1.Material basis and action mechanism of drug-containing serum of Modified Erxian Pill inhibiting macrophage pyroptosis
Siyuan LI ; Yuru WANG ; Ye XU ; Di GUO ; Nan NAN ; Yang LIU ; Jie ZHAO ; Huiqin HAO
Chinese Journal of Tissue Engineering Research 2025;29(19):4029-4037
		                        		
		                        			
		                        			BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.
		                        		
		                        		
		                        		
		                        	
2.Influencing factors for delay in healthcare-seeking, definitive diagnosis, identification in patients with pulmonary tuberculosis in Minhang District
MA Qiongjin ; YAN Huiqin ; WU Yunhua ; GUO Xu ; YANG Lijia ; TANG Lihong ; YANG Shengyuan
Journal of Preventive Medicine 2025;37(1):59-64
		                        		
		                        			Objective:
		                        			To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients.
		                        		
		                        			Methods:
		                        			Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models.
		                        		
		                        			Results:
		                        			A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560)
		                        		
		                        			Conclusions
		                        			Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.
		                        		
		                        		
		                        		
		                        	
3.Effects of wogonin on joint inflammation in collagen-induced arthritis rats via the endoplasmic reticulum stress pathway
Yuru WANG ; Siyuan LI ; Ye XU ; Yumeng ZHANG ; Yang LIU ; Huiqin HAO
Chinese Journal of Tissue Engineering Research 2025;29(5):1026-1035
		                        		
		                        			
		                        			BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.
		                        		
		                        		
		                        		
		                        	
4.Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism
Jing CHEN ; Xiaoyi YANG ; Jing CHEN ; Xin SHAN ; Jie WANG ; Huiqin XU ; Zhiyang LYU
China Pharmacy 2024;35(2):186-191
		                        		
		                        			
		                        			OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract (GBE) on renal inflammation in diabetic nephropathy (DN) model mice, and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group, positive control group [metformin 200 mg/(kg·d)], GBE low-dose and high-dose groups [100, 200 mg/(kg·d)], with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically, control group and model group were given constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The body weight, fasting blood glucose, 24-hour food intake, 24-hour urine output, monocyte chemoattractant protein-1 (MCP-1), interleukin-12 (IL-12), IL-10, advanced glycation end products (AGEs), blood urea nitrogen (BUN) and serum creatinine (Scr) of mice were measured, and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed, and the expressions of macrophage polarization marker proteins [type M1: inducible nitric oxide synthase (iNOS); type M2: arginase-1 (Arg-1)] and AGEs-the receptor of advanced glycation end products (RAGE)/Ras homolog gene pharm_chenjing@163.com family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group, the symptoms such as renal cortical hyperplasia, vacuoles, infiltration of inflammatory cells, and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups; body weight, serum level of IL-10, the expression of Arg-1 in the renal cortex were significantly higher than model group (P< 0.01); fasting blood glucose, 24-hour food intake, 24-hour urine output, serum levels of MCP-1, IL-12, BUN, Scr and AGEs, the ratio of bilateral kidneys to body weight, renal injury score, the proportion of renal interstitial fibrosis, the protein expressions of iNOS, RAGE, RhoA and ROCK1 (except for GBE low-dose group) in renal cortex were significantly lower than model group (P<0.01). CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice, the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.
		                        		
		                        		
		                        		
		                        	
5.The current situation and influencing factors of patient perception for humanistic care in 30 provincial hospitals
Fengjian ZHANG ; Haixin ZHANG ; Yilan LIU ; Shaoshan PAN ; Shujie GUO ; Xia XIN ; Yan YANG ; Huiqin XI ; Xiue LI ; Yuanjuan CHENG ; Beirong MO ; Weihua LI ; Xiaohong ZHANG ; Fang WANG ; Hongxia WANG
Chinese Journal of Nursing 2024;59(3):324-330
		                        		
		                        			
		                        			Objective To understand the current status and influencing factors of patient perception for humanistic care in China hospitals,and to provide a basis for developing nursing humanistic care measures and improving the quality of nursing humanistic care services.Methods A total of 30,099 outpatients and inpatients from 107 hospitals in 30 provinces(autonomous regions and municipalities)from July to August 2022 as survey subjects.A general information questionnaire and the Relational Caring Questionnaire-Patient Form were used for a cross-sectional survey,and a single-factor analysis was used to analyze the influencing factors of patient relationship care.Results Finally,29 108 valid questionnaires were collected,and the effective questionnaire recovery rate was 96.7%.The patient evaluation of relationship care was(65.72±8.61)points.Single-factor analysis showed that gender,age,marital status,children's situation,education level,occupation,place of residence,average family income,medical insurance type,visiting department,and location of the visiting hospital,and whether or not surgery were influencing factors of patient relationship care(P<0.05).Conclusion The evaluation score of caregiver-patient relationship care among Chinese hospital patients is above average,but there is still room for improvement in western and rural regions,seriously ill and outpatient patients,low-income and low-medical insurance reimbursement populations,and non-surgical patients.Medical institutions at all levels should optimize and improve nursing humanistic care services based on influencing factors,and further enhance patients'perception of nursing humanistic care.
		                        		
