical ventilation time more than 24 hours, 28 cases were in the intervention group and 35 cases in the control group.The average doses of midazolam and morphine in the intervention group[(1.82±0.40)μg/(kg·min), (8.64±3.03)μg/(kg·h)] were less than those in the control group[(2.73±0.79) μg/(kg·min), (14.32±5.01)μg/(kg·h), all P<0.05]. Among the 28 children in the intervention group with mechanical ventilation time more than 24 hours, 13 cases had liver damage, and 15 cases of the 35 children in the control group had liver damage.The average doses of midazolam and morphine in the intervention group[(1.42±0.51)μg/(kg·min), (6.88±2.17)μg/(kg·h)] were lower than those in the control group[(2.25±0.62)μg/(kg·min), (11.88±3.56)μg/(kg·h), all P<0.05]. The incidence of inhalation inhibition in the intervention group was lower than that in the control group ( χ2=48.303, P<0.05). Conclusion:The sedation after congenital heart disease surgery in children under the BIS is effective.

Objective:To investigate the value of quick sequential organ failure assessment (qSOFA) score in early identification for sepsis patients of different ages.Methods:A retrospective study was conducted. The clinical data of 1 529 patients with suspected infection in emergency department of Changshu No.2 People's Hospital from September 2017 to March 2020 were collected. All patients were assessed for qSOFA score, and the diagnosis and treatment were recorded. Sepsis-3 was defined as the diagnostic criteria for sepsis. All the patients were divided into five groups according to age, youth group (< 45 years old), middle-aged group (45-59 years old), presenile group (60-74 years old), elderly group (75-89 years old), and longevity group (≥90 years old). The patients' examination results, diagnosis and treatment status were collected. The distribution of different scores of qSOFA was analyzed to calculate the sensitivity, specificity, positive predictive value and negative predictive value of different qSOFA scores for the diagnosis of sepsis in patients with suspected infection of different ages. The receiver operator characteristic curve (ROC curve) was drawn to analyze the diagnostic value of qSOFA score for sepsis in patients with suspected infection at different ages.Results:Of 1 529 suspected infection patients, there were 67 patients in youth group, 129 patients in middle-aged group, 465 patients in presenile group, 778 patients in elderly group and 90 patients in longevity group. There were significant differences in lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), qSOFA score and the increased value of SOFA score compared with the basic value (ΔSOFA) among the suspected infection patients at different ages. Among suspected infection patients at different ages, the patients with qSOFA score ≥ 1 were the most, and the proportion of sepsis patients was larger. Further analysis showed that qSOFA score ≥1 had a high diagnostic sensitivity in patients with suspected infection at different ages. In the youth group, the sensitivity was 84.4%, and the specificity was the highest (74.3%). Although qSOFA score ≥ 2 had a high specificity in the diagnosis of sepsis (all > 97%), its sensitivity was very low (all < 44%). In this study, all patients with a qSOFA score of 3 were sepsis, and the positive predictive value of the diagnosis of sepsis in each group was 100%. ROC curve analysis showed that the area under ROC curve (AUC) of qSOFA score for the diagnosis of sepsis in all suspected infection patients was 0.771 [95% confidence interval (95% CI) was 0.747-0.794], when the best cut-off value was 0.5, the sensitivity was 93.4% and the specificity was 45.6%. Among suspected infection patients of all ages, the accuracy of qSOFA score in the diagnosis of sepsis in the youth group and the longevity group was relatively high, with AUC (95% CI) of 0.825 (0.724-0.927) and 0.837 (0.756-0.917), respectively; when the best cut-off value was 0.5, the sensitivity was 84.4% or 92.2%, and the specificity was 74.3% or 56.4%, respectively. Conclusions:qSOFA score has an early diagnosis value for sepsis, especially in the patients aged < 45 years old or ≥ 90 years old. Using qSOFA score ≥2 to screen patients with suspected infection is likely to cause missed diagnosis.

Objective:To explore the distribution of pelvic lymph node (PLN) metastasis and the correlative dangerous factors in early cervical cancer patients.Methods:The medical records of 508 patients who underwent extensive hysterectomy and lymphadenectomy for International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb-Ⅱb cervical cancer in Guizhou Provincial People`s Hospital were reviewed retrospectively.Results:There were 278 patients with stage Ⅰb cervical cancer, 204 patients with stage Ⅱa cervical cancer and 26 patients with stage Ⅱb cervical cancer; the positive rate of lymph node metastasis was 16.7%(85/508), and obturator lymph node metastasis was the most common (56.6%); there were 19 patients with bilateral lymph node metastasis, accounting for 22.35%(19/85); lymph node metastasis occurred 104 times (two times for bilateral simultaneous transfer), and jumping lymph node metastasis accounted for 37.5%(39/104); common iliac lymph node metastasis accounted for 18.3%(19/104). The metastasis rate of patients with stage Ⅱa and Ⅱb (including parametrial, lymph node, ovarian and oviduct metastasis) was higher than that of patients with stage Ⅰb, and the odd ratio ( OR) was 2.30 and 2.48 respectively ( P<0.05); the metastasis rate of patients with moderately differentiated tumors was significantly higher than that of patients with well differentiated and poorly differentiated tumors ( P<0.05). There was no significant difference in the positive rate of pelvic lymph node metastasis among patients with different ages and histological types ( P>0.05); the positive rate of pelvic lymph node metastasis in patients with stage Ⅱa and Ⅱb was higher than that in patients with stage Ⅰb with statistically significant difference ( P<0.05); the positive rate of pelvic lymph node metastasis in patients with moderately differentiated tumors was higher than that in patients with well differentiated and poorly differentiated tumors, with statistically significant difference ( P<0.05). Conclusions:Obturator lymph node metastasis is the most common in cervical cancer. The risk of lymph node metastasis is increased in patients with stage Ⅱa or moderately differentiated tumors. Jumping metastasis is also a common way of metastasis, which suggests that standard and complete lymph node resection is an important measure to ensure the curative effect.