		                        		
		                        		
		                        	
6.Analysis of the suspected cases of measles and rubella in Pudong New Area of Shanghai, 2013‒2022
Xiao WANG ; Aihua ZHANG ; Huiqin FU ; Yuying YANG ; Xiaoxian CUI ; Lipeng HAO ; Yanqiu ZHOU ; Lifeng PAN
Shanghai Journal of Preventive Medicine 2024;36(6):534-539
		                        		
		                        			
		                        			ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022, and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022, among which the positive rate of measles IgM antibody was 33.55% (513/1 529). The highest positive rate (20.73%) was from March to May , and the positive rate of rubella IgM antibody was 6.80% (104/1 529). The positive rate of both IgM was higher in males than that in females (P<0.05). The IgM against measles was mainly detected in 0‒ years old (63.16%, 96/152) and 20‒ years old (45.61%, 161/353). The IgM against rubella was mainly detected in 10‒20 years old (27.27%, 18/66). The IgM antibody could be detected more easily from 4 to 28 days after eruption, and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years (2013‒2019). There were 2 D8 genotype strains, and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles, and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children, in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization, and the surveillance of imported measles cases should be strengthened. 
		                        		
		                        		
		                        		
		                        	
7.Application of 9-gene panel in assisting fine needle aspiration cytology to diagnose thyroid cancer
Yanqi ZHANG ; Huan ZHAO ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Zhihui ZHANG ; Tian QIU ; Xin YANG ; Ting XIAO ; Huiqin GUO
Chinese Journal of Oncology 2024;46(11):1049-1057
		                        		
		                        			
		                        			Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P<0.01), but there is no significant difference in SN, accuracy (both P>0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.
		                        		
		                        		
		                        		
		                        	
8.Application of 9-gene panel in assisting fine needle aspiration cytology to diagnose thyroid cancer
Yanqi ZHANG ; Huan ZHAO ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Zhihui ZHANG ; Tian QIU ; Xin YANG ; Ting XIAO ; Huiqin GUO
Chinese Journal of Oncology 2024;46(11):1049-1057
		                        		
		                        			
		                        			Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P<0.01), but there is no significant difference in SN, accuracy (both P>0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.
		                        		
		                        		
		                        		
		                        	
9.Comparison of clinical manifestations, laboratory characteristics and treatment of 153 patients with acute and chronic brucellosis
Huiqin YANG ; Haipeng ZHENG ; Xudan CHEN ; Ying TAN ; Fuchun ZHANG ; Linghua LI ; Jian WANG
Chinese Journal of Endemiology 2024;43(5):398-403
		                        		
		                        			
		                        			Objective:To learn about the clinical manifestations, laboratory characteristics and treatment of patients with acute and chronic brucellosis.Methods:Clinical data of 153 brucellosis patients admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from 2012 to 2022 were retrospectively collected, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, imaging examination results, treatment and prognosis. According to the course of disease < 180 d and ≥180 d, these patients were divided into acute brucellosis group and chronic brucellosis group, and the clinical data of the two groups of patients were compared and analyzed.Results:A total of 153 patients with brucellosis were included, including 119 in the acute brucellosis group and 34 in the chronic brucellosis group. The age was (46.2 ± 13.8) years old, with 115 males (75.2%) and 38 females (24.8%), and 85 patients (55.6%) were occupational exposed. Complications occurred in 90 patients (58.8%), and the incidence of complications in the acute brucellosis group was lower than that in the chronic brucellosis group [76.5% (26/34) vs 53.8% (64/119), χ 2 = 5.62, P = 0.018]. The most common clinical manifestations were fever and arthralgia, with 128 cases (83.7%) and 124 cases (81.0%), respectively. The incidence of fever in the acute brucellosis group was higher than that in the chronic brucellosis group [87.4% (104/119) vs 70.6% (24/34), χ 2 = 5.46, P = 0.019], while the incidence of arthralgia was lower than that in the chronic brucellosis group [77.3% (92/119) vs 94.1% (32/34), χ 2 = 4.83, P = 0.027]. In laboratory tests, the positive rate of blood culture was 59.5% (91/153), and it was higher in the acute brucellosis group than that in the chronic brucellosis group [67.2% (80/119) vs 32.4% (11/34), P < 0.05]. The incidence of elevated procalcitonin [PCT, 58.6% (58/99) vs 24.1% (7/29), χ 2 = 10.65, P = 0.001] and the incidence of liver dysfunction [33.9% (40/118) vs 15.2% (5/33), χ 2 = 4.33, P = 0.037] in the acute brucellosis group were higher than those in the chronic brucellosis group. In the imaging examination, 61 patients (39.9%) experienced bone destruction, and the incidence of bone destruction in the chronic brucellosis group was higher than that in the acute brucellosis group [55.9% (19/34) vs 35.3% (42/119), χ 2 = 4.68, P = 0.031]. All patients were treated with antibiotics, with a median of 3 and 4 types of antibiotics used in the acute and chronic brucellosis groups, respectively. The overall incidence of adverse drug reactions was 5.2% (8/153). After treatment, 65 cases (42.5%) recovered, 70 cases (45.8%) improved, and 18 cases (11.8%) did not recover. Conclusions:The main clinical manifestations of brucellosis patients are fever and arthralgia, with a high incidence of complications. All patients are treated with combined antibiotics therapy. Patients in acute brucellosis group have a higher incidence of fever, positive blood culture, elevated PCT and abnormal liver function, while patients in chronic brucellosis group have a higher incidence of complications, arthralgia and bone destruction.
		                        		
		                        		
		                        		
		                        	
10.Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study
Ziwei HU ; Yangyang HU ; Shuoqi ZHANG ; Li DONG ; Xiaoqi CHEN ; Huiqin YANG ; Linchong SU ; Xiaoqiang HOU ; Xia HUANG ; Xiaolan SHEN ; Cong YE ; Wei TU ; Yu CHEN ; Yuxue CHEN ; Shaozhe CAI ; Jixin ZHONG ; Lingli DONG
Chinese Medical Journal 2024;137(15):1811-1822
		                        		
		                        			
		                        			Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.
		                        		
		                        		
		                        		
		                        	
            

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